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Polymorphic variability in the enzymes involved in biotransformation of tobacco-related pro-carcinogens plays an important role in modulating oral cancer susceptibility. CYP1A1*2 A, CYP1A1*2 C, GSTM1 and GSTT1 polymorphisms were determined in 122 oral carcinoma cases and 127 controls from Gujarat, West India using PCR-based methods. The results revealed that the polymorphic variants of CYP1A1 gene did not show association towards oral cancer risk. The GSTM1 and GSTT1 null genotypes were found to be over-represented in patients than controls, suggesting a moderate increase in risk of oral cancer. The oral cancer risk was significantly increased in the patients having either alone or concurrent deletion of GSTM1 and GSTT1. The results also suggested significant association between tobacco habits, especially chewing, variant genotypes of CYP1 A1, GSTM1 and GSTT1 and oral cancer risk. Our data have provided evidence that GST polymorphism modified the susceptibility to oral cancer and individuals with variant genotypes of the three genes with tobacco habits are at significant risk of developing oral cancer. [ABSTRACT FROM AUTHOR]

Objective: The evidence on the association between fish consumption, dietary long-chain n-3 fatty acids, and risk of type 2 diabetes is inconsistent. We therefore performed a systematic review and meta-analysis of the available prospective evidence.Research Design and Methods: Studies were identified by searching the PubMed and EMBASE databases through 15 December 2011 and by reviewing the reference lists of retrieved articles. Prospective studies were included if they reported relative risk (RR) estimates with 95% CIs for the association between fish consumption and/or dietary long-chain n-3 fatty acids and incidence of type 2 diabetes. A dose-response random-effects model was used to combine study-specific RRs. Potential sources of heterogeneity were explored by prespecified stratifications.Results: Sixteen studies involving 527,441 participants and 24,082 diabetes cases were included. Considerable statistical heterogeneity in the overall summary estimates was partly explained by geographical differences. For each serving per week increment in fish consumption, the RRs (95% CIs) of type 2 diabetes were 1.05 (1.02-1.09), 1.03 (0.96-1.11), and 0.98 (0.97-1.00) combining U.S., European, and Asian/Australian studies, respectively. For each 0.30 g per day increment in long-chain n-3 fatty acids, the corresponding summary estimates were 1.17 (1.09-1.26), 0.98 (0.70-1.37), and 0.90 (0.82-0.98).Conclusions: Results from this meta-analysis indicate differences between geographical regions in observed associations of fish consumption and dietary intake of long-chain n-3 fatty acids with risk of type 2 diabetes. In consideration of the heterogeneous results, the relationship warrants further investigation. Meanwhile, current public health recommendations on fish consumption should be upheld unchanged. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between fish and seafood intake and new-onset type 2 diabetes.Research Design and Methods: This was a population-based prospective cohort (European Prospective Investigation of Cancer [EPIC]-Norfolk) study of men and women aged 40-79 years at baseline (1993-1997). Habitual fish and seafood intake (white fish, oily fish, fried fish, and shellfish) was assessed using a semiquantitative food frequency questionnaire and categorized as less than one or one or more portions/week. During a median (interquartile range) follow-up of 10.2 (9.1-11.2) years, there were 725 incident diabetes cases among 21,984 eligible participants.Results: Higher total fish intake (one or more versus less than one portions/week) was associated with a significantly lower risk of diabetes (odds ratio [OR] 0.75 [95% CI 0.58-0.96]), in analyses adjusted for age, sex, family history of diabetes, education, smoking, physical activity, dietary factors (total energy intake, alcohol intake, and plasma vitamin C) and obesity (BMI and waist circumference). White fish and oily fish intakes were similarly inversely associated with diabetes risk, but the associations were not significant after adjustment for dietary factors (oily fish) or obesity (white fish). Fried fish was not significantly associated with diabetes risk. Consuming one or more portions/week of shellfish was associated with an increased risk of diabetes (OR 1.36 [1.02-1.81]) in adjusted analyses.Conclusions: Total, white, and oily fish consumption may be beneficial for reducing risk of diabetes, reinforcing the public health message to consume fish regularly. Greater shellfish intake seems to be associated with an increased risk of diabetes, warranting further investigation into cooking methods and mechanisms. [ABSTRACT FROM AUTHOR]

Inactivating mutations in SMARCB1 confer an oncogenic dependency on EZH2 in atypical teratoid rhabdoid tumors (ATRTs), but the underlying mechanism has not been fully elucidated. We found that the sensitivity of ATRTs to EZH2 inhibition (EZH2i) is associated with the viral mimicry response. Unlike other epigenetic therapies targeting transcriptional repressors, EZH2i-induced viral mimicry is not triggered by cryptic transcription of endogenous retroelements, but rather mediated by increased expression of genes enriched for intronic inverted-repeat Alu (IR-Alu) elements. Interestingly, interferon-stimulated genes (ISGs) are highly enriched for dsRNA-forming intronic IR-Alu elements, suggesting a feedforward loop whereby these activated ISGs may reinforce dsRNA formation and viral mimicry. EZH2i also upregulates the expression of full-length LINE-1s, leading to genomic instability and cGAS/STING signaling in a process dependent on reverse transcriptase activity. Co-depletion of dsRNA sensing and cytoplasmic DNA sensing completely rescues the viral mimicry response to EZH2i in SMARCB1-deficient tumors., (© 2024. The Author(s).)

Plasma cell invasion of the kidney in plasma cell dyscrasia is rare. We are reporting a case of plasma cell infiltration in the kidney presenting as rapidly progressing renal failure. The patient presented with generalized weakness, anemia, and advanced renal failure. The kidney biopsy revealed multifocal atypical CD138-positive plasma cell-rich interstitial inflammation and severe acute tubular injury. In the present situation of clinically unexplained renal failure with suspicion of plasma cell dyscrasia, a kidney biopsy proved to be key to the diagnosis. Hence, malignant plasma cell infiltration in the kidney could indicate underlying plasma cell dyscrasia and may serve as a future myeloma defining event (MDE)., (© Journal of the Association of Physicians of India 2024.)

Background: Cardiac ochronosis, presenting as a rare manifestation of alkaptonuria, an autosomal recessive disorder, is characterised by black pigmentation of calcified cardiac valves and atherosclerotic plaques. We report an intraoperative dilemma on the discovery on the black aortic valve in a case of an old lady with degenerative calcific aortic stenosis., Case Presentation: A 60-year-old lady was electively admitted for valve replacement with a bioprosthetic valve for severe aortic stenosis. She was symptomatic with complaints of headache and giddiness and had a pressure gradient of 113/17mmhg across the aortic valve. Intraoperatively, she was found to have cardiac ochronosis on the discovery of pigmented aortic intima extending to the valve leaflets and underwent valve replacement with a mechanical prosthetic valve. She was post-operatively evaluated for the same and diagnosed with alkaptonuria. Though the surgery went uneventful and the patient was discharged without any complication, she was advised to be on regular follow-up to assess valve gradients, paravalvular leaks and to monitor the disease progression., Conclusion: The presented case sheds light on the rare cardiac manifestation of alkaptonuria. In the absence of definitive pre-operative diagnosis, intraoperative findings played a pivotal role in guiding the surgical approach and choice of prosthetic valve. The decision to use a mechanical valve was influenced by the potential risks associated with bioprosthetic valves in the setting of ochronosis. Ongoing follow-up and monitoring are essential to assess the durability of the chosen prosthetic valve and to manage any long-term consequences of the underlying metabolic condition., (© 2024. The Author(s).)

Myoglobin cast nephropathy is a sequel of rhabdomyolysis, and is characterized by the release of free myoglobin in the circulation, direct proximal convoluted tubule injury, and obstruction by myoglobin cast in distal tubules. We report an interesting case of myoglobin cast nephropathy in a patient who was on neuroleptic drugs and who presented with neuroleptic malignant syndrome and acute kidney injury., Competing Interests: There are no conflicts of interest., (© 2024 Indian Journal of Nephrology | Published by Scientific Scholar.)

Background: The implementation of the fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet for irritable bowel syndrome (IBS) can be effectively delivered by dietitians in group settings. The initial FODMAP restriction phase is recommended to be followed for 4 weeks; however, limited efficacy data exist for 4-week FODMAP restriction in group education clinical practice., Methods: We aimed to compare 4-week versus 8-week FODMAP group treatment pathways on clinical outcomes using a prospective service evaluation design of IBS patients attending FODMAP restriction (baseline) and reintroduction (follow-up) group sessions (between 2015 and 2019). Clinical outcomes included global symptom question (GSQ) measuring satisfactory relief, gastrointestinal symptom rating scale (GSRS), stool frequency (SF), stool consistency using Bristol stool form scale (BSFS), diet acceptability, patient satisfaction with group sessions and dietary adherence. Logistic regression was used to test for differences in treatment effects when clinical outcomes were compared between groups., Results: Patients (n = 284) included were aged 18 to 86 years (mean ± SD [standard deviation], 44.6 ± 15.5), 80% female, and were split into 4-week (41%, 117/284) versus 8-week (59%, 167/284) pathways with no differences in baseline characteristics. Mean ± SD time gap between baseline and follow-up was 4.6 ± 0.9 weeks in the 4-week pathway and 9.6 ± 3.3 weeks in the 8-week pathway. When groups were compared at follow-up, no statistical differences were observed in any measures (GSQ, GSRS, SF, BSFS, dietary adherence, diet acceptability and patient satisfaction)., Conclusion: A 4-week dietitian-led group FODMAP treatment pathway is as clinically effective and maintains patient acceptability when compared to 8-weeks and should be considered as part of routine clinical practice., (© 2024 The British Dietetic Association Ltd.)

Purpose: To compare visual outcomes, ocular complications and therapies for patients with scleritis-associated intraocular inflammation (SAI) and patients with isolated scleritis (IS)., Results: A total of 52 patients (36 with SAI and 16 with IS) were reviewed. Mean age (standard deviation) at presentation was 48.4 years old (± 15.4) in the SAI group and 53 years old (± 17.1) in the IS group (p = .37). Visual acuity was worse at presentation and last visit for patients with SAI compared to IS (p = .04). Patients in the SAI group developed greater posterior segment complications than in the IS group (p = .002)., Conclusions: Scleritis with intraocular inflammation was associated with a higher rate of visual morbidity compared to isolated scleritis. More aggressive management strategies may be needed for patients who present with scleritis associated with inflammation.

Background Chronic kidney disease (CKD) is a major public health concern globally, often co-occurring with type 2 diabetes (T2D), hypertension (HTN), and cardiovascular disorders (CVD), which complicate its management and exacerbate outcomes. This study aims to investigate the epidemiological and clinical characteristics of CKD in Bihar, a region often underrepresented in national data. Methods This cross-sectional observational study was conducted at the Department of Nephrology, Indira Gandhi Institute of Medical Sciences (IGIMS) in Patna, Bihar, India. A total of 2,534 adult patients of both sexes who consented to participate were included. We collected demographic and clinical data, calculated the estimated glomerular filtration rate using the CKD-Epidemiology (CKD-EPI) Collaboration creatinine equation, and classified CKD stages. Statistical analyses were performed using IBM SPSS Statistics for Windows, version 29.0.2.0 (IBM Corp., Armonk, NY). Result The majority of the study population was male (66.5%), with a significant number residing in rural areas (76.8%). The prevalent causes of CKD included HTN (41.2%), chronic tubulointerstitial nephritis (31.8%), and T2D (23.2%). Approximately one-third of patients were in the early stages (Stages 1 and 2) of CKD. A high prevalence of anemia was noted across all stages, increasing significantly with glomerular filtration rate (GFR) reduction. Treatment analysis showed suboptimal use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) and other standard treatments like diuretics and statins, especially among T2D patients. Conclusion Chronic kidney disease in Bihar affects predominantly young males and is associated with significant rural prevalence and comorbidities like T2D, HTN, and CVD. Our results highlight the need for improved management practices, especially in the use of ACEi/ARBs and erythropoiesis-stimulating agents, to slow GFR reduction. Further multicentric, community-based studies are recommended to provide a more comprehensive understanding of CKD in Bihar., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional ethics committee, Indira Gandhi Institute of Medical Sciences, Patna issued approval 178/IEC/IGIMS/2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Singh et al.)

Pigment-induced acute kidney injury (AKI) is an important and preventable complication of rhabdomyolysis or hemolysis. It is characterized by the release of free heme pigment (myoglobin or hemoglobin) in the circulation, leading to direct injury of the proximal tubule and distal tubule obstruction by pigment cast. We are reporting eight cases of pigment-induced AKI, including six cases of myoglobin cast nephropathy and two cases of hemoglobin cast nephropathy. The causes of rhabdomyolysis were strenuous exercise, infection/febrile illness, and drug-induced neuroleptic malignant syndrome. Paroxysmal nocturnal hemoglobinuria and anti-tuberculosis treatment (rifampicin and isoniazid) had led to hemoglobin cast nephropathy each in one case. Seven cases had severe renal failure requiring dialysis. Short-term renal outcome was favorable. However, long-term follow-up is necessary to determine whether pigment-induced AKI has delayed sequelae. Therefore, clinicians should consider rhabdomyolysis or hemolysis as potential hidden causes of AKI in diverse clinical conditions, especially those of non-traumatic origin, to achieve an accurate diagnosis., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Patel et al.)

Background Acute kidney injury (AKI) is a common and serious condition affecting elderly patients. Despite its significance, comprehensive research focusing specifically on the clinical profile and short-term outcomes of AKI in this vulnerable population is lacking. Objective This study aimed to evaluate the clinical profile and short-term outcomes of AKI in elderly patients admitted to a tertiary care center. Methods A prospective observational study was conducted from December 2023 to March 2024, involving 75 elderly patients (aged ≥65 years) diagnosed with AKI. Baseline demographic data, clinical profiles, laboratory investigations, mortality rate among elderly patients diagnosed with AKI within 30 days of diagnosis, and short-term outcomes were recorded and analyzed. Descriptive statistics and appropriate statistical tests were used for the data analysis. Results The study cohort had a mean age of 72.6 years. Hypertension was present in 55 patients (73.3%), and diabetes mellitus was observed in 30 patients (40.0%). Prerenal causes of AKI were identified in 40 patients (53.3%), while acute tubular necrosis was found in 25 patients (33.3%). Stage 2 AKI was the most common, affecting 35 patients (46.7%). Out of the 75 patients, 15 patients (20.0%) succumbed to AKI within the study period. Deceased patients had longer hospital stays, with a median of 16 days compared to 10 days for survivors. ICU admission was required for 13 of the deceased patients (86.7%), compared to 32 of the surviving patients (53.3%). The need for renal replacement therapy was higher among the deceased patients, with 11 out of 15 patients (73.3%) requiring it, compared to 19 out of 60 surviving patients (31.7%). Renal function recovery was notably lower in the deceased patients. Conclusion AKI in elderly patients was associated with significant morbidity and mortality, highlighting the need for early recognition, appropriate management, and preventive strategies. A comprehensive evaluation of the clinical profile and short-term outcomes of AKI in the elderly population provides valuable insights for optimizing patient care and improving outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Indira Gandhi Institute of Medical Sciences issued approval 1308/IEC/IGIMS/2023. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Prasad et al.)

Alterations of bases in DNA constitute a major source of genomic instability. It is believed that base alterations trigger base excision repair (BER), generating DNA repair intermediates interfering with DNA replication. Here, we show that genomic uracil, a common type of base alteration, induces DNA replication stress (RS) without being processed by BER. In the absence of uracil DNA glycosylase (UNG), genomic uracil accumulates to high levels, DNA replication forks slow down, and PrimPol-mediated repriming is enhanced, generating single-stranded gaps in nascent DNA. ATR inhibition in UNG-deficient cells blocks the repair of uracil-induced gaps, increasing replication fork collapse and cell death. Notably, a subset of cancer cells upregulates UNG2 to suppress genomic uracil and limit RS, and these cancer cells are hypersensitive to co-treatment with ATR inhibitors and drugs increasing genomic uracil. These results reveal unprocessed genomic uracil as an unexpected source of RS and a targetable vulnerability of cancer cells., Competing Interests: Declaration of interests The authors declare no competing interests with this study. L.Z. is a member of the advisory board of Molecular Cell, a scientific advisor for Sirrona Therapeutics, and received research support from Calico, Pfizer, and Bristol Myers Squibb. A.N.H. received research support from Amgen, Blueprint Medicines, BridgeBio, Bristol-Myers Squibb, C4 Therapeutics, Eli Lilly, Novartis, Nuvalent, Pfizer, Roche/Genentech, and Scorpion Therapeutics and consulted for Engine Biosciences, Oncovalent, Nuvalent, TigaTx, and Tolremo Therapeutics. M.G.V.H. is a scientific advisor for Agios Pharmaceuticals, iTeos Therapeutics, Sage Therapeutics, Auron Therapeutics, and Droia Ventures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To explore characteristic imaging features of nonparaneoplastic autoimmune retinopathy (npAIR) to augment diagnostic criteria., Methods: This is a retrospective cohort study of patients with npAIR evaluated at the Emory Eye Center between 2013 and 2019. Multimodal fundus images were evaluated to characterize the evolution of the disease., Results: Twenty-one eyes of 12 patients were classified as having npAIR. Five patients (42%) were female, with median (range) age of 59 years (45-85 years). Median baseline visual acuity was 20/30 (20/20 to hand motions). Disease was asymmetric in 11 patients (92%). Common imaging findings included absence of bone spicules (86% of affected eyes), presence of attenuated vessels (86%), and speckled hypoautofluorescence in perimacular and perivenular regions. Three eyes were noted to present early with subtle splotchy fundus autofluorescence abnormality, ultimately developing characteristic speckled perimacular hypoautofluorescence. On optical coherence tomography, 18 eyes (86%) had loss of outer retinal bands with relative foveal sparing and a tapered transition zone., Conclusion: Many eyes with npAIR exhibit a subacute, asymmetric, generalized photoreceptor degeneration featuring outer retinal atrophy with relative foveal sparing, retinal vascular attenuation, absence of bone spicules, and speckled hypoautofluorescence often in a perimacular and perivenular distribution. Findings of this study augment diagnostic criteria to improve specificity and accessibility of testing for npAIR.

Objective: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy with late-presentation, site-specific heterogeneity, and high-propensity for recurrence/metastasis that has shown rise in mortality. Lately, research emphasize on dynamic interactions between tumor-cells and extracellular-matrix components within tumor-microenvironment that promote tissue integrity loss and carcinogenesis. Therefore, OSCC clinical-management is still challenging., Design: Present study validated clinical utility of a 13 gene-panel in two chief sub-sites of OSCC: Buccal mucosa squamous cell carcinoma (BMSCC) (N = 50) and Tongue squamous cell carcinoma (TSCC) (N = 52) using qRT-PCR. Principal component analysis and binary logistic regression analysis were applied to acquire definite multi gene models. Protein expression analysis was employed using the Human Protein Atlas, UALCAN and TIMER 2.0 databases to explore potential correlation between immune cells and gene-panels., Results: Significant up-regulation of CXCL8, CXCL10, FN1, GBP1, IFIT3, ISG15, MMP1, MMP3, MMP10, PLAU, SERPINE1 and SPP1 except OASL was observed in OSCC tissue in comparison of absolute normal controls. Although, this gene-panel could potentially discriminate OSCC tissues from absolute normal controls as solitarily diagnostic and/or predictive biomarkers, models generated also showed substantial discriminating efficacy. Eight-genes were found to be significantly associated with poor-prognosis on clinico-pathological association. Protein-expression confirmed overexpression of gene-panel and added advantage of being secretory-protein. Importantly, up-regulated genes in our study showed significant relation with immune-cells infiltration suggesting their contribution in immune-escape., Conclusion: Thus, we propose that the 13 gene-panel could pave the way to effective and personalized clinical-management of OSCC in terms of diagnostic and prognostic measures and thereby as therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aimed to understand the experiences of bereaved family members in view of restrictive COVID guidelines using qualitative approach. 10 Hindu, Gujarati bereaved family members who lost their loved ones during the first wave were interviewed telephonically after a month of their loss. Findings were difficulty in proper communication during hospitalization, disrupted end-of-life and funeral rituals and accepting harsh realities related to the changes imposed by using content analysis. Most of the family members felt that there was a need of staying with the patients. Telephonic mode of communication was not sufficient for them and created doubts related to death. Most of them felt remorseful as they were not able to see or bring their loved one home during their last moments and felt deprived of the traditional rituals. Also, they had to deal with their grief by themselves., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Objectives: To evaluate the standardized mortality ratio (SMR) of patients in the United States referred to a multidisciplinary clinic for treatment of functional seizures., Methods: We identified patients who had or had not died based on automated retrospective review of electronic health records from a registry of patients referred to a single-center multidisciplinary functional seizures treatment clinic. We calculated an SMR by comparing the number of observed deaths with the expected number of deaths in an age-matched, sex-matched, and race-matched population within the same state, and year records were available., Results: A total of 700 patients with functional seizures (mean age 37 years, 78% female) were followed up for 1,329 patient-years for a median of 15 months per patient (interquartile range 6-37 months). We observed 11 deaths, corresponding to a mortality rate of 8.2 per 1,000 patient-years and an SMR of 2.4 (95% confidence interval: 1.17-4.22). Five of 9 patients with identified circumstances around their death were in hospice care when they passed. None of the identified causes of death were related to seizures directly., Discussion: These data provide further evidence of elevated mortality in functional seizures soon after diagnosis and referral to treatment. These data from the decentralized health care system of the United States build on the findings from other countries with large-scale health registries., Competing Interests: W.T. Kerr writes review articles for Medlink Neurology, is a paid consultant for SK Life Sciences and Biohaven Pharmaceuticals, has collaborative or data use agreements with Eisai, Janssen, Radius Health, UCB, and GSK, and has been a site investigator for a trial including Equilibre Pharmaceuticals. N.J. Beimer has received honoraria from Medlink LLC and Decker Intellectual Properties; has received research support from the Health Resources and Services Administration (HRSA H98MC30374), National Institute of Neurologic Disorders and Stroke (R01 NS094399), and the Pediatric Epilepsy Research Foundation; serves on the Epilepsy Foundation of Michigan Professional Advisory Board; and has provided medicolegal expert testimony. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp. TAKE-HOME POINTS → Standardized mortality ratio (SMR) after diagnosis or referral was 2.4.→ Raw mortality rate was 8.2 deaths per 1,000 patient-years.→ All deaths with a known cause were attributed to comorbidities.→ These rates were comparable with epilepsy, severe mental illness, and other studies of functional seizures.→ These rates highlight the need for effective strategies to improve access to multidisciplinary care., (© 2024 American Academy of Neurology.)

Background: There is a lack of standardized treatments for patients with less than 50% crescents observed in their renal biopsies. This study aimed to analyze the crescent percentage, clinicopathological characteristics, and renal prognosis of glomerulonephritis (GN) cases with at least one crescentic lesion., Materials and Methods: This retrospective cohort study was conducted at the Indira Gandhi Institute of Medical Sciences, Patna, from January 2016 to December 2020. Consecutive patients (aged between 18 and 65 years) with renal biopsy findings suggestive of GN and at least one crescent were included in the study. Demographic details and clinical presentation were collected from the medical records., Results: A total of 145 patients were included. The mean (standard deviation (SD)) age was 33.06 (11.739) years. Hemoptysis was significantly higher in the ≥50% crescent group (P=0.011). Rapidly progressive glomerulonephritis (RPGN) was significantly higher in the ≥50% crescent group (P<0.001). There was a significant difference observed in mean creatinine (P=0.001), mean crescents (P<0.001), and mean urine polymerase chain reaction (PCR) (P=0.031). Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis was significantly higher in the ≥50% crescent group (P<0.001). Complete remission decreased as crescents increased. In GN with crescent, the presence of fibrous crescents (≥50%) is associated with a higher rate of treatment resistance (100%) compared to fibrocellular (58.33%) and cellular crescents (6.25%). In the ≥50% crescent group, death was significantly higher in patients with fibrous crescent age (57.14%)., Conclusion: Crescent percentage and crescent age were found to be significantly related to greater risk of renal failure and resistance to treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Rao et al.)

Introduction: Variation in access to parenteral nutrition (PN) in patients with intestinal failure secondary to malignant bowel obstruction (MBO) exists due to differing practice, beliefs and resource access. We aimed to examine differences in nutritional care pathways and outcomes, by referral to nutrition team for PN in patients with MBO., Methods: This is a retrospective cohort study of MBO adults admitted to eight UK hospitals within a year and 1 year follow-up. Demographic, nutritional and medical data were analysed by comparing patients referred (R) or not referred (NR) for PN. Differences between groups were tested by Kruskal-Wallis, Chi-Squared tests and multi-level regression and survival using Cox regression., Results: 232 patients with 347 MBO admissions [median 66yr, (IQR: 55-74yrs), 67 % female], 79/232 patients were referred for PN (R group). Underlying primary malignancies of gynaecological and gastrointestinal origin predominated (71 %) and 78 % with metastases. Those in the NR group were found to be older, weigh more on admission, and more likely to be treated conservatively compared to those in the R group. For 123 (35 %) admissions, patients were referred to a nutrition team, and for 204 (59 %) admissions, patients were reviewed by a dietician. Multi-disciplinary team discussion and dietetic contact were more likely to occur in the R group-123/347 admissions (R vs NR group: 27 % vs. 7 %, P = 0.001; 95 % vs 39 %, P < 0.0001). Median admission weight loss was 8 % (IQR: 0 to 14). 43/123 R group admissions received inpatient PN only, with 32 patients discharged or already established on home parenteral nutrition. Overall survival was 150 days (126-232) with no difference between R/NR groups., Conclusion: In this multi-centre study evaluating nutritional care management of patients with malignant bowel obstruction, only 1 in 3 admissions resulted in a referral to the nutrition team for PN, and just over half were reviewed by a dietician. Further prospective research is required to evaluate possible consequences of these differential care pathways on clinical outcomes and quality of life., Competing Interests: Declaration of competing interest Pinal Patel's Research Post was funded by Calea, Fresenius Kabi, UK., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Mutation signatures associated with apolipoprotein B mRNA editing catalytic polypeptide-like 3A/B (APOBEC3A/B) cytidine deaminases are prevalent across cancers, implying their roles as mutagenic drivers during tumorigenesis and tumor evolution. APOBEC3A (A3A) expression induces DNA replication stress and increases the cellular dependency on the ataxia telangiectasia and Rad3-related (ATR) kinase for survival. Nonetheless, how A3A induces DNA replication stress remains unclear. We show that A3A induces replication stress without slowing replication forks. We find that A3A induces single-stranded DNA (ssDNA) gaps through PrimPol-mediated repriming. A3A-induced ssDNA gaps are repaired by multiple pathways involving ATR, RAD51, and translesion synthesis. Both ATR inhibition and trapping of poly(ADP-ribose) polymerase (PARP) on DNA by PARP inhibitor impair the repair of A3A-induced gaps, preferentially killing A3A-expressing cells. When used in combination, PARP and ATR inhibitors selectively kill A3A-expressing cells synergistically in a manner dependent on PrimPol-generated gaps. Thus, A3A-induced replication stress arises from PrimPol-generated ssDNA gaps, which confer a therapeutic vulnerability to gap-targeted DNA repair inhibitors.