Is Venous Thromboembolism Prophylaxis Needed in Patients Undergoing Knee Arthroscopy? A Prospective Observational Study.

BACKGROUND: Although rare, deep vein thrombosis is a potentially life-threatening complication of knee arthroscopy. There are scanty literature analysing deep vein thrombosis after arthroscopy in Nepal. This study aimed to identify the prevalence of deep vein thrombosis in patients undergoing knee arthroscopy without chemoprophylaxis postoperatively at 2 weeks and 6 weeks, respectively. The study also aimed to estimate the risk of deep vein thrombosis in these patients by using Caprini Risk Assessment Model. METHODS: This prospective observational study was conducted at AKB center, B and B Hospital, Gwarko, Lalitpur, over a period of 16 months. All patients who underwent arthroscopy knee surgeries fulfilling the inclusion criteria were included in the study. The primary outcome measure was the prevalence of deep vein thrombosis as diagnosed by compression color-coded ultrasonography of the popliteal vein and calf vein at 2 weeks and 6 weeks postoperatively. The secondary outcome measure was the prevalence of deep vein thrombosis in the risk groups according to Caprini Risk Assessment Model. RESULTS: Out of 612 patients who underwent arthroscopic knee surgeries during the study period, 2 patients (0.33%) developed deep vein thrombosis at 6 weeks follow-up as diagnosed with ultrasonography of the popliteal and calf veins. The prevalence rate in high-risk group was 0.33% (1 in 307) and in very high-risk group was 5.88% (1 in 17). CONCLUSIONS: There was a low prevalence of deep vein thrombosis without chemoprophylaxis following knee arthroscopy in our study. There was higher prevalence of deep vein thrombosis in very high-risk group patients, so close monitoring of such patients during follow-up is recommended.

Exploiting the immune system in hepatic tumor targeting: Unleashing the potential of drugs, natural products, and nanoparticles.

Hepatic tumors present a formidable challenge in cancer therapeutics, necessitating the exploration of novel treatment strategies. In recent years, targeting the immune system has attracted interest to augment existing therapeutic efficacy. The immune system in hepatic tumors includes numerous cells with diverse actions. CD8+ T lymphocytes, T helper 1 (Th1) CD4+ T lymphocytes, alternative M1 macrophages, and natural killer (NK) cells provide the antitumor immunity. However, Foxp3+ regulatory CD4+ T cells (Tregs), M2-like tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs) are the key immune inhibitor cells. Tumor stroma can also affect these interactions. Targeting these cells and their secreted molecules is intriguing for eliminating malignant cells. The current review provides a synopsis of the immune system components involved in hepatic tumor expansion and highlights the molecular and cellular pathways that can be targeted for therapeutic intervention. It also overviews the diverse range of drugs, natural products, immunotherapy drugs, and nanoparticles that have been investigated to manipulate immune responses and bolster antitumor immunity. The review also addresses the potential advantages and challenges associated with these approaches.

Using latent class analysis to investigate enduring effects of intersectional social disadvantage on long-term vocational and financial outcomes in the 20-year prospective Chicago Longitudinal Study.

BACKGROUND: Class and social disadvantage have long been identified as significant factors in the etiology and epidemiology of psychosis. Few studies have explicitly examined the impact of intersecting social disadvantage on long-term employment and financial independence. METHODS: We applied latent class analysis (LCA) to 20-year longitudinal data from participants with affective and non-affective psychosis (n = 256) within the Chicago Longitudinal Research. LCA groups were modeled using multiple indicators of pre-morbid disadvantage (parental social class, educational attainment, race, gender, and work and social functioning prior to psychosis onset). The comparative longitudinal work and financial functioning of LCA groups were then examined. RESULTS: We identified three distinct latent classes: one comprised entirely of White participants, with the highest parental class and highest levels of educational attainment; a second predominantly working-class group, with equal numbers of Black and White participants; and a third with the lowest parental social class, lowest levels of education and a mix of Black and White participants. The latter, our highest social disadvantage group experienced significantly poorer employment and financial outcomes at all time-points, controlling for diagnosis, symptoms, and hospitalizations prior to baseline. Contrary to our hypotheses, on most measures, the two less disadvantaged groups did not significantly differ from each other. CONCLUSIONS: Our analyses add to a growing literature on the impact of multiple forms of social disadvantage on long-term functional trajectories, underscoring the importance of proactive attention to sociostructural disadvantage early in treatment, and the development and evaluation of interventions designed to mitigate ongoing social stratification.

Semitendinosus Autograft Transplant for Medial Meniscus.

Treatment of meniscal tears has evolved over the last few decades, and preservation has now become the gold standard of treatment. Advancements in repair technique have extended the indication of repair. However, meniscectomy has to be performed in some situations. In these situations, meniscal allograft transplantation is considered the gold standard. But allografts are not available in every part of the world. Collagen implants and synthetic polymers are also advocated. But again, its limited research, availability, and high cost have restricted its widespread use. Many authors have advocated autograft transplantation, but there are no long-term results, and there is a lack of uniform surgical techniques. There is a technique described for lateral meniscus, but a medial meniscus autograft transplant technique is not very well elaborated. In this report, we aimed to describe a medial meniscus replacement technique using a hamstring autograft.

Disparities in access to appointments for contraceptive services among Black, Hispanic, White, and recently incarcerated women in Alabama, Louisiana, and Mississippi.

OBJECTIVE: To measure differences in access to contraceptive services based on history of incarceration and its intersections with race/ethnicity and insurance status. DATA SOURCES AND STUDY SETTING: Primary data were collected from telephone calls to physician offices in Alabama, Louisiana, and Mississippi in 2021. STUDY DESIGN: We deployed a field experiment. The outcome variables were appointment offers, wait days, and questions asked of the caller. The independent variables were callers' incarceration history, race/ethnicity, and insurance. DATA COLLECTION METHODS: Using standardized scripts, Black, Hispanic, and White female research assistants called actively licensed primary care physicians and Obstetrician/Gynecologists asking for the next available appointment for a contraception prescription. Physicians were randomly selected and randomly assigned to callers. In half of calls, callers mentioned recent incarceration. We also varied insurance status. PRINCIPAL FINDINGS: Appointment offer rates were five percentage points lower (95% CI: -0.10 to 0.01) for patients with a history of incarceration and 11 percentage points lower (95% CI: -0.15 to -0.06) for those with Medicaid. We did not find significant differences in appointment offer rates or wait days when incarceration status was interacted with race or insurance. Schedulers asked questions about insurance significantly more often to recently incarcerated Black patients and recently incarcerated patients who had Medicaid. CONCLUSIONS: Women with a history of incarceration have less access to medical appointments; this access did not vary by race or insurance status among women with a history of incarceration.

Ethanol- and PARP-Mediated Regulation of Ribosome-Associated Long Non-Coding RNA (lncRNA) in Pyramidal Neurons.

Although, by definition, long noncoding RNAs (lncRNAs) are not translated, they are sometimes associated with ribosomes. In fact, some estimates suggest the existence of more than 50 K lncRNA molecules that could encode for small peptides. We examined the effects of an ethanol and Poly-ADP Ribose Polymerase (PARP) inhibitor (ABT-888) on ribosome-bound lncRNAs. Mice were administered via intraperitoneal injection (i.p.) either normal saline (CTL) or ethanol (EtOH) twice a day for four consecutive days. On the fourth day, a sub-group of mice administered with ethanol also received ABT-888 (EtOH+ABT). Ribosome-bound lncRNAs in CaMKIIα-expressing pyramidal neurons were measured using the Translating Ribosome Affinity Purification (TRAP) technique. Our findings show that EtOH altered the attachment of 107 lncRNA transcripts, while EtOH+ABT altered 60 lncRNAs. Among these 60 lncRNAs, 49 were altered by both conditions, while EtOH+ABT uniquely altered the attachment of 11 lncRNA transcripts that EtOH alone did not affect. To validate these results, we selected eight lncRNAs (Mir124-2hg, 5430416N02Rik, Snhg17, Snhg12, Snhg1, Mir9-3hg, Gas5, and 1110038B12Rik) for qRT-PCR analysis. The current study demonstrates that ethanol-induced changes in lncRNA attachment to ribosomes can be mitigated by the addition of the PARP inhibitor ABT-888.

Why Pharmacovigilance of Non-steroidal Anti-inflammatory Drugs is Important in India?

BACKGROUND: Non-steroidal Anti-Inflammatory Drugs (NSAIDs) are among the drugs that are most regularly administered to manage inflammation and pain. Over-the-Counter (OTC) NSAIDs are widely accessible, particularly in developing countries like India. This casual approach to using NSAIDs may operate as a magnet for NSAID-related adverse drug reactions (ADRs) among patients. OBJECTIVES: As patients in India are less informed about the appropriate use of NSAIDs and consumption patttern, adverse drug reactions, and the importance of reporting ADRs, the current study's objective is to promote patient safety by using pharmacovigilance as a tool to educate patients. METHODS: A targeted literature methodology was utilized to gather the data pertaining to NSAIDs, their ADRs and their pharmacovigilance. Different scientific databases, such as Science Direct, PubMed, Wiley Online Library, Springer, and Google Scholar, along with authentic textbooks, were explored as reference literature. RESULTS: In general, NSAIDs consumption pattern depends upon the different age groups. Around 1.6 billion tablets of NSAIDs are consumed in India for ailments, such as headaches, arthritis, menstrual cramps, osteoarthritis, back pain, rheumatoid arthritis, gout, osteoporosis, tendinitis, cancer pain and chronic pain. Common ADRs of NSAIDs include nausea, vomiting, headache, gastritis, abdominal pain, and diarrhoea. Also, they can cause renal damage and cardiovascular problems if not consumed in a dose-dependent manner. However, Diclofenac and Ibuprofen have both been linked to depression and dementia. There have been reports of aplastic anaemia, agranulocytosis linked to phenylbutazone, Stevens-Johnson, and Lyell's syndrome linked to isoxicam and piroxicam, as well as the vulnerability of new-borns to Reye's syndrome after aspirin use. Lack of awareness, time constraints and unpredictability, poor training in ADRs identification, etc., are some of the reasons for the under-reporting of ADR of NSAIDs in India. CONCLUSION: In order to rationally prescribe NSAIDs, it is essential to be aware of probable ADR's and establish prescription guidelines. Prescribers' behaviour can be changed toward excellent prescribing practices by conducting routine prescription assessments dealing with NSAIDs and providing feedback. In the near future, it will be critical to strengthen ADR data management and expand the reach of pharmacovigilance programs, ADR monitoring centers, and healthcare professionals' especially pharmacists' training in rural locations.

"Make and Use" All Suture Anchor-A Cost-Effective Method of Making an All-Suture Anchor.

All-suture anchors (ASA) are newer anchors that anchor soft tissues to the bone. It has several biomechanical and clinical advantages; however, the high cost of this anchor limits its use in low socioeconomic countries. The cost of the anchor dramatically increases the cost of surgery; hence, acceptance of surgery is also affected if patients have to pay their expenditure from their pocket. We have designed a simple, cost-effective method of making an ASA, which can be made instantly and used during surgery; hence, the name "make-and-use anchor." To make this anchor, few high-strength sutures are required. Over the suture, a sleeve of suture was created using an Ethibond. This sleeve will create a "ball" after deployment under the cortical bone, which provides anchorage to the sutures serving as an anchor. This anchor can be deployed both in the pull-in and push-in methods. This technical note aims to share the technique of making this cost-effective anchor, which is made instantly using locally available suture materials and can be used in various surgeries requiring anchors.

Characteristics of Patients With Second Primary Lung Cancer Following Breast Cancer: A Retrospective Descriptive Study.

BACKGROUND: Breast cancer (BC) is the most common noncutaneous malignancy in women and survivors are at an increased risk for secondary malignancy with lung cancer (LC) being the most common. There are few studies that have explored the clinicopathological specifics of LC in BC survivors. METHODS: In this single-institution, retrospective study, we identified BC survivors who subsequently developed LC, examined their breast and LC clinical and pathological characteristics and compared them to the general BC and LC population as published in the literature. RESULTS: In our study, we found the following associations that could be meaningful: an association between receiving radiation (RT) and LC (including a statistically significant P = .03 chance of ipsilateral LC after BC treatment with RT), a higher incidence and amount of smoking and LC, high BRCA positivity (78.9%) in the few patients who had germline testing, and a higher incidence of EGFR mutations in NSCLC after BC (60.9%) as well as an earlier stage of NSCLC disease. CONCLUSION: Treatments such as RT, genetic factors such as BRCA mutations, and tobacco use may increase the risk of developing LC amongst BC survivors. Exploring this further can potentially lead to better risk stratification through modified low-dose CT chest screening protocols to catch LCs earlier and ultimately improve outcomes. Past studies have shown that BC survivors who are subsequently diagnosed with NSCLC may have improved OS compared with primary NSCLC and our study showed a high incidence of EGFR mutated NSCLC, which also suggest both improved prognosis and a different molecular profile of NSCLC, which warrants further investigation. Lastly, BC survivors who subsequently are diagnosed with NSCLC had earlier stage disease in our study, perhaps a result of surveillance, highlighting the importance of close monitoring of BC survivors.

Positive Pivot Shift Test among Patients with Displaced Anterior Tibial Spine Fractures Undergoing Arthroscopic Fixation in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Understanding of displaced anterior tibial spine fractures has evolved over the years and is now considered to be anterior cruciate ligament avulsion injuries rather than intra-articular fractures. However, there are very few studies available evaluating the presence or absence of a pivot shift test, which is specific in diagnosing anterior cruciate ligament insufficiency, in patients with anterior tibial spine fractures. This study aimed to find out the prevalence of the positive pivot shift test among patients with displaced anterior tibial spine fractures undergoing arthroscopic fixation in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among patients presented with displaced anterior tibial spine fractures undergoing arthroscopic fixation. The data were collected between 1 January 2020 and 30 May 2022. Ethical approval was obtained from the Institutional Review Committee (Reference number: IRC_2019_11_09_1). All patients who presented with displaced anterior tibial spine fractures undergoing arthroscopic fixation were included in the study and those who did not provide consent were excluded. The pivot test was performed under anaesthesia. Point estimate and 90% Confidence Interval were calculated. Results: Among 48 patients, pivot shift was positive in 36 (75%) (64.75-85.25, 90% Confidence Interval). The mean age of the participants was 28.97±11.16 years, 21 (58.33%) were males and 15 (41.66%) were females. Conclusions: The prevalence of positive pivot shift test under anaesthesia in patients with displaced anterior tibial spine fractures undergoing arthroscopic fixation was higher than other studies done in similar settings. Keywords: anterior cruciate ligament; arthroscopy; knee fractures; physical examination.

Disparities in Access to Primary Care Appointments Among Asian American Subgroups, and the Impact of Concordance.

While Asian Americans experience disparate access to health services, little is known about the extent to which providers discriminate against Asian American patients. Further, research on Asian American health disparities tends to group Asian American ethnicities together, overlooking potential within-group differences. We deployed a field experiment to assess whether Asian American ethnic sub-groups experience discrimination in appointment scheduling. We further explored the impact of racial concordance between Asian patients and physicians. Overall, we did not detect significant differences in appointment offer rates between White and Asian American patients. However, we found that Asian Americans experienced longer wait times driven primarily by the treatment of patients of Chinese and Korean descent. Physician offices, surprisingly, offered concordant Asian patients appointments at significantly lower rates. The disparities Asian Americans experience relative to White Americans through longer waits for primary care appointments are not consistent across sub-groups. Increased attention to the unique experiences of people of Asian descent in accessing health services is warranted.

Effects of alcohol and PARP inhibition on RNA ribosomal engagement in cortical excitatory neurons.

We report on the effects of ethanol (EtOH) and Poly (ADP-ribose) polymerase (PARP) inhibition on RNA ribosomal engagement, as a proxy for protein translation, in prefrontal cortical (PFC) pyramidal neurons. We hypothesized that EtOH induces a shift in RNA ribosomal-engagement (RE) in PFC pyramidal neurons, and that many of these changes can be reversed using a PARP inhibitor. We utilized the translating ribosome affinity purification (TRAP) technique to isolate cell type-specific RNA. Transgenic mice with EGFP-tagged Rpl10a ribosomal protein expressed only in CaMKIIα-expressing pyramidal cells were administered EtOH or normal saline (CTL) i.p. twice a day, for four consecutive days. On the fourth day, a sub-group of mice that received EtOH in the previous three days received a combination of EtOH and the PARP inhibitor ABT-888 (EtOH + ABT-888). PFC tissue was processed to isolate both, CaMKIIα pyramidal cell-type specific ribosomal-engaged RNA (TRAP-RNA), as well as genomically expressed total-RNA from whole tissue, which were submitted for RNA-seq. We observed EtOH effects on RE transcripts in pyramidal cells and furthermore treatment with a PARP inhibitor "reversed" these effects. The PARP inhibitor ABT-888 reversed 82% of the EtOH-induced changes in RE (TRAP-RNA), and similarly 83% in the total-RNA transcripts. We identified Insulin Receptor Signaling as highly enriched in the ethanol-regulated and PARP-reverted RE pool and validated five participating genes from this pathway. To our knowledge, this is the first description of the effects of EtOH on excitatory neuron RE transcripts from total-RNA and provides insights into PARP-mediated regulation of EtOH effects.

Identification of genomic regions associated with cereal cyst nematode (Heterodera avenae Woll.) resistance in spring and winter wheat.

Cereal cyst nematode (CCN) is a major threat to cereal crop production globally including wheat (Triticum aestivum L.). In the present study, single-locus and multi-locus models of Genome-Wide Association Study (GWAS) were used to find marker trait associations (MTAs) against CCN (Heterodera avenae) in wheat. In total, 180 wheat accessions (100 spring and 80 winter types) were screened against H. avenae in two independent years (2018/2019 "Environment 1" and 2019/2020 "Environment 2") under controlled conditions. A set of 12,908 SNP markers were used to perform the GWAS. Altogether, 11 significant MTAs, with threshold value of -log10 (p-values) ≥ 3.0, were detected using 180 wheat accessions under combined environment (CE). A novel MTA (wsnp_Ex_c53387_56641291) was detected under all environments (E1, E2 and CE) and considered to be stable MTA. Among the identified 11 MTAs, eight were novel and three were co-localized with previously known genes/QTLs/MTAs. In total, 13 putative candidate genes showing differential expression in roots, and known to be involved in plant defense mechanisms were reported. These MTAs could help us to identify resistance alleles from new sources, which could be used to identify wheat varieties with enhanced CCN resistance.

GWAS scans of cereal cyst nematode (Heterodera avenae) resistance in Indian wheat germplasm.

Significant yield losses in major cereal-growing regions around the world have been linked to cereal cyst nematodes (Heterodera spp.). Identifying and deploying natural sources of resistance is of utmost importance due to increasing concerns associated with chemical methods over the years. We screened 141 diverse wheat genotypes collected from pan-Indian wheat cultivation states for nematode resistance over two years, alongside two resistant (Raj MR1, W7984 (M6)) and two susceptible (WH147, Opata M85) checks. We performed genome-wide association analysis using four single-locus models (GLM, MLM, CMLM, and ECMLM) and three multi-locus models (Blink, FarmCPU, and MLMM). Single locus models identified nine significant MTAs (-log10 (P) > 3.0) on chromosomes 2A, 3B, and 4B whereas, multi-locus models identified 11 significant MTAs on chromosomes 1B, 2A, 3B, 3D and 4B. Single and multi-locus models identified nine common significant MTAs. Candidate gene analysis identified 33 genes like F-box-like domain superfamily, Cytochrome P450 superfamily, Leucine-rich repeat, cysteine-containing subtype Zinc finger RING/FYVE/PHD-type, etc., having a putative role in disease resistance. Such genetic resources can help to reduce the impact of this disease on wheat production. Additionally, these results can be used to design new strategies for controlling the spread of H. avenae, such as the development of resistant varieties or the use of resistant cultivars. Finally, the obtained results can also be used to identify new sources of resistance to this pathogen and develop novel control methods.

SWEET11b transports both sugar and cytokinin in developing barley grains.

Even though Sugars Will Eventually be Exported Transporters (SWEETs) have been found in every sequenced plant genome, a comprehensive understanding of their functionality is lacking. In this study, we focused on the SWEET family of barley (Hordeum vulgare). A radiotracer assay revealed that expressing HvSWEET11b in African clawed frog (Xenopus laevis) oocytes facilitated the bidirectional transfer of not only just sucrose and glucose, but also cytokinin. Barley plants harboring a loss-of-function mutation of HvSWEET11b could not set viable grains, while the distribution of sucrose and cytokinin was altered in developing grains of plants in which the gene was knocked down. Sucrose allocation within transgenic grains was disrupted, which is consistent with the changes to the cytokinin gradient across grains, as visualized by magnetic resonance imaging and Fourier transform infrared spectroscopy microimaging. Decreasing HvSWEET11b expression in developing grains reduced overall grain size, sink strength, the number of endopolyploid endosperm cells, and the contents of starch and protein. The control exerted by HvSWEET11b over sugars and cytokinins likely predetermines their synergy, resulting in adjustments to the grain's biochemistry and transcriptome.

A Comprehensive Review on COVID-19: Emphasis on Current Vaccination and Nanotechnology Aspects.

COVID-19, caused by the SARS-CoV-2 virus, has been expanding. SARS-CoV caused an outbreak in early 2000, while MERS-CoV had a similar expansion of illness in early 2010. Nanotechnology has been employed for nasal delivery of drugs to conquer a variety of challenges that emerge during mucosal administration. The role of nanotechnology is highly relevant to counter this "virus" nano enemy. This technique directs the safe and effective distribution of accessible therapeutic choices using tailored nanocarriers, as well as the interruption of virion assembly, by preventing the early contact of viral spike glycoprotein with host cell surface receptors. This study summarises what we know about earlier SARS-CoV and MERS-CoV illnesses, with the goal of better understanding the recently discovered SARS-CoV-2 virus. It also explains the progress made so far in creating COVID-19 vaccines/ treatments using existing methods. Furthermore, we studied nanotechnology- based vaccinations and therapeutic medications that are now undergoing clinical trials and other alternatives.

5-Fluorouracil-induced leukoencephalopathy.

ABSTRACT: The incidence of 5-Fluorouracil (5FU)- induced leukoencephalopathy is <5% among the patients treated with this agent. It may present with disorientation, confusion, agitation, seizure, and coma. It should be suspected when patients present with any of these symptoms during or immediately after 5FU chemotherapy. Early detection of drug-induced leukoencephalopathy is important as the clinical symptoms can be reversed by early discontinuation of the drug. Therefore, clinicians should be aware of the possibility of this adverse neurologic effect of 5FU. We describe the case of a 35-year-old female with carcinoma esophagus with 5FU-induced leukoencephalopathy.

Ramp Tear among Patients Undergoing Arthroscopic Anterior Cruciate Ligament Reconstruction in a Tertiary Care Centre.

Introduction: Ramp tear is a specific injury that affects the posterior horn of the medial meniscus and its meniscosynovial or meniscocapsular attachments. The actual prevalence of ramp lesion is unknown due to the high probability of misdiagnosis or underdiagnosis caused by the low sensitivity of imaging modalities and poor visualization during arthroscopy. This study aimed to find out the prevalence of ramp tear among patients undergoing arthroscopic anterior cruciate ligament reconstruction in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among patients undergoing arthroscopic anterior cruciate ligament reconstruction after getting ethical approval from the Institutional Review Committee. Data from 1 March 2019 to 31 December 2022 was collected between 1 May 2023 to 30 May 2023 from medical records. The study included all patients who underwent arthroscopic anterior cruciate ligament reconstruction. Patients with a previous history of medial meniscus injury or repair and undergoing revision anterior cruciate ligament reconstruction were excluded. Convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Out of 412 patients who underwent arthroscopic anterior cruciate ligament reconstruction, 53 (12.86%) (9.63-16.09, 95% Confidence Interval) had ramp tears. The mean age of patients with ramp tears was 28.64±7.57 years. Among 53 patients, 42 (79.24%) were male and 11 (20.75%) were female. Conclusions: The prevalence of ramp tears in patients undergoing arthroscopic anterior cruciate ligament reconstruction in a tertiary care centre was found to be lower than other studies done in other international studies. Keywords: anterior cruciate ligament injuries; anterior cruciate ligament reconstruction; arthroscopy.

Differential H3K9me2 heterochromatin levels and concordant mRNA expression in postmortem brain tissue of individuals with schizophrenia, bipolar, and controls.

The existence of repressive and durable chromatin assemblies along gene promoters or networks, especially in the brain, is of theoretical and therapeutic relevance in a subset of individuals diagnosed with schizophrenia who experience a chronic, persistent, and treatment-resistant trajectory. We used chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) to generate an epigenomic map that includes differential sites occupied by di-methylated lysine 9 of histone 3 (H3K9me2), a repressive modification that is yet unexplored in human postmortem brain tissue. We have discovered over 150 significantly differential promoter sites in the postmortem prefrontal cortex tissue of individuals diagnosed with schizophrenia (n = 15) when compared to controls (n = 15). Potentially dysregulated gene categories include postsynaptic proteins, processing enzymes (for proproteins, lipids, and oxidative stress), cadherin family genes, the complement system, and peptide hormones. Ten genes with significantly increased or decreased H3K9me2 promoter occupation were selected through statistical analysis, function, or previous GWAS association, and Quantitative RT-PCR (qRT-PCR) was performed on an extended sample of postmortem brain tissue, adding an additional 17 controls, 7 individuals with schizophrenia, and 19 individuals with bipolar samples (n = 32 control, 22 schizophrenia, 19 bipolar). This approach revealed that mRNA expression levels correlated with chromatin modification levels in eight of 10 selected genes, and mRNA expression in the total sample could be predicted by the occupancy of H3K9me2. Utilization of this method and replication in a larger sample open a pathway to durable and restrictive epigenomic assemblies whose accumulation across the lifespan of individuals diagnosed with schizophrenia may explain treatment resistance, and advance therapeutic options.

Functional Outcome and Quality of Life Following Total Hip Replacement Surgery.

BACKGROUND: Total hip replacement surgeries are popular treatment modality for degenerative and traumatic hip condition which provides high degree of patient satisfaction and are mainly described in literatures among patient residing in western world. However activities of daily living of people in hilly area of developing country are different from western country but there are paucity of literature describing outcome of these people. METHODS: Retrospective observational study was carried out in a university teaching hospital in Nepal. Patients residing in hilly region of Nepal who underwent total joint replacement of hip joint between 2017 to 2019 AD were included in the study. The functional outcome was measured using Harris Hip Score and the quality of life was assessed using SF-12 Patient Questionnaire preoperatively , 3 months , 6 months and 1 year follow up. RESULTS: More than two-thirds of the patients were male. The mean age group of patients was 45.71 years. The most common indication of surgery was avascular necrosis of femoral head. There was significant improvement in Harris Hip Score upto 6 months postoperatively. Quality of life including both physical and mental component of SF-12 improved significantly upto 6 months. CONCLUSIONS: Total hip replacement surgery significantly improves functional outcome and quality of life of patients residing in hilly region of Nepal. However, long term follow up still is request to find out effect of joint replacement in activities of daily living in these group of people.