A Rare Case of Pulmonic and Aortic Valve Infective Endocarditis: A Case Report.

Infective endocarditis (IE) is a microbial infection affecting cardiac valves. IE most often affects the aortic valve and is commonly caused by community-acquired, penicillin-sensitive streptococcus that enters through the oral cavity. In this report, we present a case of a 66-year-old man with a medical history of congenital pulmonic stenosis status after pulmonic valve (PV) repair. The patient underwent a transesophageal echocardiogram showing a 1 cm × 0.7 cm mobile vegetation attached to the ventricular aspect of the right coronary aortic cusp and a 1.1 cm × 0.5 cm mobile vegetation attached to the arterial aspect of the PV cusp. In conclusion, concomitant right- and left-sided IE is an exceedingly rare condition. Due to its rarity and complexity of presentation, pulmonic valve endocarditis (PVE) requires a multidisciplinary approach to its perioperative management to prevent systemic complications.

Maintenance Electroconvulsive Therapy, Developmental Regression, Depression and Catatonia in an Adolescent With Down Syndrome: A Case Report.

This is a case report involving a 22-year-old male with a past medical history of Down syndrome and major depressive disorder who, at age 16, became preoccupied with returning to an infant-like state. He experienced a gradual deterioration in his mood over a year and began to show symptoms consistent with catatonia. These symptoms included waxy flexibility, hypokinesis, decreased appetite, mutism, and altered sleep habits. Pharmacologic therapy was initiated, and the patient experienced a waxing and waning pattern of improvement and regression. Over several years, various combinations of antidepressants, benzodiazepines, and second-generation antipsychotics were attempted. The patient and his family discontinued all medications except his benzodiazepine in early 2019 and decided to try electroconvulsive therapy (ECT). After more than 100 sessions of ECT between 2019 and 2022, the patient showed notable improvement in overall mood, and his appetite and sleep completely returned to baseline. His speech, affect, and movement also improved. With ECT, the patient showed the most sustained and substantial improvement in his catatonic symptoms. ECT has been historically shown to improve these types of symptoms in catatonic patients, including those who have Down syndrome. Often, clinicians do not consider the possibility of catatonia in patients with this type of presentation, which is unfortunate as misdiagnosis leads to increased morbidity. Additionally, there has not been much discussion of the optimal length of treatment and the necessity of slowly tapered maintenance therapy in the literature. This case report illustrates how catatonia can be a major cause of developmental regression in patients with Down syndrome and offers an example of a promising management strategy for the treatment of this condition.

Does oxidative DNA damage trigger histotoxic hypoxia via PARP1/AMP-driven mitochondrial ADP depletion-induced ATP synthase inhibition in Alzheimer's disease?

The low cerebral metabolic rate of oxygen despite the relatively preserved perfusion in Alzheimer's disease (AD) patients' medial temporal lobes suggest histotoxic hypoxia due to mitochondrial dysfunction that is independent of, but could precede, insulin resistance. Neuropathological, metabolomic, and preclinical evidence are consistent with the notion that this mitochondrial dysfunction may be contributed to by oxidative stress and DNA damage, leading to poly-(ADP-ribose)-polymerase-1 (PARP1) activation and consequent AMP accumulation, clogging of mitochondrial adenine nucleotide transporters (ANTs), matrix ADP deprivation, and ATP synthase inhibition. Complementary mechanisms may include mitochondrial-protein poly-ADP-ribosylation and mitochondrial-biogenesis suppression via PARPs outcompeting Sirtuin-1 (SIRT1) for nicotinamide-adenine-dinucleotide (NAD+).

Transfusion-Related Acute Lung Injury (TRALI) in Postoperative Anesthesia Care Unit (PACU) After One Unit of Platelets: A Case Report.

Transfusion-related acute lung injury (TRALI) following transfusion of all plasma-containing blood products is a rare but serious syndrome characterized by the acute onset of non-cardiogenic pulmonary edema with severe hypoxemia with or without symptoms of hypotension, pinkish frothy secretions, fever, and cyanosis. In this report, we present a case of a 66-year-old female with a medical history significant for hypertension, hyperlipidemia, hepatitis C, liver cirrhosis, tobacco use disorder, metastatic spindle cell carcinoma of the lung status post chemotherapy who developed TRALI after administration of one unit of platelets. Although a rare occurrence, there can be a considerable risk of TRALI following transfusion of all plasma-containing blood products and there is great importance in considering each patient's risk factors for TRALI development prior to blood product administration.

Clinicopathological analysis of recurrence and progression of low-grade papillary urothelial carcinoma of the urinary bladder: Predicting the outcome.

BACKGROUND: Urothelial carcinoma of the urinary bladder is the most common malignancy of the urinary system. Patients with low grade papillary urothelial carcinoma (LGPUC) usually have a low risk for tumor recurrence and progression; yet a subset of patients develop recurrence or grade/stage progression to high-grade papillary urothelial carcinoma (HGPUC). The clinicopathological and molecular factors that contribute to this progression are yet to be determined. OBJECTIVES: In our study, we aimed to assess the incidence and clinicopathological factors associated with tumor recurrence/progression of LGPUC. METHODS: Using a pathological database of surgical specimens from patients who underwent bladder biopsies and/or transurethral resection of bladder tumors (TURBTs) between August 01, 2011, and July 31, 2021, at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. RESULTS: Of the total 258 patients included, 157 (60.9 %) had "no recurrence", 85 (32.9 %) had ≥1 "recurrence of LGPUC", and 16 (6.2 %) had "grade progression to HGPUC". The mean follow-up time was 31.5 ± 32 months. Patients with "grade progression" and "recurrence of LGPUC" had larger mean tumor size on initial biopsy and multiple lesions on initial cystoscopy compared to those with "no recurrence." Interestingly, former smokers had 2.5- and 8.5-times higher risk of recurrence of LGPUC and grade progression, respectively. CONCLUSION: Since the majority of our patients did not develop recurrence, we question whether there is tendency to overclassify the papillomas as LGPUC based on the 2004 WHO/ISUP consensus grading classification.

Dissemination of the Spear & Shield Project using a Training of Trainers Model: A reflection on challenges and successes.

Several large-scale clinical trials have conclusively demonstrated that voluntary medical male circumcision (VMMC) could provide a 50%-70% reduction in HIV acquisition, but willingness to undergo VMMC has been lowest in Zambia compared to other countries in eastern and southern Africa. This manuscript describes training for "task-shifting" among local healthcare workers at Community Health Centers (CHCs) applying state of the art strategies (e.g., Training of Trainers, i.e., ToT, and Training of Facilitators, ToF) to provide novel clinical services. Staff at 96 CHCs from four Provinces in Zambia were sequentially trained to provide the Spear & Shield intervention. A total of 45,630 men (n = 23,236) and women (n = 22,394) volunteered to participate in the S&S intervention service program when offered in the CHCs. Group session (total = 5313 sessions; 2,736 men's and 2,582 women's sessions) were conducted over 4.5 years. Remarkably, both men and women's groups achieved 97% retention. Of these, 256 sessions recorded from 128 group leaders were assessed and scored for intervention fidelity; fidelity was 80%-90% among the majority of clinics. S&S program sustainment exceeded expectations among 85% of clinics (82/96) in all provinces across the duration of the study. Of note, attendance in the S&S program was encouraged by CHC staff, but no financial incentives were provided to those attending S&S. This study examined the effectiveness of the ToT/ToF model in dissemination of the S&S program, which proved to be feasible even in resource-limited settings. Benefits and challenges are discussed.

Vicarious Traumatization and Burnout among Service Providers for Victims of Commercial Sexual Exploitation.

Victims of commercial sexual exploitation (CSE) are in need of multiple community services to aid in their recovery. Service providers are critical to ensuring these victims receive needed treatment. Given the complex trauma of these victims and the necessity of long-term treatment, these service professionals may experience vicarious trauma (VT) and burnout. This qualitative study interviewed 12 professionals who have provided direct services to victims of CSE about their experiences. They had on average about 8 years of experience and three were survivors of CSE. Almost all reported instances of burnout and VT but also had strategies for the prevention of such experiences. Most participants reported experiences of VT and burnout are inevitable when working with this population, but self-care strategies and peer support are essential to combatting these negative experiences. These results can inform agencies that provide services to victims of CSE so as to ensure their staff stay healthy and avoid burnout.

Defining Disease, Diagnosis, and Translational Medicine within a Homeostatic Perturbation Paradigm: The National Institutes of Health Undiagnosed Diseases Program Experience.

Traditionally, the use of genomic information for personalized medical decisions relies on prior discovery and validation of genotype-phenotype associations. This approach constrains care for patients presenting with undescribed problems. The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) hypothesized that defining disease as maladaptation to an ecological niche allows delineation of a logical framework to diagnose and evaluate such patients. Herein, we present the philosophical bases, methodologies, and processes implemented by the NIH UDP. The NIH UDP incorporated use of the Human Phenotype Ontology, developed a genomic alignment strategy cognizant of parental genotypes, pursued agnostic biochemical analyses, implemented functional validation, and established virtual villages of global experts. This systematic approach provided a foundation for the diagnostic or non-diagnostic answers provided to patients and serves as a paradigm for scalable translational research.