Transforming Diagnosis and Therapeutics Using Cancer Genomics.

In past quarter of the century, much has been understood about the genetic variation and abnormal genes that activate cancer in humans. All the cancers somehow possess alterations in the DNA sequence of cancer cell's genome. In present, we are heading toward the era where it is possible to obtain complete genome of the cancer cells for their better diagnosis, categorization and to explore treatment options.

Towards Context-Aware Facial Emotion Reaction Database for Dyadic Interaction Settings.

Emotion recognition is a significant issue in many sectors that use human emotion reactions as communication for marketing, technological equipment, or human-robot interaction. The realistic facial behavior of social robots and artificial agents is still a challenge, limiting their emotional credibility in dyadic face-to-face situations with humans. One obstacle is the lack of appropriate training data on how humans typically interact in such settings. This article focused on collecting the facial behavior of 60 participants to create a new type of dyadic emotion reaction database. For this purpose, we propose a methodology that automatically captures the facial expressions of participants via webcam while they are engaged with other people (facial videos) in emotionally primed contexts. The data were then analyzed using three different Facial Expression Analysis (FEA) tools: iMotions, the Mini-Xception model, and the Py-Feat FEA toolkit. Although the emotion reactions were reported as genuine, the comparative analysis between the aforementioned models could not agree with a single emotion reaction prediction. Based on this result, a more-robust and -effective model for emotion reaction prediction is needed. The relevance of this work for human-computer interaction studies lies in its novel approach to developing adaptive behaviors for synthetic human-like beings (virtual or robotic), allowing them to simulate human facial interaction behavior in contextually varying dyadic situations with humans. This article should be useful for researchers using human emotion analysis while deciding on a suitable methodology to collect facial expression reactions in a dyadic setting.

A review analysis of exercise training regimes among females with polycystic ovary syndrome.

OBJECTIVE: The current systematic review was planned to provide quality assessment of different exercise regimes and their outcomes on the symptoms of polycystic ovary syndrome, and to see if one exercise regime was better than the rest. METHODS: Search was conducted on PubMed and Google Scholar databases for studies published between 2001 and 2021 whose full text was available. The search yielded 28 studies that were reviewed. RESULTS: The current evidence suggests that exercise regimes, such as high-intensity interval training, progressive resistance training, aerobic exercises, and yoga may improve polycystic ovary syndrome conditions. This is accomplished through treating associated risk factors, like body morphology, insulin resistance, hyperandrogenism, lipid profile, reproductive hormones, menstrual cycle, and quality of life. CONCLUSIONS: Exercise regimes improves several symptoms of polycystic ovary syndrome. However, selecting a specific exercise regime over others as the standardised treatment protocol remained inconclusive.

Practice and effect of pesticide use on farmers' health in Sindh, Pakistan.

OBJECTIVE: To identify the frequency and mode of pesticide application, its adverse health effects, and to assess farmers' knowledge and practice of precautionary measures. METHODS: The cross-sectional study was conducted in Matli, Badin in the Sindh province of Pakistan from February to April 2020, and comprised farmers. Data was collected through face-to-face interview using a validated questionnaire. Data was analysed using SPSS 22. RESULTS: Of the 332 farmers, 329(99.1%) were males. The overall mean age was 31.18±12.79 years (range: 21-30 years). Also, 269(81%) of them had not attended formal schooling, and the mean duration of farming practice was 1.64±0.859 years.` Further, 136(41%) participants did not follow the recommended frequency of pesticide application, accidental ingestion was reported by 208(62.7%) participants, and inhalation by 203(61.1%). Dumping of pesticide containers in open fields was a common practice for 247(74.4%) subjects, and 223(67.2%) showed interest in safety training sessions. CONCLUSIONS: Farmers of Sindh were found to be seriously exposed to pesticide risk because of inadequate knowledge.

In a digitally connected world through Likes, Hashtags and Followers - Advancing surgical research through a social media: A narrative review.

In this era of modern information technology, the world is now digitally connected through various platforms on social media, which has changed the way medical professionals work, communicate and learn. The use of social media in surgery is expanding, and it is now becoming an essential tool for surgical training, research and networking. Articles, journal clubs and surgical conferences are within reach of everyone regardless of geographical location worldwide. Electronic publications have now resoundingly replaced printed editions of journals. Collaborative research through social media platforms helps collect diverse data, enhancing the research's global generalisability. The current narrative review was planned to discuss the importance of social media in advancing surgical research and the use of different social media applications in the context of promoting and disseminating surgical research alongside its evolving ethical challenges.

Needs, gaps and opportunities for standard and e-mental health care among at-risk populations in the Asia Pacific in the context of COVID-19: a rapid scoping review.

BACKGROUND: The COVID-19 pandemic is expected to have profound mental health impact, including in the Asia Pacific Economic Cooperation (APEC) region. Some populations might be at higher risk of experiencing negative mental health impacts and may encounter increased barriers to accessing mental health care. The pandemic and related restrictions have led to changes in care delivery, including a rapid shift to the use of e-mental health and digital technologies. It is therefore essential to consider needs and opportunities for equitable mental health care delivery to the most at-risk populations. This rapid scoping review: 1) identifies populations in the APEC region that are at higher risk of the negative mental health impacts of COVID-19, 2) identifies needs and gaps in access to standard and e-mental health care among these populations, and 3) explores the potential of e-mental health to address these needs. METHODS: We conducted a rapid scoping review following the PRISMA Extension for Scoping Reviews (PRISMA-ScR). We searched Medline, Embase and PsychInfo databases and Google Scholar using a search strategy developed in consultation with a biomedical librarian. We included records related to mental health or psychosocial risk factors and COVID-19 among at-risk groups; that referred to one or more APEC member economies or had a global, thus generalizable, scope; English language papers, and papers with full text available. RESULTS: A total of 132 records published between December 2019 and August 2020 were included in the final analysis. Several priority at-risk populations, risk factors, challenges and recommendations for standard and e-mental health care were identified. Results demonstrate that e-mental health care can be a viable option for care delivery but that specific accessibility and acceptability considerations must be considered. Options for in-person, hybrid or "low-tech" care must also remain available. CONCLUSIONS: The COVID-19 pandemic has highlighted the urgent need for equitable standard and e-mental health care. It has also highlighted the persistent social and structural inequities that contribute to poor mental health. The APEC region is vast and diverse; findings from the region can guide policy and practice in the delivery of equitable mental health care in the region and beyond.

Light Tailoring: Impact of UV-C Irradiation on Biosynthesis, Physiognomies, and Clinical Activities of Morus macroura-Mediated Monometallic (Ag and ZnO) and Bimetallic (Ag-ZnO) Nanoparticles.

A nano-revolution based on the green synthesis of nanomaterials could affect all areas of human life, and nanotechnology represents a propitious platform for various biomedical applications. During the synthesis of nanoparticles, various factors can control their physiognomies and clinical activities. Light is one of the major physical factors that can play an important role in tuning/refining the properties of nanoparticles. In this study, biocompatible monometallic (AgNPs and ZnONPs) and bimetallic Ag-ZnONPs (0.1/0.1 and 0.1/0.5) were synthesized under UV-C light irradiation from the leaf extract of Morus macroura, which possesses enriched TPC (4.238 ± 0.26 mg GAE/g DW) and TFC (1.073 ± 0.18 mg QE/g DW), as well as strong FRSA (82.39%). These green synthesized NPs were evaluated for their anti-diabetic, anti-glycation, and biocompatibility activities. Furthermore, their anti-cancerous activity against HepG2 cell lines was assessed in terms of cell viability, production of reactive oxygen/nitrogen species, mitochondrial membrane potential, and apoptotic caspase-3/7 expression and activity. Synthesized NPs were characterized by techniques including ultraviolet-visible spectroscopy, SEM, EDX, FTIR, and XRD. UV-C mediated monometallic and bimetallic NPs showed well-defined characteristic shapes with a more disperse particle distribution, definite crystalline structures, and reduced sizes as compared to their respective controls. In the case of clinical activities, the highest anti-diabetic activity (67.77 ± 3.29% against α-amylase and 35.83 ± 2.40% against α-glucosidase) and anti-glycation activity (37.68 ± 3.34% against pentosidine-like AGEs and 67.87 ± 2.99% against vesperlysine-like AGEs) was shown by UV-C mediated AgNPs. The highest biocompatibility (IC50 = 14.23 ± 1.68 µg/mL against brine shrimp and 2.48 ± 0.32% hemolysis of human red blood cells) was shown by UV-C mediated ZnONPs. In the case of anti-cancerous activities, the lowest viability (23.45 ± 1.40%) with enhanced ROS/NOS production led to a significant disruption of mitochondrial membrane potential and greater caspase-3/7 gene expression and activity by UV-C mediated bimetallic Ag-ZnONPs (0.1/0.5). The present work highlights the positive effects of UV-C light on physico-chemical physiognomies as well as the clinical activities of NPs.

7ß-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z Notonipetranone Attenuates Neuropathic Pain by Suppressing Oxidative Stress, Inflammatory and Pro-Apoptotic Protein Expressions.

7ß-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid obtained from a natural source has proved to be effective in minimizing various side effects associated with opioids and nonsteroidal anti-inflammatory drugs. The current study focused on investigating the effects of ECN on neuropathic pain induced by partial sciatic nerve ligation (PSNL) by mainly focusing on oxidative stress, inflammatory and apoptotic proteins expression in mice. ECN (1 and 10 mg/kg, i.p.), was administered once daily for 11 days, starting from the third day after surgery. ECN post-treatment was found to reduce hyperalgesia and allodynia in a dose-dependent manner. ECN remarkably reversed the histopathological abnormalities associated with oxidative stress, apoptosis and inflammation. Furthermore, ECN prevented the suppression of antioxidants (glutathione, glutathione-S-transferase, catalase, superoxide dismutase, NF-E2-related factor-2 (Nrf2), hemeoxygenase-1 and NAD(P)H: quinone oxidoreductase) by PSNL. Moreover, pro-inflammatory cytokines (tumor necrotic factor-alpha, interleukin 1 beta, interleukin 6, cyclooxygenase-2 and inducible nitric oxide synthase) expression was reduced by ECN administration. Treatment with ECN was successful in reducing the caspase-3 level consistent with the observed modulation of pro-apoptotic proteins. Additionally, ECN showed a protective effect on the lipid content of myelin sheath as evident from FTIR spectroscopy which showed the shift of lipid component bands to higher values. Thus, the anti-neuropathic potential of ECN might be due to the inhibition of oxidative stress, inflammatory mediators and pro-apoptotic proteins.

The interplay between viruses and TRIM family proteins.

Novel therapeutic options are urgently needed to improve the global treatment of viral infections. Tripartite motif (TRIM) family proteins are involved in various biological and cellular functions including differentiation, development, proliferation, oncogenesis, innate immunity, and viral autophagy. Various TRIM proteins show antiviral properties against different viral infections and are now transitioning from ubiquitin proteins to an efficient and emerging therapeutic class of proteins. TRIM proteins combat viruses by targeting them at pre/post transcription levels. This review summarizes the comprehensive roles of different TRIM proteins along with their expression systems and their applications towards antiviral therapeutics.

Role of structured and supervised exercise programmes in peripheral artery disease patients with and without claudication - A Systematic Review and Metaanalysis.

OBJECTIVE: This review aimed to determine the impact of exercise protocol among peripheral artery disease patients. Literature search was done from 2005 to 2018. METHODS: Databases such as Google Scholar, Medline and PubMed was reconnoitred for the purpose of research articles by using key words like exercise training, peripheral artery disease, ankle brachial index, haemodynamic and atherosclerosis. Studies fulfilling the inclusion criteria were retrieved and encompassed in the present study. RESULTS: The heterogeneity of the studies included in the analysis and the impact of exercise programmes on outcome measures were assessed by using hedge gstatistical model.Of the54 studies found, 9(16.6%) were analysed that suggest supervised and structured exercises programmes significantly improved (p<0.05) outcome variables. CONCLUSIONS: Future randomized controlled trials related to the duration of exercises regimes are required in order to tailor the training programmes according to the need of individuals.

Why do patients with limb ischaemia present late to a vascular surgeon? A prospective cohort study from the developing world.

OBJECTIVE: To look into the factors responsible for delay in presentation of Iimb ischemia patients to a vascular surgeon. Methods: The prospective cohort study was conducted at the Aga Khan University Hospital, Karachi, from October 01, 2016, to August 10, 2018. Patients coming with delayed presentation of both acute and chronic limb ischemia were included. All the patients were assessed by qualified vascular surgeons. SPSS 23 was used for data analysis. Results: Of the 55 patients, 33(60%) had acute and 22(40%) had chronic limb ischaemia. Mean age of acute cases was 44±23.72 years and it was 60±12.49 years for chronic cases. Overall, the commonest reason behind delay was non-referral by primary physician which was the case with 11(33.3%) patients in the acute group, and 13(59%) in the chronic group. The limb loss in the acute group was 20(60%) and 8(36%) in the chronic group.. Conclusion: Delayed presentation of patients with limb ischaemia is mainly due to non-referral. A robust campaign needs to be launched to reduce the rate of limb loss.

Thyroid cancer in black thyroid glands: the effect of age and race.

BACKGROUND: Black thyroid pigmentation is a rare entity. The risk of malignancy is higher in black thyroid compared to non-black thyroid glands. We aimed to examine the effect of age and race on the risk of malignancy in black thyroid glands. METHODS: We identified a series of consecutive patients who underwent thyroidectomy at an academic institution between January 1998 and May 2013. Patient demographics, clinical characteristics, and histopathology data were reviewed. RESULTS: Among 925 patients who underwent thyroidectomy, 112 (12.1%) patients with black thyroid glands were identified. The incidence of thyroid cancer was 55.4% in black thyroid glands compared to 32.8% in non-black thyroid glands (p < 0.0001). The incidence of papillary thyroid cancer among the black and non-black thyroid glands was 34.8 and 20%, respectively (p < 0.001). The mean age (± SD) for patients with black thyroid glands and those with non-black thyroid was 54.3 ± 12.8 and 51.2 ± 15.7 years, respectively (p = 0.05). Black thyroid glands were also associated with a higher incidence of microcarcinomas (76 vs. 59%, p = 0.02). Among patients with black thyroid glands, Caucasians had a higher malignancy rate (63.4%) than African-Americans (37%; p = 0.03). CONCLUSION: The incidence of malignancy is higher in black thyroid compared to non-black thyroid glands, specifically in Caucasians.

Adherence and efficacy of screening for low bone mineral density among ulcerative colitis patients treated with corticosteroids.

OBJECTIVES: Ulcerative colitis (UC) is associated with an increased risk of metabolic bone disease and fragility fractures. The aim of this study was to assess the adherence to the guidelines issued by the American Gastroenterology Association (AGA) for the screening for low bone density in UC patients and to assess the benefits of dual-energy X-ray absorptiometry (DXA) screening among corticosteroid (CS)-treated UC patients. METHODS: Nationwide Veterans Affairs system (VA) data were obtained. UC patients followed up in the VA between 2001 and 2011 and the occurrence of fragility fractures were identified using International Classification of Diseases, Ninth Revision codes. Exposure to CSs was assessed using pharmacy data. DXA screening was assessed using the VA procedure database. Post DXA screening, medication use was also assessed from the pharmacy database. Cox regression analysis was performed to calculate the hazard ratio (HR) of fragility fractures among those patients who received DXA compared with those who did not. RESULTS: We included 5,736 patients. Among them, 80 (1.4%) patients suffered from fragility fractures during the follow-up period. Overall adherence rate to AGA guidelines was 23%. Adherence rate was highest among postmenopausal women (48%) and lowest among men above 50 years of age (20%). UC patients who received DXA screening were more likely to be started on bisfosfonates (P<0.001), calcitonin (P<0.001), vitamin D, and calcium (P<0.001) compared with those who did not receive screening. Those who received DXA screening were half as likely (HR=0.5, 0.3-0.9, P=0.03) to develop fragility fractures as compared with those who did not receive screening. The benefits were more prominent among those with higher CS exposure. CONCLUSIONS: Rates of DXA screening were low among CS-treated UC patients. Those who received DXA screening were more likely to be started on antiresorptive therapy and supplemental medications and had a 50% reduction in the risk of fragility fractures. More efforts should be directed toward raising the adherence to AGA guidelines and the awareness of DXA benefits.

Crystal structure of ethyl 2-[(4-bromo-phen-yl)amino]-3,4-di-methyl-pent-3-enoate.

In the title compound, C15H20BrNO2, there are two independent mol-ecules (A and B) comprising the asymmetric unit and these adopt very similar conformations. In A, the dihedral angle between the CO2 and MeC=CMe2 groups is 80.7 (3)°, and these make dihedral angles of 3.5 (3) and 84.09 (16)°, respectively, with the bromo-benzene ring. The equivalent dihedral angles for mol-ecule B are 78.4 (3), 2.1 (3) and 78.37 (12)°, respectively. The most prominent inter-actions in the crystal packing are amine-N-H⋯O(carbon-yl) hydrogen bonds between the two independent mol-ecules, resulting in non-centrosymmetric ten-membered {⋯OC2NH}2 synthons. Statistical disorder is noted for each of the terminal methyl groups of the ethyl residues.

Addressing the Data Gap: The Importance of National Cancer Registries.

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The Potential of Immature Platelet Fraction as a Prognostic Marker in Dengue Infection.

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Сytotoxic T lymphocyte-associated protein 4 (CTLA4) is overexpressed in a subset of prolactin- and growth hormone-secreting pituitary adenomas.

Cytotoxic T lymphocyte-associated protein 4 (CTLA4), a negative regulator typically expressed on the surface of T lymphocytes, is targeted by immunotherapy in patients with an ever-expanding spectrum of cancers. Characterizing the expression of CTLA4 in the pituitary gland could provide additional rationale for using immune checkpoint inhibitors in pituitary adenoma patients who do not respond to conventional treatments. We assessed the expression of CTLA4 mRNA and protein in a panel of 157 human pituitary glands, 45 collected at autopsy and 112 at surgery. These specimens included 50 normal glands and 107 adenomas: 41 nonsecreting, 25 PRL-, 24 ACTH-, 11 GH-, 2 TSH-, 1 FSH-secreting, and 3 atypical. Specimens were stained for CTLA4 and adenohypophyseal hormones using RNAscope in situ hybridization, immunohistochemistry, and RNAscope Multiplex Fluorescent Assay. CTLA4 mRNA was detectable in most normal pituitary glands (48 of 50, 96%) but varied in expression, with a histological score (H-score) ranging from 0.6 to 20. The variation did not depend upon the patient's gender and age and was not significantly affected by the archival storage time. CTLA4 expression was higher (P = 0.022) in pituitary adenomas than normal glands, with the greatest levels seen in PRL- and GH-secreting adenomas (P = 0.009 and 0.023 versus normal, respectively). Eight of 25 (32%) prolactinomas and 3 of 11 (27%) GH-adenomas had an H-score greater than 20, while no differences were seen for the other types. These novel data highlight the expression of an immune checkpoint such as CTLA4 on pituitary endocrine cells, a finding that could be exploited for therapeutical applications.

Battling the breath-stealers: Blastomyces and Pseudomonas triggering acute respiratory distress syndrome (ARDS).

Blastomycosis is an endemic disease in North America and commonly manifests with pulmonary symptoms. Blastomycosis should be consider when patients have persistent infiltrates on imaging in an endemic area. We present a case of a 46-year-old male who presented to the pulmonary clinic with fever, cough with production of yellowish-green sputum and culture of BAL-fluid showed growth of Pseudomonas spp. Antimicrobial therapy was started accordingly, but was not effective. A repeat bronchoscopy was performed and BAL-fluid culture was positive for Blastomyces dermatitidis and liposomal amphotericin B was initiated. Unfortunately, the patient died after withdrawing care.

The α-7 Nicotinic Receptor Positive Allosteric Modulator Alleviates Lipopolysaccharide Induced Depressive-like Behavior by Regulating Microglial Function, Trophic Factor, and Chloride Transporters in Mice.

Neuroinflammation contributes to the pathophysiology of major depressive disorder (MDD) by inducing neuronal excitability via dysregulation of microglial brain-derived neurotrophic factor (BDNF), Na-K-Cl cotransporter-1 (NKCC1), and K-Cl cotransporter-2 (KCC2) due to activation of BDNF-tropomyosin receptor kinase B (TrkB) signaling. Allosteric modulation of α7 nAChRs has not been investigated on BDNF, KCC2, and NKCC1 during LPS-induced depressive-like behavior. Therefore, we examined the effects of PNU120596, an α7 nAChR positive allosteric modulator, on the expression of BDNF, KCC2, and NKCC1 in the hippocampus and prefrontal cortex using Western blot analysis, immunofluorescence assay, and real-time polymerase chain reaction. The effects of ANA12, a TrkB receptor antagonist, on LPS-induced cognitive deficit and depressive-like behaviors were determined using the Y-maze, tail suspension test (TST), and forced swim test (FST). Pharmacological interactions between PNU120596 and ANA12 were also examined. Experiments were conducted in male C57BL/6J mice. LPS administration (1 mg/kg) resulted in increased expression of BDNF and the NKCC1/KCC2 ratio and decreased expression of KCC2 in the hippocampus and prefrontal cortex. PNU120596 pretreatment (4 mg/kg) attenuated the LPS-induced increase in the expression of BDNF and NKCC1/KCC2 ratio and the reduction in KCC2 expression in these brain regions. In addition, ANA12 (0.25 or 0.50 mg/kg) reduced the LPS-induced cognitive deficit and depressive-like behaviors measured by a reduced spontaneous alternation in the Y-maze and increased immobility duration in TST and FST. Coadministration of PNU120596 (1 mg/kg) and ANA12 (0.25 mg/kg) prevented the LPS-induced cognitive deficit and depressive-like behaviors. Overall, PNU120596 prevented the LPS-induced depressive-like behavior by likely decreasing neuronal excitability via targeting microglial α7 nAChR in the hippocampus and prefrontal cortex.

Perception of dental students and faculty regarding the practice of professionalism in dentistry using the Professionalism Mini Evaluation Exercise (P-MEX).

BACKGROUND: Professionalism is one of the fundamental traits which includes behaviors, commitments, standards, and goals that helps define a profession. OBJECTIVE: This study aimed to assess the attitude of dental students and graduates regarding the practice of professionalism in dentistry using the Professionalism Mini Evaluation Exercise (P-MEX) questionnaire. METHOD: This cross-sectional study was conducted amongst the dental undergraduates, lecturers and postgraduate faculty. Views regarding professionalism were assessed using the P-MEX. The 24-questions based survey form is comprised of questions related to doctor and patient relationship skills, reflective abilities, time management, and lastly, interprofessional relationship expertise. Data was analyzed using SPSS version 23. Descriptive statistics were done using mean and SD, whilst associations between responses were assessed using Mann-Whitney U and Kruskal-Wallis tests. P value less than 0.05 was considered significant. RESULTS: From a total of 201 participants, 95 (47.3%) were males and 106 (52.7%) were females. Statistically significant association was seen between time management, reflective skills, and interpersonal skills with gender, as well as the domains of P-MEX and years of education. CONCLUSION: The use of P-MEX provides a valid confirmation for the assessment and awareness of professionalism amongst the dental faculty and students. Females demonstrated higher traits of professionalism as compared to males. The findings from the current study identify that students and faculty members had sufficient awareness regarding professionalism and the practice of professionalism was routinely followed.