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In this research, a 3D brain organoid model is developed to study POLG‐related encephalopathy, a mitochondrial disease stemming from POLG mutations. Induced pluripotent stem cells (iPSCs) derived from patients with these mutations is utilized to generate cortical organoids, which exhibited typical features of the diseases with POLG mutations, such as altered morphology, neuronal loss, and mitochondiral DNA (mtDNA) depletion. Significant dysregulation is also identified in pathways crucial for neuronal development and function, alongside upregulated NOTCH and JAK‐STAT signaling pathways. Metformin treatment ameliorated many of these abnormalities, except for the persistent affliction of inhibitory dopamine‐glutamate (DA GLU) neurons. This novel model effectively mirrors both the molecular and pathological attributes of diseases with POLG mutations, providing a valuable tool for mechanistic understanding and therapeutic screening for POLG‐related disorders and other conditions characterized by compromised neuronal mtDNA maintenance and complex I deficiency. [ABSTRACT FROM AUTHOR]

Background  Bloodstream infections (BSIs) are one of the frequent nosocomial infections among hospitalized patients. To understand the local epidemiology and evolving antimicrobial drug resistance of blood-borne pathogens, we analyzed the distribution and antibiotic sensitivity profile of organisms causing BSI in our hospital-based study. Materials and Methods  We reviewed retrospective data of laboratory-confirmed BSIs, from January 2013 to December 2018. Causative organisms and their antibiotic susceptibility profile of primary and secondary BSI reports were determined from BacT/Alert and Vitek systems findings (bioMérieux). A 6-year multidrug resistance indexing was done to document the resistance pattern of the commonly isolated organisms. Results  A total of 1,340 (10.2%) BSIs were reported from 13,091 blood cultures. Organisms were frequently isolated from the younger population (≤20 years), especially from ages < 1 year (20.8% of total BSIs). Majority of pathogens were bacterial (97.1%) whereas 2.9% were fungal in origin. Monomicrobial growth was recorded in over 98% of BSIs. Gram-positive and gram-negative bacteria isolated were 518 (39.8%) and 783 (60.2%), respectively. Commonly isolated organisms were coagulase-negative Staphylococci (29.4%), Escherichia coli (19.8%), Klebsiella species (13.5%), Salmonella species (9.4%), and Staphylococcus aureus (7.5%). Multidrug-resistance index was observed highest in Acinetobacter species followed by Pseudomonas aeruginosa and S. aureus. Conclusion  Overall, there has been a gradual decline in the reporting of BSI. However, infections by gram-negative bacilli and multidrug-resistant organisms remain persistently high. Ages < 20 years were the vulnerable group, with infants < 1 year contributing to the maximum number of BSI cases caused by both bacteria and fungi. Therefore, additional methods are required to study the origin and causation of these infections, particularly among vulnerable patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Enterococcus is an important pathogen, and with its emergence of resistance to multiple antimicrobials, the management of infection is becoming increasingly difficult. AIM: The aim of the study is to determine the prevalence, antibiotic resistance, and risk factors associated with enterococcal infection or colonization. MATERIALS AND METHODS: In this prospective study, samples from inpatients were screened for resistant enterococci. Antibiotic susceptibility testing was performed using the disc diffusion method and minimum inhibitory concentration by the agar dilution method. A modification of a test tube method of sodium chloride-esculin hydrolysis to a spot test was evaluated for its rapidity and reliability in the presumptive diagnosis of enterococci. STATISTICAL ANALYSIS USED: Fisher's exact test was used for continuous (Student's t-test) and categorical variables. Multivariate analysis was performed with logistic regression using IBM SPSS 20.0 software (Armonk, NY, USA). RESULTS: Enterococcus species were isolated from 182 samples: Enterococcus faecalis (68.7%), Enterococcus faecium (20.9%), Enterococcus gallinarum (6%), and Enterococcus durans (4.4%). Maximum resistance was to ciprofloxacin (59.3%) and least to linezolid (0.5%). The isolation rate of vancomycin-resistant enterococci (VRE) was 13.7%; 30.2% and 20.9% were of high-level gentamicin and streptomycin, respectively. All 182 Enterococcus species gave positive results within 30–60 min by the rapid spot test. CONCLUSIONS: Overall, high-level aminoglycoside resistance (HLAR) was observed more than glycopeptide resistance. Surveillance strategies need to be upgraded and implemented in order to prevent the emergence and further spread of not only VRE but also HLAR enterococci in the hospital. The spot test gave reliable and rapid results in presumptive identification of enterococci. [ABSTRACT FROM AUTHOR]

Cardiac rhythm regulated by micro-macroscopic structures of heart. Pacemaker abnormalities or disruptions in electrical conduction, lead to arrhythmic disorders may be benign, typical, threatening, ultimately fatal, occurs in clinical practice, patients on digitalis, anaesthesia or acute myocardial infarction. Both traditional and genetic animal models are: In-vitro: Isolated ventricular Myocytes, Guinea pig papillary muscles, Patch-Clamp Experiments, Porcine Atrial Myocytes, Guinea pig ventricular myocytes, Guinea pig papillary muscle: action potential and refractory period, Langendorff technique, Arrhythmia by acetylcholine or potassium. Acquired arrhythmia disorders: Transverse Aortic Constriction, Myocardial Ischemia, Complete Heart Block and AV Node Ablation, Chronic Tachypacing, Inflammation, Metabolic and Drug-Induced Arrhythmia. In-Vivo: Chemically induced arrhythmia: Aconitine antagonism, Digoxin-induced arrhythmia, Strophanthin/ouabain-induced arrhythmia, Adrenaline-induced arrhythmia, and Calcium-induced arrhythmia. Electrically induced arrhythmia: Ventricular fibrillation electrical threshold, Arrhythmia through programmed electrical stimulation, sudden coronary death in dogs, Exercise ventricular fibrillation. Genetic Arrhythmia: Channelopathies, Calcium Release Deficiency Syndrome, Long QT Syndrome, Short QT Syndrome, Brugada Syndrome. Genetic with Structural Heart Disease: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Atrial Fibrillation, Sick Sinus Syndrome, Atrioventricular Block, Preexcitation Syndrome. Arrhythmia in Pluripotent Stem Cell Cardiomyocytes. Conclusion: Both traditional and genetic, experimental models of cardiac arrhythmias' characteristics and significance help in development of new antiarrhythmic drugs. [ABSTRACT FROM AUTHOR]

Cardiac rhythm regulated by micro-macroscopic structures of heart. Pacemaker abnormalities or disruptions in electrical conduction, lead to arrhythmic disorders may be benign, typical, threatening, ultimately fatal, occurs in clinical practice, patients on digitalis, anaesthesia or acute myocardial infarction. Both traditional and genetic animal models are: In-vitro: Isolated ventricular Myocytes, Guinea pig papillary muscles, Patch-Clamp Experiments, Porcine Atrial Myocytes, Guinea pig ventricular myocytes, Guinea pig papillary muscle: action potential and refractory period, Langendorff technique, Arrhythmia by acetylcholine or potassium. Acquired arrhythmia disorders: Transverse Aortic Constriction, Myocardial Ischemia, Complete Heart Block and AV Node Ablation, Chronic Tachypacing, Inflammation, Metabolic and Drug-Induced Arrhythmia. In-Vivo: Chemically induced arrhythmia: Aconitine antagonism, Digoxin-induced arrhythmia, Strophanthin/ouabain-induced arrhythmia, Adrenaline-induced arrhythmia, and Calcium-induced arrhythmia. Electrically induced arrhythmia: Ventricular fibrillation electrical threshold, Arrhythmia through programmed electrical stimulation, sudden coronary death in dogs, Exercise ventricular fibrillation. Genetic Arrhythmia: Channelopathies, Calcium Release Deficiency Syndrome, Long QT Syndrome, Short QT Syndrome, Brugada Syndrome. Genetic with Structural Heart Disease: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Atrial Fibrillation, Sick Sinus Syndrome, Atrioventricular Block, Preexcitation Syndrome. Arrhythmia in Pluripotent Stem Cell Cardiomyocytes. Conclusion: Both traditional and genetic, experimental models of cardiac arrhythmias' characteristics and significance help in development of new antiarrhythmic drugs. [ABSTRACT FROM AUTHOR]