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Abstract To investigate the impact on the ovarian reserve after minimally invasive ovarian cystectomy using two platforms, the Da Vinci robotic system (Xi and SP) and the laparoscopic system. Patients underwent laparoscopic or Da Vinci robotic (Xi or SP) ovarian cystectomy for benign ovarian cysts between January 1, 2018, and December 31, 2022 at Guro Hospital, Korea University Medical center. We measured the change of AMH values (%) = [(postAMH − preAMH)] × 100/preAMH. No significant differences in preoperative age, cyst size, estimated blood loss during surgery, hemoglobin drop, length of hospital stay, adhesion detachment rate and cyst rupture rate were observed. However, the operative time was significantly shorter in the laparoscopic group than that in the robotic group (67.78 ± 30.58 min vs. 105.17 ± 38.87 min, p < 0.001) The mean preAMH and postAMH were significantly higher with the Da Vinci robotic group than with the laparoscopic group (preAMH: 5.89 ± 4.81 ng/mL vs. 4.01 ± 3.59 ng/mL, p = 0.02, postAMH: 4.36 ± 3.31 ng/mL vs. 3.08 ± 2.60 ng/mL, p = 0.02). However, the mean ΔAMH was not significantly different between two groups. ΔAMH also did not demonstrate significant differences among the three groups; laparoscopic, Xi and SP robotic. Even in the patient groups with preAMH < 2 and diagnosed with endometriosis, the ΔAMH did not show significant differences between the laparoscopic and robotic groups. The Da Vinci robotic system is no inferior to conventional laparoscopic systems in preserving ovarian function.

This review aimed to summarize the complications and surgical outcomes of robot-assisted sacrocolpopexy. Nineteen original articles on 1,440 robotic sacrocolpopexies were reviewed, and three systematic reviews and meta-analyses were summarized in terms of intraoperative, perioperative, postoperative, and/or surgical outcomes. Robotic sacrocolpopexy has demonstrated low overall complication rates and favorable surgical outcomes. Nevertheless, long-term follow-up outcomes regarding objective and/or subjective prolapse recurrence, reoperation rates, and mesh-related complications remain unclear. Further research is required to demonstrate whether the robotic approach for sacrocolpopexy is feasible or can become the modality of choice in the future when performing sacrocolpopexy.

Abstract Mechanosensitive mechanisms are often used to sense damage to tissue structure, stimulating matrix synthesis and repair. While this kind of mechanoregulatory process is well recognized in eukaryotic systems, it is not known whether such a process occurs in bacteria. In Vibrio cholerae, antibiotic-induced damage to the load-bearing cell wall promotes increased signaling by the two-component system VxrAB, which stimulates cell wall synthesis. Here we show that changes in mechanical stress within the cell envelope are sufficient to stimulate VxrAB signaling in the absence of antibiotics. We applied mechanical forces to individual bacteria using three distinct loading modalities: extrusion loading within a microfluidic device, direct compression and hydrostatic pressure. In all cases, VxrAB signaling, as indicated by a fluorescent protein reporter, was increased in cells submitted to greater magnitudes of mechanical loading, hence diverse forms of mechanical stimuli activate VxrAB signaling. Reduction in cell envelope stiffness following removal of the endopeptidase ShyA led to large increases in cell envelope deformation and substantially increased VxrAB response, further supporting the responsiveness of VxrAB. Our findings demonstrate a mechanosensitive gene regulatory system in bacteria and suggest that mechanical signals may contribute to the regulation of cell wall homeostasis.

Abstract Since the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, guidance (“Japanese Guide”) has been published by a working group of several academic societies and announced by the Ministry of Health, Labour, and Welfare. Steroids as a candidate treatment for COVID-19 were noted in the Japanese Guide. However, the prescription details for steroids, and whether the Japanese Guide changed its clinical practice, were unclear. This study aimed to examine the impact of the Japanese Guide on the trends in the prescription of steroids for COVID-19 inpatients in Japan. We selected our study population using Diagnostic Procedure Combination (DPC) data from hospitals participating in the Quality Indicator/Improvement Project (QIP). The inclusion criteria were patients discharged from hospital between January 2020 and December 2020, who had been diagnosed with COVID-19, and were aged 18 years or older. The epidemiological characteristics of cases and the proportion of steroid prescriptions were described on a weekly basis. The same analysis was performed for subgroups classified by disease severity. The study population comprised 8603 cases (410 severe cases, 2231 moderate II cases, and 5962 moderate I/mild cases). The maximum proportion of cases prescribed with dexamethasone increased remarkably from 2.5 to 35.2% in the study population before and after week 29 (July 2020), when dexamethasone was included in the guidance. These increases were 7.7% to 58.7% in severe cases, 5.0% to 57.2% in moderate II cases, and 1.1% to 19.2% in moderate I/mild cases. Although the proportion of cases prescribed prednisolone and methylprednisolone decreased in moderate II and moderate I/mild cases, it remained high in severe cases. We showed the trends of steroid prescriptions in COVID-19 inpatients. The results showed that guidance can influence drug treatment provided during an emerging infectious disease pandemic.

Background: A serious shortage of cefazolin (CEZ) occurred in Japan in 2019. We compared the impact of the CEZ shortage on the selection of parenteral antibiotics at affected and non-affected hospitals. Methods: The data were extracted from a nationwide Japanese administrative database and included all hospitalized cases between April 2016 and December 2020. We defined ‘hospitals with shortage’ as those hospitals with a statistically significant decrease in the use of CEZ during the supply disruption period compared to the same months of the previous year; other hospitals as ‘hospitals without shortage’. We determined the proportion of each selected parenteral antibiotic use to the sum of all selected antibiotic use in the two groups of hospitals during the supply disruption period and during the same months of the previous year. A controlled interrupted time series (CITS) analysis was conducted to estimate the impact of the CEZ shortage on each antibiotic use and the cost of all parenteral antibiotics per patient day in hospitals with shortage as compared to those without shortage. Results: In the hospitals with shortage, the proportion of CEZ use to the sum of all selected antibiotics decreased (23.5–11.1%). The decrease in CEZ use was mainly offset by the use of ceftriaxone, ceftriaxone, and ampicillin/sulbactam. The CITS analysis showed a statistically significant increase in the use of broader-spectrum beta-lactams and clindamycin during the supply disruption period (flomoxef up 58.1%, cefotiam up 63.1%, cefmetazole up 14.5%, ceftriaxone up 13.9%, and clindamycin up 20.1%). The analysis showed no statistically significant change in the cost of all parenteral antibiotics per patient day. Conclusions: During the CEZ supply disruption, there was a statistically significant increase in the use of broader-spectrum beta-lactams and clindamycin in hospitals with shortage compared with those without shortage.

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.

Female subfertility is highly associated with endometriosis. Here the authors show that progesterone-induced MIG-6 is reduced in endometrium of infertile women and non-human primates with endometriosis, and in a mouse model find that Erbb2 is the key mediator of Mig-6 loss induced endometriosis-related infertility.

Coronavirus disease 2019 (COVID-19) is associated with a systemic inflammatory response that activates coagulation in symptomatic patients. In addition, a rare form of thrombosis has been reported in people who received the COVID-19 vaccine, most of whom were women younger than 50 years of age. Considering that hormonal contraceptive methods widely used by women of childbearing age increase the risk of thrombosis, the development of guidelines for the use of hormonal contraceptives in the era of the COVID-19 pandemic is necessary. In this context, the Korean Society of Contraception and Reproductive Health provides guidelines for issues regarding contraception and reproductive health during the pandemic.

Abstract Aims The Coronavirus Disease 2019 (COVID‐19) pandemic has had unprecedented effects on health care utilization for acute cardiovascular diseases. Although hospitalizations for acute coronary syndrome decreased during the COVID‐19 pandemic, there is a paucity of data on the trends and management of heart failure (HF) cases. Furthermore, concerns have been raised that angiotensin‐converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase susceptibility to COVID‐19. This study aimed to elucidate changes in HF hospitalizations from the COVID‐19 state of emergency in Japan and investigated changes in the prescription of ACEIs and ARBs, and in‐hospital mortality. Methods and results We performed an interrupted time series analysis of HF hospitalizations in Japan to verify the impacts of the COVID‐19 state of emergency. Changes in the weekly volume of HF hospitalizations were taken as the primary outcome measure. Between 1 April 2018 and 4 July 2020, 109 429 HF cases required admission. After the state of emergency, an immediate decrease was observed in HF cases per week [−3.6%; 95% confidence interval (CI): −0.3% to −6.7%, P = 0.03]. There was no significant change in the prescription of ACEIs or ARBs after the state of emergency (4.2%; 95% CI: −0.3% to 8.9%, P = 0.07). The COVID‐19 pandemic had no effect on in‐hospital mortality among HF patients (5.3%; 95% CI: −4.9% to 16.6%, P = 0.32). Conclusions We demonstrated a decline in HF hospitalizations during the COVID‐19 pandemic in Japan, with no clear evidence of a negative effect on the prescription of ACEIs and ARBs or in‐hospital mortality.

BackgroundThe number of people with dementia increases in an aging society; therefore, promoting policies for dementia throughout the community is crucial to creating a dementia-friendly society. Understanding the status of older adults with dementia in each region of Japan will be a helpful indicator. We calculated Dementia-free Life Expectancy and aimed to examine regional disparities and their associated factors.MethodsWe calculated Dementia-free Life Expectancy and Life Expectancy with Dementia for each secondary medical area in Japan based on the Degree of Independence in Daily Living for the Demented Elderly, using data extracted from the Japanese long-term care insurance claims database. We then conducted a partial least squares regression analysis, the objective variables being Dementia-free Life Expectancy and Life Expectancy with Dementia for both sexes at age 65, and explanatory regional-level variables included demographic, socioeconomic, and healthcare resources variables.ResultsThe mean estimated regional-level Dementia-free Life Expectancy at age 65 was 17.33 years (95% confidence interval [CI] 17.27-17.38) for males and 20.05 years (95% CI 19.99-20.11) for females. Three latent components identified by partial least squares regression analysis represented urbanicity, socioeconomic conditions, and health services-related factors of the secondary medical areas. The second component explained the most variation in Dementia-free Life Expectancy of the three, indicating that higher socioeconomic status was associated with longer Dementia-free Life Expectancy.ConclusionsThere were regional disparities in secondary medical area level Dementia-free Life Expectancy. Our results suggest that socioeconomic conditions are more related to Dementia-free Life Expectancy than urbanicity and health services-related factors.

BackgroundDischarge planning enhances the safe and timely transfer of inpatients between facilities. Predicting the discharge destination of inpatients with aspiration pneumonia is important for discharge planning. We aimed to develop and validate prediction models for the discharge destination of elderly patients with aspiration pneumonia.MethodsUsing a nationwide inpatient database, we identified aspiration pneumonia cases for patients aged ≥65 years who had been admitted to hospital from their home or from a nursing home between April 2020 and March 2021. We divided the cases into derivation and validation cohorts according to the location of the admitting hospital. We developed two prediction models by dividing the cases based on the patient's place of residence prior to admission, one model to predict the home discharge of cases admitted from home and the other to predict the home or to a nursing home discharge of cases admitted from a nursing home. The models were internally validated with bootstrapping and internal-externally validated using a validation cohort. Nomograms that could be used easily in clinical practice were also created.ResultsThe derivation cohort included 19,746 cases admitted from home and 14,359 cases admitted from a nursing home. Of the former, 10,760 (54.5%) cases were discharged home; from the latter, 7,071 (49.2%) were discharged to either home or a nursing home. The validation cohort included 6,262 cases admitted from home and 6,352 cases admitted from a nursing home. In the internal-external validation, the C-statistics of the final model for the cases admitted from home and the cases admitted from a nursing home were 0.71 and 0.67, respectively.ConclusionsWe developed and validated new prediction models for the discharge of elderly patients with aspiration pneumonia either to home or to a nursing home. Our models and nomograms could facilitate the early implementation of discharge planning.

Abstract 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.

Abstract During the coronavirus disease 2019 (COVID-19) pandemic, there have been health concerns related to alcohol use and misuse. We aimed to examine the population-level change in cases of alcohol-related liver disease and pancreatitis that required admission during the COVID-19 epidemic by interrupted time series (ITS) analysis using claims data. We defined the period from April 2020, when the Japanese government declared a state of emergency, as the beginning of the COVID-19 epidemic. This ITS analysis included 3,026,389 overall admissions and 10,242 admissions for alcohol-related liver disease or pancreatitis from 257 hospitals between July 2018 and June 2020. The rate of admissions per 1000 admissions during the COVID-19 epidemic period (April 2020–June 2020) was 1.2 times (rate ratio: 1.22, 95% confidence interval: 1.12–1.33) compared to the pre-epidemic period. Analyses stratified by sex revealed that the increases in admission rates of alcohol-related liver disease or pancreatitis for females were higher than for males during the COVID-19 epidemic period. The COVID-19 epidemic in Japan might associates an increase in hospital admissions for alcohol-related liver disease and pancreatitis. Our study could support the concern of alcohol consumption and health problems during the COVID-19 pandemic.

Objective: The coronavirus disease 2019 (COVID-19) pandemic has affected all healthcare systems. This study aimed to assess the impact of the COVID-19 pandemic on the number and severity of cases of community-acquired pneumonia (CAP) in Japan. Methods: Using claims data from the Quality Indicator/Improvement Project (QIP) database, urgent cases of inpatients for CAP from 01 August 2018 to 30 July 2020 were included. The monthly ratios of inpatient cases were compared from August 2018 to July 2019 and August 2019 to July 2020 as a year-over-year comparison. These ratios were also compared according to the “A-DROP” severity score, and an interrupted time series (ITS) analysis was performed to evaluate the impact of the COVID-19 pandemic on the monthly number of inpatient cases. Results: This study included a total of 67,900 inpatient cases for CAP in 262 hospitals. During the COVID-19 pandemic (defined as the period between March and July 2020) the number of inpatient cases for CAP drastically decreased compared with the same period in the previous year (–48.1%), despite a temporary reduction in the number of other urgent admissions. The number of inpatient cases decreased according to the severity of pneumonia. Milder cases showed a greater decrease in the year-over-year ratio than severe ones: mild –55.2%, moderate –45.8%, severe –39.4%, and extremely severe –33.2%. The ITS analysis showed that the COVID-19 pandemic significantly reduced the monthly number of inpatient cases for CAP (estimated decrease: –1233 cases; 95% CI –521 to –1955). Conclusions: This study showed a significant reduction in the number of inpatient cases for CAP during the COVID-19 pandemic in Japan. The milder cases showed a greater decrease in the year-over-year ratio of the number of inpatient cases.

Abstract 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.

Uterine disease: Regulatory pathways identified A regulatory link between two proteins involved in the progression of a debilitating uterine condition highlights a potential therapeutic target. Adenomyosis involves the invasion of cells from the inner lining of the uterus (the endometrium) into the uterine muscle wall (the myometrium), resulting in heavy, prolonged periods and chronic pain. The aberrent activation of a protein called β-catenin triggers adenomyosis, but the precise mechanisms are unclear. A team led by Jung-Ho Shin at the Korea University Medical Center, Seoul, South Korea, and Jae-Wook Jeong, Michigan State University, Grand Rapids, USA, used sequencing techniques in mice and human tissue samples to identify the pathways governed by β-catenin in adenomyosis. They found that the Tgf-β2 gene is directly regulated by β-catenin in the uterus. TGF-β2 levels were elevated in human adenomyosis lesions, suggesting the protein could be a therapeutic target.

ObjectiveThe present study assessed the prevalence of overactive bladder (OAB) symptoms in gynecologic outpatients and the effects of OAB on a patient’s quality of life.MethodsThe survey was completed by adult female patients who visited the gynecology clinic for examination or treatment of gynecologic conditions. The subjects who met the exclusion criteria were excluded. The survey included a questionnaire assessing general characteristics, the purpose of the visit, diagnosis, and the presence or absence of OAB. The subjects were asked whether they were under medical treatment for OAB symptoms, and the degree of discomfort in daily activities was evaluated.ResultsIn total, 1,990 female subjects visiting the gynecology clinics of 4 different institutions were recruited. On OAB Symptom Score, 188 subjects responded with scores of ≥2 for question #3 (≥1 time(s) weekly). The severity of OAB symptoms was as follows: 345 subjects had mild OAB, 127 subjects had moderate OAB, and 12 subjects had severe OAB. The prevalence of OAB symptoms was 10.30%.ConclusionThe present study confirmed that OAB symptoms are common, with a prevalence of 10.30%. Patients with OAB symptoms frequently neglect to seek medical intervention. Our findings will help inform patients to recognize their condition and seek medical assistance, especially in gynecologic outpatient clinics.

Background Maintaining critical care for non-Coronavirus-disease-2019 (non-COVID-19) patients is a key pillar of tackling the impact of the COVID-19 pandemic. This study aimed to reveal the medium-term impacts of the COVID-19 epidemic on case volumes and quality of intensive care for critically ill non-COVID-19 patients. Methods Administrative data were used to investigate the trends in case volumes of admissions to intensive care units (ICUs) compared with the previous years. Standardized mortality ratios (SMRs) of non-COVID-19 ICU patients were calculated in each wave of the COVID-19 epidemic in Japan. Results The ratios of new ICU admissions of non-COVID-19 patients to those in the corresponding months before the epidemic: 21% in May 2020, 8% in August 2020, 9% in February 2021, and 14% in May 2021, approximately concurrent with the peaks in COVID-19 infections. The decrease was greatest for new ICU admissions of non-COVID patients receiving invasive mechanical ventilation (IMV) on the first day of ICU admission: 26%, 15%, 19%, and 19% in the first, second, third, and fourth waves, respectively. No statistically significant change in SMR was observed in any wave of the epidemic; SMRs were 0.990 (95% uncertainty interval (UI), 0.962–1.019), 0.979 (95% UI, 0.953–1.006), 0.996 (95% UI, 0.980–1.013), and 0.989 (95% UI, 0.964–1.014), in the first, second, third, and fourth waves of the epidemic, respectively. Conclusions Compared to the previous years, the number of non-COVID-19 ICU patients continuously decreased over the medium term during the COVID-19 epidemic. The decrease in case volumes was larger in non-COVID-19 ICU patients initially receiving IMV than those undergoing other initial treatments. The standardized in-hospital mortality of non-COVID-19 ICU patients did not change in any waves of the epidemic.

The suppression of the first wave of COVID-19 in Japan is assumedly attributed to people's increased risk perception after acquiring information from the government and media reports. In this study, going out in public amidst the spread of COVID-19 infections was investigated by examining new polymerase chain reaction (PCR) positive cases of COVID-19 and its relationship to four indicators of people going out in public (the people flow, the index of web searches for going outside, the number of times people browse restaurants, and the number of hotel guests, from the Regional Economic and Social Analysis System (V-RESAS). Two waves of COVID-19 infections were examined using cross-correlation analysis. In the first wave, all four indicators of going out changed to be opposite the change in new PCR positive cases, showing a lag period of -1 to +6 weeks. In the second wave, the same relationship was only observed for the index of web searches for going outside, and two indicators showed the positive lag period of +6 to +12 weeks after the change in new PCR positive cases. Moreover, each indicator in the second wave changed differently compared to the first wave. The complexity of people's behaviors around going out increased in the second wave, when policies and campaigns were implemented and people's attitudes were thought to have changed. In conclusion, the results suggest that policies may have influenced people's mobility, rather than the number of new PCR positive cases.

Endometriosis is a chronic inflammatory condition in women, and obesity leads to an inflammatory condition that is directly involved in the etiology of endometriosis. However, observational studies have shown an inverse correlation between endometriosis and a low body mass index (BMI). Obesity does not protect against endometriosis, and on the contrary, an increased BMI may lead to more severe forms of the disease. To determine the effect of obesity on endometriosis, diet-induced and genetically engineered obese mouse models were integrated with endometriosis mouse models with fluorescence-tagged ectopic lesions. High-fat diet-induced obese mice revealed a significant increase in endometriosis development compared with regular-diet control mice. However, obese recipient mice with leptin deficiency and leptin receptor deficiency showed suppressed endometriosis development compared with control mice. Furthermore, donor uterine tissues with leptin deficiency and leptin receptor deficiency suppressed endometriosis development compared with control donor in control recipient mice. Importantly, we revealed that aberrant high levels of leptin concentration significantly increased endometriosis development compared with vehicle treatment group in control mice with normal body weight. Our results suggest that leptin and its receptor are critical for endometriosis development.

Synthesis and turnover of the bacterial cell wall must be tightly coordinated to avoid structural integrity failure and cell death. Details of this coordination are poorly understood, particularly if and how cell wall turnover enzymes are required for the activity of the different cell wall synthesis machines, the aPBPs and the Rod system.

Rare cold inducible 2 (RCI2) proteins are small hydrophobic membrane proteins in plants, and it has been widely reported that RCI2 expressions are dramatically induced by salt, cold, and drought stresses in many species. The RCI2 proteins have been shown to regulate plasma membrane (PM) potential and enhance abiotic stress tolerance when over-expressed in plants. RCI2 protein structures contain two transmembrane domains that are thought to be PM intrinsic proteins and have been observed at the PM and endomembranes. However, cellular trafficking of RCI2s are not fully understood. In this review, we discussed (i) general properties of RCI2s characterized in many species, (ii) the uses of RCI2s as a tracer in live cell imaging analyses and when they are fused to fluorescence proteins during investigations into vesicle trafficking, and (iii) RCI2 functionalities such as their involvement in rapid diffusion, endocytosis, and protein interactions. Consequently, the connection between physiological characteristics of RCI2s and traffic of RCI2s interacting membrane proteins might be helpful to understand role of RCI2s contributing abiotic stresses tolerance.

IntroductionThe coronavirus disease (COVID-19) pandemic has caused unprecedented challenges for the medical staff worldwide, especially for those in hospitals where COVID-19-positive patients are hospitalized. The announcement of COVID-19 hospital restrictions by the Japanese government has led to several limitations in hospital care, including an increased use of physical restraints, which could affect the care of elderly dementia patients. However, few studies have empirically validated the impact of physical restraint use during the COVID-19 pandemic. We aimed to evaluate the impact of regulatory changes, consequent to the pandemic, on physical restraint use among elderly dementia patients in acute care hospitals.MethodsIn this retrospective study, we extracted the data of elderly patients (aged > 64 years) who received dementia care in acute care hospitals between January 6, 2019, and July 4, 2020. We divided patients into two groups depending on whether they were admitted to hospitals that received COVID-19-positive patients. We calculated descriptive statistics to compare the trend in 2-week intervals and conducted an interrupted time-series analysis to validate the changes in the use of physical restraint.ResultsIn hospitals that received COVID-19-positive patients, the number of patients who were physically restrained per 1,000 hospital admissions increased after the government's announcement, with a maximum incidence of 501.4 per 1,000 hospital admissions between the 73rd and 74th week after the announcement. Additionally, a significant increase in the use of physical restraints for elderly dementia patients was noted (p = 0.004) in hospitals that received COVID-19-positive patients. Elderly dementia patients who required personal care experienced a significant increase in the use of physical restraints during the COVID-19 pandemic.ConclusionUnderstanding the causes and mechanisms underlying an increased use of physical restraints for dementia patients can help design more effective care protocols for similar future situations.

BackgroundThe pandemic of the coronavirus disease 2019 (COVID-19) has affected health care systems globally. The aim of our study is to assess the impact of the COVID-19 pandemic on the number of hospital admissions for ischemic stroke by severity in Japan.MethodsWe analysed administrative (Diagnosis Procedure Combination-DPC) data for cases of inpatients aged 18 years and older who were diagnosed with ischemic stroke and admitted during the period April 1 2018 to June 27 2020. Levels of change of the weekly number of inpatient cases with ischemic stroke diagnosis after the declaration of state of emergency were assessed using interrupted time-series (ITS) analysis. The numbers of patients with various characteristics and treatment approaches were compared. We also performed an ITS analysis for each group ("independent" or "dependent") divided based on components of activities of daily living (ADL) and level of consciousness at hospital admission.ResultsA total of 170,294 cases in 567 hospitals were included. The ITS analysis showed a significant decrease in the weekly number of ischemic stroke cases hospitalized (estimated decrease: -156 cases; 95% confidence interval (CI): -209 to -104), which corresponds to -10.4% (95% CI: -13.6 to -7.1). The proportion of decline in the independent group (-21.3%; 95% CI: -26.0 to -16.2) was larger than that in the dependent group (-8.6%; 95% CI: -11.7 to -5.4).ConclusionsOur results show a marked reduction in hospital admissions due to ischemic stroke after the declaration of the state of emergency for the COVID-19 pandemic. The independent cases were affected more in proportion than dependent cases.

The Legionella effector protein SidJ has recently been identified to perform polyglutamylation on another Legionella effector, SdeA, ablating SdeA’s activity. SidJ is a kinase-like protein that requires the small eukaryotic protein calmodulin to perform glutamylation. Glutamylation is a relatively uncommon type of post-translational modification, where the amino group of a free glutamate amino acid is covalently linked to the γ-carboxyl group of a glutamate sidechain in a substrate protein. This protocol describes the SidJ glutamylation reaction using radioactive [U-14C] glutamate and its substrate SdeA, the separation of proteins by gel electrophoresis, preparation of gels for radioactive exposure, and relative quantification of glutamylation activity. This procedure is useful for the identification of substrates for glutamylation, characterization of substrate and glutamylase activities due to mutations, and identification of proteins with glutamylation activity. Some studies have assayed glutamylation with the use of [3H] glutamate (Regnard et al., 1998) and the use of the GT335 antibody (Wolff et al., 1992). However, the use of [U-14C] glutamate requires a shorter radioactive exposure time with no dependence on antibody specificity.

Introduction The anterior vaginal wall is the segment most commonly affected by prolapse. Traditionally, anterior vaginal wall prolapse is repaired via anterior colporrhaphy, which is known to have a high recurrence rate. Several factors might affect the outcome of anterior colporrhaphy, and the use of absorbable sutures might also be associated with the high recurrence rate because the sutures might not be able to retain adequate strength until the plicated pubocervical fascia remodels and regains maximum tensile strength. Nonetheless, no comparative data exist about the relative efficacy and safety of anterior colporrhaphy using non-absorbable versus absorbable sutures. The objective of this study is to compare the surgical outcomes of anterior colporrhaphy using non-absorbable sutures with those of anterior colporrhaphy using absorbable sutures.Methods and analysis This is a randomised, multicentre, superiority trial. Anterior colporrhaphy will be performed in a traditional manner with midline plication of the fibromuscular layer using either non-absorbable or absorbable sutures. The primary outcome is composite surgical success 1 year after surgery defined as the absence of all of the following: (1) anterior vaginal descent beyond the hymen, (2) the presence of vaginal bulge symptoms and (3) retreatment for recurrent anterior vaginal wall prolapse with either surgery or pessary. The secondary outcomes include the individual components of the composite primary end point, anatomical outcomes, condition-specific quality of life and adverse events related to anterior colporrhaphy. The planned number of participants is 192.Ethics and dissemination This study was approved by the Institutional Review Board of Seoul National University Hospital (H-1810-037-977). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings.Trial registration number NCT03736811

BackgroundIn response to the coronavirus diseases 2019 (COVID-19) pandemic, the Japanese government declared a state of emergency on April 7, 2020. Six days earlier, the Japan Surgical Society had recommended postponing elective surgical procedures. Along with the growing public fear of COVID-19, hospital visits in Japan decreased.MethodsUsing claims data from the Quality Indicator/Improvement Project (QIP) database, this study aimed to clarify the impact of the first wave of the pandemic, considered to be from March to May 2020, on case volume and claimed hospital charges in acute care hospitals during this period. To make year-over-year comparisons, we considered cases from July 2018 to June 2020.ResultsA total of 2,739,878 inpatient and 53,479,658 outpatient cases from 195 hospitals were included. In the year-over-year comparisons, total claimed hospital charges decreased in April, May, June 2020 by 7%, 14%, and 5%, respectively, compared to the same months in 2019. Our results also showed that per-case hospital charges increased during this period, possibly to compensate for the reduced case volumes. Regression results indicated that the hospital charges in April and May 2020 decreased by 6.3% for hospitals without COVID-19 patients. For hospitals with COVID-19 patients, there was an additional decrease in proportion with the length of hospital stay of COVID-19 patients including suspected cases. The mean additional decrease per COVID-19 patient was estimated to 5.5 million JPY.ConclusionIt is suggested that the hospitals treating COVID-19 patients were negatively incentivized.

The safe and reliable operation of pressurized water reactors (PWRs) depends on the integrity of structural material. In particular, the failure of steam generator (SG) tubes on the secondary side is one of the major concerns of operating nuclear power plants. To establish remediation techniques and manage damage, it is necessary to articulate the mechanism through which various impurities affect the SG tubes. This research aims to understand the effect of impurities (e.g., S, Pb, and Cl) on the stress corrosion cracking of Alloy 600 and 690.

Background Fluid overload prior to continuous renal replacement therapy (CRRT) is an important prognostic factor. Thus, precise evaluation of fluid status is necessary to treat such patients. In this study, we investigated whether fluid assessment using bioelectrical impedance analysis (BIA) can predict outcomes in critically ill patients requiring CRRT. Methods A prospective observational study was performed in patients who were admitted to the intensive care unit and who required CRRT. BIA was conducted before CRRT; then, the ratio of extracellular water to total body water (ECW/TBW) was derived to estimate volume status. Results A total of 31 patients treated with CRRT were included. There were 18 men (58.1%), and the median age was 67 years (interquartile range, 51 to 78 years). Fourteen patients (45.2%) died within 28 days after CRRT initiation. Patients were divided into 16 with ECW/TBW ≥0.41 and 15 with ECW/TBW

Zinc homeostasis in most bacteria is achieved by a set of regulators, each responding to a certain level of intracellular zinc. Here the authors show that, inStreptomyces coelicolor, the Zur regulator modulates the expression of genes for zinc import and export over a large range of zinc concentrations.

Pseudokinases are considered to be the inactive counterparts of conventional protein kinases and comprise approximately 10% of the human and mouse kinomes. Here, we report the crystal structure of the Legionella pneumophila effector protein, SidJ, in complex with the eukaryotic Ca2+-binding regulator, calmodulin (CaM). The structure reveals that SidJ contains a protein kinase-like fold domain, which retains a majority of the characteristic kinase catalytic motifs. However, SidJ fails to demonstrate kinase activity. Instead, mass spectrometry and in vitro biochemical analyses demonstrate that SidJ modifies another Legionella effector SdeA, an unconventional phosphoribosyl ubiquitin ligase, by adding glutamate molecules to a specific residue of SdeA in a CaM-dependent manner. Furthermore, we show that SidJ-mediated polyglutamylation suppresses the ADP-ribosylation activity. Our work further implies that some pseudokinases may possess ATP-dependent activities other than conventional phosphorylation.

The transcription factor Zur controls the zinc deprivation response in Bacillus subtilis. Here, Shin and Helmann show that Zur-regulated genes are derepressed in three waves in response to zinc deprivation, and this is linked to the biochemistry of zinc sensing by Zur.

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.

Magnesium is an essential divalent metal that serves many cellular functions. While most divalent cations are maintained at relatively low intracellular concentrations, magnesium is maintained at a higher level (∼0.5-2.0 mM). Three families of transport proteins were previously identified for magnesium import: CorA, MgtE, and MgtA/MgtB P-type ATPases. In the current study, we find that expression of a bacterial protein unrelated to these transporters can fully restore growth to a bacterial mutant that lacks known magnesium transporters, suggesting it is a new importer for magnesium. We demonstrate that this transport activity is likely to be specific rather than resulting from substrate promiscuity because the proteins are incapable of manganese import. This magnesium transport protein is distantly related to the Nramp family of proteins, which have been shown to transport divalent cations but have never been shown to recognize magnesium. We also find gene expression of the new magnesium transporter to be controlled by a magnesium-sensing riboswitch. Importantly, we find additional examples of riboswitch-regulated homologues, suggesting that they are a frequent occurrence in bacteria. Therefore, our aggregate data discover a new and perhaps broadly important path for magnesium import and highlight how identification of riboswitch RNAs can help shed light on new, and sometimes unexpected, functions of their downstream genes.

"The 2024 Guidelines for Osteoporosis - Korean Society of Menopause: Part II" provides information on the pharmacologic therapy of osteoporosis. The article discusses various treatments, including hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), bisphosphonates, denosumab, and romosozumab. It highlights the effectiveness of these treatments in reducing fractures and increasing bone mineral density. The article also touches on the topics of osteopenia, sarcopenia, and medication-related osteonecrosis of the jaw (MRONJ), providing insights into diagnosis, treatment, and prevention. The document includes a comprehensive list of references for further research on osteoporosis and its treatment options. [Extracted from the article]