Risk of major congenital heart disease in pregestational maternal diabetes is modified by hemoglobin A1c.

OBJECTIVES: The association between pregestational diabetes mellitus (PDM) and risk of congenital heart disease (CHD) is well recognized; however, the importance of glycemic control and other coexisting risk factors during pregnancy is less clear. We sought to determine the relative risk (RR) of major CHD (mCHD) among offspring from pregnancies complicated by PDM and the effect of first-trimester glycemic control on mCHD risk. METHODS: We determined the incidence of mCHD (requiring surgery within 1 year of birth or resulting in pregnancy termination or fetal demise) among registered births in Alberta, Canada. Linkage of diabetes status, maximum hemoglobin A1c (HbA1c) at < 16 weeks' gestation and other covariates was performed using data from the Alberta Perinatal Health Program registry. Risk of mCHD according to HbA1c was estimated as an adjusted RR (aRR), calculated using log-binomial modeling. RESULTS: Of 1412 cases of mCHD in 594 773 (2.37/1000) births in the study period, mCHD was present in 48/7497 with PDM (6.4/1000; RR, 2.8 (95% CI, 2.1-3.7); P < 0.0001). In the entire cohort, increased maternal age (aRR, 1.03 (95% CI, 1.02-1.04); P < 0.0001) and multiple gestation (aRR, 1.37 (95% CI, 1.1-1.8); P = 0.02) were also associated with mCHD risk, whereas maternal prepregnancy weight > 91 kg was not. The stratified risk for mCHD associated with HbA1c ≤ 6.1%, > 6.1-8.0% and > 8.0% was 4.2/1000, 6.8/1000 and 17.1/1000 PDM/gestational diabetes mellitus births, respectively; the aRR of mCHD associated with PDM and HbA1c > 8.0% was 8.5 (95% CI, 5.0-14.4) compared to those without diabetes and 5.5 (95% CI, 1.6-19.4) compared to PDM with normal HbA1c (≤ 6.1%). CONCLUSIONS: PDM is associated with a RR of 2.8 for mCHD, increasing to 8.5 in those with HbA1c > 8%. These data should facilitate refinement of referral indications for high-risk pregnancy screening. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Management of clinically node-negative early-stage oral cancer: network meta-analysis of randomized clinical trials.

The best treatments for the clinically node-negative (cN0) neck in early-stage oral squamous cell carcinoma (OSCC) patients are a subject of ongoing debate and there is no consensus. A network meta-analysis (NMA) of randomized clinical trials (RCTs) was conducted to determine the most effective treatment and to rank treatments based on their effectiveness. A systematic search was performed in accordance with the PRISMA guidelines to retrieve RCTs that compared therapeutic neck dissection (TND), sentinel lymph node biopsy (SLNB), and elective neck dissection (END). The outcomes analysed were overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), and nodal recurrence. Hazard ratios and risk ratios were calculated by direct meta-analysis and NMA. Ten RCTs with a total of 1858 patients were eligible for inclusion. Direct meta-analysis showed END to be superior to TND and comparable to SLNB. The NMA revealed no statistically significant difference between END and SLNB (very low quality evidence) regarding OS, DSS, DFS, and nodal recurrence. However, END was found to significantly improve OS and DFS, and reduce nodal recurrence when compared to TND (moderate quality evidence). END ranked as probably the top treatment option for maximizing OS and DSS, and reducing nodal recurrence in early-stage OSCC, followed by SLNB and TND. There was very low quality evidence supporting SLNB as non-inferior to END for patients with early-stage OSCC. This NMA yielded favourable results for the use of END (with moderate quality evidence) in early-stage OSCC patients, although excellent results have also been obtained with SLNB. However, data in the literature for SLNB are scarce, as this technique has not yet been formalized in many countries. There is a need to further explore SLNB for early-stage OSCC patients, as well as its value in detecting occult lymph node metastases on the contralateral side. More studies comparing morbidity, quality of life, and costs between the different management strategies for the clinically negative neck in early-stage OSCC patients are needed.

Anti-tubercular therapy (ATT) induced thrombocytopenia: A systematic review.

INTRODUCTION: Drug-induced thrombocytopenia is a known adverse event of several drugs. Antitubercular therapy (ATT) is rarely reported but important cause of thrombocytopenia. The present review aimed to understand the profile of thrombocytopenia caused by first-line ATT i.e. isoniazid, rifampicin, pyrazinamide, and ethambutol. MATERIALS AND METHODS: We screened case reports, case series, and letter-to-editor from databases, like Pubmed/MEDLINE, Ovid, and EMBASE from 1970 to 2021. The PRISMA guidelines were followed in the present systematic review. RESULTS: Categorical data were expressed as n (%) and quantitative data were expressed as median (IQR). After applying the inclusion/exclusion criteria, 17 case reports and 7 letters to the editor were selected for the present review. Rifampicin was most frequently associated with thrombocytopenia (65%). A median (IQR) drop to 20,000 (49,500) platelets/mm3 was observed. Anti-rifampicin associated antibodies and anti-dsDNA positivity were found in six studies. Except for two, all patients responded to symptomatic treatment. DISCUSSION: ATT-induced thrombocytopenia can be life-threatening and require hospitalization. Clinicians should be aware of the association of ATT with thrombocytopenia and should take appropriate measures for patient management. CONCLUSION: This review provides clinicians a comprehensive picture of adverse effects and their management in ATT induced thrombocytopenia.

Sex differences in minutiae frequencies of thumbprint with respect to dermatoglyphic patterns.

Abstract: The present study is an attempt to study the sex differences in minutiae frequencies of thumbprint with respect to dermatoglyphic patterns. A sample of 100 subjects (50 males and 50 females) were gathered from Shimla, Himachal Pradesh (North India). In regards to pattern type, maximum number of minutiae was present in loop pat-tern followed by whorls and least minutiae were in the arches in the right hand of both the sexes and left hand of females only, whereas in left hand of the males highest frequency of minutiae were noticed in whorls followed by loops and lowest in the arches, thereby indicating the lessened bimanual symmetry in males. It can be inferred from the present study that the simple pattern (arch) has less discontinuance in the regular flow of the ridges, while the complex patterns (loops and whorls) exhibited more interruptions in the dermal ridges.

Effectiveness of different treatments for odontogenic keratocyst: a network meta-analysis.

Odontogenic keratocysts (OKC) are benign but aggressive lesions. As there is a lack of well randomized clinical studies assessing the effectiveness of the different treatment options for OKC, a network meta-analysis (NMA) was performed to identify the best treatment option with the lowest recurrence rate. An electronic search was performed following the PRISMA guidelines to identify all clinical studies comparing treatment options against enucleation alone. The outcome variable was recurrence. The predictor variables were treatments. The eight included treatments were: enucleation with peripheral ostectomy/curettage (E + PO/curettage); enucleation with cryotherapy (E + CRYO); enucleation with/without PO followed by modified Carnoy's solution (E ± PO+MCS); enucleation with PO and with topical 5-fluorouracil (E + PO+5FU); enucleation with/without PO followed by original Carnoy's solution (E ± PO+CS); marsupialization alone (MARS); marsupialization followed by secondary enucleation with/without PO (MARS+2°E ± PO); and resection. The odds ratio was used to estimate the recurrence rate. A frequentist NMA was performed using Stata software. A total of 2989 patients in 40 studies were included. Both direct pairwise meta-analysis and NMA showed that E + 5FU+PO was significantly superior to E ± PO+MCS. However, no statistically significant difference was found between E ± PO+CS vs E + 5FU+PO, E ± PO+MCS, and resection, respectively (all very low quality evidence). The three most effective treatments in reducing the recurrence rate were E + PO+ 5FU (98.1%; very low quality evidence), resection (83.5%; very low quality evidence), and E ± PO+CS (63.8%; moderate quality evidence). The findings from this study suggest that CS remains the most effective fixative agent after enucleation and PO until proven otherwise. Additionally, 5FU appears to be an effective method with promising results that needs further research. Finally, the efficacy of MCS remains controversial; further in vivo and in vitro studies are required to determine new protocols. As this NMA included retrospective studies, the results should be interpreted with great caution (level of evidence: type III).

An Anatomical Evaluation of Normal and Aberrant Foramen Ovale in Skull Base with Its Clinical Significance.

Introduction: Foramen ovale is one of the most significant foramina of skull base and transmits mandibular nerve. Its detailed knowledge is crucial in treatment of trigeminal neuralgia and various diagnostic practices. Aim: Aim of the study was to provide anatomical data of foramen ovale regarding number, shape, diameters and its relation to nearby bony landmarks. Material and method: The present study was ethically approved and 100 dry adult human skulls were included in the study to evaluate 200 foramina ovale. Non-metric parameters were observed and metric parameters were measured with Vernier calliper and goniometer. Results:Different kinds of shapes were found in foramen ovale. Variant features in the form of bony spine, ridge, foramen or bar were identified. The means of anteroposterior and transverse diameter of foramen ovale were found to be 8.16 and 4.97 mm on the right side, and 7.68 and 4.74 mm on the left side. The mean distance of its anterior and posterior ends from the midsagittal plane were 22.69 and 28.92 mm on the right side, and 22.18 and 22.66 mm on the left side. Distance from the lateral border of foramen ovale to the posterior end of zygoma and midpoint of infratemporal crest was found to be 30.65 and 21.05 mm on the right, and 30.30 and 20.87 mm on the left side. The mean of angle of foramen ovale with midsagittal was 45.44º on the right side and 45.78º on the left side. Conclusion:Variations found in foramen ovale are key points to keep in mind while operating in this region. Measured metric parameters were found to a higher extent on the right side than the left one. The present study will be helpful for both further research and neurosurgeons operating in this region.

Impact of rural residence and low socioeconomic status on rate and timing of prenatal detection of major congenital heart disease in a jurisdiction of universal health coverage.

OBJECTIVE: Socioeconomic status (SES) and distance of residence from tertiary care may impact fetal detection of congenital heart disease (CHD), partly through reduced access to and quality of obstetric ultrasound screening. It is unknown whether SES and remoteness of residence (RoR) affect prenatal detection of CHD in jurisdictions with universal health coverage. We examined the impact of SES and RoR on the rate and timing of prenatal diagnosis of major CHD within the province of Alberta in Canada. METHODS: In this retrospective study, we identified all fetuses and infants diagnosed with major CHD in Alberta, from 2008 to 2018, that underwent cardiac surgical intervention within the first year after birth, died preoperatively, were stillborn or underwent termination. Using maternal residence postal code and geocoding, Chan SES index quintile, geographic distance from a tertiary-care fetal cardiology center and the Canadian Index of Remoteness (IoR) were calculated. Outcome measures included rates of prenatal diagnosis and diagnosis after 22 weeks' gestation. Risk ratios (RR) were calculated using log-binomial regression and stratified by rural (≥ 100 km from tertiary care) or metropolitan (< 100 km from tertiary care) residence, adjusting for year of birth and the obstetric ultrasound screening view in which CHD would most likely be detected (four-chamber view; outflow-tract view; three-vessel or three-vessels-and-trachea or non-standard view; septal view). RESULTS: Of 1405 fetuses/infants with major CHD, prenatal diagnosis occurred in 814 (57.9%). Residence ≥ 100 km from tertiary care (adjusted RR, 1.19; 95% CI, 1.05-1.34) and higher IoR (adjusted RR, 1.9; 95% CI, 1.1-3.3) were associated with missed prenatal diagnosis of major CHD. Similarly, residence ≥ 100 km from tertiary care (adjusted RR, 1.41; 95% CI, 1.22-1.62) and higher IoR (adjusted RR, 3.6; 95% CI, 2.2-8.2) were associated with prenatal diagnosis after 22 weeks. Although adjusted and unadjusted analyses showed no association between Chan SES index quintile and prenatal-diagnosis rate overall nor for residence in rural areas, in metropolitan regions, lower SES quintiles were associated with missed prenatal diagnosis (quintile 1: RR, 1.24; 95% CI, 1.02-1.50) and higher risk of diagnosis after 22 weeks' gestation (quintile 1: RR, 1.46; 95% CI, 1.10-1.93; quintile 2: RR, 1.66; 95% CI, 1.24-2.23). CONCLUSIONS: Despite universal healthcare, rural residence in Alberta is associated with lower rate of prenatal diagnosis of major CHD and higher risk of late prenatal diagnosis (≥ 22 weeks). Within metropolitan regions, lower SES impacts negatively prenatal-diagnosis rate and timing. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

The Health and Wellness Benefits of Traditional Postnatal Practice (TPC) on Postnatal Mothers: A Systematic Review

@#Introduction: Postnatal is a transition process for the mother back to her non-pregnancy state and involves the changes in hormones level. During the postnatal period, many health issues need to be addressed for both mother and newborn. One of the upsetting health issues for the mother due to the increasing trend is postnatal depression and if it is not identified and treated early, it may cause further complicated problems not only to the mother but also to the baby, family, and local community. With this issue, the Ministry of Health Malaysia has taken a few initiatives to encourage the postnatal mother to also practice the non-medical approaches or traditional postnatal care (TPC) as a self-care for the prevention of postnatal depression. Aim: To systematically identify and review studies examining the influence of TPC on postnatal mothers. Design & Data Sources: A systematic search strategy on the research trend for the period between the years 2013 to 2020 through the Scopus database, Science Direct, and PubMed database. Methods: This review has identified 7 journal articles based on the preferred reporting items for the systematic reviews (PRISMA) framework. Results: There are many methods of TPC, such as traditional postnatal body massage, herbal consumption, herbal bath, body steaming, and body wrapping based on own culture and beliefs. Besides the TPC preparation and techniques, some studies also describe the effects of TPC on a mother’s health and wellness. Conclusion: TPC shows encouraging health trends, and it helps to enhance the well-being and good health of postpartum mothers.

Partnering for rotavirus vaccine introduction in India: A retrospective analysis.

BACKGROUND: The pre-existing partner network created in India for the delivery of polio vaccines was initially used to eradicate polio and later on embedded in the health systems network to promote routine immunization and other health interventions efficiently. The experience from this network offered lessons for strengthening the health care systems and provided a well-established network that could be utilized for other vaccine initiatives. It has also been established that successful partnerships between a broad range of stakeholders provide support, strengthen the health system, and accelerate vaccine innovation, introduction, access, logistics, and communication support. However, beyond polio eradication, there have not been too many documented success stories of vaccine introduction, which could be replicated in other new vaccine introductions and allied health initiatives. The authors have reviewed the successful and time-bound introduction of rotavirus vaccine (RVV) in India in the present article. METHODS: The review was conducted based on a partnership framework which analysed multiple factors-partnership prerequisites, partnership model, partnership process, and partnership performance, thereby providing a comprehensive insight into the successful utilization of partnership networks for rotavirus vaccine introduction under the Universal Immunization Program in India. RESULTS & CONCLUSION: The review also highlights the role of a lead agency in creating a fertile ground for lush, efficient, and effective partnerships amongst different stakeholders. The already existing RVV partnership framework reviewed by the authors can be successfully utilized for future new vaccine introductions.

Description of Stenotrophomonas sepilia sp. nov., isolated from blood culture of a hospitalized patient as a new member of Stenotrophomonas maltophilia complex.

Stenotrophomonas sepilia strain SM16975 (= JCM 32102; = KCTC 62052) is a new species isolated from the blood culture of a hospitalized patient. The biochemical characterization, phenotypic criteria, phylogenomic reconstruction, and genomic analysis were carried out to differentiate it from its phylogenetic neighbours, establishing novel species status in the genus Stenotrophomonas and within Stenotrophomonas maltophilia complex (Smc).

Barriers and facilitators related to undertaking physical activities among men with prostate cancer: a scoping review.

BACKGROUND: Prostate cancer (PC) and its treatments lead to significant acute, chronic, or latent adverse effects that result in declines in patients' physical functions, quality of life and reduced sense of masculinities. Robust evidence shows that physical activity (PA) can improve many health outcomes in men with PC; however, less is known about the facilitators, preferences, and barriers to PA engagement in this population. The purpose of this scoping review is to document the nature and extent of literature related to these aspects of PA participation among men with PC. METHODS: We conducted a scoping review of PA among men with PC. Databases searched included Medline, CINAHL, Embase, Rehabilitation & Sports Medicine Source, and SportDiscus from inception to June 30, 2020. Multiple reviewers were used in all screening and data abstractions. RESULTS: The search yielded 2788 individual citations after duplicates were removed. Following title and abstract screening, 129 underwent full-text review, and 46 articles were included. Quantitative data related to our research question showed that structured group exercise was the most commonly reported facilitator/preference among men with PC, whereas treatment-related effects and lack of time are the most common barriers. In terms of qualitative data, the most prominent theme noted related to masculinities and gender-specific needs within the context of having PC. CONCLUSION: Men with PC have unique facilitators and barriers concerning PA. More work is needed from the research and clinical practice perspectives to enable this population to engage and remain in regular PA.

Conception of Saviour Siblings: Ethical Perceptions of Selected Stakeholders in Malaysia.

The conception of saviour siblings using preimplantation genetic diagnosis coupled with human leukocyte antigen (HLA) typing or HLA typing alone is controversial and receives a wide divergence of legal responses among countries around the world. The resulting child conceived through this procedure is dubbed a 'saviour sibling' as the child can potentially act as a compatible donor for an elder ailing sibling who needs a haematopoietic stem cell transplantation. At present, the acceptability of this procedure in Malaysia is ambiguous as there is no specific statute governing assisted reproductive technology, and the guideline issued by the Malaysian Medical Council does not expressly address this issue. The ethical arguments relating to the conception of saviour siblings in the current literature are mainly thought to reflect a liberal viewpoint which is predominantly Western in nature. This paper seeks to explore the perception of selected key stakeholders on the acceptability of and ethical concerns related to this procedure in the Malaysian context. The findings indicate that stakeholders generally support the conception of saviour siblings and some of their concerns echo the Western viewpoint. Interestingly, many were highly anxious about its economic implication, which is rarely discussed in the current literature on saviour siblings.

Rapid whole cell imaging reveals a calcium-APPL1-dynein nexus that regulates cohort trafficking of stimulated EGF receptors.

The endosomal system provides rich signal processing capabilities for responses elicited by growth factor receptors and their ligands. At the single cell level, endosomal trafficking becomes a critical component of signal processing, as exemplified by the epidermal growth factor (EGF) receptors. Activated EGFRs are trafficked to the phosphatase-enriched peri-nuclear region (PNR), where they are dephosphorylated and degraded. The details of the mechanisms that govern the movements of stimulated EGFRs towards the PNR, are not completely known. Here, exploiting the advantages of lattice light-sheet microscopy, we show that EGFR activation by EGF triggers a transient calcium increase causing a whole-cell level redistribution of Adaptor Protein, Phosphotyrosine Interacting with PH Domain And Leucine Zipper 1 (APPL1) from pre-existing endosomes within one minute, the rebinding of liberated APPL1 directly to EGFR, and the dynein-dependent translocation of APPL1-EGF-bearing endosomes to the PNR within ten minutes. The cell spanning, fast acting network that we reveal integrates a cascade of events dedicated to the cohort movement of activated EGF receptors. Our findings support the intriguing proposal that certain endosomal pathways have shed some of the stochastic strategies of traditional trafficking and have evolved processes that provide the temporal predictability that typify canonical signaling.

Identification of a unique anti-Ro60 subset with restricted serological and molecular profiles.

Anti-Ro60 is one of the most common and clinically important serum autoantibodies that has a number of diagnostic and predictive capabilities. Most diagnostic laboratories report this simply as a qualitative positive/negative result. The objective of this study was to examine the clinical and serological relevance of a novel subset of anti-Ro60 in patients who display low levels of anti-Ro60 (anti-Ro60low ). We retrospectively identified anti-Ro60 sera during a 12-month period at a major immunopathology diagnostic laboratory in Australia. These all were anti-Ro60-precipitin-positive on the diagnostic gold standard counter-immuno-electrophoresis (CIEP). Lineblot immunoassay was used to stratify patients into either anti-Ro60low or anti-Ro60high subsets. We compared the medical and laboratory parameters associated with each group. Enzyme-linked immunosorbent assay (ELISA) and mass spectrometry techniques were used to analyse the serological and molecular basis behind the two subsets. Anti-Ro60low patients displayed less serological activity than anti-Ro60high patients with less intermolecular spreading, hypergammaglobulinaemia and less tendency to undergo anti-Ro60 isotype-switching than anti-Ro60high patients. Mass spectrometric typing of the anti-Ro60low subset showed restricted variable heavy chain subfamily usage and amino acid point mutations. This subset also displayed clinical relevance, being present in a number of patients with systemic autoimmune rheumatic diseases (SARD). We identify a novel anti-Ro60low patient subset that is distinct from anti-Ro60high patients serologically and molecularly. It is not clear whether they arise from common or separate origins; however, they probably have different developmental pathways to account for the stark difference in immunological maturity. We hence demonstrate significance to anti-Ro60low and justify accurate detection in the diagnostic laboratory.

Retrospective analysis of EMR database to assess the effectiveness of Saccharomyces boulardii CNCM I-745 in children with acute diarrhoea during routine clinical practice.

This study aimed to assess the efficacy of Saccharomyces boulardii, a yeast probiotic, in the management of acute diarrhoeal disorders in the paediatric population in outpatient settings. It was a multicentre retrospective analysis of medical records of children who were treated for acute diarrhoea by routine treatment (oral rehydration solution and zinc) with or without S. boulardii. Overall, 160 children presenting with acute diarrhoea at seven different outpatient paediatric settings were included in the study. Children were divided into two categories based on their treatment with S. boulardii (SB group) or without S. boulardii (Non-SB group). Baseline demographic, anthropometric and clinical variables were compared between the two groups. The median duration of diarrhoea post-treatment was significantly shorter in the S. boulardii group (3 days) than in the non-SB group (4 days). A significant reduction in the frequency of stools was observed post-treatment in the S. boulardii group (1.7 versus 2.5 in the non-SB group). There was a significant weight gain in the S. boulardii group post-treatment (300 g) in comparison with the non-SB group (mean loss of 400 g). This study established the positive role of S. boulardii in the management of acute diarrhoeal diseases in children. Moreover, the S. boulardii probiotic was seen to be effective in diarrhoeal diseases in children with dehydration.

Personal protective equipment for surgeons during COVID-19 pandemic: systematic review of availability, usage and rationing.

BACKGROUND: Surgeons need guidance regarding appropriate personal protective equipment (PPE) during the COVID-19 pandemic based on scientific evidence rather than availability. The aim of this article is to inform surgeons of appropriate PPE requirements, and to discuss usage, availability, rationing and future solutions. METHODS: A systematic review was undertaken in accordance with PRISMA guidelines using MEDLINE, Embase and WHO COVID-19 databases. Newspaper and internet article sources were identified using Nexis. The search was complemented by bibliographic secondary linkage. The findings were analysed alongside guidelines from the WHO, Public Health England, the Royal College of Surgeons and specialty associations. RESULTS: Of a total 1329 articles identified, 95 studies met the inclusion criteria. Recommendations made by the WHO regarding the use of PPE in the COVID-19 pandemic have evolved alongside emerging evidence. Medical resources including PPE have been rapidly overwhelmed. There has been a global effort to overcome this by combining the most effective use of existing PPE with innovative strategies to produce more. Practical advice on all aspects of PPE is detailed in this systematic review. CONCLUSION: Although there is a need to balance limited supplies with staff and patient safety, this should not leave surgeons treating patients with inadequate PPE.

Blood biomarkers for memory: toward early detection of risk for Alzheimer disease, pharmacogenomics, and repurposed drugs.

Short-term memory dysfunction is a key early feature of Alzheimer's disease (AD). Psychiatric patients may be at higher risk for memory dysfunction and subsequent AD due to the negative effects of stress and depression on the brain. We carried out longitudinal within-subject studies in male and female psychiatric patients to discover blood gene expression biomarkers that track short term memory as measured by the retention measure in the Hopkins Verbal Learning Test. These biomarkers were subsequently prioritized with a convergent functional genomics approach using previous evidence in the field implicating them in AD. The top candidate biomarkers were then tested in an independent cohort for ability to predict state short-term memory, and trait future positive neuropsychological testing for cognitive impairment. The best overall evidence was for a series of new, as well as some previously known genes, which are now newly shown to have functional evidence in humans as blood biomarkers: RAB7A, NPC2, TGFB1, GAP43, ARSB, PER1, GUSB, and MAPT. Additional top blood biomarkers include GSK3B, PTGS2, APOE, BACE1, PSEN1, and TREM2, well known genes implicated in AD by previous brain and genetic studies, in humans and animal models, which serve as reassuring de facto positive controls for our whole-genome gene expression discovery approach. Biological pathway analyses implicate LXR/RXR activation, neuroinflammation, atherosclerosis signaling, and amyloid processing. Co-directionality of expression data provide new mechanistic insights that are consistent with a compensatory/scarring scenario for brain pathological changes. A majority of top biomarkers also have evidence for involvement in other psychiatric disorders, particularly stress, providing a molecular basis for clinical co-morbidity and for stress as an early precipitant/risk factor. Some of them are modulated by existing drugs, such as antidepressants, lithium and omega-3 fatty acids. Other drug and nutraceutical leads were identified through bioinformatic drug repurposing analyses (such as pioglitazone, levonorgestrel, salsolidine, ginkgolide A, and icariin). Our work contributes to the overall pathophysiological understanding of memory disorders and AD. It also opens new avenues for precision medicine- diagnostics (assement of risk) as well as early treatment (pharmacogenomically informed, personalized, and preventive).

An endophytic Penicillium oxalicum isolated from Citrus limon possesses antioxidant and genoprotective potential.

AIMS: This study aimed at isolating endophytic fungi from Citrus limon (L.) possessing antioxidative and genoprotective potential. METHODS AND RESULTS: Endophytic fungi were screened for antioxidant activity using 2,2-diphenyl,1-picryl hydrazyl radical scavenging assay and maximum activity (79·70%) was exhibited by culture MP1 identified to be Penicillium oxalicum on the basis of morphological and molecular characteristics. The ethyl acetate extract of MP1 was subjected to silica column chromatography followed by LH 20 column chromatography for purification of active metabolites. The partially purified active fraction of P. oxalicum MP1 possessed good antioxidant activity as detected using various assays. It also exhibited a strong DNA damage protection potential on pUC19 plasmid DNA treated with Fenton reagent. On exposure to active fraction of MP1 significant reduction (P < 0·05) in nuclear deformities (like nuclear buds, micronuclei, nuclear ridges and binucleated cells) was observed in human lymphocytes pretreated with a toxic concentration of H2 O2 . In vivo genoprotectivity studies were conducted in fresh water fish Channa punctatus pretreated with a damaging compound 4-nonyl phenol. The active fraction of P. oxalicum MP1 caused a reduction of 94·7 and 66·60% in micronuclei and aberrant cell formation, respectively. A significant reduction (P < 0·05) in tail length and tail DNA parameters was also observed in comet assay. CONCLUSION: The endophytic P. oxalicum isolated in this study has the potential to produce metabolites possessing antioxidant and genoprotective activities. SIGNIFICANCE AND IMPACT OF THE STUDY: The isolated culture can be exploited in the field of therapeutics by virtue of its in vitro and in vivo genoprotective potential.