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Lung cancer is a pervasive and challenging disease with limited treatment options, with global health challenges often present with complex molecular profiles necessitating the exploration of innovative therapeutic strategies. Single-target drugs have shown limited success due to the heterogeneity of this disease. Multitargeted drug designing is imperative to combat this complexity by simultaneously targeting multiple target proteins and pathways, which can enhance treatment efficacy and overcome resistance by addressing the dynamic nature of the disease and stopping tumour growth and spread. In this study, we performed the molecular docking studies of Drug Bank compounds with a multitargeted approach against crucial proteins of lung cancer such as heat shock protein 5 (BIP/GRP78) ATPase, myosin 9B RhoGAP, EYA2 phosphatase inhibitor, RSK4 N-terminal kinase, and collapsin response mediator protein-1 (CRMP-1) using HTVS, SP with XP algorithms, and poses were filtered using MM\GBSA which identified [3-(1-Benzyl-3-Carbamoylmethyl-2-Methyl-1h-Indol-5-Yloxy)-Propyl-]-Phosphonic Acid (3-1-BenCarMethIn YlPro-Phosphonic Acid) (DB02504) as multitargeted drug candidate with docking and MM\GBSA score ranges from −5.83 to −10.66 and −7.56 to −50.14 Kcal/mol, respectively. Further, the pharmacokinetic and QM-based DFT studies have shown complete acceptance results, and interaction fingerprinting reveals that ILE, GLY, VAL, TYR, LEU, and GLN were among the most interacting residues. The 100 ns MD simulation in the SPC water model with NPT ensemble showed stable performance with deviation and fluctuations <2 Å with huge interactions, making it a promising multitargeted drug candidate; however, experimental studies are needed before use. [ABSTRACT FROM AUTHOR]

Introduction. Metaplastic breast carcinoma (MBC) is a rare subgroup of breast neoplasms associated with adverse outcomes because of its aggressive nature. Typically, MBCs show triple-negative hormone receptor (HR) status. Determining the HR status of breast cancer is an integral part because it is an important prognostic factor and helps in the treatment course of the disease. This study aimed to determine the HR status of MBC, its significance, and its association with various clinicopathological parameters. Methods. This was a retrospective study conducted at the Department of Histopathology, Liaquat National Hospital. A total of 140 biopsy-proven cases of MBC were enrolled in the study. Clinical and pathological data were retrieved from the institutes' archives. Immunohistochemical studies were conducted to determine the estrogen receptor (ER) and progesterone receptor (PR) status. Results. The mean age of MBC in our population was found to be 52.18 ± 12.19 years. The HR positivity rate in our population was found to be 32.9%. A significant association was found between HR status and tumor laterality, tumor size, tumor grade, tumor stage, and recurrence. ER/PR-negative MBCs were most probably associated with higher grade and higher tumor stage and were larger in size (6.62 ± 3.43 cm) than ER/PR-positive MBCs (4.20 ± 1.88 cm). Moreover, ER/PR-positive MBCs showed a higher recurrence rate than ER/PR-negative MBCs (43.5% vs. 25.5%, respectively). No statistically significant relationship was found between HR status and patient age, histological subtype, or survival rate. Conclusion. MBC is a rare breast neoplasm. MBC was found to be triple negative in most cases, but a significant percentage were HR (ER/PR) positive. Moreover, we found an association between HR status and various clinicopathological features, indicating that HR status is a significant predictor of MBC prognosis. [ABSTRACT FROM AUTHOR]

Integrating machine learning techniques into medical diagnostic systems holds great promise for enhancing disease identification and treatment. Among the various options for training such systems, the extreme learning machine (ELM) stands out due to its rapid learning capability and computational efficiency. However, the random selection of input weights and hidden neuron biases in the ELM can lead to suboptimal performance. To address this issue, our study introduces a novel approach called modified Harris hawks optimizer (MHHO) to optimize these parameters in ELM for medical classification tasks. By applying the MHHO‐based method to seven medical datasets, our experimental results demonstrate its superiority over seven other evolutionary‐based ELM trainer models. The findings strongly suggest that the MHHO approach can serve as a valuable tool for enhancing the performance of ELM in medical diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of switching from deferasirox dispersible tablet (DT) to deferasirox film-coated tablet (FCT) on serum ferritin (SF) levels in transfusion-dependent patients. Materials and Methods: Patients who received regular erythrocyte transfusion and whose treatment was switched from DT to FCT were included in the study. FCT start date was taken as the index date. Patients were followed over 2 equal and long periods, both before and after index date. Results: Thirty-two patients were included, and the comparison periods ranged from 4 to 12 months. The SF values increased from a median of 1723 ng/mL (range 717-5369 ng/mL) to 1.853 ng/mL (range 924-5478 ng/mL) after switching from DT to FCT (P = .036). While there was a significant increase in median SF after switching in Turkish patients (1467 ng/mL to 1778 ng/ mL, P = .010) and patients ≥12 years (1598-1848 ng/mL, P = .009), there was an insignificant (P = .859) decrease in SF in immigrant children. Considering only the post-switch period, there was a non-significant increase in median SF in the entire cohort, while SF decreased significantly in immigrant children (P = .026). No serious side effects were observed in any patient that would cause discontinuation of treatment. Conclusion: Overall, higher SF value was observed with FCT compared to DT in short term. There were different results between patient groups. Our results suggest that FCT is more effective than DT in patients with high basal ferritin and who are actually incompatible with treatment and should be preferred first in these patients. [ABSTRACT FROM AUTHOR]

Melanocytes in the skin and other organs generate the tumor known as malignant melanoma (MM). It has a high degree of malignancy, a deprived prognosis, and a propensity for local recurrence and distant metastasis. Although there have been tremendous advancements in MM management choices over the past ten years, there are still a dearth of clinically viable therapy alternatives and no internationally accepted treatment standard. The prognosis of MM patients has recently improved thanks to the development of immunotherapy and targeted therapy. As a result, this article examines the most recent findings from studies on the non-surgical treatment methodologies for MM and its preventive measures. [ABSTRACT FROM AUTHOR]

Kikuchi-Fujimoto disease (KFD) is a self-limiting disease of unknown etiology. The diagnosis of KFD is challenging as it shares a resemblance with many viral, autoimmune, and neoplastic diseases. KFD generally presents with histiocytic necrotizing lymphadenitis involving multiple cervical lymph nodes. The authors present a rare case report of a recurrent case of KFD in a 49-year-old female patient. Intravenous dexamethasone, hydroxychloroquine, and nonsteroidal anti-inflammatory drugs were used for controlling the initial symptoms, and later, oral methylprednisolone was used as a maintenance therapy. Intravenous dexamethasone proved to be an effective drug in the treatment of KFD as it helps in faster recovery. [ABSTRACT FROM AUTHOR]

Aims: Decongestion strategies for acute decompensated heart failure (ADHF) characterized by volume overload differ widely. The aim of this independent international academic web‐based survey was to capture the therapeutic strategies that physicians use to treat ADHF and to assess differences in therapeutic approaches between cardiologists versus non‐cardiologists. Methods and results: Physicians were invited to complete a web‐based questionnaire, capturing anonymized data on physicians' characteristics and treatment preferences based on a hypothetical clinical scenario of a patient hospitalized with ADHF. A total of 641 physicians from 60 countries participated. A wide variation in the management of the patient was observed. There was conservative use of diuretics, i.e. only 7% started intravenous furosemide at a dose ≥2 times the baseline oral dose, and infrequent use of ultrasound in assessing congestion (20.4%). Spot urinary sodium was infrequently or never measured by ≥85% of physicians. A third considered a patient with ongoing oedema as being stabilized. There were significant differences between cardiologists and non‐cardiologists in the management of ADHF, the targets for daily body weight loss and urine output, diuretic escalation strategies (66.3% vs. 40.7% would escalate diuresis by adding a thiazide) and assessment of response to treatment (27.0% vs. 52.9% considered patients with minimal congestion as stabilized). Conclusions: There is substantial variability amongst physicians and between cardiologists and non‐cardiologists in the management of patients with ADHF, with regard to clinical parameters used to tailor treatment, treatment goals, diuretic dosing and escalation strategies. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Kidney metastasis to the pituitary gland can cause hyperprolactinemia even above 250 ng/mL. Although the treatment of metastasis is palliative, surgical decompression could play a major role in the recovery of symptoms and improve quality of life. Pituitary metastasis should be considered in the evaluation of an unusual pituitary mass. Pituitary tumors are frequently encountered in the neurosurgical setting. Although the majority of them are pituitary adenomas, rare entities encompass pituitary metastasis. They should be differentiated from pituitary adenomas because their management and prognosis are different. We report a 53‐year‐old female who complained of headache and had remarkable hyperprolactinemia (271.1 ng/mL). Having considered macroprolactinoma as the initial diagnosis, medical treatment was initiated with Cabergoline. Subsequently, the patient's vision deteriorated which prompted us to perform endoscopic endonasal transsphenoidal surgery. Histologic examination of the resected tumor revealed metastatic renal cell carcinoma. Main treatment for these subjects is palliative; and unlike the pituitary adenoma, the prognosis is unfortunately poor. Pituitary metastasis should be considered in the evaluation of an unusual pituitary mass associated with hyperprolactinemia. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases kill 18 million people each year. Currently, a patient's health is assessed only during clinical visits, which are often infrequent and provide little information on the person's health during daily life. Advances in mobile health technologies have allowed for the continuous monitoring of indicators of health and mobility during daily life by wearable and other devices. The ability to obtain such longitudinal, clinically relevant measurements could enhance the prevention, detection and treatment of cardiovascular diseases. This review discusses the advantages and disadvantages of various methods for monitoring patients with cardiovascular disease during daily life using wearable devices. We specifically discuss three distinct monitoring domains: physical activity monitoring, indoor home monitoring and physiological parameter monitoring. [ABSTRACT FROM AUTHOR]

Objectives: Health care workers are one of the groups at risk of influenza. Currently, influenza vaccination is very important more than ever before. Influenza is evolutionarily similar to SARS-CoV-2, and they have some common epitopes and mechanisms. Thus reducing the severity of COVID-19 disease by influenza vaccination seems possible. Therefore, the aim of this study is to investigate the relationship between influenza vaccination and COVID-19 infection among clinical nurses. Methodology: The present study is a prospective analysis of nurses working in educational-medical hospitals of Ardabil. In this study, two groups of nurses were considered as case and control groups. The collected data were analyzed using SPSS software and descriptive (mean, standard deviation and frequency) and analytical (Chi-square) tests. Results: A total of 279 individuals were included in the study according to the research criteria. The maximum duration of the disease was one week in the control group and four weeks in the case group. Chi-square test showed that there was a significant difference in terms of disease duration between the two groups (P = 0.000). Chi-square test showed that there was a statistically significant difference in terms of disease treatment between the two groups (P = 0.000). Conclusion: Influenza vaccine reduces the incidence of COVID-19 and reduces the need for hospitalization in patients with this disease. However, due to the positive effects of influenza vaccine on COVID-19 and its low cost, it is recommended to inject influenza vaccine more than before. [ABSTRACT FROM AUTHOR]

Haematological malignancies are heterogeneous groups of cancers of the bone marrow, blood or lymph nodes, and while therapeutic advances have greatly improved the lifespan and quality of life of those afflicted, many of these cancers remain incurable. The iron-dependent, lipid oxidation-mediated form of cell death, ferroptosis, has emerged as a promising pathway to induce cancer cell death, particularly in those malignancies that are resistant to traditional apoptosis-inducing therapies. Although promising findings have been published in several solid and haematological malignancies, the major drawbacks of ferroptosis-inducing therapies are efficient drug delivery and toxicities to healthy tissue. The development of tumour-targeting and precision medicines, particularly when combined with nanotechnologies, holds potential as a way in which to overcome these obstacles and progress ferroptosis-inducing therapies into the clinic. Here, we review the current state-of-play of ferroptosis in haematological malignancies as well as encouraging discoveries in the field of ferroptosis nanotechnologies. While the research into ferroptosis nanotechnologies in haematological malignancies is limited, its pre-clinical success in solid tumours suggests this is a very feasible therapeutic approach to treat blood cancers such as multiple myeloma, lymphoma and leukaemia. [ABSTRACT FROM AUTHOR]

Uterine fibroids (UFs) are the most important benign neoplastic threat to women's health worldwide, with a prevalence of up to 80% in premenopausal women, and can cause heavy menstrual bleeding, pain, and infertility. Progesterone signaling plays a crucial role in the development and growth of UFs. Progesterone promotes the proliferation of UF cells by activating several signaling pathways genetically and epigenetically. In this review article, we reviewed the literature covering progesterone signaling in UF pathogenesis and further discussed the therapeutic potential of compounds that modulate progesterone signaling against UFs, including selective progesterone receptor modulator (SPRM) drugs and natural compounds. Further studies are needed to confirm the safety of SPRMs as well as their exact molecular mechanisms. The consumption of natural compounds as a potential anti-UFs treatment seems promising, since these compounds can be used on a long-term basis—especially for women pursuing concurrent pregnancy, unlike SPRMs. However, further clinical trials are needed to confirm their effectiveness. [ABSTRACT FROM AUTHOR]

Objective: Granulomatous mastitis is an infrequent, benign, inflammatory disease of the breast that mostly affects young women of reproductive age. The main objective of this review was to clarify the latest terminology and to provide an update on the diagnosis and management. Materials and Methods: A total of 792 granulomatous mastitis-related articles published in the English literature from 1965 to 2022 were reviewed. Results: The management of this benign but daunting condition remains controversial, and there is no worldwide consensus regarding the best systematic treatment protocol. Good judgment is required to ensure optimal diagnosis and treatment. Conclusion: This narrative review deals with the latest developments in the diagnosis, etiopathogenesis, and modern treatment of the disease. [ABSTRACT FROM AUTHOR]

Bietti crystalline dystrophy (BCD) is a rare, genetically determined chorioretinal dystrophy presenting with intraretinal crystalline deposits and varying degrees of progressive chorioretinal atrophy commencing at the posterior pole. In some cases, there can be concomitant corneal crystals noted first in the superior or inferior limbus. CYP4V2 gene, a member of the cytochrome P450 family is responsible for the disease and more than 100 mutations have been defined thus far. However, a genotype–phenotype correlation has not been established yet. Visual impairment commonly occurs between the second and third decades of life. By the fifth or sixth decade of life, vision loss can become so severe that the patient may potentially become legally blind. Multitudes of multimodal imaging modalities can be utilized to demonstrate the clinical features, course, and complications of the disease. This present review aims to reiterate the clinical features of BCD, update the clinical perspectives with the help of multimodal imaging techniques, and overview its genetic background with future therapeutic approaches. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are the leading cause of death globally as well as the leading cause of mortality and morbidity in type 2 diabetes (T2D) patients. Results from large interventional studies have suggested hyperglycemia and poor glycemic control to be largely responsible for the development of CVDs. However, the association between hypoglycemia and cardiovascular events is also a key pathophysiological factor in the development of CVDs. Hypoglycemia is especially prevalent in T2D patients treated with oral sulfonylurea agents or exogenous insulin, increasing the susceptibility of this population to cardiovascular events. The adverse cardiovascular risk of hypoglycemia can persist even after the blood glucose levels have been normalized. Hypoglycemia may lead to vascular disease through mechanisms such as enhanced coagulation, oxidative stress, vascular inflammation, endothelial dysfunction, and platelet activation. In the following review, we summarize the evidence for the role of hypoglycemia in platelet activation and the subsequent effects this may have on the development of CVD. In addition, we review current evidence for the effectiveness of therapies in reducing the risk of CVDs. [ABSTRACT FROM AUTHOR]

Background: External fixation is one of the most often utilized treatment options for complicated tibial diaphyseal fractures (TDF). The purpose of this study was to assess the efficacy of unilateral external fixators as primary and definitive therapy for complex TDF in a resource-limited setting. Materials and Methods: A retrospective study between June 2016 and March 2021 included 110 subjects with TDF who were treated with an external fixator as definitive fixation in hospitals affiliated with Ibb University. The patient's demographic characteristics, complications, and outcomes were gathered and analyzed. Factors associated with pin site infection were also investigated. Results: The mean age was 42.1 ± 10.1 years, with 92.7% being male. Rural residents accounted for 22.7%. Smoking and diabetes mellitus were present in 27.3% and 30.0%, respectively. General complications occurred in 12.0%, with pulmonary embolism being the most common at 4.5%. Orthopedic complications included pin-track infections in 27.3% (30) and osteomyelitis in 1.8% (2). Pin site infections required medical treatment in 21 cases and external fixator changes in five. Two cases each needed several debridements for osteomyelitis and soft tissue. Full union occurred in 79.1% (87) over 23.1 ± 3.2 weeks and final alignment in 97.3% (107) over 34.8 ± 4.8 weeks. Malunions occurred in 1.8% (2), and one case had hypertrophic nonunion. Factors like rural residency, smoking, diabetes, open fractures, worst fracture grade (Gustilo and Anderson type C), and general complications occurrence significantly correlated with pin site infection (all p-values < 0.05). Conclusion: A unilateral external fixator as a primary and definitive treatment is a viable, simple, and effective option for TDF with a high success rate even in a resource-limited setting. In this study, residents in rural areas, smoking, diabetes, open fracture, worst fracture grade, and general complication occurrence were associated with pin site infection occurrence. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with a high risk of metastasis and therapeutic resistance. These issues are closely linked to the tumour microenvironment (TME) surrounding the tumour tissue. The association between residing TME components with tumour progression, survival, and metastasis has been well elucidated. Focusing on cancer cells alone is no longer considered a viable approach to therapy; thus, there is a high demand for TME targeting. The benefit of using nanoparticles is their preferential tumour accumulation and their ability to target TME components. Several nano-based platforms have been investigated to mitigate microenvironment-induced angiogenesis, therapeutic resistance, and tumour progression. These have been achieved by targeting mesenchymal originating cells (e.g., cancer-associated fibroblasts, adipocytes, and stem cells), haematological cells (e.g., tumour-associated macrophages, dendritic cells, and myeloid-derived suppressor cells), and the extracellular matrix within the TME that displays functional and architectural support. This review highlights the importance of nanotechnology-based therapeutics as a promising approach to target the TME and improve treatment outcomes for TNBC patients, which can lead to enhanced survival and quality of life. The role of different nanotherapeutics has been explored in the established TME cell-driven populations. [ABSTRACT FROM AUTHOR]

Nearly, 20% of renal allografts fail after 5 years resulting in a return to hemodialysis. These patients subsequently undergo withdrawal of immunosuppressant therapy, and the failed allograft is left in situ. However, many patients (40%) develop graft intolerance syndrome, characterized by fever, pain, and hematuria. Conventionally, this is managed with low-dose maintenance immunosuppressant therapy, however, that is not without notable adverse risk. In refractory patients, transplant nephrectomy is the treatment of choice; however, this caries significant morbidity and mortality. Interventional radiology plays a substantial role of treating graft intolerance syndrome while delivering improved patient outcomes. [ABSTRACT FROM AUTHOR]

The advancement of healthcare technology is impossible without machine learning (ML). There have been numerous advances in ML to analyze, predict, and diagnose medical data. Integrating a centralized scheme and therapy for classifying and diagnosing illnesses and disorders is a major obstacle in modern healthcare. To standardize all medical data into a single repository, researchers have proposed using ML using the centralized artificial neural network model (ML-CANNM). Random tree, support vector machine, and gradient booster are just a few proposed ML classifiers. Artificial neural networks (ANNs) have been trained using a variety of medical datasets to predict and analyze outcomes. ML-CANNM collects patient data from various studies and uses ML and ANNs to determine the results. Three layers make up an ANN. ML is used to classify the given patients' data in the input layer. In the hidden layer, classification data are compared to a training dataset. The output layer's job is to identify, classify, and diagnose diseases. As a result, disease diagnosis and detection are integrated into a single healthcare database. The proposed framework has proven that ML-CANNM works with more accuracy and lesser execution time. Thus, the numerical outcome suggested ML-CANNM increased accuracy ratio of 99.2% and a prediction ratio of 97.5%. The findings further show that the execution time is enhanced by less than 2 h, decision table using ML and results in an efficiency ratio of 97.5%. [ABSTRACT FROM AUTHOR]

The goal of this study was to optimize and formulate apigenin (APG)-loaded pegylated chitosan nanoparticles (PEGylated-CNPs) via ionic gelation techniques using the Box–Behnken design (BBD). Three individual variables, X1(chitosan: TPP concentration), X2 (PEG-400 concentration), and X3 (sonication time), were investigated for their influence on response variables (Y1—particle size (PS); Y2—drug entrapment efficiency (DEE); and Y3—zeta potential (ZP). The optimized formula of APG-PEGylated CNPs was picked from the statistical design and was then examined for physical, morphological, release characterization, anti-oxidant, and anti-tumor potential. The average PS, PDI, %DEE, and ZP were found to be 139.63 ± 5.67 nm, 0.296 ± 0.014, 79.55 ± 3.12%, and 24.68 ± 1.84 mV, respectively. The optimized APG formulation was chosen and reformulated based on the desirability function. Results of the observed and predicted values of responses through the BBD process were found to be nearly identical. The resulting APG-PEGylated CNPs were spherical and smooth, according to surface morphology studies. The release study revealed that PEGylated-CNPs exhibited biphasic release patterns distinguished by an initial burst release of APG only at early phases accompanied by a delayed release near 24 h. Furthermore, APG-PEGylated CNPs demonstrated statistically increased antioxidant activities and cytotoxicity against MCF-7 cells compared to pure APG. Based on the findings, it is possible to conclude that BBD was efficient in optimizing the PEGylated CNPs formulation and recognizing the impacts of formulation variables. In conclusion, the developed formulation has a significant potential for anticancer therapy. [ABSTRACT FROM AUTHOR]

Our case highlights the occurrence of severe cutaneous adverse reactions with flurbiprofen use and alerts physicians to its odds with safer drugs. [ABSTRACT FROM AUTHOR]

Brain disorders represent 32% of the global disease burden, with 169 million Europeans affected. Constraint-based metabolic modelling and other approaches have been applied to predict new treatments for these and other diseases. Many recent studies focused on enhancing, among others, drug predictions by generating generic metabolic models of brain cells and on the contextualisation of the genome-scale metabolic models with expression data. Experimental flux rates were primarily used to constrain or validate the model inputs. Bi-cellular models were reconstructed to study the interaction between different cell types. This review highlights the evolution of genome-scale models for neurodegenerative diseases and glioma. We discuss the advantages and drawbacks of each approach and propose improvements, such as building bi-cellular models, tailoring the biomass formulations for glioma and refinement of the cerebrospinal fluid composition. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness, safety and acceptability of outpatient medical treatment of first trimester miscarriage with misoprostol. Study Design: Descriptive Longitudinal study. Setting: Outpatient Department, Gynae Unit 1 of Abbasi Shaheed Hospital. Period: September 2020 to April 2021. Material & Methods: Patients of first trimester miscarriage up to 10 weeks gestation were included in the study through non probability consecutive sampling technique. Written consent were taken from all the patients fulfilling inclusion criteria and advised patients to start tab. Misoprostol 400 microgram 4 hrly 3 doses in 24hours orally at home. Patients were advised to follow in outpatient department after 72 hours with report of ultrasound if no active complain. Those who came with heavy bleeding per vaginum or with severe pain, we abandoned the medical treatment and surgical evacuation was done. After completion of treatment either by medical or surgical we took opinion from patients regarding their satisfaction with the chosen method. Results: In this study 60 patients of first trimester miscarriage, medically managed with misoprostol were included. Overall assessment was done for effectiveness, safety and acceptability of medical management by Misoprostol. 23.3% patients needed further surgical evacuation and 76.7% patients were managed successfully by medical treatment, overall satisfaction was reported in 73.3% patients, and treatment acceptance showed by 76.7%. According to 78.3% they will prefer the treatment again. Conclusion: Misoprostol is safe and effective drug for the termination of first trimester miscarriage up to 10 weeks, orally, as outpatient treatment, with high success rates, patient acceptability and tolerable side effects. [ABSTRACT FROM AUTHOR]

Background: The pharmacist's role shifts from dispensing to bedside care, resulting in better patient health outcomes. Pharmacists in developed countries ensure rational drug use, improve clinical outcomes, and promote health status by working as part of a multidisciplinary team of healthcare professionals. However, clinical pharmacist services on healthcare utilization in low-and middle-income countries (LMICs) like Pakistan are unclear. As a result, we aim to systematically review pharmacists' clinical roles in improving Pakistani patients' therapeutic, safety, humanistic, and economic outcomes.Methods: We searched PubMed, Scopus, EMBASE, CINAHL, and Cochrane Library for relevant articles published from inception to 28th February 2021. All authors were involved in the screening and selection of studies. Original studies investigating the therapeutic, humanistic, safety, and economic impact of clinical pharmacists in Pakistani patients (hospitalised or outpatients) were selected. Two reviewers independently assessed the risk of bias in studies, and discrepancies were resolved through mutual consensus. All of the included studies were descriptively synthesised, and PRISMA reporting guidelines were followed.Results: The literature search found 751 articles from which nine studies were included; seven were randomized controlled trials (RCTs), and two were observational studies. Three RCTs included were having a low risk of bias (ROB), two RCTs were having an unclear ROB, while two RCTs were having a high ROB. The nature of clinical pharmacist interventions included one or more components such as disease-related education, lifestyle changes, medication adherence counselling, medication therapy management, and discussions with physicians about prescription modification if necessary. Clinical pharmacist interventions reduce medication-related errors, improve therapeutic outcomes such as blood pressure, glycemic control, lipid control, CD4 T lymphocytes, and renal functions, and improve humanistic outcomes such as patient knowledge, adherence, and health-related quality of life. However, no study reported the economic outcomes of interventions.Conclusions: The findings of the studies included in this systematic review suggest that clinical pharmacists play important roles in improving patients' health outcomes in Pakistan; however, it should be noted that the majority of the studies have a high risk of bias, and more research with appropriate study designs is needed. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is characterized by an absolute decline in insulin secretion and peripheral resistance and is the most prevalent metabolic and endocrine disorder. However, the pathogenesis of DM also includes adipocyte insulin resistance, increased glucagon secretion, increased renal glomerular glucose absorption, and neurotransmitter dysfunction. Although there is a wide spectrum of therapeutics available for glycemic control, owing to the identification of various pathogenic determinants of DM, management of DM remains challenging and complex. Current therapeutic interventions against DM focus mostly on glycemic control without considering the other pathological determinants that eventually lead to treatment failure and the progression of DM. Furthermore, long-term use of these conventionally available anti-diabetic drugs leads to various side effects, henceforth development of novel drugs against DM remains an unending search strategy for researchers. Various studies conducted in various parts of the world have proposed that these novel therapeutic interventions target multiple and alternate pathogenic hotspots involved in DM. The current review article discusses novel therapeutic options that hold particular promise to support their safety and discuss the side effects resulting from their use so that these novel candidate drugs can be effectively fabricated into potential drugs for the treatment of DM. [ABSTRACT FROM AUTHOR]

Introduction: Small cell neuroendocrine carcinoma (NEC) that arises from the tonsil is a particularly rare head and neck carcinoma. This kind of neoplasm mainly originated from the bronchopulmonary area; however, there were reported cases of extrapulmonary areas. The prognosis is poor as the tumour is an aggressive tumour and have a high risk of metastasis. Case Report: We experienced a patient presented with painless right neck swelling and hard tonsillar hypertrophy for past six month. Computer tomography showed the tumour extended to the parapharyngeal space and metastasized to the thoracolumbar vertebras. The intraoral biopsy of the tonsil confirmed primary small cell neuroendocrine carcinoma of the tonsil. The clinical presentation, radiological imaging, histopathological investigations, and methods of treatment are discussed. Conclusions: Due to the rarity of this disease, there is no definitive treatment yet for this disease. The physicians must thoroughly understand the nature and characteristic of the disease to find the best treatment. The latest discoveries in chemotherapy drugs and radiotherapy may improve the treatment modalities in the future. [ABSTRACT FROM AUTHOR]

Both personalized medicine and nanomedicine are new to medical practice. Nanomedicine is an application of the advances of nanotechnology in medicine and is being integrated into diagnostic and therapeutic tools to manage an array of medical conditions. On the other hand, personalized medicine, which is also referred to as precision medicine, is a novel concept that aims to individualize/customize therapeutic management based on the personal attributes of the patient to overcome blanket treatment that is only efficient in a subset of patients, leaving others with either ineffective treatment or treatment that results in significant toxicity. Novel nanomedicines have been employed in the treatment of several diseases, which can be adapted to each patient-specific case according to their genetic profiles. In this review, we discuss both areas and the intersection between the two emerging scientific domains. The review focuses on the current situation in personalized medicine, the advantages that can be offered by nanomedicine to personalized medicine, and the application of nanoconstructs in the diagnosis of genetic variability that can identify the right drug for the right patient. Finally, we touch upon the challenges in both fields towards the translation of nano-personalized medicine. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder which has multifactorial etiology. Parents of children diagnosed with ASD often use complementary and alternative medicine (CAM) on the grounds that they do not benefit from traditional medical treatments. In this article it is aimed to clarify the definition of CAM, to examine the prevalence of the use of CAM in ASD, to examine the CAM interventions and their efficacy used in ASD, and to review the studies about use of CAM among children diagnosed ASD in Turkey. For this purpose, publications in the Science Citation Index (SCI) and SCI-Expanded, MEDLINE, PsycINFO, DergiPark, TÜBİTAK/ULAKBİM-Turkish Medical Index, Turkish Psychiatry Index and Turkish Medline indexes were reviewed. Although current data on the effectiveness of CAM is limited, considering the usage rates, physicians should be informed about CAM interventions, clearly ask about the use of CAM and share information on the subject. [ABSTRACT FROM AUTHOR]

• ILs play crucial function in ovarian cancer. • IFNs role in prevention or development of ovarian cancer. • ILs and IFNs can be applied in ovarian cancer therapy. Ovarian cancer poses significant challenges and remains a highly lethal disease with limited treatment options. In the context of ovarian cancer, interleukins (ILs) and interferons (IFNs), important cytokines that play crucial roles in regulating the immune system, have emerged as significant factors influencing its development. This article provides a comprehensive review of the involvement of various ILs, including those from the IL-1 family, IL-2 family, IL-6 family, IL-8 family, IL-10 family, and IL-17 family, in ovarian cancer. The focus is on their impact on tumor growth, metastasis, and their role in evading immune responses within the tumor microenvironment. Additionally, the article conducts an in-depth examination of the oncogenic or antitumor roles of each IL in the context of ovarian cancer pathogenesis and progression. Besides, we elucidated the enhancements in the treatment of ovarian cancer through the utilization of type-I IFN and type-II IFN. Recent research has shed light on the intricate mechanisms through which specific ILs and IFNs contribute to the advancement of the disease. By incorporating recent findings, this review also seeks to inspire further investigations into unexplored mechanisms, fostering ongoing research to develop more effective therapeutic strategies for ovarian cancer. Moreover, through an in-depth analysis of IL- and IFN-associated clinical trials, we have highlighted their promising potential of in the treatment of ovarian cancer. These clinical trials serve to reinforce the significant outlook for utilizing ILs and IFNs as therapeutic agents in combating this disease. [ABSTRACT FROM AUTHOR]

Background: Cancer is one of the critical issues of the global health system with a high mortality rate even with the available therapies, so using novel therapeutic approaches to reduce the mortality rate and increase the quality of life is sensed more than ever. Main body: CAR-T cell therapy and oncolytic viruses are innovative cancer therapeutic approaches with fewer complications than common treatments such as chemotherapy and radiotherapy and significantly improve the quality of life. Oncolytic viruses can selectively proliferate in the cancer cells and destroy them. The specificity of oncolytic viruses potentially maintains the normal cells and tissues intact. T-cells are genetically manipulated and armed against the specific antigens of the tumor cells in CAR-T cell therapy. Eventually, they are returned to the body and act against the tumor cells. Nowadays, virology and oncology researchers intend to improve the efficacy of immunotherapy by utilizing CAR-T cells in combination with oncolytic viruses. Conclusion: Using CAR-T cells along with oncolytic viruses can enhance the efficacy of CAR-T cell therapy in destroying the solid tumors, increasing the permeability of the tumor cells for T-cells, reducing the disturbing effects of the immune system, and increasing the success chance in the treatment of this hazardous disease. In recent years, significant progress has been achieved in using oncolytic viruses alone and in combination with other therapeutic approaches such as CAR-T cell therapy in pre-clinical and clinical investigations. This principle necessitates a deeper consideration of these treatment strategies. This review intends to curtly investigate each of these therapeutic methods, lonely and in combination form. We will also point to the pre-clinical and clinical studies about the use of CAR-T cell therapy combined with oncolytic viruses. [ABSTRACT FROM AUTHOR]

Noise-induced hearing loss (NIHL) is a common sensorineural hearing impairment that lacks U.S. Food and Drug Administration-approved drugs. To fill the gap in effective screening models, we used an in silico transcriptome-based drug screening approach, identifying 22 biological pathways and 64 potential small molecule treatments for NIHL. Two of these, afatinib and zorifertinib [epidermal growth factor receptor (EGFR) inhibitors], showed efficacy in zebrafish and mouse models. Further tests with EGFR knockout mice and EGF-morpholino zebrafish confirmed their protective role against NIHL. Molecular studies in mice highlighted EGFR's crucial involvement in NIHL and the protective effect of zorifertinib. When given orally, zorifertinib was found in the perilymph with favorable pharmacokinetics. In addition, zorifertinib combined with AZD5438 (a cyclin-dependent kinase 2 inhibitor) synergistically prevented NIHL in zebrafish. Our results underscore the potential for in silico transcriptome-based drug screening in diseases lacking efficient models and suggest EGFR inhibitors as potential treatments for NIHL, meriting clinical trials. [ABSTRACT FROM AUTHOR]

Dementia exists as a 'progressive clinical syndrome of deteriorating mental function significant enough to interfere with activities of daily living', with the most prevalent type of dementia being Alzheimer's disease (AD), accounting for about 80% of diagnosed cases. AD is associated with an increased risk of comorbidity with other clinical conditions such as hypertension, diabetes, and neuropsychiatric symptoms (NPS) including, agitation, anxiety, and depression as well as increased mortality in late life. For example, up to 70% of patients diagnosed with AD are affected by anxiety. As aging is the major risk factor for AD, this represents a huge global burden in ageing populations. Over the last 10 years, significant efforts have been made to recognize the complexity of AD and understand the aetiology and pathophysiology of the disease as well as biomarkers for early detection. Yet, earlier treatment options, including acetylcholinesterase inhibitors and glutamate receptor regulators, have been limited as they work by targeting the symptoms, with only the more recent FDA-approved drugs being designed to target amyloid-β protein with the aim of slowing down the progression of the disease. However, these drugs may only help temporarily, cannot stop or reverse the disease, and do not act by reducing NPS associated with AD. The first-line treatment options for the management of NPS are selective serotonin reuptake inhibitors/selective noradrenaline reuptake inhibitors (SSRIs/SNRIs) targeting the monoaminergic system; however, they are not rational drug choices for the management of anxiety disorders since the GABAergic system has a prominent role in their development. Considering the overall treatment failures and side effects of currently available medication, there is an unmet clinical need for rationally designed therapies for anxiety disorders associated with AD. In this review, we summarize the current status of the therapy of AD and aim to highlight novel angles for future drug therapy in our ongoing efforts to alleviate the cognitive deficits and NPS associated with this devastating disease. [ABSTRACT FROM AUTHOR]

Similarly, our results show LPPAI scores three months post-treatment, indicating the decrease of LPPAI and the clinical effectiveness of adipose tissue injection (Table 1). This study introduced a novel method of autologous adipose tissue injection as a potential treatment for LPP. To the best of our knowledge, adipose tissue injection in the treatment of alopecia is a relatively novel modality. [Extracted from the article]

Peptic ulcer is one of the most common gastrointestinal tract disorders worldwide, associated with challenges such as refractory morbidity, bleeding, interference with use of anticoagulants, and potential side effects associated with long-term use of proton pump inhibitors. A peptic ulcer is a defect in gastric or duodenal mucosa extending from muscularis mucosa to deeper layers of the stomach wall. In most cases, ulcers respond to standard treatments. However, in some people, peptic ulcer becomes resistant to conventional treatment or recurs after initially successful therapy. Therefore, new and safe treatments, including the use of stem cells, are highly favored for these patients. Adipose-derived mesenchymal stem cells are readily available in large quantities with minimal invasive intervention, and isolation of adipose-derived mesenchymal stromal stem cells (ASC) produces large amounts of stem cells, which are essential for cell-based and restorative therapies. These cells have high flexibility and can differentiate into several types of cells in vitro. This article will investigate the effects and possible mechanisms and signaling pathways of adipose tissue-derived mesenchymal stem cells in patients with refractory peptic ulcers. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 was declared as ''Pandemic'' by World Health Organization (WHO) on March 11th, 20120. Since this time, various awareness campaigns by health authorities and healthcare professionals have been conducted for knowledge and ultimately prevention of transmission of the disease. Proper attitude and knowledge toward the disease is the key point for prevention of COVID-19 as there is currently no treatment of vaccine available. Objective: Main objective of the study is to assess attitude, knowledge and perspective of COVID-19 in Pakistani Population. Methodology: An online - based and paper - based questionnaire was filled from both healthcare - related and non - healthcare - related individuals. Frequencies were analyzed using SPSS 21.0. Results: A total of 3256 individuals participated in the study, including both healthcare - related (2244/68.91%) and non - healthcare - related (1012/31.08%). Majority of the population had good knowledge in maximum questions. 89.60% believed COVID-19 as a contagious disease. 94.25% agreed that the cause of disease is primarily a virus, though small percentage didn't agree on this point. Regarding treatment, 68.08% individuals agreed that there is currently no treatment of COVID-19, followed by some believed antibiotics (4.39%), antiviral (14.52%) and passive immunization (2.64%) as treatment of the disease. Majority of population had good knowledge regarding clinical features of COVID-19. Conclusion: The knowledge, attitude and perspective of population were good as most of the people were agreed on standard facts. The reason behind this knowledge is awareness campaigns by health authorities and healthcare personnel, especially through media. Still there is lack of knowledge in some points due to misconceptions and false beliefs of population towards COVID-19. More campaigns with scientific data is required for prevention of the disease. [ABSTRACT FROM AUTHOR]

• Tuberculosis, has now re-emerged in the developed countries following the surging waves of immigration. • Tuberculous mastitis is a rare presentation of tuberculosis that has been called the 'great masquerader' due to its multifaceted presentations. • Solitary breast mass is the most common clinical presentation of tuberculous mastitis and is associated with inflammatory findings in the majority of cases. • Multiple intercommunicating breast masses with axillary lymphadenopathy are the most common ultrasound appearance. Breast tuberculosis (TB) is a rare disease, still present in endemic areas. The significance of breast TB is due to its rare occurrence and its resemblance to malignant breast lesions. The objective of this study was to study various clinical presentations and imaging features of different forms of tuberculous mastitis. A retrospective study was conducted over a 10-year period. Thirty-two consecutive patients diagnosed with tuberculous mastitis were included. There was only one male patient in this series. The patients ranged in age from 25 to 60 years (mean age was 33.69 years). A solitary breast mass was the most common clinical presentation, which was associated with inflammatory findings in the majority of cases. The most common mammographic finding was diffusely increased density and the most common pathological finding was solitary mass. The most common appearance on ultrasound was of multiple intercommunicating breast masses with axillary lymphadenopathy. Breast TB should be considered in the differential diagnosis in the presence of a painful breast mass, discharging sinuses, mastitis, or a breast abscess that does not respond to conventional medical treatment. A multidisciplinary approach is required to aid timely diagnosis and to provide appropriate management and treatment in order to avoid complications. [ABSTRACT FROM AUTHOR]

Tumors of the genital system are common and imaging is of crucial importance for their detection and diagnosis. Several non-neoplastic diseases may mimic these tumors and differential diagnosis may be difficult in certain cases. Misdiagnosing non-neoplastic diseases as tumor may prompt unnecessary medical treatment or surgical interventions. In this article, we aimed to present the imaging characteristics of non-neoplastic diseases of the male and female genital systems that may mimic neoplastic processes. Increasing awareness of the imaging specialists to these entities may have a severe positive impact on the management of these patients. [ABSTRACT FROM AUTHOR]

Background: Genes in the Ras pathway have somatic mutations in at least 60 % of colorectal cancers. Despite activating the same pathway, the BRAF V600E mutation and the prevalent mutations in codon 12 and 13 of KRAS have all been linked to different clinical outcomes, but the molecular mechanisms behind these differences largely remain to be clarified. Methods: To characterize the similarities and differences between common activating KRAS mutations and between KRAS and BRAF mutations, we used genome editing to engineer KRAS G12C/D/V and G13D mutations in colorectal cancer cells that had their mutant BRAF V600E allele removed and subjected them to transcriptome sequencing, global proteomics and metabolomics analyses. Results: By intersecting differentially expressed genes, proteins and metabolites, we uncovered (i) two-fold more regulated genes and proteins when comparing KRAS to BRAF mutant cells to those lacking Ras pathway mutation, (ii) five differentially expressed proteins in KRAS mutants compared to cells lacking Ras pathway mutation (IFI16, S100A10, CD44, GLRX and AHNAK2) and 6 (CRABP2, FLNA, NXN, LCP1, S100A10 and S100A2) compared to BRAF mutant cells, (iii) 19 proteins expressed differentially in a KRAS mutation specific manner versus BRAF V600E cells, (iv) regulation of the Integrin Linked Kinase pathway by KRAS but not BRAF mutation, (v) regulation of amino acid metabolism, particularly of the tyrosine, histidine, arginine and proline pathways, the urea cycle and purine metabolism by Ras pathway mutations, (vi) increased free carnitine in KRAS and BRAF mutant RKO cells. Conclusions: This comprehensive integrative -omics analysis confirms known and adds novel genes, proteins and metabolic pathways regulated by mutant KRAS and BRAF signaling in colorectal cancer. The results from the new model systems presented here can inform future development of diagnostic and therapeutic approaches targeting tumors with KRAS and BRAF mutations. [ABSTRACT FROM AUTHOR]

Diabetes is the most common cause of end-stage kidney disease. Randomised controlled trials have shown a significant benefit of sodium-glucose transporter-2 inhibitors in patients with diabetic kidney disease (DKD), and guidelines now suggest these drugs should be considered in all patients with DKD irrespective of glucose control. Glucagon-like peptide-1 receptor agonists have shown some benefit in reducing progression of albuminuria in DKD and should also be considered early in the therapeutic pathway. Management of diabetes in patients on renal replacement therapy (dialysis or transplantation) is uniquely challenging. This article outlines guidance on management of glucose in these vulnerable groups of patients. [ABSTRACT FROM AUTHOR]

Background: The disease process involves the occurrences happening during the disease and treatment course for the patient. Investigating this process is a significant and necessary issue for all diseases, including coronavirus disease 2019 (COVID-19). Materials and Methods: Using the information of 4372 patients with COVID-19 referring to Dr. Masih Daneshvari Hospital in Tehran during the COVID-19 epidemic, being hospitalized, cared for, and home quarantined due to having mild symptoms, the COVID-19 process and its related occurrences were investigated during the treatment course. Results: In the COVID-19 course, considering the disease severity, the likelihood of hospitalization in the general ward or the intensive care unit (ICU) ward, the likelihood of isolation or home quarantine, and the likelihood of occurrences such as recovery or death at the end of the disease course were taken into consideration. Based on the results of this study, the likelihood of hospitalization in the general ward, the ICU ward, and isolation or home quarantine was determined to be approximately 49.54%, 14.73%, and 35.73%, respectively. Also, for patients hospitalized in the general ward, the ICU ward, and isolated or home quarantined, the likelihood of recovery was estimated at approximately 64.79%, 10.82%, and 96.31%, respectively, and the likelihood of death was also estimated at about 35.21%, 89.18%, and 3.69% respectively. Conclusion: Investigating the COVID-19 process and estimating the likelihood of incidence of its related occurrences during the treatment course both create an accurate prognosis and provide the possibility of achieving an efficient treatment for these patients. [ABSTRACT FROM AUTHOR]

Introduction: Preventing tuberculosis (TB) disease requires treatment of latent TB infection (LTBI) as well as prevention of person-to-person transmission. We estimated the LTBI prevalence for the entire United States and for each state by medical risk factors, age, and race/ethnicity, both in the total population and stratified by nativity. Methods: We created a mathematical model using all incident TB disease cases during 2013–2017 reported to the National Tuberculosis Surveillance System that were classified using genotype-based methods or imputation as not attributed to recent TB transmission. Using the annual average number of TB cases among US-born and non-US-born persons by medical risk factor, age group, and race/ethnicity, we applied population-specific reactivation rates (and corresponding 95% confidence intervals [CI]) to back-calculate the estimated prevalence of untreated LTBI in each population for the United States and for each of the 50 states and the District of Columbia in 2015. Results: We estimated that 2.7% (CI: 2.6%–2.8%) of the U.S. population, or 8.6 (CI: 8.3–8.8) million people, were living with LTBI in 2015. Estimated LTBI prevalence among US-born persons was 1.0% (CI: 1.0%–1.1%) and among non-US-born persons was 13.9% (CI: 13.5%–14.3%). Among US-born persons, the highest LTBI prevalence was in persons aged ≥65 years (2.1%) and in persons of non-Hispanic Black race/ethnicity (3.1%). Among non-US-born persons, the highest LTBI prevalence was estimated in persons aged 45–64 years (16.3%) and persons of Asian and other racial/ethnic groups (19.1%). Conclusions: Our estimations of the prevalence of LTBI by medical risk factors and demographic characteristics for each state could facilitate planning for testing and treatment interventions to eliminate TB in the United States. Our back-calculation method feasibly estimates untreated LTBI prevalence and can be updated using future TB disease case counts at the state or national level. [ABSTRACT FROM AUTHOR]

Objective: To describe the technique and results of mucosectomy; A surgical technique that is easy to perform, and has a lower morbidity and complication rate as compared to standard appendectomy in cases of complicated appendicitis. Study Design: Quasi-experimental study. Place and Duration of Study: Surgical - A Unit, Ayub Teaching Hospital, in Abbottabad, from Mar 2017 to Mar 2019. Methodology: Patients included were those who presented with appendicular mass, phlegmon, recurrent appendicitis, appendicitis in uncommon locations, presence of adhesions, those cases of appendicular mass and phlegmon which was either not responding to medical treatment, or diagnosed per operatively being clinically not palpable or not seen on ultrasound. Per operative and post-operative variables were documented and analyzed. In mucosectomy, thesubserosal portion of the appendix i-emuscularis and mucosa of the appendix was dissected out from the serosa after ligation of the appendicular base, or ligation done after delivering the appendix out of the serosa. The serosa that was adherent to the surrounding gut, omentum or other viscera was left intact. Results: A total of 192 patients were included in this study, half of which underwent standard appendectomy and a mucosectomy was performed on the rest. The mean time of surgery was 30 ± 1.2min as compared to the standard appendectomy group (55min ± 3.6). More than half of the patients undergoing standard appendectomy required extension of the incision (56.2%), and only 8% required so from those on whom mucosectomy was performed. Per operative hemorrhage was seen in 32.2%, however inmucosectomy group only 1%. Conclusion: Mucosectomy is a safer modification of standard appendicectomy in patients with appendicular mass, early mass formation, phlegmon, recurrent appendicitis and where the appendix is in an uncommon site, inflamed and adherent. [ABSTRACT FROM AUTHOR]

Objective: The goal of this manuscript was to provide a comprehensive review of the surgical treatment for migraine headaches with a focus on trigger points and their clinical presentations, and to emphasize the importance of appropriate patient selection.Background: Migraine is a prevalent neurological disease with headache being a disabling component of it. Surgical treatment for migraine headache became available two decades ago, which is based on proper identification and the deactivation of the specific trigger sites in the head and neck area.Design: This manuscript reviews the discovery and evolution of migraine surgery with changes in patients' selection throughout the years.Conclusion: Patients with migraine headaches who do not respond or cannot tolerate the medical treatment might benefit from trigger site deactivation surgery. The success of the surgery is closely related to proper identification of trigger point (s) and close collaboration with a neurologist or a headache specialist. This collaboration would enhance patients' positive outcomes and help to rule out other causes of the headache. [ABSTRACT FROM AUTHOR]

Nano-based drug delivery systems are increasingly used for diagnosis, prevention and treatment of several diseases, thanks to several beneficial properties, including the ability to target specific cells or organs, allowing to reduce treatment costs and side effects frequently associated with chemotherapeutic medications, thereby improving treatment compliance of patients. In the field of communicable diseases, especially those caused by intracellular bacteria, the delivery of antibiotics targeting specific cells is of critical importance to maximize their treatment efficacy. Brucella melitensis , an intracellular obligate bacterium surviving and replicating inside macrophages is hard to be eradicated, mainly because of the low ability of antibiotics to enter these phagocityc cells. Although different antibiotics regimens including gentamicin, doxycycline and rifampicin are in fact used against the Brucellosis, no efficient treatment has been attained yet, due to the intracellular life of the respective pathogen. Nano-medicines responding to environmental stimuli allow to maximize drug delivery targeting macropages, thereby boosting treatment efficacy. Several drug delivery nano-technologies, including solid lipid nanoparticles, liposomes, chitosan, niosomes, and their combinations with chitosan sodium alginate can be employed in combination of antibiotics to successfully eradicate Brucellosis infection from patients. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a severe medical condition with a number of treatment options, the majority of which are introduced without consideration of the underlying mechanisms driving it within an individual and thus a lack of tailored approach to treatment. The one exception is a patient presenting with apparent pulmonary arterial hypertension and shown to have vaso‐responsive disease, whose clinical course and prognosis is significantly improved by high dose calcium channel blockers. PH is however characterized by a relative abundance of available data from patient cohorts, ranging from molecular data characterizing gene and protein expression in different tissues to physiological data at the organ level and clinical information. Integrating available data with mechanistic information at the different scales into computational models suggests an approach to a more personalized treatment of the disease using model‐based optimization of interventions for individual patients. That is, constructing digital twins of the disease, customized to a patient, promises to be a key technology for personalized medicine, with the aim of optimizing use of existing treatments and developing novel interventions, such as new drugs. This article presents a perspective on this approach in the context of a review of existing computational models for different aspects of the disease, and it lays out a roadmap for a path to realizing it. [ABSTRACT FROM AUTHOR]

Cardiac failure is a clinical syndrome that may develop in children owing to cardiac dysfunction or underlying structural heart diseases. Considering the differences in diagnostic and therapeutic approaches for pediatric heart failure (PHF) and adult heart failure, we have reviewed the current literature on PHF. Relevant studies were extracted from MEDLINE/PubMed, Google Scholar, and Clinical Trial Registries using the terms "pediatric heart failure" or "heart failure in children" and "management" or "decongestive therapy." Recent advances in diagnostic approaches, such as cardiac magnetic resonance, speckletracking echocardiography, tissue Doppler imaging, and molecular diagnostic techniques, have increased our under - standing of PHF. It is imperative that clinicians evaluate the interrelated factors responsible for the develop ment of PHF, including myocardial function, pulmonary and systemic blood flow, heart rhythm, valve function, and nutritional status. Although recent advances have demon strated the efficacy of many new drugs in adult heart failure trials, it cannot be concluded that these drugs will show similar efficacy in children, considering the heterogeneous nature of the underlying mechanisms and variable pharmacodynamics and pharmacokinetics. Therefore, the underlying pathophysiology of PHF and the mechanisms of action of different drugs should be considered when selecting appropriate therapies. Further trials are needed to establi sh the efficacy and safety of these drugs, and a combined multi disciplinary strategy will help enhance PHF outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To compare efficacy of 10-mg of vonoprazan daily & on alternate days by Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) Method: This prospective interventional cohort was done at Department of Medicine/Gastroenterology Dow Medical College, Karachi, Pakistan during the period August 2022 & January 2023. Potential participants fulfilling inclusion and exclusion criteria were asked to fill out GSAS questionnaires after their written consent. Patients were allocated in to two groups using random tables. Group-A was given Tab Vonoprazan 10-mg daily for two weeks. Group-B was given Tab Vonoprazan 10-mg on alternate day. GSAS was scored by totaling scores across symptoms and then they are divided by the total number of non-missing symptom scores. Both groups were assessed week-0 & week-2. Results: Only 90 proformas that were completely filled were included, Group-A had 30 males and 15 females while Group-B had 29 males and 16 females. No significant difference in score was found in GSAS score at week-0 except that in item 'gurgling' while at week two there was no significant difference between any of the items. Total GSAS score were significantly lower at Week-2 than at week-0 (p = <.001). Conclusions: Vonoprazan of 10-mg on alternate day is equally effective as 10-mg daily in maintenance of GERD patients at two weeks. [ABSTRACT FROM AUTHOR]

Schizophrenia is one of the most severely debilitating mental disorders that affects 1.1% of the world's population. The exact cause of the disease is not known, but genetics, environmental factors (such as infectious agents, season and region of birth, exposure to viruses, low birth weight, advanced paternal age, and tobacco), and immune system dysfunction can all contribute to the development of schizophrenia. Recently, the role of the immune system in schizophrenia has received much attention. Both acquired and innate immune systems are involved in the pathogenesis of schizophrenia and facilitate the disease's progression. Almost all cells of the immune system including microglia, B cells, and T cells play an important role in the blood-brain barrier damage, inflammation, and in the progression of this disease. In schizophrenia, the integrity of the blood-brain barrier is reduced and then the immune cells are recruited into the endothelium following an increase in the expression of cell adhesion molecules. The entry of immune cells and cytokines leads to inflammation and antibody production in the brain. Accordingly, the results of this study strengthen the hypothesis that the innate and acquired immune systems are involved in the pathogenesis of schizophrenia. [ABSTRACT FROM AUTHOR]

Background: To determine the effects of Subscapularis Neuromuscular Reduction (NMR) in Adhesive Capsulitis patients on pain, Range of Motion (ROM) and Quality of life. Methods: In this randomized controlled trail patients with freezing and frozen stage of Adhesive capsulitis and limited range of movement were included. Patients were randomly divided into control (Group A) and experimental group (Group B). The patients of Group A were treated with conventional physical therapy treatment protocol and patients of group B were treated with subscapularis neuromuscular reduction along with conventional physical therapy. The patient outcome measures were assessed using numeric pain rating scale (NPRS), SPADI (shoulder pain and disability index) and ranges via goniometry. Data was analyzed by SPSS 21. Results: Both group showed significant improvement, but the end value comparison showed significant difference. NMR (Neuromuscular Reduction) on Subscapularis muscles improved the pain, ROM and Patient functional status more as compared to the conventional physical therapy group. The NPRS mean value for control group was 2.90±1.09 and mean value for experimental group was 2.05±1.10with p value of 0.021 while the mean value of SPADI for control group was33.52±9.96 and for experimental group was 26.72±8.00 with p value of 0.026. Conclusion: Treatment groups showed improvement by reducing pain, improving range of motion and functional status but neuromuscular reduction of subscapularis muscles was found to be more effective. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the effect of Livergol on the improvement of fatty liver in patients with cancer undergoing irinotecan- and oxaliplatin-based chemotherapy regimen. Materials and Methods: This was an add-on nonrandomized clinical trial study on thirty selected eligible cancer patients undergoing irinotecan (8 patients) and oxaliplatin (22 patients) with diagnosed fatty liver disease-based liver ultrasonography, as well as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Patients in each group received Livergol at a dose of 140 mg daily for 1 month. ALT and AST levels as well as grade of fatty liver were evaluated before and after intervention. Results: In the oxaliplatin/Livergol group, 40% and 44.4% of patients who were in Grade 2 and 3 before intervention were altered to Grades 1 and 2, respectively (P = 0.005), and in irinotecan/Livergol group, the mentioned percentages were 80% and 66.7% (P = 0.014). The mean levels of ALT and AST enzymes were decreased in both groups after tacking Livergol; however, the observed decreases were not significantly different between groups. Conclusion: It was concluded that the adding of Livergol to oxaliplatin and irinotecan regimens significantly improved the fatty liver of patients and none of them was superior. [ABSTRACT FROM AUTHOR]