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Purpose of Review: This study aims to assess the current state of cardio-oncology in reference to advocacy efforts, access to care, and perspective of stakeholders in their ability to provide patient care as well as development of "across the aisle" synergy among cardiologists and oncologists and academic and non-academic centers in various worldwide locations., Recent Findings: During the last decade, there has been a significant and diverse growth in cardio-oncology. We reviewed the experience from cardiologists and oncologists across different healthcare systems, the global trends, the role of collaborative networks, and the importance of advocacy efforts. Cardio-oncology will continue to grow, but there is an unmet need to increase awareness, improve education, and expand access to care to larger segments of the cancer population in order to have a more significant impact on their health. The growing collaboration through professional societies and collaborative networks provides an opportunity to advance the cardiovascular care of cancer patients to meet the projected needs in a growing and more diverse population.

"Transitional-age youth" describes those whose ages range from 16-24 years old. In this phase, the youth face new challenges and new experiences which may increase the risk for having mental health problems, yet not very many seek help from mental health professionals. In Indonesia, no data are available about mental health problems and the needs of transitional-age youth. This study explores common mental health problems experienced during this stage and assesses how they cope with problems and their expectations from health services. This was a cross-sectional study involving 393 Indonesians aged 16-24 years in May 2020. More than 90% of students had financial and academic difficulties and felt lonely. The most prevalent mental health problem among students was anxiety (95.4%). Most of the students, ranging from 90% to 96.4%, had positive coping strategies. However, around 50% of respondents reported self-harming and having suicidal thoughts. The results of subcategories analysis between ages and faculties were similar. Their most important expectations from mental health services included confidentiality (99.2%) and being welcoming and friendly (99.2%). In conclusion, this study highlighted the most common problems transitional-age youth experience in Indonesia. While some of them already knew how to deal with their problems, not all the participants had good coping mechanisms. Their healthcare expectations were also explored, thereby providing a useful background to revise and amend the current conditions.

Introduction: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus which has not been identified previously in humans. The disease leads to respiratory problems, systemic disorders, and death. To stop the virus transmission, physical distancing was strongly implemented, including working and school from home (WFH & SFH). The limitation altered daily routines and needs advanced to adapt. Many have felt uncomfortable and this could have triggered anxiety symptoms. This study aimed to evaluate the proportion of significant anxiety symptoms and its association with COVID-19-related situations in an Indonesian context during the initial months of the pandemic. Methods: An online community survey was distributed through social media and communication platforms, mainly WhatsApp, targeting people >18 years old in Indonesia. Anxiety symptoms were assessed using Generalized Anxiety Disorder-7 (Indonesian Version). Demographical data and information on social situation related to the COVID-19 pandemic were collected. The proportion of clinically significant anxiety symptoms was calculated and the association with demographic and social factors was assessed using chi square test (χ 2 ) and logistic regression for multivariate analysis. Results: Out of 1215 subjects that completed the survey, 20.2% ( n = 245) exhibited significant anxiety symptoms. Several factors, such as age (AOR = 0.933 CI 95% = 0.907-0.96), sex (AOR = 1.612 CI 95% = 1.097-2.369), medical workers (AOR = 0.209 CI 95% = 0.061-0.721), suspected case of COVID-19 (AOR = 1.786 CI 95% = 1.001-3.186), satisfaction level of family support (AOR = 3.052 CI 95% = 1.883-4.946), and satisfaction level of co-workers (AOR = 2.523 CI 95% = 1.395-4.562), were associated with anxiety. Conclusion: One out of five Indonesian people could have suffered from anxiety during the COVID-19 pandemic. The riskiest group being young females, people who had suspected cases of COVID-19, and those with less satisfying social support. Nevertheless, health workers were found to have a lesser risk of developing anxiety. Accessible information and healthcare, social connection, supportive environment, and mental health surveillance are important to prevent bigger psychiatric problems post-pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Anindyajati, Wiguna, Murtani, Christian, Wigantara, Putra, Hanafi, Minayati, Ismail, Kaligis, Savitri, Uiterwaal and Diatri.)

Purpose: This study systematically investigated the potential of four model drugs (verapamil HCl, flurbiprofen, atenolol, and furosemide), each belonging to a different class of Biopharmaceutics Classification Systems (BCS) to be developed into oral modified release dosage forms after loading with halloysite nanotubes (HNTs)., Methods: The drugs were studied for their loading (mass gain %) by varying solvent system, method, pH, and ratios of loading into the nanotubes using D-optimal split-plot design with the help of Design Expert software. Drug-loaded halloysites were characterized by XRD, DTA, FTIR, SEM, and HPLC-UV-based assay procedures. Dissolution studies were also performed in dissolution media with pH 1.2, 4.5, and 6.8. Moreover, the optimized samples were evaluated under stress stability conditions for determining prospects for the development of oral dosage forms., Results: As confirmed with the results of XRD and DTA, the drugs were found to be converted into amorphous form after loading with halloysite (HNTs). The drugs were loaded in the range of ~7-9% for the four drugs, with agitation providing satisfactory and equivalent loading as compared to vacuum plus agitation based reported methods. FTIR results revealed either only weak electrostatic (verapamil HCl and flurbiprofen) or no interaction with the surface structure of the HNTs. The dissolution profiling depicted significantly retarded release of drugs with Fickian diffusion from a polydisperse system as a model that suits well for the development of oral dosage forms. HPLC-UV-based assay indicated that except furosemide (BCS class IV), the other three drugs are quite suitable for development for oral dosage forms., Conclusion: The four drugs investigated undergo phase transformation with HNTs. While agitation is an optimum method for loading drugs with various physicochemical attributes into HNTs; solvent system, loading ratios and pH play an important role in the loading efficiency respective to the drug properties. The study supports the capability of developing HNT-based modified release oral dosage forms for drugs with high solubility., Competing Interests: The authors report no conflicts of interest for this work., (© 2021 Husain et al.)

The 2019 novel coronavirus (2019-nCoV), commonly known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), was first revealed in late 2019 in Wuhan city, Hubei province, China. It was subsequently spread globally and thereby declared as a pandemic by WHO in March 2020. The disease causes severe acute respiratory illness and is highly contagious due to the fast-onward transmission. As of the mid of November 2020, the disease has affected 220 countries with more than 16 million active cases and 1.3 million deaths worldwide. Males, pregnant women, the elderly, immunosuppressed patients, and those with underlying medical conditions are more vulnerable to the disease than the general healthy population. Unfortunately, no definite treatment is available. Although remdesivir as an antiviral had been approved for use in those above 12 years of age and 40 kg weight group, it has been observed to be ineffective in large-scale SOLIDARITY trials by WHO. Moreover, dexamethasone has been found to increase the recovery rate of ventilated patients; oxygen and inhaled nitric oxide as a vasodilator have been given emergency expanded access. In addition, more than 57 clinical trials are being conducted for the development of the vaccines on various platforms. Two vaccines were found to be significantly promising in phase III results. It is concluded that till the approval of a specific treatment or development of a vaccine against this deadly disease, the preventive measures should be followed strictly to reduce the spread of the disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shoaib, Ahmed, Sikandar, Yousuf and Saleem.)

Background and Aim: Different polymerase chain reaction (PCR) techniques have and are still being used for the direct detection of Brucella DNA in serum samples of different animal species and humans without being validated or properly validated, resulting in discrepancies. Thus, this study aimed to evaluate the diagnostic performance of the TaqMan Real-Time-PCR (RT-PCR) targeting the bcsp31 gene versus conventional PCR for the accurate diagnosis of brucellosis at the genus level in cattle sera., Materials and Methods: One hundred and eighty-four serum samples were collected from bacteriologically positive and negative cows with ages ranging from 1 to 5 years old at some infected private farms in the Nile Delta under quarantine measures as well as brucellosis free farms. These samples were classified into four groups after serological diagnosis and investigated by TaqMan RT-PCR and conventional PCR targeting the IS711 gene for Brucella DNA detection. The diagnostic performance characteristics of both PCR techniques were estimated considering the bacteriological results as a gold standard., Results: TaqMan RT-PCR revealed superiority over conventional PCR; it was able to detect Brucella DNA in 95% (67/70) and 89% (25/28) of the cattle sera samples belonging to Group 1 (serologically and bacteriologically positive) and Group 2 (serologically negative but bacteriologically positive), respectively. On evaluating the diagnostic performance, TaqMan RT-PCR showed superior diagnostic sensitivity (93.9%), diagnostic specificity (88.4%), performance index (182.3), almost perfect kappa agreement (0.825±0.042), strong positive correlation (r=0.826), high accuracy based on the receiver operating characteristic (ROC) curve, and area under the ROC curve (0.911) at p<0.05 and CI of 95%., Conclusion: A cattle serum sample is not the metric of choice for targeting Brucella genomic DNA by conventional PCR. The time-saving and rapid TaqMan RT-PCR method revealed a better diagnostic performance in the detection of Brucella DNA in cattle sera. Such performance offered by TaqMan RT-PCR may be considered a step toward the possibility of using such technology in the direct differentiation between Brucella -infected and -vaccinated cattle immunized by smooth vaccines from cattle sera using primers specific for such vaccines., (Copyright: © Abdel-Hamid, et al.)

Background: Stigma is one of the main factors causing pasung (physical restraint or confinement in Indonesian terms) in schizophrenia patients. It is the main obstacle to reducing the number of pasung throughout the world. Thus, there is a need for appropriate interventions to reduce stigma in schizophrenia patients who go through pasung . This study aims to identify multilevel stigma interventions in people with schizophrenia who go through pasung (physical restraint and confinement). It can be applied and adapted to various cultural contexts. Design and Methods: Quasi-experimental research with pretest and post-test analysis consists of 82 people with schizophrenia who go through pasung . Respondents were divided into the intervention group and the control group. A multilevel stigma intervention was given to the intervention group for three months. Results: There was a significant difference in the average stigma score in the control group (moderate category stigma) and the intervention group (mild category stigma) after multilevel stigma intervention (p-value = 0.04). The average stigma score of schizophrenia patients in the intervention group decreased by 8.2%, while the average stigma score in the control group increase of 20.4%. Conclusions: Multilevel stigma interventions are effective in reducing stigma in people with schizophrenia who go through pasung . We underline that multilevel stigma interventions through collaboration from various parties can provide great opportunities in stigma reduction programs in people with schizophrenia who go through pasung ., (©Copyright: the Author(s).)

Purpose: To develop the osmotically controlled-release gastroprokinetic metoclopramide HCl tablets, using quality by design (QbD)-numerical and graphical optimization technique for the treatment of gastroparesis and prophylaxis of delayed nausea and vomiting induced by low-high emetogenic chemotherapy., Methods: Formulations were designed by central composite design using Design Expert version 11.0.0, with osmogen concentration (X 1 ), orifice size (X 2 ), and tablet weight gain after coating (X 3 ) as input and in-vitro drug release at 1hr. (Y 1 ), 6 hrs. (Y 2 ), and 12 hrs. (Y 3 ), and the regression coefficient of drug release data fitted to zero-order, RSQ zero (Y 4 ) as output variables. Core tablets prepared by direct compression were coated with Opadry ® CA. The experimental design was validated by the polynomial equation. A correlation between predicted and observed values was evaluated by random checkpoint analysis. The optimized formulations were characterized for drug release, pH effect, osmolarity, agitation intensity, surface morphology, and stability study, and were subjected to accelerated studies according to ICH guidelines., Results: The interaction charts and response surface plots deduced a significant simultaneous effect of X variables on in vitro drug release and RSQ zero. The numerical optimization model predicted >90% drug release with X 1 (13.30%), X 2 (0.6 mm), and X 3 (7.96%). Random checkpoint analysis showed a good correlation between predicted and observed values. The optimized formulation followed zero-order kinetics (r 2 =0.9703) drug release. Shelf life calculated was 2.8 years as per ICH guidelines., Conclusion: The QbD-based approach was found successful in developing controlled release osmotic tablets of metoclopramide HCl, for reducing the dosage frequency, better emetic control, and improve patient compliance., Competing Interests: The authors have no conflicts of interest., (© 2020 Farooqi et al.)

The COVID-19 pandemic does not affected only physical but also mental health and socioeconomic part. The social distancing, social quarantine, school from home, and work from becomes a new normal these days. Being adolescence, the above conditions may be challenging due to their developmental milestones. Therefore, this brief report aimed to preliminary identify proportion of adolescents' emotional and behavior problems and several factors related to it during COVID-19 pandemic in Indonesia. The findings might raise some understanding of youth mental well-being and programs that can be applied in schools and community in general to overcome the issues. The study was designed as cross sectional and used online survey that started on April 2020. During April 15-May 10, 2020, there were 113 adolescents participated on this survey. Strength and Difficulties Questionnaire (SDQ) 11-17 years old was used to assess adolescent emotional and behavior problems; and specific life experience questionnaire was designed to collect other independents variables (Cronbach's α = 0.75). All participants fulfilled the online informed consent before they started to complete the questionnaire. All data was analyzed by using SPSS version 20 for Mac. The average age of research subjects were 14.07 (2.18) years old; 98.2% was school from home. There was 14.2% of the total research subject at risk on total difficulties problems; 38.1% of adolescent was at risk on peer-relationship problems, 28.3% at risk on pro-social behavior problems, 15% at risk on conduct behavior and 10.6% at risk on emotional problems. The number of adolescent that perceived worse to significantly worse self-mental well-being prior COVID-19 increased during COVID-19 pandemic in Indonesia ( p < 0.05). There was significantly association between having mental health information and conduct behavior (OR = 10.34, 95%CI = 1.27-78.86); Subjective anxiety due to COVID-19 pandemic and pro-social behavior problems (OR = 2.37, 95% CI = 1.00-5.63), parental support and total difficulties (OR = 0.09, 95% CI = 0.14-0.60) and pro-social behavior problems (OR = 0.09, 95% CI = 0.01-0.82); friends support during COVID-19 pandemic and conduct behavior (OR = 0.20, 95% CI = 0.04-1.00) and pro-social behavior problems (OR = 0.14, 95% CI = 0.02-0.75). To be concluded, during phase 1 and 2 COVID-19 pandemic and school closures in Indonesia, adolescents were at risk for having emotional and behavior problems. Therefore, maintain clear mental health information, keep them on connection with school by designing an optimal tele-education, tele-consultation, and virtual activity programs to accommodate adolescents' biopsychosocial needs in the near future., (Copyright © 2020 Wiguna, Anindyajati, Kaligis, Ismail, Minayati, Hanafi, Murtani, Wigantara, Putra and Pradana.)

Background: Traumatic thoracic aortic injuries (TAIs) carry a substantial mortality. Our study aim was to evaluate the impact of insurance status on outcomes in severely injured trauma patients after either thoracic endovascular aortic repair (TEVAR) or open repair using the National Trauma Data Bank Research Data Set (NTDB-RDS)., Methods: The NTDB-RDS was reviewed for outcomes in severely injured patients and TAI repair method (TEVAR vs open). Patients were divided into insured (Medicaid, Medicare, private insurance) and uninsured (self-pay) status groups. Patients were further divided by injury severity score (ISS) of 15-24 and ≥25 to adjust for injury burden. Demographic characteristics and outcome measures were compared. Chi-square, t -test, and analysis of variance were used with significance defined as P < .05., Results: Within the NTDB-RDS, a review of nearly 1 million patients led to 241 that underwent repair for TAI and had insurance status and repair type documented. 88.8% (214/241) of patients were insured, while 11.2% (27/241) of patients were uninsured. There were no significant differences in repair type based on insurance status. For open repair with an ISS ≥25, mortality was significantly higher in the uninsured group compared with insured (55.5% vs 21.9%, P = .001)., Conclusion: For open repair in patients with TAI and high injury burden, uninsured status was associated with a significant increase in mortality rate compared with insured patients. Future studies should investigate the effect of insurance type on TAI outcomes and causes of higher mortality in uninsured patients.

Purpose: The present study reports chitosan functionalized green synthesized CS-AgNPs, conjugated with amoxicillin (AMX), cefixime (CEF), and levofloxacin (LVX) for safe and enhanced antibacterial activity., Methods: The CS-AgNPs and conjugates CS-AgNPs+AMX CS-AgNPs+CEF, and CS-AgNPs+LVX were characterized by UV-Vis, FTIR, SEM, TEM, EDX spectroscopy. The size distribution and zeta potential were measured using the dynamic light scattering (DLS) technique. The interaction between CS-AgNPs and antibiotic molecules was also investigated using UV-Vis spectroscopy at the concentrations of 5, 50, 500, and 5000 µM for each antibiotic. Antibacterial activity and synergism were assessed by the Fractional Inhibitory Concentration (FIC) index. The mechanism for synergistic activity was investigated by the detection of hydroxyl species based on the chemiluminescence of luminol. The biocompatibility index (BI) was calculated from IC 50 using the HeLa cell line. In vivo toxicity and tissue distribution of silver ions were evaluated on Sprague Dawley rats. Physical interactions of antibiotics and significant (P<0.05) antibacterial activity were observed after loading on CS-AgNPs surfaces., Results: The spherical shape nanocomposites of CS-AgNPs with different antibiotics were prepared with mean size ranges of 80-120 nm. IC 50 of antibiotics-conjugated CS-AgNPs decreased compared to CS-AgNPs. The biocompatibility (BI) index showed that antibiotics-conjugated CS-AgNPs have high antibacterial potential and low toxicity. Highly significant (P<0.005) increase in the generation of hydroxyl species indicated the radical scavenging mechanism for synergistic activity of CS-AgNPs after combined with different antibiotics. Biochemical analysis and histopathological examinations confirmed low toxicity with minor hepatotoxicity at higher doses. After oral administration, extensive distribution of Ag ion was observed in spleen and liver., Conclusion: The study demonstrates positive attributes of antibiotics-conjugated CS-AgNPs, as a promising antibacterial agent with low toxicity., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Asghar et al.)

Present work reports the green synthesis of chitosan functionalized silver nanoparticles (CS-AgNPs) using ethanolic buds extract of Sygyzium aromaticum. CS-AgNPs were characterized physically, evaluated for antibacterial, anticoagulant and antiplatelet activities, and toxicity profile. The physical characterization of CS-AgNPs was done by UV/vis, SEM, TEM, FTIR and EDX. The sphericity was found uniform. FTIR and EXD showed noninterfering few impurities. The antibacterial activity against VRSA (ZI, 23.2 ± 0.51 mm) and MRSA (ZI, 25.8 ± 0.32 mm) were determined. The rise in bleeding and thromboplastin was observed highly significant while increased in prothrombin and activated partial prothrombin time in significant manner at both the doses of CS-AgNPs (0.025 mg/kg and 0.05 mg/kg). Reduction in the levels of fibrinogen was also highly significant. Platelet aggregation decreased at high dose of CS-AgNPs i.e. 55.14 ± 8.25% (arachidonic acid) and 13.06 ± 2.17% (collagen). Thrombin antithrombin (TAT) complex activity was found highest for CS-AgNPs. Cytotoxicity was assessed using HeLa cell lines (LC 50 ; 125 μg/ml) and brine shrimp lethality tests (LC 50; 518 μg/ml). The work suggests that green synthesized chitosan functionalized silver nanoparticles may be utilized as an effective antibacterial agent and anticoagulant with low toxicity. The current findings will open a new window for nanomedicine development and future clinical application., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Diabetic neuropathy is the most common long-term complications of diabetes, frequently presenting as painful diabetic peripheral neuropathy (PDPN), which can significantly impair patients' quality of life (QOL). This study set to estimate the prevalence of PNPD and health-related quality of life (HRQoL) in the setting of primary health care in Saudi Arabia., Methods: This study was conducted in primary health-care centers affiliated with the National Guard Health Affairs in Western Saudi Arabia. Arabic version of the Douleur Neuropathique 4 questionnaire was administered on diabetic patients to screen for neuropathic pain and short-form 12 questionnaire to assess HRQoL., Results: The study screened ( n = 349) Type 2 diabetic patients. The prevalence of PDPN was 33.2%. PDRN was more likely to affect females (adjusted odds ratio ["AOR"] =1.96, P = 0.024), and those living with diabetes for over 15 years (AOR = 2.26, P = 0.039), and those on insulin treatment (AOR: 2.33, P = 0.010) alone or in combination (AOR = 1.78, P = 0.034). Both physical and mental components (MCs) of QOL scores were significantly higher in diabetic patients without PDPN compared to those with it; 49.57 ± 9.31 versus 40.77 ± 8.14 for physical component QOL and 51.72 ± 9.36 versus 44.35 ± 8.12 for MC QOL, P < 0.001., Discussion and Conclusion: Painful peripheral neuropathy is relatively common among type 2 diabetic patients in Western Saudi Arabia and impacts both physical and MCs of the QOL of affected patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Family Medicine and Primary Care.)

This study is based on the QbD development of extended-release (ER) extruded-spheronized pellets of Meclizine HCl and its comparative pharmacokinetic evaluation with immediate-release (IR) pellets. HPLC-fluorescence method was developed and validated for plasma drug analysis. IR drug cores were prepared from lactose, MCC, and PVP using water as granulating fluid. Three-level, three-factor CCRD was applied for modeling and optimization to study the influence of Eudragit (RL100-RS100), TEC, and talc on drug release and sphericity of coated pellets. HPLC-fluorescence method was sensitive with LLOQ 1 ng/ml and linearity between 10 and 200 ng/ml with R 2  > 0.999. Pharmacokinetic parameters were obtained by non-compartmental analysis and results were statistically compared using logarithmically transformed data, where p > 0.05 was considered as non-significant with a 90% CI limit of 0.8-1.25. The AUC 0-t and AUC 0-∞ of ER pellets were not significantly different with geometric mean ratio 1.0096 and 1.0093, respectively. The C max of IR pellets (98.051 ng/ml) was higher than the ER pellets (84.052 ng/ml) and the T max of ER pellets (5.116 h) was higher than the IR pellets (3.029 h). No significant food effect was observed on key pharmacokinetic parameters of ER pellets. Eudragit RL100 (6%) coated Meclizine HCl pellets have a potential therapeutic effect for an extended time period.

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder among children resulting in disturbances in their daily functioning. Virtual reality (VR) and machine learning technologies, such as deep learning (DL) application, are promising diagnostic tools for ADHD in the near future because VR provides stimuli to replace real stimuli and recreate experiences with high realism. It also creates a playful virtual environment and reduces stress in children. The DL model is a subset of machine learning that can transform input and output data into diagnostic values using convolutional neural network systems. By using a sensitive and specific ADHD-VR diagnostic tool prototype for children with DL model, ADHD can be diagnosed more easily and accurately, especially in places with few mental health resources or where tele-consultation is possible. To date, several virtual reality-continuous performance test (VR-CPT) diagnostic tools have been developed for ADHD; however, they do not include a machine learning or deep learning application. A diagnostic tool development study needs a trustworthy and applicable study design and conduct to ensure the completeness and transparency of the report of the accuracy of the diagnostic tool. The proposed four-step method is a mixed-method research design that combines qualitative and quantitative approaches to reduce bias and collect essential information to ensure the trustworthiness and relevance of the study findings. Therefore, this study aimed to present a brief review of a ADHD-VR digital game diagnostic tool prototype with a DL model for children and the proposed four-step method for its development., (Copyright © 2020 Wiguna, Wigantara, Ismail, Kaligis, Minayati, Bahana and Dirgantoro.)

This paper describes the development and validation of a high performance liquid chromatography (HPLC-UV) method for the simultaneous quantitative determination of artemether and lumefantrine in fixed dose combination tablets. Chromatographic quantitation was carried out on a C-18 column Mediterrania Sea 18 (250×4.6 mm i.d.; 5 µm particle size) using a mobile phase consisting of 80:20 v/v mixture of acetonitrile and 0.05 % trifluoroacetic acid with final pH adjusted to 2.35 at flow rate of 1 ml/minute. The eluents was detected using photo diode array detector at wavelength of 210nm for artemether and 286 nm for lumefantrine. The retention times were ~5.8 mins for artemether and ~7.3 mins for lumefantrine. The newly developed method was validated and was found linear (r2 &gt;0.99), precise (R.S.D. &lt;2.0%), accurate, specific and robust. The artemether contents in the tablet formulation varied from 99.026 % to 99.347%, while lumefantrine contents were 99.546-99.728 %.

Epibrassinolide (EBR), a polyhydroxysteroid belongs to plant growth regulator family, brassinosteroids and has been shown to have a similar chemical structure to mammalian steroid hormones. Our findings indicated that EBR could trigger apoptosis in cancer cells via induction of endoplasmic reticulum (ER) stress, caused by protein folding disturbance in the ER. Normal cells exhibited a remarkable resistance to EBR treatment and avoid from apoptotic cell death. The unfolded protein response clears un/misfolded proteins and restore ER functions. When stress is chronic, cells tend to die due to improper cellular functions. To understand the effect of EBR in non-malign cells, mouse embryonic fibroblast (MEF) cells were investigated in detail for ER stress biomarkers, autophagy, and polyamine metabolism in this study. Evolutionary conserved autophagy mechanism is a crucial cellular process to clean damaged organelles and protein aggregates through lysosome under the control of autophagy-related genes (ATGs). Cells tend to activate autophagy to promote cell survival under stress conditions. Polyamines are polycationic molecules playing a role in the homeostasis of important cellular events such as cell survival, growth, and, proliferation. The administration of PAs has been markedly extended the lifespan of various organisms via inducing autophagy and inhibiting oxidative stress. Our data indicated that ER stress is induced following EBR treatment in MEF cells as well as MEF Atg5 -/- cells. In addition, autophagy is activated following EBR treatment by targeting PI3K/Akt/mTOR in wildtype (wt) cells. However, EBR-induced autophagy targets ULK1 in MEF cells lacking Atg5 expression. Besides, EBR treatment depleted the PA pool in MEF cells through the alterations of metabolic enzymes. The administration of Spd with EBR further increased autophagic vacuole formation. In conclusion, EBR is an anticancer drug candidate with selective cytotoxicity for cancer cells, in addition the induction of autophagy and PA metabolism are critical for responses of normal cells against EBR.

Objective: Although cisplatin (CIS) acts as potent chemotherapy, nephrotoxicity still its major life-threatening side effect. The purpose of this study was to discuss and compare the renoprotective effects of curcumin (CUR) and etoricoxib (ETB) against CIS-induced nephrotoxicity., Materials & Methods: Thirty six adult female rats were divided equally into 6 groups: Group I (control), Group II (CIS) received cisplatin (7.5 mg/kg i.p), Group III (CUR) and group IV (ETB) received curcumin (200 mg/kg/day) or etoricoxib (10 mg/kg/day) respectively via gavage for seven continuous days. Group V (CIS + CUR) and Group VI (CIS + ETB) received curcumin (200 mg/kg/day) or etoricoxib (10 mg/kg/day) via gavage for seven continuous days. On the 4th day, the rats received cisplatin (7.5 mg/kg i.p) as a single injection 1 h after last curcumin or etoricoxib administration. At the assigned time, blood and tissue samples were collected for biochemical, histochemical, histopathological, immunohistochemical, and RT-PCR gene expression studies., Results: Curcumin administration significantly decreased CIS-induced elevation of serum creatinine and blood urea nitrogen (BUN), and reversed oxidative stress markers; glutathione (GSH) and malondialdehyde (MDA) to control level. Suppression of inflammatory and apoptotic responses by CUR co-treatment was evidenced by decreased iNOS and BAX immunohistochemical reactions, and TNF-α and Caspase3 gene expressions which were detected by RT-PCR in kidney tissues. To our knowledge, this is the first time to discuss the effect of ETB on CIS induced nephrotoxicity. Although ETB reduced the previously mentioned inflammatory and apoptotic markers, its effect was less than that of CUR. Administration of ETB couldn't modify the disturbed levels of creatinine, BUN, GSH, and MDA., Conclusion: In conclusion, CUR provided a promising renoprotective effect against CIS induced nephrotoxicity. Further studies are recommended to approve or disapprove the protective role of ETB in CIS induced nephrotoxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

The consumption of probiotics in the prevention and treatment of diarrhea have been clinically justified, comprehensive studied and explored in many products around the world. In Pakistan, recommendation of probiotic formulations is being emerged to control the increased mortality and morbidity from diarrhea under 5 years of age children. The objective of the study was to evaluate the antimicrobial potential of isolated Lactobacillus strains against diarrheagenic Escherichia coli. Twelve strains were isolated from different probiotic pharmaceutical formulations available in Pakistan. Physiological and biochemical characteristics of isolates were analyzed. Selective media was used for the growth of probiotic isolates and E. coli. Agar spot and well diffusion methods were employed to evaluate the antimicrobial activity of isolates and measured as a zone of inhibition (mm). Changes in cell morphology was observed by Scanning Electron Microscopy. Statistical analysis was adopted with a level of significance p<0.05. L. reuteri (28 mm) and L.plantarum (26 mm) showed significant inhibitory actions against E. coli due to increased organic acids and bacteriocins formations. Rest of isolates exhibited mild to moderate activity with an average inhibition (20 mm). L. sporogenes demonstrated weak antagonistic behavior. Use of multiple strains of Lactobacillus along with L. reuteri or L.plantarum as a therapeutic agent or in nutritional supplements could be a novel approach for the prevention and treatment of pediatric diarrhea.

This study aimed to identify factors that promote and impede research participation and productivity by Eastern Association for the Surgery of Trauma (EAST) surgeons. In addition, the study aimed to determine what changes can be implemented by surgical departments to improve this research productivity and granting. A 25-question anonymous research survey tool was offered to EAST surgeons. The questions analyzed factors including demographics, career accomplishments, current institution type, educational/research background, perceived barriers to research, and current research productivity, including grants. Chi-square tests were used to analyze significance at P < 0.05. The overall response rate was 26.2 per cent (445/1699). Most respondents reported not having any protected research time (86.3%), and no research resources were provided by their institution (78.7%). Factors that were significantly associated with greater research productivity included protected research time ( P < 0.0001), having a mentor ( P < 0.001), practicing in a university-affiliated hospital ( P < 0.0001), publication(s) before completing residency training ( P = 0.02), having institutional resources dedicated to research ( P = 0.015), and male gender ( P = 0.003). Age, race, marital status, and additional educational qualifications were not associated with statistically significant differences in research productivity in this study ( P > 0.05). EAST surgeons are more likely to have scholarly productivity if they are supported with protected time, mentors, nonclinical staff dedicated to research, a history of research before completion of residency, and research resources from their institution. Barriers to research productivity include lack of institutional support, lack of protected research time, and increased regulatory policies.

While previous studies have examined factors that affect research productivity for surgeons in general, few studies address research productivity specifically of burn specialists. This study aimed to identify factors that promote and impede research participation and productivity of burn surgeons and help elucidate what changes can be made by departments/divisions to improve the research productivity. A 44-question anonymous research survey tool was administered to burn surgeons who are members of the American Burn Association (ABA). The questions analyzed factors such as demographics, career accomplishments, current institution type, educational background, research background, barriers to conducting research, and current research productivity. Chi-square tests were used to analyze significance at P < .05. Most respondents reported not having any protected research time (71.4%) or resources provided by their institution (84.5%). A majority believed increasing regulatory policies/institutional review board restrictions have negatively impacted productivity (65.1%). Factors associated with positive impact on research productivity included having a mentor, conducting research prior to completing residency, and provision of research resources from the institution such as statistical support, start-up funds, grant writing support, and laboratory space. Age and sex had no statistical impact on research productivity. Burn surgeons are more likely to publish research and to receive grants when they have mentors, a history of research prior to completion of residency, and research resources from their institution. Barriers to research productivity include lack of institutional support, lack of protected research time, and increased regulatory policy., (© American Burn Association 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To evaluate and compare the pharmacokinetic (PK) characteristics of a newly developed oral osmotically controlled drug delivery system of Eperisone 150 mg tablets with Eperisone immediate release (IR) marketed tablet brand as a reference formulation. It was a single dose, two treatment, two sequence, randomized, crossover study, involving 12 healthy human subjects. A modified, sensitive LC-ESI-MS/MS method was developed and validated as per FDA guidelines for estimation of Eperisone in plasma using a simple extraction and quick protein precipitation method. Non-compartmental pharmacokinetic model was used for PK analysis. Results were statistically compared using logarithmically transformed data, where p > 0.05 was considered as non-significant with 90% CI limit of 0.8-1.25. The bio-analytical method used for estimating drug plasma concentration was found to be simple, selective, linear, accurate and precise with 0.01 ng/ml as limit of detection. The comparative PK analysis revealed an insignificant difference in AUC 0-∞, AUC 0-t, V z /F, Cl/F and t 1/2λz , whereas a significant difference in C max , T max and MTTs were found. The relative bioavailability of Eperisone osmotic tablet was 109.7%. The osmotic controlled release drug formulation was found to release Eperisone for an extended period with less inter individual fluctuation in pharmacokinetic variables.

Objective: Surgeons are unevenly distributed across the United States (U.S.), possibly as a result of disproportionately distributed General Surgery (GS) residencies. This study primarily aimed to examine the relationship between the distribution of GS residency positions and population by U.S. region and states. Differences in the distribution by race and gender were also examined., Design: A review of the Accreditation Council for Graduate Medical Education (ACGME) and the American Osteopathic Association (AOA) National Residency Matching Program (NRMP) data over 5 years. Categorical Surgery Residency PGY1 positions (SurgPGY1) were categorized into Northeast, Midwest, South, and West regions. SurgPGY1 to population ratios were compared by region. The distribution of SurgPGY1s by race/gender was also compared., Participants: Medical students who match into SurgPGY1 positions through the NRMP., Results: The mean SurgPGY1s per 10 6 population was 4.18 ± 0.52 for 2018. Most commonly, SurgPGY1s are concentrated in the Northeast (5.79 ± 0.64) then the South (5.12 ± 1.41), then the Midwest (4.22 ± 0.37), and lastly the West (1.91 ± 0.39). NY, MA, and DC had significantly higher SurgPGY1s ratios, with DC topping at 27.05. Four States had no SurgPGY1s (AK, ID, MT, WY), while AR, MS, and UT were under 2 SurgPGY1s/10 6 . From 2014 to 2018, the percent of ACGME positions given to females increased 2.93%, while the AOA positions increased 11.84%. When adjusted for the population the race with the most residencies for their population was Asian (482.42% ACGME, 324.52% AOA)., Conclusion: There is a significant disproportion in the distribution of GS residencies and not proportional to population, race or gender., (Copyright © 2019. Published by Elsevier Inc.)

The drug-in-adhesive (DIA)-type matrix patches of lamotrigine are developed using variable permeation enhancers (oleic acid, PG, lemon oil and aloe vera), and drug in vitro release and its permeation are evaluated. Lamotrigine has been long used as an anti-epileptic, mood stabilizer, to treat bipolar disorder in adults and off label as an antidepressant. lamotrigine matrix patches comprising of Eudragit ® RS100 (rate-controlling polymer) and DuroTak ® 387-2510 (adhesive) were prepared by pouring the solution on backing membrane (3M-9720). The thickness of 120 µm was adjusted through micrometer film applicator. USP Apparatus V was used for the evaluation of release profile, which was fitted into various mathematical models. Quality characteristics of patches were determined through weight variation, moisture content, moisture uptake and drug content evaluation. FTIR studies were performed for drug-excipient compatibility; Franz diffusion cell was employed for studying in vitro permeation parameters such as flux, lag time, and ER. Skin sensitivity study of optimized patch was also performed. The release from patches comprising of PG and oleic acid was maximum, i.e., 96.24 ± 1.15% and 91.12 ± 1.11%, respectively. Formulations (A1-A5) exhibited Makoid-Banakar release profile. Formulation A3 consisting of oleic acid was optimized due to enhanced permeation of drug across skin compared to other enhancers with enhancement ratio of 3.55. Skin sensitivity study revealed patch as safe and non-allergenic. The study demonstrates that oleic acid can be used as a suitable permeation enhancer for transdermal delivery of lamotrigine from matrix-type patches.

Mother-infant bonding scale (MIBS) is a questionnaire that can be used to elaborate the quality dyad between mother and infant; however it is not validated in Indonesian language optimally. This study aimed to identify the validity and reliability of the MIBS-Indonesian (MIBS-I) version based on Japanese MIBS (MIBS-J) that could be used in general population and hospital setting. Design of the study was cross sectional and involving 150 mother-infant dyads recruited from Growth and Developmental Clinic dr. Cipto Mangunkusumo General Hospital-Jakarta and Beji Volunteer-Staffed Integrated Health Service (Posyandu)-Depok/West Java. Infant was categorized as children from 0-36 months old. Mother with at least junior high-school background fulfilled MIBS-Indonesian version and also demographic data. SPSS version 21 for Mac and Lisrel 8.8 program for Windows was applied to analyze the data. Results of the study demonstrated that the content validity was good with I-CVI=0.9875 and S-CVI=0.99; and EFA results of 3 components total variance was 57.90% and CFA results showed three factors structure out of eight items and it fullfiled an adequate goodness of fit with each factor CR >0.7; factor 1:'desire to love and denial', factor 2: 'hate and being closed', and factor 3: 'rejection feeling'. Cronbach's alpha for the eight items of MIBS-I was 0.535. To be concluded, MIBS-I was a multidimentional scale with three-factor model and it was confirmed valid and reliable to be implemented in Indonesian children from 0-36 months old., (Copyright © 2019. Published by Elsevier B.V.)

Halloysite is a unique biocompatible aluminosilicate clay mineral with powder particles predominantly comprising of concentrically rolled nanotubular aggregates. Some recent studies have also contributed to its prospective case in oral drug delivery and dosage forms albeit with limited commercial viability. In this study, we have investigated the use of halloysite nanotubes (HNTs) as a directly compressible multifunctional tableting excipient using SeDeM diagram expert tool. SeDeM experimentations revealed that ~68% HNTs in the formulations were enough to be used as a directly compressible filler, binder, and disintegrant in diclofenac potassium formulations. In the next phase, a total of 8 formulations blends (IRF1-8) of diclofenac potassium (50 mg) with HNTs and Starch 1500® were prepared in different ratio using simple lattice mixture design and all were found satisfactory for direct compression. Compressed tablets (167 mg) had narrow weight variation (SD = ± 1.78 mg), good hardness (~9-9.5 kg), acceptable friability (<0.7%) and fast disintegration time (<1.5 min). Moreover, the cumulative dissolution at 1 h in phosphate buffer pH 6.8 was found compliant with the compendial criteria (> 92% against 75%). The dissolution profile was best fitted with Peppas-Sahlin model with Fickian diffusion as the only mechanism. f 2 similarity test revealed that almost all the tablets were pharmaceutical equivalent to the marketed formulation of the drug. A shelf-life of ~34 months was found upon long-term stability testing of the optimized formulation. This study demonstrates that this novel and economically viable clay material has a strong potential for commercial use in tableting of drug by direct compression., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The effect of timing in patients requiring tracheostomy varies in the literature. The purpose of this study was to evaluate the impact of early tracheostomy on outcomes in trauma patients with and without traumatic brain injury (TBI). This study is a four-year review of trauma patients undergoing tracheostomy. Patients were divided into two groups based on TBI/non-TBI. Each group was divided into three subgroups based on tracheostomy timing: zero to three days, four to seven days, and greater than seven days postadmission. TBI patients were stratified by the Glasgow Coma Scale (GCS), and non-TBI patients were stratified by the Injury Severity Score (ISS). The primary outcome was ventilator-free days (VFDs). Significance was defined as P < 0.05. Two hundred eighty-nine trauma patients met the study criteria: 151 had TBI (55.2%) versus 138 (47.8%) non-TBI. There were no significant differences in demographics within and between groups. In TBI patients, statistically significant increases in VFDs were observed with GCS 13 to 15 for tracheostomies performed in four to seven versus greater than seven days ( P = 0.005). For GCS <8 and 8 to 12, there were significant increases in VFDs for tracheostomies performed at days 1 to 3 and 4 to 7 versus greater than seven days ( P ≪ 0.05 for both). For non-TBI tracheostomies, only ISS ≥ 25 with tracheostomies performed at zero to three days versus greater than seven days was associated with improved VFDs. Early tracheostomies in TBI patients were associated with improved VFDs. In trauma patients with no TBI, early tracheostomy was associated with improved VFDs only in patients with ISS ≥ 25. Future research studies should investigate reasons TBI and non-TBI patients may differ.

Objective: In this study, pharmacokinetics (PKs) and bioavailability of newly developed extended release (ER) Itopride HCl 150 mg encapsulated ER pellets (test) and 150 mg Ganaton ER once-daily (OD) tablets (reference) were compared and evaluated under fasted and fed conditions., Methods: Twelve healthy human subjects were enrolled in a single dose, randomized; two treatments, two sequences, four period crossover study. A modified and validated liquid chromatographic method was used for the estimation of Itopride HCl in plasma samples. The data were analyzed through non-compartmental model using PK software Phoenix Winnonlin version 7. The outcome was measured on logarithmically transformed data, where p > 0.05 was considered as non-significant with 90% CI limit of 0.8-1.25., Results: The C max , AUC 0- t , and AUC 0-∞ values of Itopride HCl 150 mg ER pellets versus that of OD 150 mg tablets, in fed and fasted states, were within the limits specified by FDA to establish bioequivalence. The relative bioavailability of Itopride HCl 150 mg ER pellets were 1.019 (fed) and 1.081(fasted). The 90% CIs of AUC values for Itopride HCl 150 mg ER pellets and OD 150 mg tablets in fed versus fast were significantly greater and were not within 80-125% limit., Conclusion: The test and reference formulations had similar pharmacokinetic parameters in each condition studied. However, an increase in the amount of drug was observed in the fed state.

Introduction: Cases of inguinal bladder hernia are rare, with bladder involvement seen in 1-4% of inguinal hernias. The majority of cases are diagnosed intraoperatively, with only 7% of bladder hernias identified prior to surgery. Diagnosis may be challenging as patients are often asymptomatic or have nonspecific symptoms. Surgical repair is currently the standard treatment, and careful surgical planning is necessary to avoid complications including bladder injury., Presentation of Case: A 58-year-old man presented to our Emergency Department with 2-day history of progressively worsening left lower quadrant pain, groin bulge, and dysuria. Physical exam revealed an irreducible left inguinal hernia associated with urinary urgency on attempted reduction. Plain CT was ordered and demonstrated inguinal hernia with bladder protrusion into the left scrotum. The patient underwent open surgical reduction and hernia repair and made a quick postoperative recovery without complications., Discussion: Inguinal bladder hernia most often presents in older, obese males and clinicians should have a high index of suspicion when assessing patients with inguinal hernia. Preoperative diagnosis based on history, physical, and radiologic imaging allow for careful surgical planning and prevention of severe complications including bladder injury and leakage., Conclusion: We present a case report of inguinal bladder hernia in a middle-aged man that presented as left lower quadrant pain, groin pain, and dysuria. Diagnosis was confirmed preoperatively with radiographic imaging. The hernia was surgically reduced and the defect repaired without complications., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A Simple, sensitive and accurate high-performance liquid chromatographic (HPLC) method for effective and specific analysis of Loxoprofen (LXP) in the mobilephase and human plasma was developed. Effective chromatographic separation was attained on a Mediterranean Sea C18 column (250×4.6mm, 5um) with mobilephase containing acetonitrile and 0.01 M NaH2PO4 buffer (55:45) by adjusting pH 6.5 with sodium dihydrogen phosphate buffer at a flow rate of 1ml/min. Calibration ranges from 0.1ppm to 10 ppm with a coefficient of relation value (R2=0.999) by using a linear regression method and lower limit of quantification was 0.1ppm. The current method showed inter-day and intra-day accuracy and precision within the range of ±10%. % RSD was found to be less than 5 %. Analytical recovery was more than 90% which confirmed the reliability of current method. The proposed method was found appropriate for assessment of LXP in pharmacokinetic and bioequivalence study.

Objective: Follow-up of cardiac index and systemic vascular resistance index by bedside echocardiography until resuscitation., Methods: A set of hemodynamic parameters was obtained, including cardiac output, stroke volume, cardiac index, systemic vascular resistance index, velocity time integral, myocardial performance index, capillary refill time, and heart rate at 0 hours after fluid boluses before the start of inotropes, and followed up after 6 hours and 24 hours., Results: Included were 45 patients with community-acquired septic shock. Septic foci were gastroenteritis (24%), intestinal perforation requiring emergency surgery (24%), pneumonia (20%), central nervous system infection (22%) and soft tissue infection (8%). Klebsiella and Enterobacter were the most frequent isolates. We estimated the factors affecting the cardiac index: high central venous pressure at zero time (r = 0.33, p = 0.024) and persistently high heart rate at hour 6 (r = 0.33, p = 0.03). The systemic vascular resistance index was high in most patients at 0 and 24 hours and at the time of resuscitation and inversely affected the cardiac index as well as affecting the velocity time integral (r = -0.416, -0.61, 0.55 and -0.295). Prolonged capillary refill time was a clinical predictor of the low velocity time integral at 24 hours (r = -0.4). The mortality was 27%. Lower systemic vascular resistance index and higher cardiac output were observed in nonsurviving patients., Conclusion: There was a persistently high systemic vascular resistance index in cold shock patients that influenced the stroke volume index, cardiac index, and velocity time integral. The use of echocardiograms for hemodynamic measurements is important in pediatric septic shock patients to adjust dilators, and vasopressor doses and achieve resuscitation targets in a timely manner.

In this study cost effective direct compression technique was used for the development and optimization of intermediate release (IntR) ketoprofen tablets using central composite design (CCRD). Fifteen different formulations (F1-F15) were developed using (X1) microcrystalline cellulose (Avicel PH-102) (18-51%), (X 2 ) methocel K4M (0.1-25%) and (X3) starch (1.5-18%) as selected variables while responses were % friability and Carr's Index (compressibility index). Powder blends of all formulations were evaluated using Angle of Repose, Carr's Index and porosity. Results of powder blends comply with USP standards and are classified as Fair Excellent. From F1-F15 only four formulations i.e. F6, F7, F14 and F15 were selected on acceptable weight basis, micromeritic properties and on the concentration of excipients. For the assessment of physico chemical properties of the optimized formulations different tests were performed. All results were found to be adequate range. In vitro assessment of the optimized formulations were also carried out in different dissolution media i.e. pH 1.2, phosphate buffer 4.5, pH 6.8 and pH 7.5. Release behaviour of F6, F7, F14 and F15 were estimated by using one - way ANOVA, model - independent, model dependent methods. Results of f 1 and f 2 showed that all the test formulations i.e. F6, F7, F14 were found to be similar with the reference formulation i.e. F15 at various dissolution media. Also all the formulations followed Hixson-Crowell kinetic model. The parameter n showed Anomalous transport (non - fickian diffusion). The mean dissolution time (MDT) was found to be in the range of 2.632-2.922. Results of ANOVA indicated no significant difference within and between formulations at different dissolution media as p values were found to be >0.05. Also all the selected formulations were found to be stable at accelerated conditions.

Use of the human volunteers in bioequivalence studies is being discouraged by the Food and drug administration after the introduction of biowaiver approaches. In-vitro in-vivo correlation (IVIVC) with the level A is accepted for the registration of new molecules. In the present study deconvolution technique with numeric approaches was applied after compressing and in vitro validating the 100mg Nimesulide immediate, intermediate and slow release tablets. Single centered, crossover, randomized study was conducted in four phases with a two-week washout period to obtain the plasma drug concentration data after administrating test and reference products in male healthy volunteers. KineticaTM 4.4.1 (Thermoelectron corp, USA) was used for the calculation of two ways ANOVA with 90% CI from both log transformed and non- transformed data and Phoenix WinNonlin 7 and it's IVIVC toolkit version 7.0 was used for the application of numeric approaches of IVIVC. Results revealed that the individual internal percentage prediction error for AUCinf and Cmax were found to be < 15% while their average values were < 10% in all medium. Numeric values of % PE at pH 6.8 and pH 7.4 (50 rpm in USP II and 100 rpm in USP I and II apparatus) were found to be (2.5842, 2.9789 and, 7.1732; 7.0944, 2.4721 and 4.350) for AUCinf and (2.5842, 0.5736 and 4.6928; 5.6214, 3.0551 and -2.4711) values for Cmax respectively. The low values of prediction errors demonstrate that the correlation model is projecting the in vivo response of each formulation. Percentage External error (% PE) was not required because individual values of percentage internal error (%PE) of Cmax and AUClast were not >15. In order to predict point to point correlation between fraction drug dissolved and drug absorbed, their mean r2 value was found to be > 0.9112 which showed a linear correlation in slightly alkaline pH., Competing Interests: The authors have declared that no competing interests exist.

Background: The study was to develop an extended release (ER) encapsulated and compacted pellets of Atenolol using hydrophobic (wax based and polymeric based) and high viscosity grade hydrophilic matrix formers to control the release of this highly water soluble drug by extrusion/spheronization (ES). Atenolol is used for cardiovascular diseases and available as an immediate release (IR) tablet dosage form. The lipids, Carnauba wax (CW), Glyceryl monostearate (GMS) and cellulose based i.e. Hydroxypropyl methylcellulose (HPMC) and Ethyl cellulose (EC) were used in preparing Atenolol ER pellets. Thermal sintering and compaction techniques were also applied to control the burst release of Atenolol., Method: For this purpose, thirty-six trial formulations (F1-F36) were designed by Response Surface Methodology (RSM), using Design-Expert 10 software, keeping (HPMC K4M, K15 M & K100 M), (EC 7FP, 10FP & 100FP), waxes (GMS, & CW), their combinations, sintering temperature and duration, as input variables. Dissolution studies were performed in pH, 1.2, 4.5 and 6.8 dissolution media. Drug release kinetics using different models such as zero order, first order, Korsmeyer-Peppas, Hixon Crowell, Baker-Lonsdale and Higuchi kinetics were studied with the help of DDsolver, an excel based add-in program., Results: The formulations F35 and F36 showed compliance with Korsmeyer-Peppas Super case II transport model (R 2  = 0.975-0.971) in dissolution medium pH 4.5. No drug excipient interaction observed by FTIR. Stereomicroscopy showed that sintered combination pellets, (F35), were highly spherical (AR = 1.061, and sphericity = 0.943). The cross-sectional SEM magnification (at 7000X) of F34 and F35 showed dense cross-linking. The results revealed that the optimized formulations were F35 (sintered pellets) and F36 (compacted pellets) effectively controlling the drug release for 12 h., Conclusion: Extended-release encapsulated, and compacted pellets were successfully prepared after the combination of lipids CW (10%) and GMS (20%) with EC (10FP 20% & 100FP 20%). Sintering and compaction, in addition, stabilized the system and controlled the initial burst release of the drug. Extended release (ER) Atenolol is an effective alternative of IR tablets in controlling hypertension and treating other cardiovascular diseases.

A swift, precise and simple HPLC bioanalytical technique with UV detection was established and validated for quantitative estimation of valsartan in human plasma. The analyte was separated from plasma by protein precipitation with acetonitrile and chromatographically separated on Zorbax SB-C18 (5μm, 4.6mm × 15cm) column. The solvent mixture system consisting of acetonitrile, water and glacial acetic acid (40:59:1 v/v), was pumped using isocratic mode at 1mL/min flow rate. Samples' detection of drug was made spectrophotometrically at a wavelength of 264nm. The analyte response was instituted to be linear from 0.06 to 8μg/mL with a regression value of 0.999. The accuracy of the proposed method was ranged between 97.2-100.3% with 5% RSD. The analytical recovery (>95%) was consistently observed and satisfactory sample stability was also found at different environmental conditions. In conclusion the reported bio-analytical method is easy and robust that was successfully utilized in estimation of valsartan in a pharmacokinetic study.

Introduction: Several studies showed that DAT1 polymorphism closed related with ADHD although the results were not consistently found. Studies in China, South Korea, Japan revealed that 10-repeat allele gave a risk for ADHD. Based on that understanding, this study tried to identify whether the similar polymorphism of DAT1 was also apparent in Indonesian children with ADHD., Method: This was a case - control study. Case was 50 Indonesian origin children with ADHD and without any other mental disorders and metal retardation. Control is Indonesian origin children without ADHD, other mental disorders and mental retardation. ADHD diagnosis was taken after doing the psychiatric interview and observation based on the DSM-IV TR diagnostic criteria for ADHD at the Child and Adolescent Psychiatry Out-patient Clinic, Dr. Cipto Mangunkusumo National Referral Hospital - Faculty of Medicine Universitas Indonesia. DNA isolation, DNA purity and concentration were measured. PCR was done by using a primer based on Homo sapiens solute carrier family 6 (neurotransmitter transporter), member 3 (SLC6A3), RefSeq Gene on chromosome 5 with accession number NG&#95;015885.1. To identify the serial of repeated allele, we used the sequencing technique., Results: There were 47 children with ADHD and 48 children without ADHD that involved in the final analysis. The mean of age amongst ADHD group was 9.18 (2.42) and 8.10 (2.46) years old in non-ADHD group. The 10-repeated allele of DAT1 was the highest proportion in both., Conclusion: This finding was apparently similar with other studies on DAT1 polymorphism across Asian., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Cefaclor was analyzed in the human plasma by developing a simple, precise and accurate assay method which was then validated for its accuracy, specificity and precision. The mobile phase comprised of a mixture of sodium 1-pentanesulfonate, water, triethylamine and methanol. Phosphoric acid was used to adjust the pH to 2.5±0.1. The flow rate was maintained at 1.5ml/min and the wavelength was set at 265 nm. A C-18 HPLC, column 5um particle size, L x 1.D. 25cm x 4.6mm (Supelcosil) was utilized for chromatographic separation. The retention time of Cefaclor was found to be 17min. This method was validated for selectivity, accuracy, precision, repeatability, reproducibility, recovery, linearity, and stability. Calibration curves were found linear were in the range of 0.39µg/ml to50µg/mland the coefficient of correlation (R 2 ) was found to be 0.999. Hence, this method has been found useful for the determination of Cefaclor in plasma.

A new, simple, accurate, precise and specific method has been developed for the analysis of Cefpodoxime Proxetil in human plasma. The proposed method was developed and validated with the aim to be used in Bioavailability/Bioequivalence studies for quantification of drug in human plasma. The mobile phase components were acetonitrile, methanol, and water in the ratio of 20:50:30. Ortho phosphoric acid was used to adjust at pH5.0. Flow rate and wavelength were kept 1ml/min and 247nm respectively. The column was C-18 HPLC column 5um particle size, L x 1.d. 25cm x4.6mm. (Supelcosil). Retention time of Cefpodoxime Proxetil was found to be 10.967min. The developed method was validated for selectivity, recovery, accuracy, precision, repeatability, reproducibility, stability and linearity in the range of 0.195mcg/ml to 50mcg/ml. The accuracy and Precision of the proposed method were well within the predefined limits i.e. ±15% for all the calibration standards other than LLOQ (Lower Limit of Quantification) where it was well within ±20% of the nominal value. The analytical recovery was always above 89% showing satisfactory recovery. The coefficient of correlation (R 2 ) was 0.999. The developed method was found suitable for the estimation of Cefpodoxime Proxetil in plasma.

In the present study the pharmacokinetic and bioequivalence parameter of Ketoprofen 100 mg fast dispersible tablets (test) were measured with marketed (reference) product. This study was accomplished following FDA guidance. A single dose, open labeled, cross over (two way), randomized study design was used to conduct investigation on 12 Pakistani healthy volunteers. At various time points blood samples (10mL) were drawn i.e. at 0.25, 0.5, 1, 1.5, 2, 3, 4, 8, 12 and 13hr. Plasma was then separated and ketoprofen concentrations were estimated by validated HPLC technique using LC 20A pump (Shimadzu Corp, Japan) and Spectrophotometric SPD-20Adetector (Shimadzu Corp, Japan). Ketoprofen concentrations were then analyzed by Kinetica TM 4.4.1 (Thermo electron corp, USA) to estimate various compartmental and noncompartmental pharmacokinetic parameters. Various parameters of bioequivalence including AUC tot , AUC 0-oo , AUC last , T maxcalc and C maxcalc w ere compared using ANOVA method (two way). For log and non-log transformed data the 90% confidence interval values for AUC oo0-oo , (1.0087-1.0704; 1.0099-1.0714), AUC tot , (0.95482- 1.0093; 0.95486-1.0098), AUC last (0.93373-0.98605; 0.93404-0.98603), C maxcalc (0.92978-0.9955; 0.92962-0.99663) and T maxcalc (0.89019-0.94116; 0.89095-0.94288) for test and reference products respectively. Results were found to be within the FDA satisfactory range. For the results verification, Schuirman's one sided t test was used. SPSS 17.0 (SPSS Inc.) was utilized for the determination of wilcoxon sign rank test. Results showed no carry over effect after first study period. Also test product met the regulatory criteria for bioequivalence with the reference product. Both the formulations were well tolerated.

Cefpodoxime proxetil is a third generation cephalosporin antibiotic demonstrates pH dependent solubility and is highly soluble only in acidic pH. The purpose of this investigation was to design and develop immediate release tablets of cefpodoxime proxetil by direct compression method and determine the effect of different solid buffers (organic acids) such as fumaric acid (formulations F1-F4), maleic acid (formulations M1-M4) and citric acid (formulations C1-C4) by using cefpodoxime and acid in the ratios of 4:1, 2:1, 1:1 and 1:2 to achieve pH-independent release of the drug. Physical parameters and assay were found to be within the acceptable range as prescribed in USP 36 / NF 31. In vitro dissolution studies of each formulation were performed in distilled water, USP dissolution medium, HCl buffer solution of pH 1.2, phosphate buffer solutions of pH 4.5 and 6.8 to observe the drug release. The formulations F3, F4, M4 were selected for film coating on the basis of better drug release profile, to protect the drug from chemical degradation through hydrolysis. Film coated formulation F3, F4 and M4 showed a remarkable in vitro release of the drug (72.88±0.43 to 92.67±0.71%) within 30min of observation in all dissolution media and further evaluated by model independent and model dependent approaches. The drug release was found to be best fit to Weibull model as highest r 2 adjusted (0.924-0.998) and lowest AIC (18.416-54.710) values were obtained in all dissolution media. R Gui® applied for stability studies of F3 and F4 formulations, showing shelf lives of 28 & 27months at ambient and 33 months at accelerated temperatures. Formulation F4 was chosen as best formulation on the basis of physical properties, highest dissolution rate and stability studies.

Background: Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated., Methods: Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol ® ), Glyceryl palmitostearate (Precirol ® ), Glyceryl behenate (Compritol ® ) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found., Results: Sphericity indicated by shape factor (e R ) varied with type and concentration of lipids: Geleol ® (e R  = 0.891-0.997), Precirol ® (e R  = 0.611-0.743), Compritol ® (e R  = 0.665-0.729) and Carnauba wax (e R  = 0.499-0.551). Highly spherical pellets were obtained with Geleol ® (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol ® and Compritol ® , (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax. Scanning electron microscopy of Compritol ® pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol ® and Compritol ® pellets, explained by Korsmeyer-Peppas (R 2  = 0.978-0.993) indicated non-Fickian diffusion (n = 0.519-0.597). Combinations of (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax pellets followed Zero-order (R 2  = 0.991-0.995). Similarity test was performed using combination of Geleol ® and Compritol ® (i) as a reference., Conclusions: Matrices for the extended release of Meclizine HCl from extruded-spheronized pellets were successfully formed by using three lipids (Geleol ® , Compritol ® and Carnauba wax) in different combinations. The encapsulated pellets of Meclizine HCl can be effectively used for treatment of motion sickness, nausea and vertigo for extended period of time.

The objective of this study was to assess the quality of six different brands of enteric coated Ketoprofen 100 mg tablets, KPB 2 to KPB6 are available in commercial market of Karachi, Pakistan, while KPB1 was obtained from international source. We performed different physico-chemical assessments i.e. weight variation, diameter, hardness, friability, thickness, disintegration, content uniformity, assay and dissolution test. Results of all the investigations were found to be in adequate limits. Also pharmaceutical equivalence was determined by selecting different tests and assay assessment. Furthermore, in vitro therapeutic equivalence was also estimated at phosphate buffer pH 6.8 and 7.5. Results were evaluated by one way ANOVA, model independent and model dependent methods. ANOVA results showed that release behaviour were found to be similar as p values >0.05, also KPB 1 - KPB 6 followed Weibull model at different dissolution media. Results indicated that innovator and brands not only passes the pharmaceutical equivalence assessment but also comply with the in vitro therapeutic equivalence.

The aim of the study was to develop a reservoir-type transdermal patch for a controlled delivery of dexibuprofen and to evaluate its in vivo anti-inflammatory activity in Albino Wistar rats. In order to develop these patches, six formulations of dexibuprofen microemulsion comprising ethyl oleate, Tween 80: PG (2 : 1), and water were prepared by simplex lattice design and characterized. The reservoir compartment was filled with these microemulsions and in vitro release and skin permeation were assessed. The optimized patch was obtained on the basis of the responses: Q 24 and flux. The impact of drug loading, surface area, membrane thickness, adhesive, and agitation speed on drug release and permeation was also studied. The skin sensitivity reaction and in vivo anti-inflammatory activity of optimized patch were evaluated. Stability study at three different temperatures for three months was carried out. The result suggests that a membrane based patch with zero-order release rate, Q 24 of 79.13 ± 3.08%, and maximum flux of 331.17  µ g/cm 2 h can be obtained exhibiting suitable anti-inflammatory activity with no visible skin sensitivity reaction. The outcomes of stability study recommend storage of patches at 4°C having shelf-life of 6.14 months. The study demonstrates that the reservoir-type transdermal patch of dexibuprofen microemulsion has a potential of delivering drug across skin in controlled manner with required anti-inflammatory activity.

The objective of this study was validation of a reverse phase HPLC method for the estimation of metoclopramide HCl in plasma already validated for determination of metoclopramide HCl in tablets dosage form. A reverse chromatographic method was used for estimation of metoclopramide HCl with the mobile phase of acetonitrile, 20mM potassium dihydrogen phosphate buffer solution (pH 3.0 adjusted with orthophosphoric acid) in the ratio of 40: 60. The column used was Waters C18 3.9×300mm µBondapak (RP). The flow rate of the mobile phase was 2ml/ minute. The detector was set at the wavelength of 275nm. This method validated in plasma and was found to be linear, with correlation coefficient (R 2 ), value of 0.9988, in the range of 48 ng/ml-0.25ng/ml. The method modified was accurate, precise, sensitive and showed good stability results. The % RSD of the retention time and peak area of metoclopramide HCl was 0.19% and 1.44% respectively. All the parameters such as specificity, linearity, range, accuracy, precision, system suitability, solution stability, detection and quantification limits were evaluated to validate this method and were found within the acceptance limits. The method can be effectively used for estimation of metoclopramide HCl in plasma.

Context: Cancer-related fatigue is one of the most commonly reported symptoms in cancer patients. Short but good assessment is essential to detect and manage this symptom. Brief Fatigue Inventory (BFI) is a valid and reliable short instrument to assess cancer-related fatigue., Objective: To examine the validity and reliability of the Indonesian BFI., Methods: Forward and backward translation approach, followed by cognitive debriefing process, was done to develop Indonesian BFI. One hundred twenty-one consecutive adult outpatients with cancer who are willing to participate in this study filled in Indonesian BFI along with the Medical Outcome Study Quality of Life Short Form 36 (MOS SF-36). Demographic and health data were collected., Results: The Indonesian BFI had an overall Cronbach's alpha for the nine items of 0.956. The results of the factor analysis suggested a one-factor solution, supporting the hypothesis of unidimensionality of the Indonesian BFI. The Indonesian BFI score was compared with MOS SF-36 subscale to evaluate convergent validity. An expected inverse correlation between Indonesian BFI and all domains of MOS SF-36 was observed (r = -0.388 to -0.676; P < 0.0000). Discriminant validity analysis showed that the Indonesian BFI mean score significantly increased with increasing Eastern Cooperative Oncology Group Performance Status values (P = 0.000)., Conclusion: Indonesian BFI is a reliable and valid instrument for Indonesian cancer patients., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Depot medroxyprogesterone acetate (DMPA) contraception is widely used all over the world; however, it may lead to a decrease in high-density lipoproteins and an increase in low-density lipoproteins (LDL) and triglycerides. These changes in lipid profile have a direct effect on cardiovascular disease risk. This study has been conducted to investigate the relationship between DMPA use and lipid profile, and the effect of worsening of lipid profile on fasting blood glucose. The objective of the present study is to ascertain the effects of DMPA on lipid profiles and Castelli indices, and to estimate the risk of cardiovascular disease in the women using progesterone-only methods for contraception., Methods: This was a multicenter case-control study including females of reproductive age. A total of 893 women were selected according to inclusion and exclusion criteria described below with the age range of 19-49 years. Among these, 477 were females who were beginning DMPA for contraception whereas 416 were the matched controls of same age and socioeconomic status. The lipid profiles, Castelli indices and fasting blood sugar were evaluated before initiation of DMPA and thereafter at 3, 6, 9 and 12 months. Controls were also analyzed for the same parameters in the same manner as that of treated group. The results were analyzed by repeated measure analysis of variance followed by Tukey׳s post hoc test for the multiple comparisons., Results: The results showed statistically significant differences in all parameters of lipid profile, namely cholesterol (180.7 ± 38.8 versus 133.03 ± 14.8mg/dL, and P = 0.000), LDL (120.04 ± 36.2 versus 94.27 ± 19.6mg/dL, and P = 0.000), very low-density lipoprotein cholesterol (24.6 ± 10.0 versus 20.99 ± 8.66mg/dL, and P = 0.000), high-density lipoprotein (39.67 ± 3.6 versus 44.13 ± 4.22mg/dL, and P = 0.000), total cholesterol (713.05 ± 110.2 versus 569.19 ± 80.4mg/dL, and P = 0.000), triglycerides (126.33 ± 48.8 versus 99.03 ± 30.6mg/dL, and P = 0.000), Castelli index I (4.61 ± 1.2 versus 3.02 ± 0.31, and P = 0.000) and Castelli index II (3.08 ± 1.07 versus 2.13 ± 0.41, and P = 0.000) between treated and control groups, respectively. Serum glucose levels were significantly higher (P ≤ 0.001) among the cases of DMPA (84.6394 ± 7.425mg/dL) compared with that in the control (77.822 ± 7.733mg/dL)., Conclusions: This study clearly revealed that there is an increase in all deleterious lipid parameters and a decrease in favorable lipid measures. Hence, it can be concluded that continued use of DMPA may predispose females to the risk of cardiovascular disease in the long run., (Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Respiratory tract infection is a major cause of hospitalization in children. Although most such infections are viral in origin, it is difficult to differentiate bacterial and viral infections, as the clinical symptoms are similar. Multiplex polymerase chain reaction (PCR) methods allow testing for multiple pathogens simultaneously and are, therefore, gaining interest. This prospective case-control study was conducted from October 2013 to February 2014. Nasopharyngeal (NP) and oropharyngeal (throat) swabs were obtained from children admitted with severe acute respiratory infection (SARI) at a tertiary hospital. A control group of 40 asymptomatic children was included. Testing for 16 viruses was done by real-time multiplex PCR. Multiplex PCR detected a viral pathogen in 159/177 (89.9 %) patients admitted with SARI. There was a high rate of co-infection (46.9 %). Dual detections were observed in 64 (36.2 %), triple detections in 17 (9.6 %), and quadruple detections in 2 (1.1 %) of 177 samples. Seventy-eight patients required intensive care unit (ICU) admission, of whom 28 (35.8 %) had co-infection with multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected among asymptomatic children. This study confirms the high rate of detection of viral nucleic acids by multiplex PCR among hospitalized children admitted with SARI, as well as the high rate of co-detection of multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected in asymptomatic children, resulting in challenges in clinical interpretation. Studies are required to provide quantitative conclusions that will facilitate clinical interpretation and application of the results in the clinical setting.

Background: Expression of the tumor necrosis factor (TNF) family member APRIL (a proliferation-inducing ligand) is low in normal tissues but is elevated in various autoimmune diseases., Objectives: This study explored serum APRIL in children with atopic eczema (AE) during flare and quiescence., Methods: A case-control study including 50 patients with AE and 40 control subjects was conducted. The severity of AE was assessed according to each of the Leicester Sign Score (LSS), the Simple Scoring System (SSS), the SCORing of Atopic Dermatitis (SCORAD) index, and the Objective SCORAD. Serum measurements of APRIL, total immunoglobulin E, and lactate dehydrogenase were obtained in all subjects. Data were obtained during both flare and quiescence in AE subjects. Data were analyzed using the Mann-Whitney U-test and Pearson's correlation coefficient. P-values of <0.05 were considered to indicate statistical significance., Results: Serum APRIL levels were significantly elevated in children with AE in comparison with control subjects during both flare and quiescence (P < 0.0001 for both). Serum APRIL levels during AE flare and quiescence were positively correlated (P < 0.001). Serum APRIL levels and scores on each of the LSS, SSS, and SCORAD showed significant positive correlations (P < 0.01 for all)., Conclusions: Serum APRIL levels were significantly elevated in children with AE during both flare and quiescence. This confirms the importance of APRIL in the pathophysiology of pediatric AE. Serum APRIL is a reliable marker of the severity of AE in children. APRIL may be a new target in the treatment of AE., (© 2016 The International Society of Dermatology.)

Background: Microsomal epoxide hydrolase enzyme (mEPHX) is involved in xenobiotics detoxification. Two variants of mEPHX, Tyr113His and His139Arg, have been described. Both may lead to acquired aplastic anemia (AA)., Objectives: Assessing mEPHX genetic polymorphisms and detecting their impact on susceptibility and prognosis in Egyptian AA patients., Participants and Methods: mEPHX 113 and 139 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 100 patients with AA and 100 control subjects., Results: Both mEPHX Tyr113His and His139Arg gene polymorphisms were associated with increased risk of developing AA, and have a significant impact of bad prognosis (p value < 0.01)., Conclusions: These mEPHX gene polymorphisms can be considered as risk factors and predictive molecular markers for prognosis in AA patients.