Severe Murine Typhus Presenting with Acalculous Cholecystitis: A Case Report and Literature Review

A 54-year-old otherwise healthy male, who was being evaluated for prolonged fever, developed clinical and ultrasonographic signs compatible with acute acalculous cholecystitis. Diagnosis of murine typhus was confirmed by serology and the patient was treated with doxycycline. He improved rapidly and all clinical and laboratory abnormalities returned to normal. The present case dictates that knowledge of the local epidemiology and keeping a high index of clinical suspicion can help recognize uncommon manifestations of murine typhus, in order to treat appropriately and avoid unnecessary investigations and interventions

Expansion of KPC-producing klebsiella pneumoniae with various mgrB-mutations giving rise to colistin-resistance:the role of ISL3 on plasmids

BACKGROUND: mcr-1 has been reported as first plasmid gene to confer colistin-resistance. In KPC-producing Klebsiella pneumoniae (KPC-KP) isolates, however, colistin resistance is rapidly emerging through other mechanisms. This is frequently the result of disruption of mgrB gene by insertion sequences, for instance ISL3. The aim of this study is to investigate the expansion of mgrB-mutated KPC-KP. In addition, we identify localization and targets of ISL3 sequences within the core and accessory genome of common KPC-KP lineages. METHODS: Twenty-nine clinical isolates of K. pneumoniae collected from Italian patients were randomly selected. Whole genome sequences (WGS) were analysed for resistance genes, plasmids, and insertion sequences. Additionally, 27 colistin-resistant KPC-KP isolates from a previous study from Crete was assessed. FINDINGS: We observed clonal expansion of KPC-KP isolates with various mutations in mgrB among all lineages. In two Italian MLST ST512 isolates, and eight Greek ST258 isolates an identical copy of the ISL3 was inserted in mgrB nucleotide position 133. ISL3s, transposable restriction modification systems of 8154 nucleotides, were positioned on pKpQIL carrying isolates and may transpose into the chromosome. In 4 isolates, chromosomal integration of ISL3 in diverse inner-membrane proteins other than mgrB was identified. INTERPRETATION: Colistin resistance is most often explained by clonal expansion of isolates with mutated mgrB. pKpQIL-like plasmids, which are omnipresent in KPC-KP, carry insertion sequences such as ISL3 that have mgrB as a target hotspot for transposition. Transposition of insertion sequences from plasmids and subsequent clonal expansion may contribute to the emerging colistin resistance in KPC-KP

Adrenal Aging and Its Implications on Stress Responsiveness in Humans

Normal aging results in subtle changes both in ACTH and cortisol secretion. Most notable is the general increase in mean daily serum cortisol levels in the elderly, without a noteworthy alteration in the normal circadian rhythm pattern. Glucocorticoid excess seen in the elderly population can have serious consequences in both the structural and functional integrity of various key areas in the brain, including the hippocampus, amygdala, prefrontal cortex, with consequent impairment in normal memory, cognitive function, and sleep cycles. The chronically elevated glucocorticoid levels also impinge on the normal stress response in the elderly, leading to an impaired ability to recover from stressful stimuli. In addition to the effects on the brain, glucocorticoid excess is associated with other age-related changes, including loss of muscle mass, hypertension, osteopenia, visceral obesity, and diabetes, among others. In contrast to the increase in glucocorticoid levels, other adrenocortical hormones, particularly serum aldosterone and DHEA (the precursor to androgens and estrogens) show significant decreases in the elderly. The underlying mechanisms for their decrease remain unclear. While the adrenomedullary hormone, norephinephrine, shows an increase in plasma levels, associated with a decrease in clearance, no notable changes observed in plasma epinephrine levels in the elderly. The multiplicity and complexity of the adrenal hormone changes observed throughout the normal aging process, suggests that age-related alterations in cellular growth, differentiation, and senescence specific to the adrenal gland must also be considered

Clinical significance of P-class pumps in cancer (Review)

P-class pumps are specific ion transporters involved in maintaining intracellular/extracellular ion homeostasis, gene transcription, and cell proliferation and migration in all eukaryotic cells. The present review aimed to evaluate the role of P-Type pumps [Na+/K+ ATPase (NKA), H+/K+ ATPase (HKA) and Ca2+-ATPase] in cancer cells across three fronts, namely structure, function and genetic expression. It has been shown that administration of specific P-class pumps inhibitors can have different effects by: i) Altering pump function; ii) inhibiting cell proliferation; iii) inducing apoptosis; iv) modifying metabolic pathways; and v) induce sensitivity to chemotherapy and lead to antitumor effects. For example, the NKA β2 subunit can be downregulated by gemcitabine, resulting in increased apoptosis of cancer cells. The sarcoendoplasmic reticulum calcium ATPase can be inhibited by thapsigargin resulting in decreased prostate tumor volume, whereas the HKA α subunit can be affected by proton pump inhibitors in gastric cancer cell lines, inducing apoptosis. In conclusion, the present review highlighted the central role of P-class pumps and their possible use and role as anticancer cellular targets for novel therapeutic chemical agents

Burnout and motivation to study medicine among students during the COVID-19 pandemic

AimTo investigate medical students’ burnout and motivation levels in each of the six years of their studies during the COVID-19 pandemic and identify independent predictors of burnout and motivation.MethodsAn anonymous cross-sectional survey was sent to the students of all six years within our school. Burnout was measured with the adapted Oldenburg Burnout Inventory questionnaire (OLBI-S) and motivation with the updated Strength of Motivation for Medical School (SMMS-R) questionnaire. Univariate analysis was performed with the Kruskal–Wallis test and Spearman’s correlation, while multivariable analysis with linear regression models.ResultsA total of 333 medical students (52% of student body) responded. Higher burnout levels correlated with lower motivation to study medicine (rho = −0.30, p < 0.001). Burnout levels differed between the six years of medical studies, peaking in years two and four whereas being the lowest in year one (p = 0.01). Motivation levels differed significantly as well, peaking in years one and four whereas being the lowest in years five and six (p = 0.012). In the multivariable linear regression models, being a female (b = 2.22, p = 0.016), studying in the fourth year vs. first year (b = 2.54, p = 0.049), having a perceived beginner/intermediate vs. advanced/expert technology level (b = 2.05, p = 0.032) and a perceived poor school support system (b = 6.35, p < 0.001) were independently associated with higher burnout levels. Furthermore, studying in the fifth year vs. first year (b = −5.17, p = 0.019) and a perceived poor school support system (b = −3.09, p = 0.01) were independently associated with a reduced motivation to study medicine.ConclusionOur study highlighted potential areas for intervention to decrease the rate of burnout and low motivation among medical students. However, further research is needed to unravel the full effect of the pandemic on medical students

Clinical epidemiology, treatment and prognostic factors of extensively drug-resistant Acinetobacter baumannii ventilator-associated pneumonia in critically ill patients

Limited data exist regarding prognostic factors and optimal antimicrobial treatment of infections caused by extensively drug-resistant Acinetobacter baumannii (XDR-AB). This retrospective cohort study included 93 adult patients who developed ventilator-associated pneumonia (VAP) due to XDR-AB in the ICU of the University Hospital of Heraklion, Greece, from October 2012 to April 2015. XDR-AB isolates were mainly susceptible to colistin (93.5%) and tigecycline (25.8%), whereas 6 (6.5%) were pandrug-resistant. Prior to infection, patients had long durations of mechanical ventilation and hospital stay and multiple exposures to antibiotics. Median Charlson co-morbidity and APACHE II scores were 2 and 17, respectively. Mortality at 28 days of infection onset was high (34.4%) despite high rates of in-vitro-active empirical (81.7%) and definitive (90.3%) treatment. Active colistin-based combination therapy (n = 55) and monotherapy (n = 29) groups had similar 28-day mortality (27.6% vs. 30.9%, respectively) and Kaplan–Meier survival estimates over time. In multivariable Cox regression, advanced age (aHR = 1.05 per year increase, 95% CI 1.02–1.09), rapidly fatal underlying disease (aHR = 2.64, 95% CI 0.98–9.17) and APACHE II score (aHR = 1.06 per unit increase, 95% CI 0.99–1.14) were identified as independent predictors of 28-day mortality, but no difference in mortality hazards between the active colistin-based combination therapy and monotherapy groups was produced (aHR = 0.88, 95% CI 0.35–2.38). These results support the use of colistin as a first-line agent against VAP in settings where XDR-AB is endemic, but oppose the introduction of colistin-based combination therapy as standard treatment