Topiramate-induced acute eosinophilic pneumonia.

A man in his 40s with a known history of alcohol dependence syndrome was admitted with presenting symptoms of alcohol withdrawal. During his admission, he developed breathlessness, cough and wheezing. Investigations revealed raised absolute eosinophil count and serum IgE levels. Chest imaging showed ill-defined opacities and fibreoptic bronchoscopy with bronchoalveolar lavage confirmed eosinophilic pneumonia. Extensive workup for the cause of eosinophilia was negative. The patient's medicines were reviewed, and it was realised that the onset of eosinophilia occurred after starting topiramate for an alcohol withdrawal seizure. The drug was stopped, leading to the complete resolution of symptoms and radiological abnormalities. This case highlights the importance of considering drug-induced causes of eosinophilic pneumonia.

Detection of γ-OHPdG in Circulating Tumor Cells of Patients With Hepatocellular Carcinoma as a Potential Prognostic Biomarker of Recurrence.

Background and Aims: Blood-based biomarkers for hepatocellular carcinoma (HCC) and its recurrence are lacking. We previously showed that hepatic γ-hydroxy-1,N 2 -propano-2'-deoxyguanosine (γ-OHPdG), an endogenous DNA adduct derived from acrolein by lipid peroxidation, increased during hepatocarcinogenesis. Additionally, higher hepatic γ-OHPdG from HCC patients after surgery were strongly associated with poor survival (P < .0001) and recurrence-free survival (P = .007) (Fu et al, Hepatology, 2018). These findings suggest that γ-OHPdG is a potential prognostic biomarker for HCC and its recurrence. To attain the goal of using γ-OHPdG as a biomarker in future preventive and therapeutic trials, we developed a blood-based method to detect γ-OHPdG in circulating liver tumor cells from HCC patient blood. Methods: We first established the specificity of anti-γ-OHPdG antibody by determining its dose-response in HepG2 cells treated with acrolein. Then, HepG2 cells in spiked blood of healthy volunteers and circulating tumor cells (CTCs) from 32 HCC patients were isolated using a RosetteSep CD45 Depletion Cocktail and Ficoll Paque. The HCC CTCs identified with anti-asialoglycoprotein receptor 1, a surface protein expressed solely in hepatocytes, were stained with an anti-γ-OHPdG antibody. The number of total HCC CTCs and γ-OHPdG-positive CTCs, as well as the staining intensity, were quantified using MetaMorph software. As an initial effort toward its clinical application, we also evaluated γ-OHPdG in CTCs from these patients along with certain clinical features. Results: The γ-OHPdG antibody specificity was demonstrated by an acrolein concentration-dependent increase of γ-OHPdG-positive HepG2 cells and the intensity of γ-OHPdG staining. The recovery of HepG2 cells from spiked blood was ∼50-60%, and the positivity rate of CTCs in blood from 32 patients with advanced HCC was 97%. The MetaMorph analysis showed a wide variation among patients in total number of CTCs, γ-OHPdG positivity, and staining intensity. Statistical analysis revealed that γ-OHPdG in CTCs of these patients appears to be associated with multifocality and poor differentiation. Conclusion: A blood-based method was developed and applied to HCC patients to evaluate the potential of γ-OHPdG in CTCs as a prognostic biomarker.

Association of Neutrophil-Lymphocyte Ratio and Red Blood Cell Distribution Width with Poor Outcome in Pediatric Cardiac Surgery - A Retrospective Observational Study.

BACKGROUND: Neutrophil-lymphocyte ratio (NLR) is a valuable indicator for evaluating inflammatory response and red blood cell distribution width (RBDW), a routinely available biomarker of likely erythropoietic dysfunction, which may be associated with adverse outcomes after cardiac surgery. This study aimed to investigate the association between these two readily available haematological parameters, with the poor outcomes in paediatric patients undergoing cardiac surgery. METHODS: A comprehensive review of medical records for paediatric patients who underwent cardiac surgery at our tertiary care centre between April 2022 and June 2023 was carried out. RBDW and NLR values were collected from complete blood count reports obtained on admission to the ICU. Demographic data, surgical details, and postoperative complications were also recorded. A receiver operating characteristic (ROC) curve and multivariable logistic regression were applied to identify the prognosis performance of preoperative NLR and RBDW for poor outcomes. RESULTS: The study included 219 patients meeting the inclusion criteria of which a total of 90 (41%) children experienced at least one of the poor outcomes. Preoperative NLR (AUC=0.88, 95%CI 0.36-0.70, cut off- 4.2) and RBDW (AUC=0.88, 95%CI 0.39-0.73, cut off- 18.5%) showed prognostic significance in the perioperative period. CONCLUSION: This retrospective observational study highlights a significant association between elevated Red Blood Cell Distribution Width (RBDW) and Neutrophil Lymphocyte Ratio (NLR) values and poor outcomes in paediatric patients undergoing cardiac surgery. These readily available haematological parameters could serve as potential prognostic indicators for identifying patients at risk of poor outcomes.

Plant-based diets and postprandial hyperkalemia.

This Letter to the Editor is a response to St-Jules and Fouque and their interpretation of postprandial hyperkalemia, especially regarding plant-based diets. Based on the reviewed literature review, potassium kinetic studies cited by the authors include only 1 study with a food-based intervention that actually showed reduced postprandial hyperkalemia with plant-based diets. The remainder of the studies used potassium salts or supplements that behave differently compared with whole plant foods. As such, we recommend avoiding restriction of whole plant foods in patients with chronic kidney disease when solely based on the theoretical risk of postprandial hyperkalemia.

Effect of Chronic Apical Periodontitis in Primary Molars on Succedaneous Permanent Teeth: An Observational Retrospective Study.

INTRODUCTION: Periapical infection of primary molars affects the development of permanent teeth (premolars). Therefore, the present study was conducted to test the null hypothesis in children aged 4-10 years with chronic apical periodontitis (CAP) of the primary molars. MATERIALS AND METHODS: A retrospective, cross-sectional study was conducted on 185 panoramic radiographs of healthy children aged 4-10 years with CAP in the primary molars. A total of 256 infected primary molars (144 teeth in females, 112 teeth in males) were analyzed, radiographically, and compared with 245 healthy primary molars on the contralateral side. Permanent successors were evaluated for follicular damage, maturation, morphology, and deviation in the eruption path. Primary molars were evaluated for root resorption. Sixteen permanent teeth on the affected side and five teeth on the control side were excluded due to abnormal development. Student's t-test and the chi-square test were used to analyze the data. RESULTS: The null hypothesis is rejected. There were significant differences in the developmental status of permanent successors on the affected side, compared to the normal side at four to seven years (p<0.05). There were no significant sex differences in the abnormalities of permanent successors on the affected side (p>0.05). As the root resorption of the primary molars increased, the follicular damage observed in the permanent successors also increased (p<0.05), which suggests that, as the infection of primary molars increases, more damage is caused to underlying permanent successors (premolars). CONCLUSION: Apical periodontitis of the primary molars retards the development of permanent successors (premolars), affects their shape, causes follicular damage, and alters the eruption path.

2,2-Diphenethyl Isothiocyanate Enhances Topoisomerase Inhibitor-Induced Cell Death and Suppresses Multi-Drug Resistance 1 in Breast Cancer Cells.

We previously reported that phenethyl isothiocyanate (PEITC), a dietary-related compound, can rescue mutant p53. A structure-activity relationships study showed that the synthetic analog 2,2-diphenylethyl isothiocyanate (DPEITC) is a more potent inducer of apoptosis than natural or synthetic ITCs. Here, we showed that DPEITC inhibited the growth of triple-negative breast cancer cells (MDA-MB-231, MDA-MB-468, and Hs578T) expressing "hotspot" p53 mutants, structural (p53R280K, p53R273H) or contact (p53V157F), at IC50 values significantly lower than PEITC. DPEITC inhibited the growth of HER2+ (p53R175H SK-BR-3, p53R175H AU565) and Luminal A (p53L194F T47D) breast cancer (BC) cells harboring a p53 structural mutant. DPEITC induced apoptosis, irrespective of BC subtypes, by rescuing p53 mutants. Accordingly, the rescued p53 mutants induced apoptosis by activating canonical WT p53 targets and delaying the cell cycle. DPEITC acted synergistically with doxorubicin and camptothecin to inhibit proliferation and induce apoptosis. Under these conditions, DPEITC delayed BC cells in the G1 phase, activated p53 canonical targets, and enhanced pS1981-ATM. DPEITC reduced the expression of MDR1 and ETS1. These findings are the first report of synergism between a synthetic ITC and a chemotherapy drug via mutant p53 rescue. Furthermore, our data demonstrate that ITCs suppress the expression of cellular proteins that play a role in chemoresistance.

Clinical profile and molecular typing of viral etiological agents associated with Hand, Foot and Mouth Disease (HFMD): A study from Udhampur, Northern India.

PURPOSE: Hand, Foot and Mouth disease (HFMD) is a contagious pediatric viral disease caused due to enteroviruses (EV) of the family Picornaviridae. Cases of HFMD were reported from a tertiary care health centre, Udhampur, (Jammu and Kashmir), Northern India. The present study highlights the clinical and molecular virological aspects of HFMD cases. MATERIAL AND METHODS: Cases reported during August 2016-September 2017, and clinically diagnosed as HFMD of all age groups were included. Clinical, Biochemical and molecular virology aspects were compared. Clinical samples (n â€‹= â€‹50) such as vesicle swab, buccal and throat swabs were collected for enterovirus detection. EV-RNA was detected by 5'NCR based RT-PCR and genotyping by VP1 gene amplification and cycle sequencing. RESULTS: Of the cases of HFMD enrolled (n â€‹= â€‹50), highest (84%) were of children aged <5 years, presented either or both anathemas and exanthemas with prodromal symptoms (fever, irritability). Clinical presentations involved mainly oral ulcers on lips and tongue (48%). Oral erosions were either single or multiple in numbers. Exanthemas were seen on hand and palm, widely spread up to buttocks, legs, arms and trunk. Of these, six patients were found anemic. Complete blood count (CBC) indicated lymphocytosis and C-reactive protein (n â€‹= â€‹10) in children aged <5 years. EV-RNA was detected in 78% (39/50) of the clinical samples. VP1 gene based typing indicated the presence of CV-A16, CVA6 and EV-A71 types. CONCLUSIONS: The study highlights association of EVs in HFMD cases in the reported region. CV-A16, CV-A6 and EV-A71 types were reported for the first time from Udhampur (J&K), Northern India. No differences were observed in the clinical profile of EV strains detected. Circulation of the strains warrant and alarm outbreaks. More focused studies on HFMD and monitoring of viral strains is mandatory.

The linker domain of the initiator DnaA contributes to its ATP binding and membrane association in E. coli chromosomal replication.

DnaA, the initiator of Escherichia coli chromosomal replication, has in its adenosine triphosphatase (ATPase) domain residues required for adenosine 5'-triphosphate (ATP) binding and membrane attachment. Here, we show that D118Q substitution in the DnaA linker domain, a domain known to be without major regulatory functions, influences ATP binding of DnaA and replication initiation in vivo. Although initiation defective by itself, overexpression of DnaA(D118Q) caused overinitiation of replication in dnaA46ts cells and prevented cell growth. The growth defect was rescued by overexpressing the initiation inhibitor, SeqA, indicating that the growth inhibition resulted from overinitiation. Small deletions within the linker showed another unexpected phenotype: cellular growth without requiring normal levels of anionic membrane lipids, a property found in DnaA mutated in its ATPase domain. The deleted proteins were defective in association with anionic membrane vesicles. These results show that changes in the linker domain can alter DnaA functions similarly to the previously shown changes in the ATPase domain.

Acute amebic appendicitis in early pregnancy.

Parasitic infections of the intestine are a major health problem, which is found more prevalent in developing countries such as India. They are one of the important causes of morbidity and mortality among people all over the world. Acute amoebic appendicitis is a rare entity. We came across a case of acute appendicitis in a young pregnant woman, which revealed colonies of Entamoeba histolytica trophozoites in the mucosal epithelium and submucosal layer of the appendix with marked evidence of acute appendicitis. This report highlights acute appendicitis of amoebic origin and emphasises the importance of thorough examination of the appendix at various levels during histopathology and about the combined treatment of appendicectomy combined with antimicrobials as the treatment of choice. Appendicectomy removes the focus of infection, and antimicrobials reduce the incidence of septic complications.