Pharmacist-initiated interventions to test quantitative bone mineral density and prescribe osteoporosis medications to prevent steroid-induced osteoporosis.

Fragility fractures associated with glucocorticoid-induced osteoporosis (GIO) can markedly impair quality of life. However, only 20% of patients are treated in compliance with the relevant management guidelines, and bone mineral density analysis with dual-energy X-ray absorptiometry (DXA) is only rarely performed. We report the intervention methods suggested by pharmacists and describe their efficacy. Patients who visited the outpatient clinic of the General Medicine Department of Ogaki Municipal Hospital and received steroids were enrolled. The rates of DXA implementation and compliance with GIO pharmacotherapy guidelines before and after pharmacist to physician-suggested interventions were compared. Guideline compliance was defined as prescription of osteoporosis drugs to patients with a score of ≥3. Administered prophylaxes and bone mineral density were subsequently assessed. The before and after intervention DXA rates were 1% (1/100 patients) and 96.0% (96/100 patients; P<0.01), respectively. Overall, 96.9% (93/96) of the patients met the GIO criteria for pharmacotherapy initiation (score ≥3), and the guideline compliance rates before and after the intervention were 39.8% (37/93) and 93.5% (87/93; P<0.01), respectively. Of the 56 patients who did not receive prophylaxis, 52 were recommended treatment, yielding an acceptance rate of 82.7% (43/52). Among the 37 patients receiving prophylaxis, 20 (54.1%) had a DXA-related young adult mean of ≤70%, of whom 11 (55.0%) agreed to drug therapy. The acceptance rate of pharmacotherapy recommendations for patients not receiving prophylaxis was higher than that for those receiving prophylaxis (P=0.03). Pharmacist-initiated interventions for GIO facilitates the administration of appropriate pharmacotherapy.

Association between lifestyle habits and presenteeism.

BACKGROUND: Presenteeism is affected by work-related and individual factors. Among individual factors, the effect of combining various lifestyle habits on presenteeism is unknown. AIMS: This study aimed to determine the relationship between changes in multiple good lifestyle habits with a change in presenteeism and to examine the effect of psychological factors on this relationship. METHODS: We performed a 1-year retrospective cohort study on employees of large Japanese companies. Data were collected from health check-ups and a self-administered questionnaire. Changes in presenteeism were measured using the Quality and Quantity method. Changes in lifestyle habits were measured using a modified form of Breslow's seven health practices. Psychological factors were measured using the Kessler 6-Item Psychological Distress Scale. Linear regression was used for statistical analysis. RESULTS: The number of practised lifestyle habit changes was negatively correlated with a change in presenteeism. This result was consistent when adjusted for age, sex and company (B, -0.010; P < 0.05), but became non-significant when additionally adjusted for psychological distress (B, -0.006). When analysed separately, only an improvement in the body mass index (B, -0.054; P < 0.05) and a worsened sleep habit (B, 0.040; P < 0.01) influenced a change in presenteeism. CONCLUSIONS: This study suggests that improving various practised lifestyle habits in combination, rather than improving a single lifestyle habit, is beneficial in reducing presenteeism. Our finding that psychological distress altered the relationship of practised lifestyle habit changes with presenteeism indicates the importance of organizational-level intervention in presenteeism.

Prevalence of and risk factors for depressive symptoms in non-tuberculous mycobacterial pulmonary disease.

BACKGROUND: The presence of depressive symptoms in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD) is an important research topic; however, the prevalence of depressive symptoms and the factors that influence their development are unclear.OBJECTIVE: To analyse the association between CES-D (Center for Epidemiological Studies Depression Scale) scores and clinical parameters such as age, disease duration, pulmonary function, imaging findings, blood data, physical functions, sleep disturbances, respiratory symptoms and health-related quality of life (HRQOL).METHODS: We conducted a cross-sectional retrospective study of 114 patients with NTM-PD at a single centre from March 2016 to January 2021 to evaluate the relationship between CES-D scores and clinical parameters.RESULTS: Participants had a median age of 64 years; 32.5% of them had depressive symptoms. Disease duration, albumin, C-reactive protein, pulmonary function, dyspnoea, exercise capacity, respiratory symptoms, cough-related HRQOL and sleep disturbances were associated with depressive symptoms. Binomial logistic regression analyses indicated that the CES-D score was significantly associated with cough-related HRQOL and sleep disturbances.CONCLUSION: A high percentage of NTM-PD patients in this study experienced depressive symptoms, and these patients had abnormalities of various clinical parameters. Cough-related HRQOL and sleep disturbance had a strong influence on the development of depressive symptoms.

Alcohol abuse has a potential association with unfavourable clinical course and brain atrophy in patients with status epilepticus.

AIM: To evaluate chronological changes on serial magnetic resonance imaging (MRI) examinations and clinical prognosis in patients with status epilepticus (SE), as well as the effect of alcohol abuse and heavy alcohol use on clinicoradiological findings. MATERIALS AND METHODS: This retrospective, single-centre study was approved by the institutional review board. Among 345 patients with seizures between January 2010 and October 2021, 27 patients with SE who had undergone both initial MRI (within a week after onset) and follow-up MRI (within 1 month after the initial MRI) were included. Five and three patients with concurrent or previous alcohol abuse and heavy alcohol-use history were included, respectively, and they were classified into the AL (Alcohol use) group. The remaining 19 patients were classified into the non-AL group. Two neuroradiologists independently evaluated both initial and follow-up MRI examinations of each patient; MRI findings were compared between the AL and non-AL groups using Fisher's exact test. In 15 patients, including four patients from the AL group, clinical information 6 months after the onset of SE was available; this information was compared between the two groups. RESULTS: Brain atrophy (5/8 versus 2/19, p=0.011; odds ratio, 12.29 [95% confidence interval, 1.32-189.2]) and unfavourable clinical course with uncontrollable seizures (3/4 versus 1/11, p=0.033; odds ratio, 30[1.43-638.19]) were significantly more frequent in the AL group than in the non-AL group. CONCLUSION: Among patients with SE, alcohol abuse and heavy alcohol-use history were associated with unfavourable seizure control and brain atrophy.

Multicenter external validation of the radical cystectomy pentafecta in a European cohort of patients undergoing robot-assisted radical cystectomy with intracorporeal urinary diversion for bladder cancer.

OBJECTIVE: To perform an external validation of this RC-pentafecta. METHOD: Between January 2014 and December 2019, 104 consecutive patients who underwent RARC with ICUD within 6 urological centers were analyzed retrospectively. Patients who simultaneously demonstrated negative soft tissue surgical margins (STSMs), a lymph node (LN) yield ≥ 16, absence of major (Clavien-Dindo grade III-V) 90-day postoperative complications, absence of UD-related long-term sequelae, and absence of 12-month clinical recurrence were considered to have achieved RC-pentafecta. A multivariable logistic regression model was used to measure predictors for achieving RC-pentafecta. We analyzed the influence of this RC-pentafecta on survival, and the impact ofthe surgical experience. RESULTS: Since 2014, 104 patients who had completed at least 12 months of follow-up were included. Over a mean follow-up of 18 months, a LN yield ≥ 16, negative STSMs, absence of major complications at 90 days, and absence of UD-related surgical sequelae and clinical recurrence at ≤ 12 months were observed in 56%, 96%, 85%, 81%, and 91% of patients, respectively, resulting in a RC-pentafecta rate of 39.4%. Multivariate analysis showed that age was an independent predictor of pentafecta achievement (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.90. 0.99; p = 0.04). The surgeon experience had an impact on the validation of the criteria. CONCLUSION: This study confirmed that the RC-pentafecta is reproducible and could be externally used for the outcome assessment after RARC with ICUD. Therefore, the RC-pentafecta could be a useful tool to assess surgical success and its impact on different outcomes.

Intervention of dementia support team pharmacists and its effects for the proper use of rivastigmine.

Pharmacist participation in the medical team is expected in dementia care. We investigated the use of rivastigmine, the intervention of pharmacists for its proper use, and its effects. The number of prescription proposals from the dementia care team pharmacist to the doctor was 87, and the number of acceptances was 57. The content of the proposal was 31/52 for additions/changes (number of acceptances/number of proposals), 21/28 for dose increase, 3/4 for discontinuation of administration, 2/2 for usage changes, and 1/1 for others. In increasing the dose, the number of patients who increased the maintenance dose to 18 mg was significantly higher in the group with the intervention of the pharmacist in the dementia care team than in the group without the intervention (3/12 cases vs. 0/24 cases, p = 0.031). The dose of the brought-in drug also significantly increased with pharmacist intervention compared with that in the non-intervention group (7/12 cases vs. 1/24 cases, p <0.001). The pharmacists of the dementia care team often intervened in the proper use of rivastigmine, which was found to be effective when increasing the dose. Thus, we believe that the active participation of pharmacists is necessary in dementia medication.

Health-related quality of life associates with clinical parameters in patients with NTM pulmonary disease.

BACKGROUND: Previous studies have shown a reduction in health-related quality of life (HRQoL) in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD). However, the causes of this decline and the factors that contribute to it are unknown. This study was conducted to analyse the association between the St George´s Respiratory Questionnaire (SGRQ) and clinical parameters, including age, disease duration, body composition, pulmonary function, chest X-ray findings, blood data and physical function.METHODS: We performed a single-centre, cross-sectional, retrospective study of 101 patients with NTM-PD from December 2016 to October 2019. The relationship between the SGRQ scores and clinical parameters was evaluated.RESULTS: The median patient age was 67.0 years. Pulmonary function, radiological score, albumin levels, C-reactive protein levels and incremental shuttle walk test distance (ISWD) were significantly correlated with the total and component scores on the SGRQ. Multiple regression analysis showed that the SGRQ score was significantly associated with radiological score, pulmonary function and ISWD.CONCLUSION: This study was the first to assess the effect of clinical parameters on the SGRQ in patients with NTM-PD. HRQoL as determined using the SGRQ was associated with the radiological score, pulmonary function and ISWD in patients with NTM-PD.

Comprehensive assessment of multiple tryptophan metabolites as potential biomarkers for immune checkpoint inhibitors in patients with non-small cell lung cancer.

PURPOSE: Tryptophan metabolites have immunomodulatory functions, suggesting possible roles in cancer immunity. METHODS: Plasma tryptophan metabolites were measured using liquid chromatography/mass spectrometry before immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). RESULTS: The 19 patients with NSCLC had significantly lower levels of tryptophan (p = 0.002) and xanthurenic acid (p = 0.032), and a significantly higher level of 3-hydroxyanthranilic acid (3-HAA) (p = 0.028) compared with the 10 healthy volunteers. The patients achieving objective responses had significantly lower levels of 3-HAA than those who did not (p = 0.045). Receiver operating characteristic analyses determined that the cutoff value of 3-HAA for objective response was 35.4 pmol/mL (sensitivity: 87.5% and specificity: 83.3%). The patients with 3-HAA < 35.4 pmol/mL had significantly longer median progression-free survival (7.0 months) than those without (1.6 months, p = 0.022). CONCLUSIONS: Tryptophan metabolites may have a potential for predicting the efficacy of ICIs. REGISTRATION NUMBER: University Hospital Medical Information Network Clinical Trial Registry 000026140.

Detection of norovirus in food samples collected during suspected food-handler-involved foodborne outbreaks in Tokyo.

Although norovirus (NoV) is the major cause of gastroenteritis, with the largest number of NoV food poisoning cases in Japan, limited information is available regarding NoV detection in food. This study aimed to detect NoV in food samples during the 2015-2016 suspected foodborne outbreaks in Tokyo; 352 food samples from 64 NoV food poisoning outbreaks were collected. Bacterial culturing was performed for sample pretreatment and real-time reverse transcription polymerase chain reaction was conducted for NoV screening. The NoV detection rate was 1·7% (6/352). NoV-positive food samples included leftover boxed lunch, mackerel fillet (foodstuff), aburi salmon slice (partially seared salmon slice), raw tuna as a chirashizushi ingredient, raw amberjack as a sushi topping and ice for drinks. Since fresh fish as sushi toppings or ingredients and ice were consumed without heating, they may present a higher risk of viral infection. NoV-positive food samples were obtained from five outbreaks, wherein food handlers were NoV-positive in four. Each partial VP1 sequence from food samples matched completely with those in NoV-positive individuals and food handlers. Hence, food handlers play a potentially important role in food-based NoV transmission in all five outbreaks; therefore, hygiene education among them is essential to prevent NoV foodborne outbreaks. SIGNIFICANCE AND IMPACT OF THE STUDY: Significance and Impact of the Study: Norovirus (NoV) is a leading cause of foodborne outbreak in Japan. The most frequent route of transmission in NoV foodborne outbreaks is secondary contamination via infected food handlers. However, limited information is available regarding NoV contamination in food samples. This study reports the detection of NoV in food samples to elucidate the source and route of NoV infection leading to outbreaks for 2 years in Tokyo. Our data potentially contribute to education and the development of safe food-handling strategies among food handlers and employees in the food industry through elucidation of risk factors associated with NoV contamination.

Direct Measurement of the Cosmic-Ray Proton Spectrum from 50 GeV to 10 TeV with the Calorimetric Electron Telescope on the International Space Station.

In this paper, we present the analysis and results of a direct measurement of the cosmic-ray proton spectrum with the CALET instrument onboard the International Space Station, including the detailed assessment of systematic uncertainties. The observation period used in this analysis is from October 13, 2015 to August 31, 2018 (1054 days). We have achieved the very wide energy range necessary to carry out measurements of the spectrum from 50 GeV to 10 TeV covering, for the first time in space, with a single instrument the whole energy interval previously investigated in most cases in separate subranges by magnetic spectrometers (BESS-TeV, PAMELA, and AMS-02) and calorimetric instruments (ATIC, CREAM, and NUCLEON). The observed spectrum is consistent with AMS-02 but extends to nearly an order of magnitude higher energy, showing a very smooth transition of the power-law spectral index from -2.81±0.03 (50-500 GeV) neglecting solar modulation effects (or -2.87±0.06 including solar modulation effects in the lower energy region) to -2.56±0.04 (1-10 TeV), thereby confirming the existence of spectral hardening and providing evidence of a deviation from a single power law by more than 3σ.

Influence of radiologic expertise in detecting lung tumors on chest radiographs.

PURPOSE: To analyze the influence of radiologic expertise in detecting lung tumors on chest radiographs. MATERIALS AND METHODS: We retrieved posteroanterior chest radiographs and CT examination obtained from 283 patients with solitary primary malignant lung tumors who underwent surgical resection. There were 176 men and 107 women with a mean age of 67.0±9.1 (SD) years (range: 33-88 years). Thirteen first-year post-graduate (PGY-1) trainees and nine pulmonary specialists (three radiologists, three thoracic surgeons, and three pulmonologists) interpreted the chest radiographs. Detection rates among trainees and specialists were compared using Student t test. RESULTS: The total numbers of detected tumors ranged from 103 (36.4%) to 136 (48.1%) with a mean of 127.9±9.1 (45.2±3.2%) in the trainee group, and 137 (48.4%) to 182 (64.3%) with a mean of 161.6±13.1 (57.1±4.6%) in the specialist group; the intergroup difference was statistically significant (P<0.001). Significant intergroup detectability differences of >10% were noted for tumors in the peripheral zone with (i) ground glass opacity (GGO) ratio ≥10% and <70% and any size, or (ii) GGO ratio <10% and size ≤2cm; and for tumors hidden by the mediastinum, heart, or diaphragm with (i) GGO ratio ≥10% and <30% and size >3cm, or (ii) GGO ratio <10% and size >2cm. CONCLUSION: Our study demonstrates significant differences in lung tumor detectability on chest radiographs between PGY-1 trainees and pulmonary specialists according to tumor size, extent of GGO, and tumor location.

Impaired residual renal function predicts denosumab-induced serum calcium decrement as well as increment of bone mineral density in non-severe renal insufficiency.

Denosumab treatment of osteoporotic patients, except those with severe renal insufficiency, reduced cCa levels. Low baseline cCa, low estimated glomerular filtration rate, and high bone turnover increased the risk of lower cCa, while increasing bone mineral density. Pretreatment with antiresorptive agents was beneficial in reducing the risk of hypocalcemia. INTRODUCTION: Although denosumab-induced hypocalcemia has been frequently observed in patients with chronic kidney disease (CKD) stages 4-5D being treated with denosumab for osteoporosis, few studies have assessed the risk factors for serum-corrected calcium (cCa) reductions in patients with non-severe renal insufficiency. This study assessed the risk factors for reduced cCa concentration following denosumab administration and analyzed factors predictive of changes in bone mineral density (BMD). METHODS: Seventy-seven osteoporotic patients, not including those with CKD stages 4-5D, were treated with 60 mg denosumab once every 6 months. Biochemical parameters and BMD were analyzed from prior to the initial dose until 1 month after the second dose. RESULTS: Following the first administration of denosumab, cCa levels decreased, reaching a minimum on day 7. Multiple linear regression analyses showed that baseline cCa, estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, tartrate-resistant acid phosphatase-5b (TRACP-5b), and bone alkaline phosphatase (BAP) or pretreatment with antiresorptive agents were significant factors independently associated with the absolute reduction in cCa from baseline to day 7 (ΔcCa0-7 days). ΔcCa0-7 days after the second dose of denosumab was significantly lower than that after the first dose. After 6 months of denosumab treatment, both LS-BMD and FN-BMD significantly increased from baseline. LS-BMD and FN-BMD correlated significantly with baseline TRACP-5b or BAP and eGFR, respectively. CONCLUSIONS: Both low eGFR and high bone turnover were independent risk factors for denosumab-induced cCa decrement, and for increases in BMD. Pretreatment with antiresorptive agents may reduce the risk of hypocalcemia.

Association of preoperative inflammation-based prognostic score with survival in patients undergoing salvage esophagectomy.

Salvage esophagectomy (SALV) is potentially beneficial for patients with residual or relapsed esophageal carcinoma after definitive chemoradiotherapy (dCRT), although preoperatively identifying good candidates for SALV remains difficult. We investigated the prognostic impacts of inflammatory and nutritional status in patients undergoing SALV after dCRT. Forty-seven SALV patients were retrospectively reviewed, of whom 46 (98%) had squamous cell carcinoma and 1 (2%) adenocarcinoma. Possible prognostic factors included patients' demographic data, physical status, blood chemistry profiles, and clinical/pathological tumor features. The Glasgow prognostic score (GPS) was derived from preoperative C-reactive protein (CRP) and albumin values. Thirty (64%), 11 (23%), and 6 (13%) patients were classified into the GPS 0, 1, and 2, respectively, groups. None of the possible prognostic factors showed significant correlations with GPS. Patients with GPS 0 had better outcomes than those with GPS 1 or GPS 2 (Median survivals: 37.8, 15.9, and 5.1 months, respectively, P < 0.001). In the multivariable Cox proportional hazards model, GPS 1 (HR 5.62, 95% CI 1.94-16.4, P = 0.002), GPS 2 (HR 9.10, 95% CI 2.60-31.8, P < 0.001), R1/2 resection (HR 16.3, 95% CI 3.62-86.7, P < 0.001) and incomplete response to dCRT (HR 3.53, 95% CI 1.12-12.5, P = 0.03) were all independent risk factors for a poor outcome. Preoperative GPS is potentially useful for predicting outcomes in esophageal cancer patients undergoing SALV.

Extended Measurement of the Cosmic-Ray Electron and Positron Spectrum from 11 GeV to 4.8 TeV with the Calorimetric Electron Telescope on the International Space Station.

Extended results on the cosmic-ray electron + positron spectrum from 11 GeV to 4.8 TeV are presented based on observations with the Calorimetric Electron Telescope (CALET) on the International Space Station utilizing the data up to November 2017. The analysis uses the full detector acceptance at high energies, approximately doubling the statistics compared to the previous result. CALET is an all-calorimetric instrument with a total thickness of 30 X_{0} at normal incidence and fine imaging capability, designed to achieve large proton rejection and excellent energy resolution well into the TeV energy region. The observed energy spectrum in the region below 1 TeV shows good agreement with Alpha Magnetic Spectrometer (AMS-02) data. In the energy region below ∼300 GeV, CALET's spectral index is found to be consistent with the AMS-02, Fermi Large Area Telescope (Fermi-LAT), and Dark Matter Particle Explorer (DAMPE), while from 300 to 600 GeV the spectrum is significantly softer than the spectra from the latter two experiments. The absolute flux of CALET is consistent with other experiments at around a few tens of GeV. However, it is lower than those of DAMPE and Fermi-LAT with the difference increasing up to several hundred GeV. The observed energy spectrum above ∼1 TeV suggests a flux suppression consistent within the errors with the results of DAMPE, while CALET does not observe any significant evidence for a narrow spectral feature in the energy region around 1.4 TeV. Our measured all-electron flux, including statistical errors and a detailed breakdown of the systematic errors, is tabulated in the Supplemental Material in order to allow more refined spectral analyses based on our data.

Twenty Years After Enactment of the Organ Transplant Law in Japan: Why Are There Still So Few Deceased Donors?

BACKGROUND: Twenty years have passed since the 1997 enactment of the Organ Transplant Law in Japan, but the number of deceased donors remains extremely low. In this study we examine why deceased donation has continued to remain so infrequent. METHODS: This investigation was a secondary analysis of published data from the Japan Organ Transplant Network, 2016 Fact Book of Organ Transplantation in Japan, and International Registry on Organ Donation and Transplantation. RESULTS: In the past 20 years, donation intent declarations, knowledge, and respect for family member's wishes have increased, whereas resistance toward transplantation has decreased. Despite this, the traditional perspective on corpses of gotai manzoku (ie, the soul cannot be put to rest without being physically intact and without defect), the family-centricism, and reward-seeking altruism have not changed much. Living organ transplants have alleviated the organ deficiency somewhat, and the law requiring family consent seems to have contributed to the observed small increase in deceased donors. CONCLUSION: The number of deceased donors is unlikely to increase suddenly. However, 8 strategies are proposed to increase the number of deceased donors, including: increasing the number of donor procurement coordinators and establishing a training system; increasing the number of organ procurement facilities; creating hub transplant centers and training transplant surgeons; implementing radical reform in public education; reducing workload and improving education of emergency physicians, neurosurgeons, and pediatricians; revisiting the stringent standards of brain-death determination; revisiting the registration process; and considering development of a Japanese version of organ procurement organizations as well as revisions to the Organ Transplant Law. The Japanese government and academic societies must work together to increase the number of deceased donors in Japan.

A case of a rare variant of Klinefelter syndrome, 47,XY,i(X)(q10).

Klinefelter syndrome is a condition in which a male patient has one Y chromosome and one or more extra X chromosomes. It is the most common sex chromosome disorder. Klinefelter syndrome is distinguished by many clinical features, such as infertility, high gonadotropin and low testosterone levels, increased height, and sparse body and facial hair. We report the case of a 32-year-old man who visited our hospital complaining of male infertility. Semen analysis showed azoospermia, and chromosomal analysis revealed a 47,XY,i(X)(q10) karyotype, which is a rare variant of Klinefelter syndrome. No spermatozoon was found on microdissection testicular sperm extraction, and the testis biopsy histology showed only Sertoli cells and hyalinised seminiferous tubules. 47,XY, i(X)(q10) has an additional isochromosome made of the long arm of the X chromosome, which shares some features of classical Klinefelter syndrome in many aspects, but patients are usually shorter than average height and have normal intelligence. In addition, to the best of our knowledge, no successful sperm extractions from 47,XY, i(X)(q10) patients were reported in the literature. The reports of patients who have undergone microdissection testicular sperm extraction are very rare. Further reports and studies of this chromosomal abnormality are needed.

Paradoxical roles of ATF6α and ATF6ß in modulating disease severity caused by mutations in collagen X.

Whilst the role of ATF6α in modulating the unfolded protein response (UPR) has been well documented, the function of its paralogue ATF6ß is less well understood. Using knockdown in cell culture and gene ablation in mice we have directly compared the roles of ATF6α & ß in responding to the increased ER stress induced by mutant forms of type X collagen that cause the ER stress-associated metaphyseal chondrodysplasia type Schmid (MCDS). ATF6α more efficiently deals with the disease-associated ER stress in the absence of ATF6ß and conversely, ATF6ß is less effective in the absence of ATF6α. Furthermore, disease severity in vivo is increased by ATF6α ablation and decreased by ATF6ß ablation. In addition, novel functions for each paralogue are described including an ATF6ß-specific role in controlling growth plate chondrocyte proliferation. The clear demonstration of the intimate relationship of the two ATF6 isoforms and how ATF6ß can moderate the activity of ATF6α and vice versa is of great significance for understanding the UPR mechanism. The activities of both ATF6 isoforms and their separate roles need consideration when deciding how to target increased ER stress as a means of treating MCDS and other ER stress-associated diseases.

Histological and immunohistochemical evaluation of granulosa cells during different stages of folliculogenesis in bovine ovaries.

Bovine granulosa cells (GC) vary in their morphological aspect during different stages of folliculogenesis. In this study, 10 morphologically normal bovine ovaries were collected to study the structural aspects of different stages of GC using intermediate filament protein antibodies including cytokeratin AE1/AE3 (AE1/AE3), vimentin, nectin-4 and desmin. Hormonal immunolocalization was assessed using the immunomarkers anti-Müllerian hormone (AMH) and inhibin alpha. In addition, tumour markers and proliferation markers using c-erbB-2 oncoprotein and proliferating cell nuclear antigen, respectively, were investigated. The immunolabelling of AE1/AE3 in GC was strongest in the early follicle stage and gradually decreased when reaching the Graafian follicle stage. Its immunolabelling increased again as the stage progressed from stage I to stage III. The immunolabelling of inhibin alpha was inversely proportional to that of AE1/AE3 in the developing ovarian follicles as their immunolabelling is opposite to each other during folliculogenesis. AMH was immunopositive in almost all GC stages in different intensities and percentages, except for some negative staining in the atretic IV follicles. The atretic IV follicle is a unique type of atretic follicle that shows Call-Exner body formation, which was mainly found in older cows in this study. The distinct patterns of immunoreactivity for various types of immunomarkers in the different GC stages will play an important role in diagnostic assistance of various follicle conditions, including cystic ovaries and GC tumours.

Respiratory impedance is correlated with airway narrowing in asthma using three-dimensional computed tomography.

BACKGROUND: Respiratory impedance comprises the resistance and reactance of the respiratory system and can provide detailed information on respiratory function. However, details of the relationship between impedance and morphological airway changes in asthma are unknown. OBJECTIVE: We aimed to evaluate the correlation between imaging-based airway changes and respiratory impedance in patients with asthma. METHODS: Respiratory impedance and spirometric data were evaluated in 72 patients with asthma and 29 reference subjects. We measured the intraluminal area (Ai) and wall thickness (WT) of third- to sixth-generation bronchi using three-dimensional computed tomographic analyses, and values were adjusted by body surface area (BSA, Ai/BSA, and WT/the square root (√) of BSA). RESULTS: Asthma patients had significantly increased respiratory impedance, decreased Ai/BSA, and increased WT/√BSA, as was the case in those without airflow limitation as assessed by spirometry. Ai/BSA was inversely correlated with respiratory resistance at 5 Hz (R5) and 20 Hz (R20). R20 had a stronger correlation with Ai/BSA than did R5. Ai/BSA was positively correlated with forced expiratory volume in 1 second/forced vital capacity ratio, percentage predicted forced expiratory volume in 1 second, and percentage predicted mid-expiratory flow. WT/√BSA had no significant correlation with spirometry or respiratory impedance. CONCLUSIONS & CLINICAL RELEVANCE: Respiratory resistance is associated with airway narrowing.

Treatment modalities and risk factors associated with refractory neurosensory disturbances of the inferior alveolar nerve following oral surgery: a multicentre retrospective study.

Little research has been conducted into hypoesthesia, and no studies have elucidated the risk factors for refractory hypoesthesia and compared treatment modalities. The purpose of this multicentre retrospective cohort study was to investigate the relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Risk factors for refractory hypoesthesia after oral surgery were evaluated using univariate and multivariate analysis. To minimize the selection bias associated with a retrospective data analysis, a propensity score analysis was performed between the medication and non-medication groups (65 sites in each group). Moderate or severe hypoesthesia (odds ratio 13.42) and no or late administration of ATP/vitamin B12 (odds ratio 2.28) were significantly associated with refractory hypoesthesia. In the propensity score analysis, the incidence rate of refractory hypoesthesia in the medication group was lower than that in the non-medication group (P<0.001). This study demonstrated the multivariate relationships between various risk factors, treatment modalities, and refractory hypoesthesia. Moderate or severe hypoesthesia and no or late administration of ATP/vitamin B12 were significantly associated with refractory hypoesthesia. Therefore, clinicians should consider these risk factors and initiate early oral administration of ATP/vitamin B12 in cases of hypoesthesia.