Intraoperative Complications and Perioperative and Surgical Outcomes of Single-Port Robotics-Assisted Sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: The objective was to assess intraoperative and postoperative complication rates, along with perioperative and surgical outcomes, following single-port robotics-assisted sacrocolpopexy. METHODS: This retrospective case series included 200 patients who underwent single-port robotics-assisted sacrocolpopexy to treat Pelvic Organ Prolapse Quantification (POPQ) stage 2-4 symptomatic prolapse between April 2020 and August 2023 by a single surgeon. Intraoperative and postoperative complications and perioperative outcomes were evaluated for all the patients, whereas surgical outcomes for 74 patients were assessed at 1-year follow-up. Surgical failure was defined as the presence of any of the following: the presence of vaginal bulging symptoms, any prolapse beyond the hymen, or retreatment for prolapse. RESULTS: During the study period, 200 single-port robotics-assisted sacrocolpopexies were performed. The median age and body mass index were 65.0 years and 24.6 kg/m2 respectively. Most patients had POPQ stage 3 or 4 prolapse and underwent concomitant total hysterectomy. The median total operation time was 212.0 min, and none of the patients required conversion to laparoscopy or laparotomy. The intraoperative cystotomy rate was 2.5%, and one patient had a blood transfusion owing to presacral vessel injury. Postoperative complications of mesh exposure and wound hernia were 0.5% and 2.0% respectively. At 1 year postoperatively, the rate of composite surgical failure was 9.5%, with a 5.4% anatomical recurrence rate. None of the patients experienced apical prolapse recurrence, and one received anterior colporrhaphy for anterior compartment prolapse recurrence. CONCLUSIONS: Single-port robotics-assisted sacrocolpopexy is safe and effective, with low complication rates and favorable perioperative and surgical outcomes.

Presenteeism and social interaction in the "new normal" in Japan: a longitudinal questionnaire study.

BACKGROUND: Although social interaction and social support during the "new normal" due to coronavirus disease 2019 (COVID-19) may be related to presenteeism, the effect between these factors has not been clear for Japanese workers. The aim of this study was to describe the presenteeism of Japanese workers with reference to social interaction and social support following the lifestyle changes due to COVID-19 and to assess whether social interaction and social support affected their presenteeism. METHODS: The data were obtained from internet panel surveys from October 2020. Descriptive statistics were calculated, and multiple linear regression was conducted using the data from the first, fourth and fifth surveys, which were conducted during October to November 2020, July to August 2021, and September to October 2021, respectively. To measure presenteeism, questions from "absenteeism and presenteeism questions of the World Health Organization's Heath and Work Performance Questionnaire", short version in Japanese was utilized. Multiple linear regressions were conducted to investigate the effects of social interaction and social support-related factors on presenteeism. RESULTS: A total of 3,407 participants were included in the analysis. The mean score of absolute presenteeism from the fifth survey was 58.07 (SD = 19.71). More time spent talking with family, a larger number of social supporters and a higher satisfaction level for social support were associated with a higher absolute presenteeism score. CONCLUSIONS: Our results suggested that social support reduced the presenteeism of the Japanese workers during the "new normal" due to the COVID-19 pandemic. Social interaction with family also relieved presenteeism.

A multifaceted cellular damage repair and prevention pathway promotes high-level tolerance to ß-lactam antibiotics.

Bactericidal antibiotics are powerful agents due to their ability to convert essential bacterial functions into lethal processes. However, many important bacterial pathogens are remarkably tolerant against bactericidal antibiotics due to inducible damage repair responses. The cell wall damage response two-component system VxrAB of the gastrointestinal pathogen Vibrio cholerae promotes high-level ß-lactam tolerance and controls a gene network encoding highly diverse functions, including negative control over multiple iron uptake systems. How this system contributes to tolerance is poorly understood. Here, we show that ß-lactam antibiotics cause an increase in intracellular free iron levels and collateral oxidative damage, which is exacerbated in the ∆vxrAB mutant. Mutating major iron uptake systems dramatically increases ∆vxrAB tolerance to ß-lactams. We propose that VxrAB reduces antibiotic-induced toxic iron and concomitant metabolic perturbations by downregulating iron uptake transporters and show that iron sequestration enhances tolerance against ß-lactam therapy in a mouse model of cholera infection. Our results suggest that a microorganism's ability to counteract diverse antibiotic-induced stresses promotes high-level antibiotic tolerance and highlights the complex secondary responses elicited by antibiotics.

Cost-effectiveness analysis of adult living-donor liver transplantation in Japan.

AIM: Living-donor liver transplantation (LDLT) is a highly effective life-saving procedure; however, it requires substantial medical resources, and the cost-effectiveness of LDLT versus conservative management (CM) for adult patients with end-stage liver disease (ESLD) remains unclear in Japan. METHODS: We performed a cost-effectiveness analysis using the Diagnostic Procedure Combination (DPC) data from the nationwide database of the DPC research group. We selected adult patients (18 years or older) who were admitted or discharged between 2010 and 2021 with a diagnosis of ESLD with Child-Pugh class C or B. A decision tree and Markov model were constructed, and all event probabilities were computed in 3-month cycles over a 10-year period. The willingness-to-pay per quality-adjusted life-year (QALY) was set at 5 million Japanese yen (JPY) (49,801 US dollars [USD]) from the perspective of the public health-care payer. RESULTS: After propensity score matching, we identified 1297 and 111,849 patients in the LDLT and CM groups, respectively. The incremental cost-effectiveness ratio for LDLT versus CM for Child-Pugh classes C and B was 2.08 million JPY/QALY (20,708 USD/QALY) and 5.24 million JPY/QALY (52,153 USD/QALY), respectively. The cost-effectiveness acceptability curves showed the probabilities of being below the willingness-to-pay of 49,801 USD/QALY as 95.4% in class C and 48.5% in class B. Tornado diagrams revealed all variables in class C were below 49,801 USD/QALY while their ranges included or exceeded 49,801 USD/QALY in class B. CONCLUSIONS: Living-donor liver transplantation for adult patients with Child-Pugh class C was cost-effective compared with CM, whereas LDLT versus CM for class B patients was not cost-effective in Japan.

Structural basis of peptidoglycan endopeptidase regulation.

Most bacteria surround themselves with a cell wall, a strong meshwork consisting primarily of the polymerized aminosugar peptidoglycan (PG). PG is essential for structural maintenance of bacterial cells, and thus for viability. PG is also constantly synthesized and turned over; the latter process is mediated by PG cleavage enzymes, for example, the endopeptidases (EPs). EPs themselves are essential for growth but also promote lethal cell wall degradation after exposure to antibiotics that inhibit PG synthases (e.g., ß-lactams). Thus, EPs are attractive targets for novel antibiotics and their adjuvants. However, we have a poor understanding of how these enzymes are regulated in vivo, depriving us of novel pathways for the development of such antibiotics. Here, we have solved crystal structures of the LysM/M23 family peptidase ShyA, the primary EP of the cholera pathogen Vibrio cholerae Our data suggest that ShyA assumes two drastically different conformations: a more open form that allows for substrate binding and a closed form, which we predicted to be catalytically inactive. Mutations expected to promote the open conformation caused enhanced activity in vitro and in vivo, and these results were recapitulated in EPs from the divergent pathogens Neisseria gonorrheae and Escherichia coli Our results suggest that LysM/M23 EPs are regulated via release of the inhibitory Domain 1 from the M23 active site, likely through conformational rearrangement in vivo.

Artificial intelligence approaches to the determinants of women's vaginal dryness using general hospital data.

The aim of this study is to analyse the determinants of women's vaginal dryness using machine learning. Data came from Korea University Anam Hospital in Seoul, Republic of Korea, with 3298 women, aged 40-80 years, who attended their general health check from January 2010 to December 2012. Five machine learning methods were applied and compared for the prediction of vaginal dryness, measured by a Menopause Rating Scale. Random forest variable importance, a performance gap between a complete model and a model excluding a certain variable, was adopted for identifying major determinants of vaginal dryness. In terms of the mean squared error, the random forest (1.0597) was much better than linear regression (17.9043) and artificial neural networks with one, two and three hidden layers (1.7452, 1.7148 and 1.7736, respectively). Based on random forest variable importance, the top-10 determinants of vaginal dryness were menopause age, age, menopause, height, thyroid stimulating hormone, neutrophils, years since menopause, lymphocytes, alkaline phosphatase and blood urea nitrogen. In addition, its top-20 determinants were peak expiratory flow rate, low-density lipoprotein cholesterol, white blood cells, monocytes, cancer antigen 19-9, creatinine, eosinophils, total cholesterol, triglyceride and amylase. Machine learning presents a great decision support system for the prediction of vaginal dryness. For preventing vaginal dryness, preventive measures would be needed regarding early menopause, the thyroid function and systematic inflammation.Impact StatementWhat is already known on this subject? Only a few studies have investigated the risk factors of vaginal dryness in middle-aged women. More research is to be done for finding its various risk factors, identifying its major risk groups and drawing its effective clinical implications.What do the results of this study add? This study is the first machine-learning study to predict women's vaginal dryness and analyse their determinants. The random forest could discuss which factors are more important for the prediction of vaginal dryness. Based on random forest variable importance, menopause age was the most important determinant of vaginal dryness and their association was discovered to be negative in this study. Vaginal dryness was closely associated with the height, rather than the body weight or body mass index. The importance rankings of blood conditions related to systematic inflammation were within the top-20 in this study: neutrophils, lymphocytes, white blood cells, monocytes and eosinophils.What are the implications of these findings for clinical practice and/or further research? Machine learning presents a great decision support system for the prediction of vaginal dryness. For preventing vaginal dryness, preventive measures would be needed regarding early menopause and systematic inflammation.

Nationwide multicenter questionnaire surveys on countermeasures against antimicrobial resistance and infections in hospitals.

BACKGROUND: The goals of the National Action Plan on Antimicrobial Resistance (AMR) of Japan include "implementing appropriate infection prevention and control" and "appropriate use of antimicrobials," which are relevant to healthcare facilities. Specifically, linking efforts between existing infection control teams and antimicrobial stewardship programs was suggested to be important. Previous studies reported that human resources, such as full-time equivalents of infection control practitioners, were related to improvements in antimicrobial stewardship. METHODS: We posted questionnaires to all teaching hospitals (n = 1017) regarding hospital countermeasures against AMR and infections. To evaluate changes over time, surveys were conducted twice (1st survey: Nov 2016, 2nd survey: Feb 2018). A latent transition analysis (LTA) was performed to identify latent statuses, which refer to underlying subgroups of hospitals, and effects of the number of members in infection control teams per bed on being in the better statuses. RESULTS: The number of valid responses was 678 (response rate, 66.7%) for the 1st survey and 559 (55.0%) for the 2nd survey. More than 99% of participating hospitals had infection control teams, with differences in activity among hospitals. Roughly 70% had their own intervention criteria for antibiotics therapies, whereas only about 60 and 50% had criteria established for the use of anti-methicillin-resistant Staphylococcus aureus antibiotics and broad-spectrum antibiotics, respectively. Only 50 and 40% of hospitals conducted surveillance of catheter-associated urinary tract infections and ventilator-associated pneumonia, respectively. Less than 50% of hospitals used maximal barrier precautions for central line catheter insertion. The LTA identified five latent statuses. The membership probability of the most favorable status in the 2nd study period was slightly increased from the 1st study period (23.6 to 25.3%). However, the increase in the least favorable status was higher (26.3 to 31.8%). Results of the LTA did not support a relationship between increasing the number of infection control practitioners per bed, which is reportedly related to improvements in antimicrobial stewardship, and being in more favorable latent statuses. CONCLUSIONS: Our results suggest the need for more comprehensive antimicrobial stewardship programs and increased surveillance activities for healthcare-associated infections to improve antimicrobial stewardship and infection control in hospitals.

Effects of periodontal management for patients with type 2 diabetes on healthcare expenditure, hospitalization and worsening of diabetes: an observational study using medical, dental and pharmacy claims data in Japan.

AIMS: To investigate the effects of regular periodontal management for people with type 2 diabetes on total healthcare expenditure, hospitalization and the introduction of insulin. MATERIALS AND METHODS: We collected data of individuals who were prescribed diabetes medications during the fiscal year 2015 from the claims database of a prefecture in Japan. We fitted generalized linear models that had sex, age, comorbidities and the status of periodontal management during the previous two years as predictors. RESULTS: A total of 16,583 individuals were enrolled. The annual healthcare expenditure in the third year was 4% less (adjusted multiplier 0.96, 95% confidence interval [CI] 0.92-1.00) in the group receiving periodontal management every year. The adjusted odds ratio (aOR) for all-cause hospitalization was 0.90 (95% CI: 0.82-0.98). The aOR of introducing insulin in the third year for those who had not been prescribed insulin during the previous two years (n = 13,222) was 0.77 (95% CI: 0.64-0.92) in the group receiving periodontal management every year. CONCLUSION: Regular periodontal management for diabetic people was associated with reduced healthcare expenditure, all-cause hospitalization and the introduction of insulin therapy.

Early impact of school closure and social distancing for COVID-19 on the number of inpatients with childhood non-COVID-19 acute infections in Japan.

Many countries have implemented school closures as part of social distancing measures intended to control the spread of coronavirus disease 2019 (COVID-19). The aim of this study was to assess the early impact of nationwide school closure (March-May 2020) and social distancing for COVID-19 on the number of inpatients with major childhood infectious diseases in Japan. Using data from the Diagnosis Procedure Combination system in Japan, we identified patients aged 15 years or younger with admissions for a diagnosis of upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), influenza, gastrointestinal infection (GII), appendicitis, urinary tract infection (UTI), or skin and soft tissue infection (SSTI) between July 2018 and June 2020. Changes in the trend of the weekly number of inpatients between the two periods were assessed using interrupted time-series analysis. A total of 75,053 patients in 210 hospitals were included. The overall weekly number of inpatients was decreased by 52.5%, 77.4%, and by 83.4% in the last week of March, April, and May 2020, respectively, when compared on a year-on-year basis. The estimated impact was a reduction of 581 (standard error 42.9) inpatients per week in the post-school-closure period (p < 0.001). The main part of the reduction was for pre-school children. Remarkable decreases in the number of inpatients with URI, LRTI, and GII were observed, while there were relatively mild changes in the other groups.Conclusion: We confirmed a marked reduction in the number of inpatients with childhood non-COVID-19 acute infections in the post-school-closure period. What is Known: • Most countries have implemented social distancing measures to limit the spread of the novel coronavirus disease 2019 (COVID-19). • A large decrease in pediatric emergency visits has been reported from several countries after the social distancing. What is New: • Based on administrative claims data, a marked reduction in the number of inpatients for childhood non-COVID-19 acute infections was found in the post-school-closure period in Japan. • The magnitude of the reduction was different between the disease groups.

Caffeine-induced hypokalemia: a case report.

BACKGROUND: With an increase in the global popularity of coffee, caffeine is one of the most consumed ingredients of modern times. However, the consumption of massive amounts of caffeine can lead to severe hypokalemia. CASE PRESENTATION: A 29-year-old man without a specific past medical history was admitted to our hospital with recurrent episodes of sudden and severe lower-extremity weakness. Laboratory tests revealed low serum potassium concentration (2.6-2.9 mmol/L) and low urine osmolality (100-130 mOsm/kgH2O) in three such prior episodes. Urinary potassium/urinary creatinine ratio was 12 and 16 mmol/gCr, respectively. The patient was not under medication with laxatives, diuretics, or herbal remedies. Through an in-depth interview, we found that the patient consumed large amounts of caffeine-containing beverages daily, which included > 15 cups of coffee, soda, and various kinds of tea. After the cessation of coffee intake and concomitant intravenous potassium replacement, the symptoms rapidly resolved, and the serum potassium level normalized. CONCLUSIONS: An increased intracellular shift of potassium and increased loss of potassium in urine due to the diuretic action have been suggested to be the causes of caffeine-induced hypokalemia. In cases of recurring hypokalemia of unknown cause, high caffeine intake should be considered.

Machine Learning Approaches to Identify Factors Associated with Women's Vasomotor Symptoms Using General Hospital Data.

BACKGROUND: To analyze the factors associated with women's vasomotor symptoms (VMS) using machine learning. METHODS: Data on 3,298 women, aged 40-80 years, who attended their general health check-up from January 2010 to December 2012 were obtained from Korea University Anam Hospital in Seoul, Korea. Five machine learning methods were applied and compared for the prediction of VMS, measured by the Menopause Rating Scale. Variable importance, the effect of a variable on model performance, was used for identifying the major factors associated with VMS. RESULTS: In terms of the mean squared error, the random forest (0.9326) was much better than linear regression (12.4856) and artificial neural networks with one, two, and three hidden layers (1.5576, 1.5184, and 1.5833, respectively). Based on the variable importance from the random forest, the most important factors associated with VMS were age, menopause age, thyroid-stimulating hormone, and monocyte, triglyceride, gamma glutamyl transferase, blood urea nitrogen, cancer antigen 19-9, C-reactive protein, and low-density lipoprotein cholesterol levels. Indeed, the following variables were ranked within the top 20 in terms of variable importance: cancer antigen 125, total cholesterol, insulin, free thyroxine, forced vital capacity, alanine aminotransferase, forced expired volume in 1 second, height, homeostatic model assessment for insulin resistance, and carcinoembryonic antigen. CONCLUSION: Machine learning provides an invaluable decision support system for the prediction of VMS. For managing VMS, comprehensive consideration is needed regarding thyroid function, lipid profile, liver function, inflammation markers, insulin resistance, monocyte count, cancer antigens, and lung function.

Surgical volume reduction and the announcement of triage during the 1st wave of the COVID-19 pandemic in Japan: a cohort study using an interrupted time series analysis.

PURPOSE: The coronavirus disease (COVID-19) pandemic has caused unprecedented challenges for surgical staffs to minimize exposure to COVID-19 or save medical resources without harmful patient outcomes, in accordance with the statement of each surgical society. No research has empirically validated declines in surgical volume in Japan, based on the usage of surgical triage. We aimed to identify whether the announcement of surgical priorities by each Japanese surgical society may have affected the surgical volume decline during the 1st wave of this pandemic. METHODS: We extracted 490,719 available cases of patients aged > 15 years who underwent elective major surgeries between July 1, 2018, and June 30, 2020. After the categorization of surgical specialities, we calculated descriptive statistics to compare the year-over-year trend and conducted an interrupted time series analysis to validate the decline of each surgical procedure. RESULTS: Monthly surgical cases of eight surgical specialities, especially ophthalmology and ear/nose/throat surgeries, decreased from April 2020 and reached a minimum in May 2020. An interrupted time series analysis showed no significant trends in oncological and critical surgeries. CONCLUSION: Non-critical surgeries showed obvious and statistically significant declines in case volume during the 1st wave of the COVID-19 pandemic according to the statement of each surgical society in Japan.

Characterization of an anti-FLAG antibody binding protein in V. cholerae.

FLAG-tags are commonly used for protein abundance measurements and for identification of protein-protein interactions in living cells. We have observed that the cholera pathogen Vibrio cholerae encodes a FLAG-antibody-reactive protein and identified this protein as an outer membrane porin, Porin4, which contains a sequence very similar to the 3xFLAG epitope tag. We have demonstrated the binding affinity of the conserved peptide sequence (called Porin 4 tag) in Porin4 against monoclonal anti-FLAG M2 antibody. In addition, we created a porin4 deletion mutant, which can be used for background-less FLAG antibody detection experiments.

Effects of Repetitive Transcranial Magnetic Stimulation on Improvement of Mental Health and Clinical Parameters in Depressed Hemodialysis Patients: a Pilot Study.

BACKGROUND: This study aimed to evaluate the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) as a nonpharmacologic treatment in depressed hemodialysis patients. METHODS: Patients who scored ≥ 5 on the Patient Health Questionnaire-9 were randomized to either the rTMS (n = 7) or sham group (n = 7). The rTMS group was stimulated with a 110% motor threshold and 10 Hz on the left dorsolateral prefrontal cortex for 20 minutes, three times a week, for 4 weeks. In the sham group, the "1-wing 90-degree method" was used. We analyzed clinical indices before and after the intervention, as well as data from quantitative electroencephalography (frontal alpha asymmetry [FAA]), and various psychiatric questionnaires (Beck Depression Inventory-II, Beck Anxiety Inventory [BAI], Symptom Checklist-90-Revised Somatization Subscale [SCL-90R-SOM]), and Perceived Stress Scale. RESULTS: One month after rTMS, the changes in hemoglobin A1c levels in the rTMS group were significantly greater than those in the sham group (F = 6.687, P = 0.032). The changes in BAI scores in the rTMS group were significantly greater than those in the sham group (F = 6.700, P = 0.025), and the changes in SCL-90R-SOM scores in the rTMS group were greater than those in the sham group (F = 4.943, P = 0.048). In addition, the changes in the FAA value at the F7 and F8 electrodes in the rTMS group were greater than those in the sham group (F = 6.468, P = 0.027). CONCLUSION: In depressed hemodialysis patients, rTMS may improve anxiety and somatization symptoms, which may lead to improvements in clinical measures. Trial Registration Clinical Research Information Service Identifier: KCT0004082.

Spheroplast-Mediated Carbapenem Tolerance in Gram-Negative Pathogens.

Antibiotic tolerance, the ability to temporarily sustain viability in the presence of bactericidal antibiotics, constitutes an understudied and yet potentially widespread cause of antibiotic treatment failure. We have previously shown that the Gram-negative pathogen Vibrio cholerae can tolerate exposure to the typically bactericidal ß-lactam antibiotics by assuming a spherical morphotype devoid of detectable cell wall material. However, it is unclear how widespread ß-lactam tolerance is. Here, we tested a panel of clinically significant Gram-negative pathogens for their response to the potent, broad-spectrum carbapenem antibiotic meropenem. We show that clinical isolates of Enterobacter cloacae, Klebsiella aerogenes, and Klebsiella pneumoniae, but not Escherichia coli, exhibited moderate to high levels of tolerance of meropenem, both in laboratory growth medium and in human serum. Importantly, tolerance was mediated by cell wall-deficient spheroplasts, which readily recovered wild-type morphology and growth upon removal of antibiotic. Our results suggest that carbapenem tolerance is prevalent in clinically significant bacterial species, and we suggest that this could contribute to treatment failure associated with these organisms.

Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis?

In the healthy endometrium, progesterone and estrogen signaling coordinate in a tightly regulated, dynamic interplay to drive a normal menstrual cycle and promote an embryo-receptive state to allow implantation during the window of receptivity. It is well-established that progesterone and estrogen act primarily through their cognate receptors to set off cascades of signaling pathways and enact large-scale gene expression programs. In endometriosis, when endometrial tissue grows outside the uterine cavity, progesterone and estrogen signaling are disrupted, commonly resulting in progesterone resistance and estrogen dominance. This hormone imbalance leads to heightened inflammation and may also increase the pelvic pain of the disease and decrease endometrial receptivity to embryo implantation. This review focuses on the molecular mechanisms governing progesterone and estrogen signaling supporting endometrial function and how they become dysregulated in endometriosis. Understanding how these mechanisms contribute to the pelvic pain and infertility associated with endometriosis will open new avenues of targeted medical therapies to give relief to the millions of women suffering its effects.

Bacillus subtilis MntR coordinates the transcriptional regulation of manganese uptake and efflux systems.

The Bacillus subtilis MntR metalloregulatory protein senses manganese, an essential element required for central metabolism, oxidative stress resistance and replication. An mntR null mutant is highly sensitive to Mn(II) intoxication, which is attributed in part to the constitutive expression of two importers: the proton-dependent NRAMP family transporter MntH and the ABC transporter MntABCD. Here, we show that an mntR null mutant is still sensitive to Mn(II) intoxication even if both of the import systems are absent. This Mn(II) sensitivity results from the requirement for MntR to activate the transcription of two genes encoding cation diffusion facilitator (CDF) family efflux pumps. Physiological studies indicate that MneP (formerly YdfM) serves as the primary Mn(II) efflux pump with MneS (formerly YeaB) playing a secondary role. Mutant strains lacking mneP are Mn(II) sensitive and accumulate elevated levels of Mn(II), and these effects are exacerbated in a mneP mneS double mutant. DNA-binding and in vitro transcription studies demonstrate that MntR binds to both the mneP and mneS regulatory regions and directly activates transcription in response to levels of Mn(II) several-fold higher than required for repression of import genes. These results highlight the delicate balance of Mn(II) uptake and efflux systems controlled by MntR.

Genetic Determinants of Penicillin Tolerance in Vibrio cholerae.

Many bacteria are resistant to killing (tolerant) by typically bactericidal antibiotics due to their ability to counteract drug-induced cell damage. Vibrio cholerae, the cholera agent, displays an unusually high tolerance to diverse inhibitors of cell wall synthesis. Exposure to these agents, which in other bacteria leads to lysis and death, results in a breakdown of the cell wall and subsequent sphere formation in V. cholerae Spheres readily recover to rod-shaped cells upon antibiotic removal, but the mechanisms mediating the recovery process are not well characterized. Here, we found that the mechanisms of recovery are dependent on environmental conditions. Interestingly, on agarose pads, spheres undergo characteristic stages during the restoration of rod shape. Drug inhibition and microscopy experiments suggest that class A penicillin binding proteins (aPBPs) play a more active role than the Rod system, especially early in sphere recovery. Transposon insertion sequencing (TnSeq) analyses revealed that lipopolysaccharide (LPS) and cell wall biogenesis genes, as well as the sigma E cell envelope stress response, were particularly critical for recovery. LPS core and O-antigen appear to be more critical for sphere formation/integrity and viability than lipid A modifications. Overall, our findings demonstrate that the outer membrane is a key contributor to beta lactam tolerance and suggest a role for aPBPs in cell wall biogenesis in the absence of rod-shape cues. Factors required for postantibiotic recovery could serve as targets for antibiotic adjuvants that enhance the efficacy of antibiotics that inhibit cell wall biogenesis.

Influence of Major Coping Strategies on Treatment Non-adherence and Severity of Comorbid Conditions in Hemodialysis Patients.

BACKGROUND: Non-adherence and comorbidities are prevalent among hemodialysis patients and are associated with increased mortality and financial burden. We aimed to investigate the influence of major coping strategies (CSs) on non-adherence and comorbidities in hemodialysis patients. METHODS: A total of 49 patients were enrolled. We collected participant data including CS measured by a Korean version of the ways of coping questionnaire (K-WCQ), comorbidities measured by age-adjusted Charlson comorbidity index (CCI), and adherence measured by the 8-item Morisky medication adherence scale (MMAS-8). RESULTS: Regarding major CS, 61.2% of participants reported use of support-seeking CS (SUP group), 14.3% reported use of problem-focused CS (PRO group), and 24.5% reported use of hopeful-thinking CS (HOP group). The mean MMAS-8 score was higher in the PRO group than in the HOP group (P = 0.024). The mean CCI score was lower in the PRO group than in the HOP group (P = 0.017). In the HOP group, the severity of somatic symptoms was positively correlated with the scores for the emotion-focused CS subscale (r = 0.39, P = 0.029) and the hopeful-thinking CS subscale (r = 0.38, P = 0.036) of the K-WCQ. The level of life satisfaction positively correlated with the score for the problem-focused CS subscale in the HOP group (r = 0.40, P = 0.027). CONCLUSION: We should pay more attention to the CSs of hemodialysis patients and provide interventions that promote problem-focused CSs, especially for nonadherent patients with high comorbidity rates who mainly use a hopeful-thinking CS.

Variation in MicroRNA Expression Profile of Uterine Leiomyoma with Endometrial Cavity Distortion and Endometrial Cavity Non-Distortion.

The expression profile of microRNA (miRNA) in uterine leiomyoma (UL) cells is different from that in normal uterine myometrial (UM) cells. The effect of UL cells on uterine receptivity might vary according to their ability to distort the uterine endometrial cavity. However, the variation in miRNA expression profiles between endometrial cavity-distorting leiomyoma (ECDL) and endometrial cavity non-distorting leiomyoma (ECNDL) cells remains unknown. This study aimed to elucidate whether the expression profile of miRNAs in ECDL cells is dissimilar to that of ECNDL cells in uterus. Pelviscopic myomectomy was performed to obtain tissue samples of UL and their corresponding normal UM tissues (matched) from patients with UL (n = 26), among whom women with ECNDL and ECDL numbered 15 and 11, respectively. The relative expression of hsa-miR-15b, -29a, -29b, -29c, -197, and -200c as well as the candidate target genes in UL cells was compared to those in the matched UM cells using qRT-PCR to assess their ability to cause ECD. The spatial expression of miRNAs and target genes in the UL tissues was analyzed using in situ hybridization. Target gene expression was analyzed using qPCR after transfection with the mimics and inhibitors of miRNAs in UL cells. The relative expression level of miR-15b was upregulated, and the relative expression levels of miR-29a, -29b, -29c, -197, and -200c were downregulated in UL cells compared to those in UM cells. The relative expression levels of progesterone receptor, estrogen receptor, and matrix metalloproteinases (MMPs) were upregulated in UL cells compared to those in UM cells. The relative expression levels of miR-29c and -200c were downregulated, and the relative expression levels of estrogen receptor, MMPs and tissue inhibitors of metalloproteinases (TIMPs) were upregulated in ECDL cells compared to those in ECNDL cells. The expression profile of miRNAs in UL cells varied with respect to the occurrence or absence of endometrial cavity distortion. The biochemical properties of UL might be regulated by miRNAs in order to alter their effect on structural homeostasis of the uterus.