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Immuno-positron emission tomography (immuno-PET) is a powerful tool to noninvasively characterize the in vivo biodistribution of engineered antibodies (Abs). Methods L1 cell adhesion molecule (L1CAM)-targeting HuE71 immunoglobulin G1 (IgG1) and immunoglobulin G4 (IgG4) Abs bearing identical variable heavy and light chain sequences but different fragment crystallizable (Fc) portions were radiolabeled with Zirconium-89 (89Zr) and the in vivo biodistribution was studied in SKOV3 ovarian cancer xenografted nude mice. Results In addition to showing uptake in L1CAM-expressing SKOV3 tumors like its parental counterpart HuE71 IgG1, the afucosylated variant having enhanced Fc-receptor (FcR) affinity showed high nonspecific uptake in lymph nodes. On the other hand, aglycosylated HuE71 IgG1 with abrogated FcR binding did not show lymphoid uptake. The use of IgG4 subclass showed high nonspecific uptake in the kidneys, which was prevented by mutating serine at position 228 to proline (S228P) in the hinge region of the IgG4 Ab to mitigate in vivo fragment antigen-binding (Fab) arm exchange. Conclusion Our findings highlight the influence of Fc-modifications and the choice of IgG subclass on the in vivo biodistribution of Abs and the potential outcomes thereof.

Background: Hypothermia is a well-known contributor to neonatal morbidity and mortality, especially for preterm and low-birth weight neonates. Identifying the predictors for admission hypothermia which are specific to the settings is important to initiate quality improvement projects and improve clinical outcomes. Methods: Study was conducted over a period of 6 months from 1 April to 31 September 2018. All inborn infants needing neonatal intensive care unit (NICU) admission were eligible for the study. The study involved measuring temperatures at exit from delivery room (DR) and at admission to NICU. Hypothermia was defined as core admission temperature Results: One hundred and ninety-three infants were enrolled in the study. The incidence of admission hypothermia (Conclusion: Significant proportion of neonates is hypothermic at the time of admission to NICU. DR temperature significantly predicts hypothermia at admission in neonates needing NICU admission.

AIM: The current work establishes an easy, reliable technique for the estimation of serum Olanzapine concentration which correlates it clinically. SUBJECTS AND METHODS: The work was agreed in 61 schizophrenic patients who were on olanzapine. Serum drug amount was estimated by normal-phase high-performance liquid chromatography and brief psychiatry rating scale was used to determine disease progression. RESULTS: Samples provided 61 patients, 40 were under sub-therapeutic range, 18 were under therapeutic range and 3 were above the therapeutic range. CONCLUSION: Therapeutic drug monitoring must be a part of clinical practice in psychiatric hospitals for optimizing the dose of an individual patient along with the correlation of serum concentration with the clinical assessment scales.

It is a prospective, in-vivo randomized cross sectional questionnaire based study to determine general esthetic preference of Indian population and to find out whether this preference was affected by sex, age, education, social status and geographic location. Toward these aims, 30 well balanced facial profiles are selected (15 males and 15 females) in the age group of 18-30 years. The most attractive facial profile of 1 male and 1 female subject is selected by three panel of Judges. Profile selected for each sex were morphed by an Adobe Photoshop version cs2 technique and then scored by 200 participants. Subjects were asked to rank the profiles in ascending order of attractiveness on scoring scale 1 to 10. Morphing is done in 2 dimensions Sagittal and Vertical. Profile digital photographs were altered by 2mm and 4mm increments to produce different combinations of mandibular sagittal positions and vertical facial heights and to assess whether interactions and magnitude of the sagittal and vertical facial dimensions influence perception of facial attractiveness. Analysis of variance (ANOVA) and independent sample t-tests were used to compare the preferences of the groups. The orthognathic profile and straight profile in both sexes was selected as the most preferred profile whereas the convex profile with a prognathic maxilla and a retrognathic mandible were the least preferred. The public also admired fuller and protrusive lips in females and retrusive lips in males. Sex, age, education, social status and geographic location were also shown to affect the public’s profile preferences. Keywords: ANOVA, facial perception morphing questionnaire study ttests.

Background of the study: Inaccuracy in writing and poor legibility of handwriting or incomplete writing of a prescription can lead to misinterpretation, thus leading to errors in dispensing and administration. Both individual and system related factors are responsible for prescribing errors. Recognition is the essential step in building safer systems and preventing errors. These errors can be detected by systematic analysis of prescriptions through a prescription audit. Hence, this project was proposed to improve the prescription practice by recommending the prescribing and therapeutic interventions in a selected setting of Anantapur. Research Methodology: The study was approved by the ethical committee of the hospital. Before starting the study, the researcher obtained formal permission from Government General Hospital, Anantapuramu. The data collection period was for 6 months. A prospective observational design was adopted for this study. The prescriptions were selected on the basis of inclusion criteria. Descriptive statistics like frequency and percentage were calculated to describe the data. Results and discussion: The overall observation made from this study was that clinical pharmacist could identify some drug related problems, provides clinical pharmacy services and contribute to better patient care being a part of the healthcare team. Conclusion: There is enormous scope for the clinical pharmacist to play an important role in health care in various aspects like monitoring ADRs, provision of drug information, identifying DRPs and patient counseling which will bring better patient outcome. Key words: Adverse drug reactions, Clinical audit, Clinical Pharmacist, prescription audit

Context: Childhood-onset of depression is often associated with childhood family adversity, parental neglect, and problematic peer relationships. Emotional and behavioral problems and high rates of depression were more common in orphans when compared to nonorphan. Aim: The aim was to study and compare the depression and behavioral problems among children residing at welfare hostels and orphanages. Materials and Methods: This study is a cross-sectional and descriptive study. Three welfare hostels and four orphanages run by nongovernment organizations were approached, and children between the ages of six and fourteen were recruited. Children residing at home were taken as controls. Children's Depression Rating Scale and Rutter's Behavior Scale for Children were applied to assess depression and behavioral problems, respectively. Statistical Analysis Used: Statistical analysis was done using Epi Info software. Results: Depression is found to a greater extent among children in the orphanages' group than in the welfare group. Rutter's score ≥9 was observed in 15%, 8.3%, and 5% of children in the welfare hostels' group, orphanages' group, and controls' group, respectively. Conclusions: The prevalence of depression is found to be more among orphanage children, followed by children residing at welfare hostels compared to the control group. Behavior problems are more among children residing at welfare hostels than children residing at orphanages.

Acetylcholinesterase (AChE) inhibitors such as donepezil, galantamine and rivastigmine are used for the management of dementia in Alzheimer's Disease (AD). These drugs elevate endogenous acetylcholine (ACh) levels at the M1 muscarinic receptor in the brain to achieve therapeutic benefits. However, their side effects, such as nausea, vomiting, dizziness, insomnia, loss of appetite, altered heart rate, etc., are related to non-specific peripheral activation of M2–M5 muscarinic subtypes. It is logical, therefore, to develop drugs that selectively activate brain M1 receptors. Unfortunately, the orthosteric site homology among the receptor subtypes does not permit this approach. An alternative approach is to use positive allosteric modulator (PAM) of M1 receptors like benzyl quinolone carboxylic acid (BQCA). PAMs although devoid of M1 agonist activity, however, when bound, enhance the binding affinity of orthosteric ligand, Ach. The current challenge with PAMS is their low brain half-life, permeability, and higher elimination rates. This study reports active targeting of brain M1 receptors using surface modified nano lipid–drug conjugates (LDC) of M1 PAM, BQCA, to treat AD. Polysorbate-80 (P-80) surface modified stearylamine (SA)-BQCA conjugated nanoparticles (BQCA-SA-P80-NPs) were prepared by conjugating BQCA to SA, followed by the formation of nanoparticles (NPs) using P-80 by solvent injection method. The BQCA-SA-P80-NPs are near-spherical with a particle size (PS) of 166.62 ± 1.24 nm and zeta potential (ZP) of 23.59 ± 0.37 mV. In the in vitro cytotoxicity (SH-SY5Y cells) and hemolysis assays, BQCA-SA-P80-NPs, show acceptable safety and compatibility. In mice, Alzheimer's model, BQCA-SA-P80-NPs significantly prevent STZ induced changes in memory, neuronal Aβ1–42, p-Tau, APP, NF-κB, and BACE levels and neuronal cell death, when compared to untreated disease control and naive BQCA treated group. Further, BQCA-SA-P80-NPs significantly improve the therapeutic efficacy of AChE inhibitor, donepezil (DPZ), indicating its potentiating effects. In vivo biodistribution studies in mice show selective accumulation of BQCA-SA-P80-NPs in the brain, suggesting an improved brain bioavailability and reduced peripheral side effects of BQCA. The study results demonstrate that BQCA-SA-P80-NPs can improve brain bioavailability and therapeutic efficacy of BQCA in AD.

Objective To evaluate the results of microsurgical clipping for single intracranial aneurysm (SIA) and multiple intracranial aneurysms (MIA) and compare the outcomes. Methods All patients who underwent surgery for intracranial aneurysm (IA) at our institution over a 3-year period (June 2013 to May 2016) were included in this study. Results A total of 157 patients with 225 IAs were included. Forty-one of these patients had MIA (109 IAs, mean, 2.7 ± 1.2; range, 2–7), and remaining 116 had SIA. In the patients with MIA, all aneurysms were secured during the same admission whenever possible. Depending on the locations of the IAs and condition of brain during surgery (tense/lax), all aneurysms were secured on same day (in a single session, single or multiple craniotomy in 28 patients) or on different days (multiple sessions in 13 patients). Postoperative control angiography (DSA) before discharge could be done for 216 aneurysms (MIA, n = 105; SIA, n = 111). Successful occlusion of the aneurysm from circulation was noted in 96.2% (101/105) of MIA and 93.7% (104/111) of SIA. Follow-up of 6 months or longer was available for 146 patients. A modified Rankin Scale score ≤2 was considered a good outcome. Univariate analysis of the entire group revealed no significant difference in clinical outcomes between patients with SIA and MIA both at discharge (good outcome: MIA, 82.9%; SIA, 93.1%; P = 0.068) and at a final follow-up of ≥6 months (good outcome: MIA, 87.2%; SIA, 94.4%; P = 0.164). Clipping for MIA was not associated with poor outcome in multivariate analysis. Conclusions Comparable clinical outcomes and high rates of complete aneurysm occlusion following microsurgical clipping can be expected in patients with SIA and patients with MIA.

Background: Chronic obstructive pulmonary disease (COPD) is associated with structural and mechanical changes in the pulmonary vascular bed that increase right ventricular (RV) afterload and subsequently right heart failure. Objectives: The aim of the study was to elucidate RV dysfunction at rest by echocardiography in a cohort of COPD patients and to study its impact on prognosis. Methods: 84 patients of COPD and 40 matching healthy controls were evaluated at baseline. Evaluation included clinical examination, pulmonary function tests; 6 minutes walk test and echocardiography. Patient with COPD were again evaluated after 6 months. Results: All echocardiographic parameters of RV function were significantly impaired in COPD patients as compared to controls. Clinical deterioration in COPD group was much more in patients with baseline abnormal RV function (89%) and patients with RV systolic pressure ≥35 mmHg (P = 0.018). All the six patients who died had three or more abnormal RV systolic function parameters. Conclusions: RV myocardial performance index and basal strain showed largest difference between controls and COPD cases. Clinical deterioration was more common in patients with abnormal RV function parameters and pulmonary hypertension.

Fresh water production through sustainable approaches such as solar thermal sources is attracting widespread attention. One of the recently developed approaches aims at utilizing black particles to enhance evaporation and steam generation through efficient photo-thermal conversion process in direct solar thermal desalination systems. Activated carbon serves as one such material for meeting the objectives of freshwater production with negligible increments in cost of the overall system. A series of chemical and physical characterizations were performed to explore the possibility of using activated carbon as a stable carbon source. Optical characterization showed granular activated carbon to have 96.35% solar absorptance and its dispersion in water to have less than 1.5% transmittance (absorbance of 1.85) at 100 mg/L concentration. Outdoor experiments were performed at the University of California-Merced in the month of September (2019), with peak irradiation of 0.8 suns. The comparative measurements showed that the total evaporation enhancement was 38% and 100% for granular activated carbon and activated carbon dispersions, respectively, when compared to pure DI water.

Triple-negative breast cancer (TNBC) is the most aggressive and heterogeneous cancer subtypes. High rates of metastasis, poor prognosis, and drug resistance are the major problems associated with TNBC. The current chemotherapeutics eliminate only the bulk tumor cells (non-BCSCs) and do not affect breast cancer stem cells (BCSCs). The BCSCs which are left behind after chemotherapy is reported to promote recurrence and metastasis of TNBC. Death receptor-5 (DR-5) is exclusively expressed in TNBCs and mediates the extrinsic pathway of apoptosis. DR-5, therefore, can be exploited for targeted drug delivery and to induce apoptosis. Gamma-secretase mediated Notch signaling in BCSCs regulates its proliferation, differentiation, and metastasis. The endogenous ligand, Delta-like ligand 4 (DLL4), is reported to activate this Notch signaling in TNBC. Blocking this signaling pathway using both gamma-secretase inhibitors (GSIs) and DLL4 monoclonal antibody (mAb) may produce synergistic benefits. Further, the GSIs (DAPT, LY-411575, RO4929097, MK0752, etc.) suffer from poor bioavailability and off-target side effects such as diarrhea, suppression of lymphopoiesis, headache, hypertension, fatigue, and ventricular dysfunctions. In this hypothesis, we discuss Solid lipid nanoparticles (SLNs) based drug delivery systems containing GSIs and surface modified with DR-5 and DLL4 monoclonal antibodies (mAb) to effectivity target and treat TNBC. The delivery system is designed to deliver the drug cargo precisely to TNBCs through its DR-5 receptors and hence expected to reduce the off-target side effects of GSIs. Further, DLL4 mAb and GSIs are expected to act synergistically to block the Notch signal mediated BCSCs proliferation, differentiation, and metastasis.

The descriptive observational study was conducted over six months among inpatients of the orthopaedics department. The aim is to observe the prescribing pattern of drugs, to find out the percentage of analgesics given and most commonly prescribed analgesic, to compare the prescribed drugs whether they are in NLEM, WHO list and calculate DDD/100 Bed-days and to analyze the drugs for WHO prescribing drugs. A total of 250 patients were included in the study. Out of this, 168 were male, and 82 were female. Most of the patients were in the age group of 31-40[45 in number with 18%]. The most common condition was found to fracture [113 in number with 95.2%]. Commonly prescribed drugs were analgesics 447 with 26.76%. Among all the NSAID's, PCM was most commonly prescribed analgesic with 34.4%. The highest no, of drugs was found to be 4drugs/prescription with 24%. Monthly one analgesic was prescribed per prescription with 38.8%. Utilization of analgesics in term of DDD/100 Bed-days was 55.26; Drugs will be evaluated per prescription as per prescribing indicators of WHO was done, the average no. of drugs per prescription was found to be 0.45, percentage of drugs prescribed by generic name was found to be 13.3%, percentage of encounters with antibiotics prescribed were found to be 94.4%, In ratio percentage of drugs prescribed from the national list of essential medicine was found to be 92.6%. This study would help to facilitate better health care delivery.

Hypothermia is a common problem especially in preterm neonates and has been associated with increased neonatal mortality and morbidities. The objective of our study was to look into the distribution of admission temperature among VLBW neonates getting admitted to the NICU, association of admission temperatures to selected neonatal morbidities/mortality, and to evaluate for modifiable factors contributing to hypothermia.Infants with birth weight between 500 and 1499 g and gestation ≥ 25 weeks without major congenital malformations delivered between October 2017 and March 2020 who were admitted directly from the delivery room to the NICU were included in the study. Data were collected prospectively on perinatal/birth characteristics to look for their association with admission hypothermia, and to look into the association of admission temperature with selected neonatal morbidities/mortality.There were a total of 538 neonates with the mean birth weight of 1206 ± 271 g included in the study. Mean admission temperature was 35.8 ± 1.3 °C. Low delivery room temperature was the most important contributor to admission hypothermia. Also, 3.3% of neonates were hyperthermic at admission to NICU, all of them having been delivered to mothers with intrapartum pyrexia. On adjusted analysis, we found that low admission temperature significantly increased therisk of adverse composite neonatal outcomes with admission temperature34.5 °C having 42% increased risk of the adverse outcome when compared to normothermic neonates.Admission hypothermia remains a common problem in preterm neonates which is significantly associated with adverse neonatal outcome.

Shock is a state of circulatory dysfunction and its diagnosis is complex in neonates. Hemodynamic assessment using echocardiography has potential to guide better management regimes in neonates with shock. Objective of this study is to analyze changes in the echocardiographic parameters in preterm neonates with shock at presentation and after resolution. In this prospective pragmatic Cohort study, eligible neonates with shock were monitored for changes in echocardiographic parameters at onset of shock and after resolution of shock. Paired data analysis was done for observed changes in the parameters. Based on initial clinical parameters and echocardiographic parameters, infants were assigned into different types of shock. Data of 37 infants were analyzed for baseline clinical and echocardiographic parameters, and data of 31 infants were analyzed for the changes in the observed parameters after shock resolution. Statistically significant changes were observed in inferior vena cava collapsibility index (ICI), left ventricular end diastolic volume (LVEDV), isovolemic ventricular relaxation time (IVRT), left and right ventricular stroke volume, and ejection fraction (EF). There was no agreement between clinical and echocardiographic definitions of shock.Conclusion: We noticed shock has overlapping pathophysiologic features. Our study highlights the importance of baseline documentation of echocardiographic parameters of all infants who are at risk of shock and repeat echocardiography at onset of shock to observe the changes in ICI, LVEDV, IVRT, stroke volume, and EF. This would guide pathophysiological management of shock in neonates. What is Known: • In neonates pathophysiology of shock is overlapping. • Echocardiography can help in better understanding and management of shock. What is New: • Study gives median changes in major echocardiographic parameters in neonatal shock. • These changes can guide for selection of volume and inotropes in management.

Shock is an acute state of circulatory dysfunction. The diagnosis of shock is complex in neonates. The relative sensitivity of current clinical or laboratory findings for detecting shock is largely unknown, especially for preterm neonates. For preload assessment, inferior vena cava (IVC) collapsibility can be a useful bedside echocardiography parameter. plethysmography variability index (PVI) is a marker of fluid responsive shock in adults and children, but not well defined in neonates. In this prospective observational study, we evaluated the changes in PVI in preterm neonates with shock. Among the 37 infants enrolled in the study, the mean blood pressure (MAP) was 45 (± 4 mm of Hg) and none of infants had hypotension. The mean pulse pressure was 28 mm of Hg, the mean PVI was 28% (±5), the mean arterial blood gas pH was 7.20 (±0.07), and the mean base deficit was 9.9 (±2.53) at the onset of shock. Thirty (96.77%) of the 31 infants with resolution of shock showed decrease in PVI with an average decrease of 11% (±5). Conclusion: Significant proportion of neonates show an increase in PVI at the onset of shock.

Background and aims Angiopoietin-2 (ANG-2) mediates endothelial inflammation to initiate atherosclerosis and angiogenesis. Here we determined the serum levels of ANG-2 in hyperinsulinemic subjects and whether insulin increases its expression and release. Methods Healthy male subjects were recruited from the D-CLIP and CURES studies and, based on their fasting insulin levels, were classified as normoinsulinemic (n = 228) and hyperinsulinemic (n = 32). Serum proteins were estimated by ELISA. Endothelial inflammation was scored as the number of THP-1 monocytes adhered to HUVEC monolayer. Gene expression was determined with promoter reporter assays and semi-quantitative RT-PCR. Western blotting was used to assess changes in protein expression and activation. Immunofluorescence imaging and ChIP assay were used for nuclear localization and promoter binding studies, respectively. Results ANG-2 and sTIE2 levels were higher in hyperinsulinemic subjects. Hyperinsulinemic serum elicited endothelial inflammation, which was abrogated by an ANG-2 blocker antibody. Insulin (100 nM) increased mRNA and protein expression of ANG-2, and its release from HUVECs. It induced activation of p38 MAPK and an increase in protein levels and nuclear localization of cFOS. Binding of cFOS to the −640 to −494 promoter region mediated insulin dependent ANG-2 transcription. p38 MAPK inhibitor (25 μM) blocked insulin-induced nuclear localization of cFOS, expression of ANG-2 and ICAM-1, and release of ANG-2 into the culture medium. Spent medium collected from insulin treated cells enhanced endothelial inflammation, which was lost upon ANG-2 knockdown as well as upon p38 MAPK inhibition. Conclusions ANG-2 levels are high in hyperinsulinemic subjects and insulin induces expression and release of ANG-2 from HUVECs through p38 MAPK-cFOS pathway to elicit endothelial inflammation.

Objective: Rare cancers are creating a massive challenge to the world. It has associated with genetic mutations or socio-environmental factors, which includes genes, smoking, alcohol, ionizing radiation exposure, organic-inorganic chemicals, air and water pollution, viruses, and bacteria. When 15 cases per 1,00,000 people per year, we can consider it as a rare case as per the National Cancer Institute This study aim is the importance of antibiotics in various unique metastasis along with cytotoxic therapy at tertiary care hospital. Methods: The inclusion criteria of our study include a person who is suffering from rare metastasis at an early stage. We excluded the data that are those who are suffering from the typical type of cancers, multiple co-morbid conditions. This study was carried out the Prospective Cohort Study conducted between June 2018 to March 2020. Results: Number of 20 rare cancers we consider for final analysis, the overall antibiotics use in this study 18 antibiotics they prescribed in overall cases, prescribed cytotoxic drugs are 23. the chi-square test value is P=0.001, the confidence interval(CI) is 95%, the likelihood ratio is 54.4, odd’s ratio is 2.0(CI 95%, P=0.711), Male patients more than the female patients. Conclusion: Cancer is a complex disorder, which is occurred through gene proliferation and socio-environmental factors. Rare metastasis is challenging to physicians and patients, however as per our observation, cytotoxic therapy with antibiotics can reduce the risk of rare metastasis and as well improved therapeutic adhesion, and we need clear supporting evidence on it through clinical trials.

Ovarian cancer is the fifth leading cause of cancer deaths amongst women, accounting for more deaths than any other cancer of the female reproductive system. The foundation of its management consists of cytoreductive surgery (CRS) followed by systemic chemotherapy, with the completeness of surgical resection consistently identified as one of the most important prognostic factors for the disease. The goal of our investigation is the development of a near-infrared fluorescence (NIRF) imaging agent for the intraoperative imaging of high-grade serous ovarian cancer (HGSOC). As surgeons are currently limited to the visual and manual assessment of tumor tissue during CRS, this technology could facilitate more complete resections as well as serve important functions at other points in the surgical management of the disease. Elevated levels of cancer antigen 125 (CA125) have proven a useful biomarker of HGSOC, and the CA125-targeting antibody B43.13 has shown potential as a platform for immunoPET imaging in murine models of ovarian cancer. Herein, we report the development of a NIRF imaging agent based on B43.13: (ss)B43.13-IR800. We site-specifically modified the heavy chain glycans of B43.13 with the near-infrared dye IRDye(®) 800CW using a chemoenzymatic approach developed in our laboratories. SDS-PAGE analysis confirmed the specificity of the conjugation reaction, and flow cytometry, immunostaining, and fluorescence microscopy verified the specific binding of (ss)B43.13-IR800 to CA125-expressing OVCAR3 human ovarian cancer cells. NIRF imaging studies demonstrated that (ss)B43.13-IR800 can be used to image CA125-expressing HGSOC tumors in subcutaneous, orthotopic, and patient-derived xenograft mouse models. Finally, ex vivo analyses confirmed that (ss)B43.13-IR800 can bind and identify CA125-expressing cells in primary tumor and metastatic lymph node samples from human patients with HGSOC.

Majority of people with chronic diseases have poor adherence to their therapeutic regimen. It can result in various complications physialogically with undesirable metabolic conditions. The main objective of this study is to assess the level of satisfaction attained after medication in comorbidities (either having diabetes only or having hypertension only or having Hypertension and Diabetes) and also focussed on creating awareness in patients who do not follow the medication. A prospective cross sectional study was conducted at tertiary care hospital, Khammam, Telangana. 200 patients were approached and were interviewed with their consent. The purpose of the same was to collect the information on socio demographics, medication that is followed, and behavioural characteristics. A structured questionnaire MMAS-8 an eight itemed scale was involved to identify individuals, determine their levels, the reliability and validity of the medication followed. The scrutiny of this study found that there is a better medication adherence in individual’s diseases (Hypertension, Diabetes) whereas in hypertension and diabetes condition high and low adherence were reported because of their awareness, negligence and risk factors respectively. The study concludes that there is an increase in Medication adherence in individual diseases whereas in hypertension and diabetes there are equal ranges of both low and high adherence.

Introduction Despite its limitations, CA125 remains the most widely used biomarker for the diagnosis and treatment monitoring of ovarian cancer. Targeting the unshed portion of serum biomarkers such as CA125/MUC16 may afford more specific imaging and targeting of MUC16-positive tumors in High Grade Serous Ovarian Cancer (HGSOC) patients. Methods Six monoclonal antibodies raised against the 58 amino acid sequence between the extracellular cleavage site and the transmembrane region of MUC16 were radiolabeled with [89Zr]Zr4+. The radioimmunoconjugates were evaluated in vitro for molar activities, target binding affinity, cellular internalization and serum stability. In vivo characterization was performed via longitudinal positron emission tomography (PET) imaging and ex vivo biodistribution studies in mice bearing subcutaneous xenografts of SKOV3 cells transfected with the proximal 114 amino-acids of MUC16 carboxy-terminus (SKOV3+). Results In vitro screening identified 9C9 and 4H11 as the lead antibody candidates based on their comparable binding affinities, serum stability and cellular internalization profiles. Despite an identical molecular footprint for binding to MUC16, [89Zr]Zr-DFO-4H11 yielded a more favorable in vivo radiopharmacologic profile. Furthermore, a humanized variant of 4H11 capable of binding MUC16 in vitro also yielded excellent in vivo profile in subcutaneous xenograft models of SKOV3+, OVCAR3 tumors and a patient-derived xenograft model representative of HGSOC. Conclusion Radiopharmacologic screening of antibodies early during their development can provide crucial information pertinent to the in vitro characterization and in vivo pharmacokinetics. The favorable in vivo profile demonstrated by humanized 4H11 combined with the use of its murine predecessor for immunohistochemical staining of biopsied tumor tissues from HGSOC patients makes a unique pair of antibodies that is poised for clinical translation.

Mother’s own milk (MOM) for premature infants is a complete nutrition. It is an ideal issue for a quality improvement (QI) initiative. To increase the proportionate usage of MOM as enteral feeds. A QI study conducted in Tertiary care NICU involving all eligible very low birth weight (VLBW) infants and mother dyads. The proportionate usages of MOM as enteral feeds were the main outcomes. Education, milk expression, and mother–infant interaction formed the key drivers. We studied 282 mother infant dyads during the QI period. The proportionate usage of MOM as the enteral feed increased from 55% (±34) at baseline to 80% (±27) during the intervention and to 88% (±16) in sustenance phase. A QI initiative resulted in 60% relative improvement in proportionate usage of MOM as enteral feeds in VLBW infants during hospital stay.

Background Hypothermia is an important contributor to neonatal morbidity and mortality, more so in the preterm and extreme low birth weight infants. Methods Study was conducted over a period of 3 months from 1st January to 31st March 2018 with an aim of evaluating rate of change of temperature of newborn neonates from delivery to NICU admission and factors effecting rate of change of temperature in these neonates. A unique compact continuous temperature monitoring device was used for this study. Temperature changes in the baby were monitored with a help of smart phone where temperature is updated every 5 s. Results Thirty neonates with mean gestation of 31 ± 3 weeks were enrolled for study. Mean temperature at admission to NICU was 35.34 ± 0.74 °C. There was no temperature loss while stabilization of neonate under radiant warmer or during transport to NICU. Maximum temperature loss happened before baby reached to radiant warmer. Delivery room temperature and gestation were found to be most important factors effecting admission temperature to NICU. Conclusion Significant proportion of neonates after birth is hypothermic at admission to NICU. Low delivery room temperature and prematurity are associated with neonatal hypothermia. Implementing WHO recommendation of increasing delivery room temperature to 25 °C and above can help in reducing the incidence of neonatal hypothermia.

The present research reports the beneficial effects of surface modified chitosan and tumor-homing peptide conjugated liposomes of capecitabine (CAP) for treating breast cancer. Liposomal formulation of CAP was prepared by film hydration method using cholesterol-THP conjugate (CTHP-CAP-LPs) to achieve active targeting through HER2 receptors. CTHP-CAP-LPs significantly improved the specificity and efficacy of CAP by improving cell uptake, cytotoxicity and tumor regression in tumor bearing mice. CTHP-CAP-LPs, therefore, is a promising approach to improve the anticancer effects of CAP.

Rationale: The overwhelming majority of radioimmunoconjugates are produced via random conjugation methods predicated on attaching bifunctional chelators to the lysines of antibodies. However, this approach inevitably produces poorly defined and heterogeneous immunoconjugates because antibodies have several lysines distributed throughout their structure. To circumvent this issue, we have previously developed a chemoenzymatic bioconjugation strategy that site-specifically appends cargoes to the biantennary heavy chain glycans attached to CH2 domains of the immunoglobulin's Fc region. In the study at hand, we explore the effects of this approach to site-specific bioconjugation on the Fc receptor binding and in vivo behavior of radioimmunoconjugates. Methods: We synthesized three desferrioxamine (DFO)-labeled immunoconjugates based on the HER2-targeting antibody pertuzumab: one using random bioconjugation methods (DFO-nsspertuzumab) and two using variants of our chemoenzymatic protocol (DFO-sspertuzumab-EndoS and DFO-sspertuzumab-βGal). Subsequently, we characterized these constructs and evaluated their ability to bind HER2, human FcγRI (huFcγRI), and mouse FcγRI (muFcγRI). After radiolabeling the immunoconjugates with zirconium-89, we conducted PET imaging and biodistribution studies in two different mouse models of HER2-expressing breast cancer. Results: MALDI-ToF and SDS-PAGE analysis confirmed the site-specific nature of the bioconjugation, and flow cytometry and surface plasmon resonance (SPR) revealed that all three immunoconjugates bind HER2 as effectively as native pertuzumab. Critically, however, SPR experiments also illuminated that DFO-sspertuzumab-EndoS possesses an attenuated binding affinity for huFcγRI (17.4 ± 0.3 nM) compared to native pertuzumab (4.7 ± 0.2 nM), DFO-nsspertuzumab (4.1 ± 0.1 nM), and DFO-sspertuzumab-βGal (4.7 ± 0.2 nM). ImmunoPET and biodistribution experiments in athymic nude mice bearing HER2-expressing BT474 human breast cancer xenografts yielded no significant differences in the in vivo behavior of the radioimmunoconjugates. Yet experiments in tumor-bearing humanized NSG mice revealed that 89Zr-DFO-sspertuzumab-EndoS produces higher activity concentrations in the tumor (111.8 ± 39.9 %ID/g) and lower activity concentrations in the liver and spleen (4.7 ± 0.8 %ID/g and 13.1 ± 4.0 %ID/g, respectively) than its non-site-specifically labeled cousin, a phenomenon we believe stems from the altered binding of the former to huFcγRI. Conclusion: These data underscore that this approach to site-specific bioconjugation not only produces more homogeneous and well-defined radioimmunoconjugates than traditional methods but may also improve their in vivo performance in mouse models by reducing binding to FcγRI.

Rocaglates are a class of eukaryotic translation initiation inhibitors that are being explored as chemotherapeutic agents. They function by targeting eukaryotic initiation factor (eIF) 4A, an RNA helicase critical for recruitment of the 40S ribosome (and associated factors) to mRNA templates. Rocaglates perturb eIF4A activity by imparting a gain-of-function activity to eIF4A and mediating clamping to RNA. To appreciate how rocaglates could best be enabled in the clinic, an understanding of resistance mechanisms is important, as this could inform on strategies to bypass such events as well as identify responsive tumor types. Here, we report on the results of a positive selection, ORFeome screen aimed at identifying cDNAs capable of conferring resistance to rocaglates. Two of the most potent modifiers of rocaglate response identified were the transcription factors FOXP3 and NR1I3, both of which have been implicated in ABCB1 regulation—the gene encoding P-glycoprotein (Pgp). Pgp has previously been implicated in conferring resistance to silvestrol, a naturally occurring rocaglate, and we show here that this extends to additional synthetic rocaglate derivatives. In addition, FOXP3 and NR1I3 impart a multi-drug resistant phenotype that is reversed upon inhibition of Pgp, suggesting a potential therapeutic combination strategy.

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer with high rates of tumor relapse and metastasis. The existing drugs for treatment of TNBC are unable to target the cells of origin (breast cancer stem cells) of TNBC. TNF-α related apoptosis inducing ligand (TRAIL) has propensity to target TNBC cells including cancer stem cells. However, resistance to TRAIL due to activation of anti-apoptotic mechanisms is a limitation for TRAIL based anticancer therapy for TNBC. In the present study we propose an hypothesis for effective targeting of triple negative breast cancer by overcoming TRAIL resistance.

Falls are the foremost cause of injury-related mortality among adults of age 65 and more grown, and the age-related fall death is rising to 64 deaths per 1, 00,000 older adults. Senior citizens who have experienced falls several times feel scared about falling again and lose confidence in self-care. Fall detection and reliable surveillance are necessary to eliminate the effects of falls in the elderly. In this paper, we propose a fall detection system, the SMART SCAPE, which provides an easy access to detect falls and boosts the confidence in elderly and physically disabled individuals. SMART SCAPE design is user-friendly, comfortable, and economically intelligent shoe, when compared with the other fall detection models. A rule based detection algorithm has been used for communicating the data through an Internet of Things (IoT) device to alert the caretaker through various methods based on the situation analysis such as voice announcement, location plotting, and condition monitoring using artificial intelligence photography, auto ambulance, and auto complaint registration when a fall is detected.

Respiratory infections corona virus 2-caused inflammatory disorders are CORONAVIRUS DISEASE 2019 (COVID-19) (SARS-CoV-2). A serious corona virus acute disease arose in 2019. Wuhan, China, was the first location to find the virus in December 2019, which has now been spreading all over the world. Recurrent neural networks, together with the use of LSTMs, fail to provide solutions to numerous issues (RNNs). So this paper has proposed RNN with Gated Recurrent Units for the COVID-19 prediction. This paper utilizes system, which was developed to assist nations (the Czech Republic, the United States, India, and Russia) combat the early stages of a newly emerging infection. For instance, the system tracks confirmed and reported cases, and monitors cures and deaths on a daily basis. This was done to allow the relevant parties to have an early grasp of the disastrous damage the lethal virus will bring. The implemented is an ensemble approach of RNN and GRU that work has computed the RMSE value for the different cases such as infected, cure and death across the four different countries.

Beveling of the calvarial bone is reported in firearm exit wounds and stabbing injuries in forensic literature. Beveling in entry wounds is rare. We report a case of a 27-year-old man who sustained a nonfatal penetrating craniofacial injury due to motorbike brake handle, and completely recovered after conservative management. We describe the characteristic inward as well outward beveling on imaging due the penetrating trajectory of the motorbike break handle.

Objectives: To assess the impact, timing, the intra and early post-operative complications and the survival outcome of tracheostomy in critically ill neurosurgery patients. Methods: This study was a retrospective data mining where data was collected from hospital records from 175 consecutive patients who underwent tracheostomy in the department of Neurosurgery at the Narayna Medical College Hospital, Nellore, India from Jan 2016 to April 2018. A proforma was used to note down the details on the patient status before and after tracheostomy: Glasgow coma scale (GCS), procedure and intra and post-operative complications, type of tracheostomy cannula, details of decannulation, respiration difficulties, and problems with wound, swallowing difficulties, and voice difficulties, stay in intensive care unit (ICU) and hospital and survival status of the patient. Results: In our series, mean age of TBI cases was 47.42±16.62; mean hospital stay and ICU stay was 18.81±10.22 and 12.58±7.36 days respectively. In all age groups, more tracheostomy was needed in cranial injury cases and surgery was major intervention. Commoner complications were mucous deposition (6.86%), blockage of tracheostomy canula (6.29%), bleeding from multiple attempts (6.06%), excessive bleeding (2.94%). Cranial injury needed tracheostomy more in all age groups and more done at operation theatre without significant improvement of GCS score. Survival was statistically higher after tracheostomy irrespective of GCS status or venue of intervention. Conclusion: Tracheostomy should be considered as soon as the need for airway access is identified during intervention of the critically ill neurosurgical patients.

Close monitoring of growth pattern in preterm neonates is essential to identify any deviations from the normal pattern. But, there is no international consensus regarding how the growth of preterm neonates should be monitored or what constitutes the ideal pattern of growth in these premature infants.To compare the incidence of IUGREUGR in preterm neonates ≤32 weeks gestational age based on Fenton 2013 growth curves and Intergrowth-21 growth standards.Retrospective Cohort Study.Tertiary care neonatal unit with nearly 1000 admissions to the neonatal unit.All newborns with gestational age ≤32 weeks (230 6/7 days) admitted to the NICU within 24 h of birth over a period of 3 years from 1 January 2015 to 31 December 2017.Out of 821 neonates born during the study period 603 were included. The mean birth weight, length, and head circumference were 1356.683 ± 335.91 g, 39.244 ± 3.124 cm, and 27.819 ± 1.906 cm, respectively. The mean discharge weight, length, and head circumference were 1550.70 ± 185.122 g, 41.606 ± 2.026 cm, and 29.398 ± 1.221 cm, respectively. The proportion of infants identified as IUGR at birth with respect to weight, length, and head circumference on both the charts was 15.1, 14.4, and 9%, respectively. The proportion of infants identified as EUGR at discharge with respect to weight, length, and head circumference on both the charts was 45.7, 29.8, and 32.3%, respectively.The proportion of infants identified as IUGR at birth and EUGR at discharge differed on the usage of Intergrowth charts (Birth reference and postnatal) in comparison to Fenton growth charts. The infants identified as IUGR at birth by Intergrowth charts and not by Fenton growth charts had higher incidence of morbidities.

Skin cancer is one of the leading causes of cancer-related deaths worldwide. It is estimated that by 2030, there will be around 13.1million deaths can occur due to skin cancer. Current treatment of skin cancer includes surgery, radiation and chemotherapy. Chemo-resistance, off-target effects and poor bioavailability are the major challenges for currently available drugs for the treatment of skin cancer. Transfersomes is a novel, elastic vesicular drug carrier composed of phospholipids, surfactants and ethanol for enhanced transdermal delivery. This article we have reviewed about merits/demerits, liposomes vs transfersomes, preparation methods, characterization, mechanism of skin delivery, and application and regulatory aspects of transfersomes in treating various skin cancers.