Occurrence of Existing BCR-ABL Baseline Mutations and Associated Haplotype (NmR) Among CML Patients with Diverse IM Response: A Hospital-based Study from North-East India.

Highly polymorphic BCR-ABL kinase domains have been reported to harbor more than a hundred mutations, and among these, 40-60% have been identified as influencers of imatinib mesylate (IM) resistance. The emergence of IM resistance poses a significant challenge in the management of Chronic Myeloid Leukemia (CML). M351T (rs121913457), E255K (rs387906517), and Y253H (rs121913461) are of particular clinical significance due to their association with high-level imatinib resistance. This study was conducted to investigate the potential role of three significant SNPs in CML progression due to IM resistance. During the study period from 2018 to 2022 (48 months), the blood samples from 219 Reverse transcriptase-PCR-confirmed CML patients following RNA extraction and cDNA preparation were subjected to M351T, E255K, and Y253H mutation analysis by PCR-RFLP. After agarose gel visualization, the samples were subjected to Sanger sequencing to confirm the nucleotide change at the polymorphic loci. The wild-type genotype of all three ABL1 SNPs under investigation exhibits a significant reduction in frequency among IM non-responders compared to the responder group. The CGT haplotype frequency exhibits a significant difference between IM responder (4.2%) and non-responder (11.8%) (p = 0.002 < 0.05). Further, CGC haplotype was observed solely among the imatinib non-responder patients with a frequency percentage of 3.3% (p = 0.004), whereas the said genotype was absent among the responder group. A reduced overall survival rate was observed with deviation from wild-type genotype (M351T loci (T > C) with 1.217 times, E255K (G > A) with 1.485 and Y253H (T > C) with 1.399 times increase in hazard ratio) thereby enhancing mortality risk due to disease progression. The significant increase in the frequency of M351T, E255K, and Y253H loci among the IM non-responder group indicated their probable association with the development of IM resistance among CML patients. A haplotype frequency distribution pattern analysis of ABL1 loci further identified the CGC haplotype as an independent predictor for IM resistance. As such the study highlights the importance of patient characteristics, genotype distribution, and haplotype frequency distribution in predicting the response to IM treatment and clinical outcomes of CML patients.

A randomized controlled trial of spinal morphine with an enhanced recovery pathway and its effect on duration of analgesia after cesarean delivery.

BACKGROUND: Intrathecal morphine is frequently administered after cesarean delivery to provide pain relief lasting up to 24 h. An enhanced recovery after cesarean pathways reduces the amount of postoperative opioids needed. The ideal dose of intrathecal morphine when combined with a pathway has not been determined. METHODS: This was a non-inferiority trial in 72 healthy women undergoing a scheduled cesarean delivery. Women were randomized to receive either 50 mcg, 150 mcg, or 250 mcg of intrathecal morphine during spinal anesthesia, with a standardized postoperative enhanced recovery pathway. The time to request supplemental opioids was the primary outcome. Secondary outcomes included pain scores, side effects, and quality of recovery at 24 h. RESULTS: The duration of analgesia with 50 mcg of morphine (median 24.5 h [IQR: 3.5-34.4]) was inferior to 150 mcg (29.4 h [24.5-72]), and both doses were inferior to 250 mcg (32 h [30.5-72]). Women who received 50 mcg morphine had higher pain scores than the other doses, received more supplemental opioids, and had lower quality recovery scores. The secondary outcomes between 150 mcg and 250 mcg were similar. Side effects were similar among all groups. 63% of women who received 250 mcg remained opioid-free at 72 h, compared to 150 mcg (52%) and 50 mcg (30%). CONCLUSIONS: The duration of analgesia using intrathecal morphine with an enhanced recovery pathway was longer with 250 mcg than with lower doses, and side effects were similar. 50 mcg provided inferior pain relief over 24 h. More than half of our patients avoided additional opioids for up to 72 h with either 150 mcg or 250 mcg doses. REGISTRATION: Clinical trial number NCT05069012.

Epigenetic Modulation of DDIT3 and MGMT Expression Acts Synergistically with Resistance to Imatinib towards CML Disease Progression: A Hospital based Study.

INTRODUCTION: Imatinib Mesylate is an authenticated drug that aids in the treatment of Chronic Myeloid Leukaemia and Philadelphia patients which is recognized as a BCR-ABL tyrosine kinase inhibitor. Indeed, DNA Methylation occupies a key role in the stability of chromosomes. OBJECTIVE: Changes in the methylation status of genes may impart to the advancement of Chronic Myeloid Leukaemia. The present investigation aims to assess the role of expression analysis and methylation status of DDIT3 and MGMT genes in imatinib-resistant and nonresistant cases. METHODS: The Imatinib resistance was screened through RFLP. In this case maximum number of patients were recorded in the chronic phase belonging to the age group 40-59 and the accelerated and blast phase is more common in elderly patients showing the progressive nature of the disease with age. Hemoglobin and platelet count are found to be higher in cases where WBC count was minimal. A history of long-term alcohol consumption is found to be associated with the progression of the disease. RESULTS: The maximum level of expression of the DDIT3 gene was recorded in the chronic phase regardless of upstream (67.8%) and downstream (57.9%) regulation. The highest MGMT expression regulation was also observed in the case of chronic phase in both upstream (78.9%) and downstream (44%) regulation. Further, the MGMT gene showed the highest methylation of 6.6% and DDIT3 showed 3.3% in CML cases. CONCLUSION: In the present study notable depletion of survivality was established in the Imatinib resistance patients manifesting genetic malfunction of BCR-ABL transcripts among the North East Indian inhabitants and advocating for the expansion of the disease.

Transgenic mouse models support a protective role of type I IFN response in SARS-CoV-2 infection-related lung immunopathology and neuroinvasion.

Type I interferon (IFN-I) response is the first line of host defense against invading viruses. In the absence of definite mouse models, the role of IFN-I in SARS-CoV-2 infection remains perplexing. Here, we develop two mouse models, one with constitutively high IFN-I response (hACE2; Irgm1-/-) and the other with dampened IFN-I response (hACE2; Ifnar1-/-), to comprehend the role of IFN-I response. We report that hACE2; Irgm1-/- mice are resistant to lethal SARS-CoV-2 infection. In contrast, a severe SARS-CoV-2 infection along with immune cell infiltration, cytokine storm, and enhanced pathology is observed in the lungs and brain of hACE2; Ifnar1-/- mice. The hACE2; Irgm1-/-Ifnar1-/- double-knockout mice display loss of the protective phenotype observed in hACE2; Irgm1-/- mice, suggesting that heightened IFN-I response accounts for the observed immunity. Taking the results together, we demonstrate that IFN-I protects from lethal SARS-CoV-2 infection, and Irgm1 (IRGM) could be an excellent therapeutic target against SARS-CoV-2.

Evaluation and analysis of novel germline variants in ethanol metabolism pathway genes predisposition to liver disease.

The pathogenetic events of liver disease are seemingly determined by factors linked to ethanol metabolism. The variations in genes encoding enzymes of the ethanol metabolic pathway can influence exposure to alcohol and thus may act as risk factors for the development of liver disease. The present study aimed to understand the genetic aspect of germline variations in ethanol metabolic pathway genes in two major categories of liver disease i.e. ALD and NAFLD. Targeted Re-sequencing was performed in the two disease categories along with healthy control followed by an assessment and evaluation of the variants in a case vs control manner. The pathogenicity prediction was evaluated using SIFT, PolyPhen, PROVEN, LRT, CADD, FATHMM, EIGEN, REVEL and VarSome, while MD simulation of a novel significant variant was performed using the GROMACS 5.1.4 package. The annotation of targeted re-sequencing results revealed 2172 variants in different locations of the genes. Upon recurrent assessment predominantly focusing on exonic missense variants from these genes of the alcohol metabolism pathway, the ALDH1L2 [c.337C > G, p.Pro113Ala, (rs199841702)] variant was found highly significant with comprehensive results. The amino acid substitution tool that predicted protein stability due to a point mutation showed a decrease in stability. The genotyping distribution of the identified novel variant in the population revealed that heterozygosity is significantly distributed in ALD patients. However, the predominant association between the inherited variant and the cause of developing disease needs further robust study.

Gender disparities among students at Jordanian universities during COVID-19.

This study aims to show how the COVID-19 pandemic has affected the online learning process at Jordanian universities from a gender-based perspective. In Jordan, the government has taken various measures to contain the spread of the pandemic in the country by locking down schools and higher education institutions and replacing face-to-face lectures with online learning. To this end, a questionnaire was developed and distributed to students from Jordanian universities to evaluate whether family support, technology use, and stress and depression during online learning are influenced by gender differences. The findings reveal that gender disparities were present and significant. Utilizing the gender structure theory and the intersectional theory as incorporated with branches of feminist theories, the study underscores reasons that are conducive to the persistence of gender disparities mostly in favor of men at Jordanian universities. In the process, we recommend culturally specific remedial approaches that have the potential to reduce this gender gap.

A proteomic perspective and involvement of cytokines in SARS-CoV-2 infection.

Infection with the SARS-CoV-2 virus results in manifestation of several clinical observations from asymptomatic to multi-organ failure. Biochemically, the serious effects are due to what is described as cytokine storm. The initial infection region for COVID-19 is the nasopharyngeal/oropharyngeal region which is the site where samples are taken to examine the presence of virus. We have now carried out detailed proteomic analysis of the nasopharyngeal/oropharyngeal swab samples collected from normal individuals and those tested positive for SARS-CoV-2, in India, during the early days of the pandemic in 2020, by RTPCR, involving high throughput quantitative proteomics analysis. Several proteins like annexins, cytokines and histones were found differentially regulated in the host human cells following SARS-CoV-2 infection. Genes for these proteins were also observed to be differentially regulated when their expression was analyzed. Majority of the cytokine proteins were found to be up regulated in the infected individuals. Cell to Cell signaling interaction, Immune cell trafficking and inflammatory response pathways were found associated with the differentially regulated proteins based on network pathway analysis.

Down regulation of defensin genes during SARS-CoV-2 infection.

Defensins, crucial components of the innate immune system, play a vital role against infection as part of frontline immunity. Association of SARS-CoV-2 infection with defensins has not been investigated. In this study, we have investigated the expression of defensin genes in the buccal cavity from patients with COVID-19 infection along with negative control samples. Nasopharyngeal/oropharyngeal swab samples collected for screening SARS-CoV-2 infection in early 2020 from Hyderabad, India, were analyzed for the expression of major defensin genes by the quantitative real-time reverse transcription polymerase chain reaction, qRT-PCR. Forty SARS-CoV-2 infected positive and 40 negative swab samples were selected for this study. Based on the qRT-PCR analysis involving gene specific primers for defensin genes, 9 defensin genes were found to be expressed in the nasopharyngeal/oropharyngeal cavity. Four defensin genes were found to be significantly down regulated in SARS-CoV-2 infected patients in comparison with the control samples based on differential expression analysis. The significantly down regulated genes were defensin beta 4A/B, 106B, 107B, and 103A. Down regulation of human beta defensin 2, 3, 6 and 7 suggests that antiviral innate immune response provided by defensins may be compromised in SARS-CoV-2 infection resulting in progression of the disease. Correction of the down regulation process through appropriate defensin peptide-based therapy could be an attractive method of treatment. Keywords: host defense; defensins; COVID-19; gene regulation; SARS-CoV-2.

Gramicidin S and melittin: potential anti-viral therapeutic peptides to treat SARS-CoV-2 infection.

The COVID19 pandemic has led to multipronged approaches for treatment of the disease. Since de novo discovery of drugs is time consuming, repurposing of molecules is now considered as one of the alternative strategies to treat COVID19. Antibacterial peptides are being recognized as attractive candidates for repurposing to treat viral infections. In this study, we describe the anti-SARS-CoV-2 activity of the well-studied antibacterial peptides gramicidin S and melittin obtained from Bacillus brevis and bee venom respectively. The EC50 values for gramicidin S and melittin were 1.571 µg and 0.656 µg respectively based on in vitro antiviral assay. Significant decrease in the viral load as compared to the untreated group with no/very less cytotoxicity was observed. Both the peptides treated to the SARS-CoV-2 infected Vero cells showed viral clearance from 12 h onwards with a maximal viral clearance after 24 h post infection. Proteomics analysis indicated that more than 250 proteins were differentially regulated in the gramicidin S and melittin treated SARS-CoV-2 infected Vero cells against control SARS-CoV-2 infected Vero cells after 24 and 48 h post infection. The identified proteins were found to be associated in the metabolic and mRNA processing of the Vero cells post-treatment and infection. Both these peptides could be attractive candidates for repurposing to treat SARS-CoV-2 infection.

COVID-19 Vaccination Acceptance among Healthcare Staff in Sudan, 2021.

Elderly and patients with comorbid conditions have higher risk of infection and complications. Vaccination hesitancy is defined as the refusal of vaccine or the delay in accepting it despite the availability of vaccines and vaccination services. This study was aimed at assessing knowledge, perception, and acceptability of healthcare staff towards different types of COVID-19 vaccination. A multicenter hospital-based descriptive cross-sectional study was implemented to study the knowledge, perception, and acceptability of healthcare staff towards COVID-19 vaccination. Multistage sampling technique was applied. Data were collected through a self-administered questionnaire filled by the participants. 400 participants were studied. 61% of the participants were females, and the most frequent age reported was between 18 and 35 years (67%). A statistically significant association (p = 0.048) was found between knowledge about vaccination and professions. The most common vaccine type known and accepted was AstraZeneca vaccine. On assessing acceptability of COVID-19 vaccination, acceptance rate was high (63.8%) and 22.7% of the participants had already got vaccinated. The rejection rate among our staff was 27.4%. This study was conducted in April, 2021. Majority of our healthcare staff believed that vaccination is the key to combat the pandemic. One of the issues and concerns about vaccination was the safety and the risk of developing acute adverse events (p = 0.001). Encouraging factor for vaccination was the fear of getting infection themselves and their families. The present study revealed the presence of good knowledge and acceptability among medical staff towards COVID-19 vaccinations in Sudan.

Identification of functional tumor necrosis factor-alpha promoter variants associated with Helicobacter pylori infection in the Sudanese population: Computational approach.

BACKGROUND: Helicobacter pylori (H. pylori) is a ubiquitous bacterium that affects nearly half of the world's population with a high morbidity and mortality rate. Polymorphisms within the tumor necrosis factor-alpha (TNF-A) promoter region are considered a possible genetic basis for this disease. AIM: To functionally characterize the genetic variations in the TNF-A 5'-region (-584 to +107) of Sudanese patients infected with H. pylori using in silico tools. METHODS: An observational study was carried out in major public and private hospitals in Khartoum state. A total of 122 gastric biopsies were taken from patients who had been referred for endoscopy. Genomic DNA was extracted. Genotyping of the TNF-A-1030 polymorphism was performed using PCR with confronting two-pair primer to investigate its association with the susceptibility to H. pylori infection in the Sudanese population. Furthermore, Sanger sequencing was applied to detect single nucleotide polymorphisms in the 5'-region (-584 to +107) of TNF-A in H. pylori-infected patients. Bioinformatics analyses were used to predict whether these mutations would alter transcription factor binding sites or composite regulatory elements in this region. A comparative profiling analysis was conducted in 11 species using the ECR browser and multiple-sequence local alignment and visualization search engine to investigate the possible conservation. Also, a multivariate logistic regression model was constructed to estimate odds ratios and their 95% confidence intervals for the association between TNF-A-1030, sociodemographic characteristics and H. pylori infection. Differences were statistically significant if P < 0.05. Statistical analyses were performed using Stata version 11 software. RESULTS: A total of seven single nucleotide polymorphisms were observed in the TNF-A 5'-region of Sudanese patients infected with H. pylori. Only one of them (T > A, -76) was located at the in silico-predicted promoter region (-146 to +10), and it was predicted to alter transcription factor binding sites and composite regulatory elements. A novel mutation (A > T, +27) was detected in the 5' untranslated region, and it could affect the post-transcriptional regulatory pathways. Genotyping of TNF-A-1030 showed a lack of significant association between -1030T and susceptibility to H. pylori and gastric cancer in the studied population (P = 0.1756) and (P = 0.8116), respectively. However, a significant association was detected between T/C genotype and H. pylori infection (39.34% vs 19.67%, odds ratio = 2.69, 95% confidence interval: 1.17-6.17, P = 0.020). Mammalian conservation was observed for the (-146 to +10) region in chimpanzee (99.4%), rhesus monkey (95.6%), cow (91.8%), domesticated dog (89.3%), mouse (84.3%), rat (82.4%) and opossum (78%). CONCLUSION: Computational analysis was a valuable method for understanding TNF-A gene expression patterns and guiding further in vitro and in vivo experimental validation.

Transcriptomic and proteomic insights into patulin mycotoxin-induced cancer-like phenotypes in normal intestinal epithelial cells.

Patulin (PAT) is a natural contaminant of fruits (primarily apples) and their products. Significantly, high levels of contamination have been found in fruit juices all over the world. Several in vitro studies have demonstrated PAT's ability to alter intestinal structure and function. However, in real life, the probability of low dose long-term exposure to PAT to humans is significantly higher through contaminated food items. Thus, in the present study, we have exposed normal intestinal cells to non-toxic levels of PAT for 16 weeks and observed that PAT had the ability to cause cancer-like properties in normal intestinal epithelial cells after chronic exposure. Here, our results showed that chronic exposure to low doses of PAT caused enhanced proliferation, migration and invasion ability, and the capability to grow in soft agar (anchorage independence). Moreover, an in vivo study showed the appearance of colonic aberrant crypt foci (ACFs) in PAT-exposed Wistar rats, which are well, establish markers for early colon cancer. Furthermore, as these neoplastic changes are consequences of alterations at the molecular level, here, we combined next-generation RNA sequencing with liquid chromatography mass spectrometry-based proteomic analysis to investigate the possible underlying mechanisms involved in PAT-induced neoplastic changes.

Understanding the complexity of epimorphic regeneration in zebrafish caudal fin tissue: A transcriptomic and proteomic approach.

The complex epimorphic regeneration of zebrafish caudal fin tissue is hasty and absolute. This study was executed to understand the role of various genes/proteins involved in the regeneration of zebrafish caudal fin tissue through differential transcriptomics and proteomics analysis. Based on our study 1408 genes and 661 proteins were found differentially regulated in the regenerating caudal fin tissue for having at least 1-log fold change. Interleukin, Solute carrier, Protein arginine methyltransferase, Homeobox, Neurotransmitter and several novel genes were found to be associated with regeneration for its differential regulation during the mechanism. Based on the network and pathway analysis the differentially regulated genes and proteins were found allied with activation of cell proliferation, cell viability, cell survival & cell movement and inactivation of organismal death, morbidity, necrosis, death of embryo & cell death. This study has mapped a detailed insight of the genes/proteins expression associated with the epimorphic regeneration more profoundly.

Incidental intra-operative finding of a rare uterine fusion abnormality in a primigravida with breech presentation at term: A case report.

Uterine malformations are often asymptomatic but can be associated with a wide range of reproductive problems. We report a case of uterine fusion defect diagnosed intra-operatively in a 20-year-old primigravida who had elective caesarean section at term on account of breech presentation at term. Intraoperative findings included a cone-shaped uterus with narrowed fundus and the appendages emerging at the fundus and lower uterine segment on the right and left respectively. This is a rare fusion defect and makes a case for review of the existing uterine malformation classification systems, to make it all encompassing.

Chlorophytum alismifolium mitigates microvascular complications of type 2 diabetes mellitus: the involvement of oxidative stress and aldose reductase.

OBJECTIVES: Chlorophytum alismifolium (C. alismifolium) tubers are used in the management of diabetes. This research evaluated the effect of ethylacetate extract of C. alismifolium (EACA) on microvascular complications and the possible association of oxidative stress and aldose reductase in type 2 diabetic rats. METHODS: C. alismifolium tubers were subjected to sequential extraction until ethylacetate extract was obtained using a soxhlet apparatus. The LD50 was determined using the OECD 425 guideline. The animals were placed on high fat diet for 42 days and then induced with hyperglycaemia using 40 mg/kg of streptozotocin. Diabetic neuropathy was evaluated using thermal and mechanical methods. Serum was used for the assessment of oxidative stress markers and biochemical markers of retinopathy and nephropathy. Serum aldose reductase was investigated by utilizing the principle of enzyme-linked immunosorbent assay. RESULTS: The median lethal dose of EACA was assessed to be above 5,000 mg/kg and it caused no mortality. Treatment with EACA significantly reduced the withdrawal times in both thermal and mechanical hyperalgesic methods (p<0.05). EACA also significantly reduced the levels of urea (p<0.001), albumin (p<0.05) and uric acid (p<0.001) in hyperglycaemic rats. EACA significantly decreased the amounts of low density lipoprotein and triglycerides (p<0.001). There was a remarkable elevation in the levels of high density lipoprotein (p<0.05). A significant (p<0.05) increase in the levels of magnesium was observed in the EACA-treated groups. EACA significantly increased catalase (p<0.05) and reduced malondialdehyde levels (p<0.05). The levels of aldose reductase was significantly (p<0.001) reduced by EACA compared to the hyperglycaemic control. CONCLUSIONS: The ethylacetate extract of C. alismifolium has beneficial effects in alleviating microvascular complications of diabetes through the inhibition of oxidative stress and aldose reductase in diabetic rats.

Corrigendum to "Consumers' Perception of Generic Medicines and Evaluation of In Vitro Quality Control Parameters of Locally Manufactured Paracetamol Tablets in Asmara, Eritrea: A Cross-Sectional Study".

[This corrects the article DOI: 10.1155/2021/6642826.].

Consumers' Perception of Generic Medicines and Evaluation of In Vitro Quality Control Parameters of Locally Manufactured Paracetamol Tablets in Asmara, Eritrea: A Cross-Sectional Study.

Generic medicines are clinically equivalent and can be used interchangeably for their intended use. Globally, the usage of generic medicines is highly recommended because of their affordability and accessibility. However, consumers hold a negative perception and attitude of using generic medicine as they consider it poor and having inferior quality compared to branded medicines. This study was conducted to assess the consumers' general view of generic medicines and in vitro evaluation of a locally produced generic medicine, paracetamol. An analytical and cross-sectional study was conducted in three selected hospitals, and in vitro quality control evaluation was done in National Drug Quality Control Laboratory between October 26 and November 21, 2017, in Asmara, Eritrea. A systematic random sampling design was employed, and the data was collected using a questionnaire and a check-list for recording the quality control parameters of paracetamol tablets. A total of 403 respondents were included in the study. The majority of the study participants were females (61.8%). Generally, about half (49.1%) of the respondents choose locally manufactured paracetamol over the imported ones. More than half (68.5%) of the respondents did not believe expensive medicines are of better quality. The main reason consumers prefer the local paracetamol (Azemol) tablet to the imported one was due to their good experience (62.1%). About three-fourths (78.1%) of the consumers also believed that medicines manufactured abroad confer higher quality. At the multivariate level, having educational backgrounds such as elementary (AOR = 4.19, 95% CI: 1.251, 14.035) and junior (AOR = 2.4, 95% CI: 1.146, 5.028) was associated with preferability to local paracetamol as a pain killer over the brand ones. The in vitro test of the local paracetamol met the standard specification for the identification test, weight variation test, pharmacopeial test, friability test, disintegration test, and dissolution test. In conclusion, the majority of the consumers considered local paracetamol as having an inferior quality when compared with brand paracetamol. However, the reality revealed that the local paracetamol was of the same quality as the brand ones. To facilitate widespread use of generic medicines, healthcare professionals should educate consumers on the advantages of these medicines.

Coronavirus Disease 2019 and Kidney Transplantation in Saudi Arabia: Outcomes and Future Opportunities.

BACKGROUND Kidney transplant services all over the world were severely impacted by the coronavirus disease 2019 pandemic. The optimum management of kidney transplant recipients with coronavirus disease 2019 remains uncertain. MATERIAL AND METHODS We conducted a multicenter cohort study of kidney transplant recipients with coronavirus disease 2019 infection in Saudi Arabia. Multivariable Cox regression analysis was used to study predictors of graft and patient outcomes at 28 days after coronavirus disease 2019 diagnosis. RESULTS We included 130 kidney transplant recipients, with a mean age of 48.7(±14.4) years. Fifty-nine patients were managed at home with daily follow-up utilizing a dedicated clinic, while 71 (54.6%) required hospital admission. Acute kidney injury occurred in 35 (26.9%) patients. Secondary infections occurred in 38 (29.2%) patients. SARS-CoV-2 antibodies testing was carried out in 84 patients, of whom 70 tested positive for IgG and/or IgM. Fourteen patients died (10.8%). A multivariable Cox regression analysis showed that age, creatinine at presentation, acute kidney injury, and use of azithromycin were significantly associated with worse patient survival. Graft loss was associated with requiring renal replacement therapy and development of secondary infections. CONCLUSIONS Despite kidney transplant recipients with coronavirus disease 2019 infection having higher rate of hospital admission and mortality compared to the general population, a significant number of them can be managed using a telemedicine clinic. Most kidney transplant patients seem to mount an antibody response following coronavirus disease 2019 infection, and it remains to be seen if they will have a similar response to the incoming vaccines.

Proteome profile of telencephalon associates attenuated neurogenesis with chronic stress induced mood disorder phenotypes in zebrafish model.

Debilitating mental illness like depression and related mood disorders is due to the disruption in circuitry that controls emotion, motivation, and reward, characterized by disparate phenotypes like decrease in socialization, motivation, threshold for threat apprehension, etc. Chronic stress is a major factor in the etiology of these disorders. Here, using a chronic unpredictable stress (CUS) paradigm the characterization of an array of mood disorder phenotypes in adult zebrafish, in comparison to normal control unstressed fish, was achieved using a battery of behavioral assays including novel ones comprising social interaction test, feed approach test, threat response test and novel tank test. For the predictive validity of the model for mood disorders, the mitigative role of a slow (imipramine) and fast (ketamine) acting antidepressant was assessed. The molecular changes associated with CUS-induced mood disorder phenotype was investigated utilizing a high throughput method called isobaric tag for relative and absolute quantification (iTRAQ) in telencephalon, the region critically associated with the processing of emotional information in the fish brain. Out of 222 proteins identified to be significantly altered, 58 were differentially expressed across the stress and antidepressant-treatment groups at more than one fold (in log2) change. Of these proteins, some were implicated in earlier studies on mood disorders such as CABP1, PER2, mTOR, etc. The enrichment of altered proteins by Ingenuity Pathway Analysis (IPA) led us to mTOR and opioid signaling pathways, the top canonical pathways affected in the fish telencephalon. Interestingly, most of the pathways affected converge at the one controlling cell proliferation thus indicating altered neurogenesis, which was validated using immunohistochemistry for cell proliferation markers BrdU, SOX2, and BLBP. The study concludes that molecules that regulate telencephalon neural progenitor cell proliferation or neurogenesis are crucially involved in chronic stress-induced mood disorders by affecting the circuitry that controls emotion and reward.