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Background Invasive pneumococcal disease (IPD), caused by Streptococcus pneumoniae , remains a major global health concern, particularly for children. Among more than 100 pneumococcal serotypes, 19A is known for its multidrug resistance (MDR) and increased incidence following PCV7/PCV10 introduction in many countries. Bangladesh introduced PCV10 in 2015 considering the low burden of 19A in the country. Methods Utilizing our IPD surveillance from 2004 to 2023, we investigated the hospital incidence of serotype 19A before and after PCV10 introduction among < 5 years old children in Bangladesh. Whole-genome sequencing was done for 153 serotype 19A isolates from IPD, otitis media, carriage, and urine samples. We used phylogenetic and BEAST analyses to investigate population structure, circulating subtypes, global pneumococcal sequence clusters (GPSCs), sequence types (STs), and antimicrobial resistance genes, and compared them with global 19A genomes. Results Our findings indicate no increase in hospital IPD incidence due to serotype 19A following PCV10 introduction. The MDR 19A-ST320 lineage (GPSC1) remains absent in Bangladesh. ST12888 (GPSC84) became dominant in the post-PCV10 introduction (from 15% to 70%). GPSC84 carries the capsular locus of 19A subtype-I (19A-I), which emerged independently from the standard 19A locus. Macrolide resistance is increasing within the 19A-I/GPSC84 lineage and is estimated to have originated between 2007 and 2011. Conclusions This study presents the first comprehensive genomic analysis of the serotype 19A population in Bangladesh, supporting the decision to introduce PCV10 in Bangladesh based on local pneumococcal serotype burden data. However, the rapid evolution within the local 19A population highlights the need for continuous epidemiological and genomic surveillance to support effective vaccination programs.

The impact of Human Resource Management (HRM) practices on performance behavior and job satisfaction have drawn much attention around the world over the past 25 years (Khera, 2010; Savaneviciene& Stankeviciute, 2012).Past researchwas conducted on either HRM practices and job satisfaction or HRM practices and employee performance. Researchers in the study try to integrate both the topics in a single edge. Covering the existing research gap, the study aims at to predict high school teachers’ operational performance on HRM practices and notice whether the job satisfaction mediates the relationship between HR practices and operational performance. The research is a non-experimental study utilizing structured questionnaires. During the survey, information confidentiality and respondents’ anonymous were established. The study has adopted the cross-sectional survey approach and investigated 140 teachers from 14 high schools, located at Sylhet City, Bangladesh. A three-step hierarchical regression model was fitted to regress operational performance on control variable, HRM related independent variables as well as job satisfaction to know the variance explained by each step and to test the effect size. Further, three mediation models were also developed to delineate how HRM practices i.e., discipline and compensation were related to operational performance through job satisfaction. In doing so, mediating role (either complete or partial) of job satisfaction was examined. Results revealed that training and development, discipline and compensation significantly predictedhigh school teachers’ perceived operational performance effort; and job satisfaction has shown both partial and complete mediation effects in the relationships between HRM practices and operational performance. Moderating variable, viz., gender did moderate none of relationships among independent, mediator and predicted variables. Thus, school teachers’ operational performance and job satisfaction resultant from HRM practices do not differ significantly by gender status. The key implication of the study is assisting the management committee of higher secondary schools in focusing on specific HRM practices to draw out school teachers’ performance effort. And all HR practices more or less important for educational institutions but to boost up employee performance effort training & development, discipline and compensation system are more imperative.

Key Clinical Message Spontaneous superior mesenteric artery (SMA) dissection is a rare, but potentially fatal disease. Prompt diagnosis and treatment of SMA dissections result in a lower prevalence of intestinal infarction and mortality. In the current era, imaging techniques can promptly diagnose SMA dissection; however, no definitive guidelines have been established to treat this condition. Spontaneous superior mesenteric artery (SMA) dissection is a rare, but potentially fatal disease. Prompt diagnosis and treatment of SMA dissections result in a lower prevalence of intestinal infarction and mortality. In the current era, imaging techniques can promptly diagnose SMA dissection; however, no definitive guidelines have been established to treat this condition.

Abstract Background Typhoid and paratyphoid remain the most common bloodstream infections in many resource-poor settings. The World Health Organization recommends typhoid conjugate vaccines for country-specific introduction, but questions regarding typhoid and paratyphoid epidemiology persist, especially regarding their severity in young children. Methods We conducted enteric fever surveillance in Bangladesh from 2004 through 2016 in the inpatient departments of 2 pediatric hospitals and the outpatient departments of 1 pediatric hospital and 1 private consultation clinic. Blood cultures were conducted at the discretion of the treating physicians; cases of culture-confirmed typhoid/paratyphoid were included. Hospitalizations and durations of hospitalizations were used as proxies for severity in children <12 years old. Results We identified 7072 typhoid and 1810 paratyphoid culture-confirmed cases. There was no increasing trend in the proportion of paratyphoid over the 13 years. The median age in the typhoid cases was 60 months, and 15% of the cases occurred in children <24 months old. The median age of the paratyphoid cases was significantly higher, at 90 months (P < .001); 9.4% were in children <24 months old. The proportion of children (<12 years old) hospitalized with typhoid and paratyphoid (32% and 21%, respectively) decreased with age; there was no significant difference in durations of hospitalizations between age groups. However, children with typhoid were hospitalized for longer than those with paratyphoid. Conclusions Typhoid and paratyphoid fever are common in Dhaka, including among children under 2 years old, who have equivalent disease severity as older children. Early immunization with typhoid conjugate vaccines could avert substantial morbidity, but broader efforts are required to reduce the paratyphoid burden.

Designing comprehensive surveillance to generate credible burden estimates of enteric fever in an endemic country can be challenging because care-seeking behavior is complex and surveillance in different healthcare facilities may lead to documentation of different epidemiological characteristics. We conducted retrospective surveillance in 3 healthcare facilities to identify culture-confirmed enteric fever cases in Dhaka, Bangladesh, from January 2012 through December 2016. The study settings included (1) hospital in-patient department (IPD), (2) hospital out-patient department (OPD), and (3) private consultation center OPD. We analyzed the cases to understand their distribution, age ranges, and antibiotic susceptibility patterns across the settings. Of the 1837 culture-confirmed enteric fever cases, 59% (1079 of 1837) were OPD cases. Children with enteric fever hospitalized in the IPDs were younger than children seeking care at the hospital OPD (median age: 45 vs 60 months) or private OPD (median age: 45 vs 72 months). Multidrug resistance rates were slightly higher in hospital IPD cases than in private OPD cases (26% vs 24%). In each facility, we identified different epidemiological characteristics, and lack of consideration of any of these may result in misinterpretation of disease burden, identification of different age groups, and/or antibiotic susceptibility patterns.

Disclosure: J. Seidenberg: None. M.J. Ansari: None. Background: Resistant HTN, blood pressure remaining above goal despite concurrent use of three antihypertensives of different classes at maximum doses is a common presentation in both endocrinology and primary care settings. Patients can often be prescribed multiple max-dosed antihypertensives with varying results and adverse effects and still spend years with uncontrolled HTN leading to long term health concerns. Hyperaldosteronism is diagnosed for resistant HTN in 4% of primary care patients and 10% endocrinology-referred patients. Adrenal adenomas account for 40% of all cases characterized by high aldosterone/renin activity ratio, hypokalemia, mild hypernatremia and hypomagnesemia commonly diagnosed with a mass found in the adrenals on CT. Clinical Case: Patient is a 39 year old Female who presented to the endocrinology office due to elevated urine metanephrine levels, BP 159/100. Patient had resistant HTN since her early 20s treated currently with labetalol and nifedipine, and hypokalemia treated with potassium supplements. Lab results revealed potassium 3.4 mmol/L (3.6 -5.2 mmol/L), normetanephrines 787 mcg/g (0-145 mcg/g) , aldosterone 11 ng/dL (2-9 ng/dL) , renin 0.2 ng/mL/h (0.7- 3.3 ng/mg/hr), aldosterone/renin activity ratio 55 (<25) . Renal US showed no renal artery stenosis. The patient was suspected of having hyperaldosteronism using cutoff ratios aldosterone renin ratio >30, and 15 years of potassium levels between 3.0 and 3.5. CT of the adrenals revealed no masses. Patient underwent IR guided venous sampling which indicated R adrenal gland producing 45x more aldosterone than the L adrenal gland. Patient underwent R sided adrenalectomy for definitive management of primary hyperaldosteronism. Pathology showed cortical adenoma. Patient was continued on chlorthalidone, losartan and nifedipine, and within 3 months her BP averaged 120/70 mmHg, with potassium within normal limits, Aldosterone 13 ng/dL, renin 1.25 ng/mL. Conclusion: Concurrent hyperaldosteronism with essential HTN is an uncommon but potential cause of resistant HTN. Patients with resistant HTN, prescribed multiple max-dosage antihypertensive medications while also having negative renal artery US result should undergo aldosterone and renin lab work. CT scans can have low sensitivity for adrenal adenoma. Concerning lab work should be followed up by IR-guided venous sampling for evaluation of an adrenal cortical adenoma, which can be treated surgically. Underlying essential HTN will still require treatment, but at significantly decreased medication dosages. Patients with resistant HTN should be evaluated for hyperaldosteronism early in their disease course regardless of a negative CT to prevent sequelae of untreated hyperaldosteronism including cardiac hypertrophy, arrhythmias, nephrogenic diabetes insipidus and neuromuscular symptoms. Presentation: Friday, June 16, 2023

Disclosure: J. Seidenberg: None. M.J. Ansari: None. Background: Prembrolizumab, like other immunotherapies, have become a commonplace treatment for certain cancers. Its method of action is binding of the programmed cell death I receptor that blocks the binding of the programmed cell death ligand 1. PD1-1 receptors have been reported to cause autoimmune endocrinopathies including type 1 diabetes. Many patients who present with the adverse reaction of autoimmune diabetes type 1 present with ketoacidosis. However, patients already diagnosed with diabetes type 2 on insulin could have this strong initial presentation masked. Clinical Case: Patient is a 76 year old female who was recently diagnosed with bladder cancer and started on Pembrolizumab. She presented to the endocrinology clinic due to new onset poor blood sugar control with self-tested glucose levels ranging from 300-400. This patient was previously diagnosed with diabetes type II and was taking metformin, Levemir 18 units daily, Humalog 6 units AC. A C peptide level was obtained during euglycemia, which was undetectable, indicating autoimmune destruction of pancreas. Patient was continued on Pembrolizumab due to her clinical response to it and a low probability of pancreatic beta cells functioning again. Patient’s C peptide continued to be undetectable 1 year after her presentation. Conclusion: Autoimmune destruction of pancreatic beta cells from Pembrolizumab is a rare but important adverse effect. Pembrolizumab has been reported to be associated with autoimmune-related pancreatitis leading to type 1 diabetes in only 0.1% of all patients in clinical trials. We present this patient, who was already being treated with insulin for type 2 diabetes and thus was being tested for elevated glucose regularly. She was able to notice a significant change in glucose control prior to onset of symptoms. All patients who take Pembrolizumab, especially those with underlying diabetes, should be regularly evaluated for interference with pancreatic beta cells with regular glucose labs and if hyperglycemia occurs, with a C peptide level should then be ordered. Presentation: Thursday, June 15, 2023

ABSTRACT Elatostema sessile is used by traditional medicinal practitioners to treat various diseases. The methanol extract (MES) and its fractions, including petroleum ether (PES), carbon tetrachloride (TES), chloroform (CES), and aqueous soluble fractions (AES), were tested for their antioxidant, cytotoxic, analgesic, and sedative properties on Swiss albino mice. In addition, we used GCMS to determine the bioactive compounds present in the MES of E. sessile. The MES had the lowest IC50 value (24.95 μg/mL) for antioxidant activity, measured by DPPH free radical scavenging, whereas the IC50 value for ascorbic acid was 5.80 μg/mL. In cytotoxic test with brine shrimp, PES exhibited the lowest LC50 value of 6.10 μg/mL among all the extract. Using the formalin‐induced paw licking method, MES and PES showed substantial results (p < 0.001) at 400 mg/kg dose. The tail immersion test showed significant (p < 0.05) findings for MES, PES, and TES after 30, 60, and 90 min following 400 mg/kg dose administration. The hole‐cross test demonstrated highly statistically significant results (p < 0.001) for the sedative activity of PES at a dose of 400 mg/kg after 30 min of administration and for CES after 90 min. According to molecular docking investigations, the extract has the potential to function as a pain‐relieving drug by inhibiting the enzymatic activity of cyclooxygenases 1 and 2. In summary, the results indicate that E. sessile offers significant therapeutic promise in the creation of innovative therapies for cancer, pain, and sleep problems. Elatostema sessile exhibits remarkable antioxidant properties, effectively scavenging free radicals and reducing oxidative stress, crucial in preventing various diseases. Additionally, its cytotoxic potential suggests promising anticancer applications, while its analgesic effects help in pain management by modulating nociceptive pathways. Furthermore, the plant demonstrates sedative activity, contributing to CNS depression and relaxation, making it a valuable candidate for developing natural therapeutic agents in pharmacology and traditional medicine.

Introduction: Virilization in a postmenopausal woman requires evaluation for an androgen-secreting tumor. The differential diagnosis includes adrenal carcinomas and adenomas and Sertoli-Leydig cell tumors, granulosa-theca cell tumors, and hilus-cell tumors of the ovaries. We present a case of virilization in a postmenopausal woman caused by a Sertoli-Leydig cell tumor (SLCT) in which evaluation was complicated by the pattern of androgen elevation, bilateral adrenal nodules, and absence of an adnexal mass. Case: A 64-year-old female was referred for evaluation of hyperandrogenism. Hirsutism, temporal hairline regression, and unusually deep voice were noted on examination. Two total testosterone levels obtained one month apart were 146 ng/dL (2-45), and measurements of dehydroepiandrosterone sulfate (DHEAS) and androstenedione were 299 mcg/dL (12-133) and 1.84 ng/mL (0.130-0.820), respectively. Abdominal CT revealed bilateral adrenal nodules - 2 cm and - 5 Hounsfield units (HU) on the left, and 1.5 cm and 5 HU on the right - but no ovarian masses. Transvaginal ultrasonography also failed to identify a discrete ovarian mass but showed endometrial hyperplasia. Virilization, magnitude of testosterone elevation, and results of imaging were felt to be most strongly indicative of ovarian hyperthecosis, and the patient underwent laparoscopic bilateral salpingo-oophorectomy and hysterectomy. The right ovary was 2.3 cm in largest diameter and approximately 90% replaced by an orange-red mass that showed Sertoli and Leydig cells on microscopy, immunohistochemical staining for the sex cord proteins inhibin and calretinin, and presence of the Leydig cell marker melan A. It was classified as well differentiated. Additional CT imaging and robotic assisted laparoscopy confirmed a stage IA tumor. One month after surgery, hyperandrogenemia had completely resolved (total testosterone < 10 ng/dL, androstenedione 0.379 ng/mL, and DHEAS 99 mcg/dL), and changes of virilization had mostly regressed at an eight months appointment. Discussion: SLCTs are a type of sex-cord stromal ovarian tumor. They constitute < 0.5% of ovarian tumors but account for approximately 75% of testosterone-secreting ovarian masses. This patient’s case was unusual for multiple reasons: 1. Age - most SLCTs are diagnosed in the second or third decade, 2. Imaging - CT and ultrasonography usually show a solid or solid and cystic adnexal mass, and co-existing adrenal nodules are rare, likely due to typical young age of presentation, and 3. Pattern of androgen elevation - DHEAS was more than two-fold elevated, and usually < 10% of DHEA and DHEAS are produced by the ovaries. However, DHEAS fell significantly after oophorectomy. SLCTs are a potential etiology of virilization in postmenopausal women even in the absence of a detectable adnexal mass and when biochemistries and imaging raise the possibility of an adrenal source of androgen.

Background. Primary hyperparathyroidism (PHPT) is often overlooked as a potential etiology of hypercoagulability and thrombosis. We present a case in which PHPT was the only identifiable risk factor for an episode of venous thromboembolism (VTE). Case. A 64 year old female with no chronic health problems presented to the emergency department for evaluation of dyspnea and right lower extremity pain. Symptoms had steadily increased in severity over approximately one week. The patient denied any long distance travel, sustained immobility, or tobacco use, and she was not taking any prescription or over-the-counter medications. Examination was notable for right distal lower extremity pain to palpation, but no swelling or erythema was observed. Elevated D-dimer (4.00 mg/mL, < 0.50) and hypercalcemia (12.7 mg/dL, 8.8–10.5) were discovered on initial laboratory testing, and an ECG showed sinus tachycardia. CT angiography of the chest revealed extensive, bilateral pulmonary emboli, and lower extremity venous Doppler studies confirmed a right lower extremity deep venous thrombus (DVT). Unequivocally elevated intact parathyroid hormone (PTH) level (235 pg/mL, 12–88) confirmed a diagnosis of PHPT, and an apparent left lower parathyroid adenoma was identified by both Tc99m parathyroid scintigraphy and neck ultrasonography. After hydration, serum calcium remained in the range of 11.5–12.0 mg/dL. The patient was discharged home on the direct factor Xa inhibitor rivaroxaban (Xarelto™) with a plan for six months of anticoagulation before parathyroidectomy. Conclusions. The skeletal, neuromuscular, cardiovascular, and neuropsychiatric manifestations of PHPT are well described, but little is published regarding PHPT and VTE. In a multivariate analysis of participants in the fourth and fifth Tromsø surveys controlled for age, sex, and BMI, simultaneous elevations of PTH and serum calcium were associated with a nearly 80% increased risk of VTE. PHPT has been linked to several changes that predispose to a hypercoagulable state and thrombosis including dehydration, vasoconstriction, increased platelet count and levels of coagulation factors VII and X, elevated tissue plasminogen activator inhibitor-1 and D-dimer levels, and diminished tissue factor pathway inhibitor levels. Unfortunately, risk of VTE is not addressed in series documenting long-term outcomes for patients undergoing parathyroidectomy for management of PHPT. However, in cases of VTE where PHPT is diagnosed, parathyroidectomy should be considered to potentially improve hypercoagulability and reduce the risk of subsequent VTE.