The association between epidural labour analgesia and postpartum depression: a randomised controlled trial.

There is conflicting evidence regarding the association between epidural labour analgesia and risk of postpartum depression. Most previous studies were observational trials with limited ability to account for confounders. We aimed to determine if epidural analgesia was associated with a significant change in the incidence of postpartum depression in this randomised controlled trial. We enrolled women aged 21-50 years old with a singleton fetus ≥ 36 weeks gestation. Patients were advised regarding available labour analgesic modalities during enrolment (epidural block; intramuscular pethidine; nitrous oxide; or intravenous remifentanil). On request for analgesia, patients were offered the modality that they had been allocated randomly to first. Blinded investigators recorded patient and obstetric characteristics within 24 h of delivery and assessed for postpartum depression at 6-10 weeks following delivery using the Edinburgh Postnatal Depression Scale (score ≥ 13 considered positive for postpartum depression). The modified intention-to-treat population consisted of all patients who received any form of labour analgesia, while per-protocol consisted of patients who received their randomised modality as their first form of labour analgesia. Of 881 parturients allocated randomly (epidural n = 441, non-epidural n = 440), we analysed 773 (epidural n = 389, non-epidural n = 384); 62 (15.9%) of women allocated to epidural group developed postpartum depression compared with 65 (16.9%) women allocate to the non-epidural group. There were no significant differences in the incidence of postpartum depression between the two groups (adjusted risk difference (95%CI) 1.6 (-3.0-6.3%), p = 0.49). Similar results were obtained with per-protocol analysis (adjusted risk difference (95%CI) -1.0 (-8.3-6.3%), p = 0.79). We found no significant difference in the risk of postpartum depression between patients who received epidural labour analgesia and those who utilised non-epidural analgesic modalities.

The outcome of 12-week corticosteroid therapy in COVID-19-related diffuse interstitial lung abnormalities.

INTRODUCTION: The efficacy of long-course corticosteroid therapy in treating COVID-19-related diffuse interstitial lung abnormalities (DILA) needs to be better understood. We aimed to investigate the benefits of 12-week corticosteroid treatment in COVID-19-related DILA by evaluating computed tomography (CT) lung severity scores. MATERIALS AND METHODS: This retrospective, single-centre observational study included patients aged 18 years or older admitted with moderate to severe COVID-19 pneumonia who received 12 weeks of oral prednisolone between January 2021 and December 2021. We recorded clinical parameters, baseline CT scores and post-treatment, modified Medical Research Council (mMRC) dyspnoea scale and pulmonary function tests. RESULTS: A total of 330 patients were analysed. The mean (standard deviation, SD) age was 54.6 (14.2) years, and 43% were females. Three-point nine per cent (3.9%) require noninvasive ventilation (NIV), while 14.6% require mechanical ventilation (MV). On follow-up at 12 weeks, the CT patterns showed improvement in ground-glass opacities, perilobular density and consolidation. There was an improvement in the mean (SD) CT score before and after prednisolone therapy, with values of 17.3 (5.3) and 8.6 (5.5), respectively (p<0.001). The median mMRC was 1 (IQR 0-1), and 98.8% had a radiological response. The common side effects of prednisolone therapy were weight gain (13.9%), hyperglycaemia (1.8%) and cushingoid habitus (0.6%). CONCLUSION: A 12-week treatment with prednisolone showed significant improvement in CT scores with minimal residual dyspnoea and was relatively safe. Longer duration of steroids may be beneficial in moderate to severe COVID-19- related DILA.

Risk factors for persistent pain after breast cancer surgery: a multicentre prospective cohort study.

Identifying factors associated with persistent pain after breast cancer surgery may facilitate risk stratification and individualised management. Single-population studies have limited generalisability as socio-economic and genetic factors contribute to persistent pain development. Therefore, this prospective multicentre cohort study aimed to develop a predictive model from a sample of Asian and American women. We enrolled women undergoing elective breast cancer surgery at KK Women's and Children's Hospital and Duke University Medical Center. Pre-operative patient and clinical characteristics and EQ-5D-3L health status were recorded. Pain catastrophising scale; central sensitisation inventory; coping strategies questionnaire-revised; brief symptom inventory-18; perceived stress scale; mechanical temporal summation; and pressure-pain threshold assessments were performed. Persistent pain was defined as pain score ≥ 3 or pain affecting activities of daily living 4 months after surgery. Univariate associations were generated using generalised estimating equations. Enrolment site was forced into the multivariable model, and risk factors with p < 0.2 in univariate analyses were considered for backwards selection. Of 210 patients, 135 (64.3%) developed persistent pain. The multivariable model attained AUC = 0.807, with five independent associations: age (OR 0.85 95%CI 0.74-0.98 per 5 years); diabetes (OR 4.68, 95%CI 1.03-21.22); pre-operative pain score at sites other than the breast (OR 1.48, 95%CI 1.11-1.96); previous mastitis (OR 4.90, 95%CI 1.31-18.34); and perceived stress scale (OR 1.35, 95%CI 1.01-1.80 per 5 points), after adjusting for: enrolment site; pre-operative pain score at the breast; pre-operative overall pain score at rest; postoperative non-steroidal anti-inflammatory drug use; and pain catastrophising scale. Future research should validate this model and evaluate pre-emptive interventions to reduce persistent pain risk.

[Application of multiplex PCR capillary electrophoresis and analysis of distribution characteristics of HPV infection subtypes].

Objective: To analyze the characteristics of human papillomavirus (HPV) infection and the distribution of HPV subtypes in Shijiazhuang, Hebei Province, and to explore the application evaluation of multiple PCR capillary electrophoresis fragment analysis for HPV typing test. Methods: A population-based cross-sectional study was conducted among 434 women (age range 17 to 74 years old, 260 patients and 174 physical examinations) included from May to August 2022 in Hebei General Hospital. HPV typing was detected by multiple PCR-capillary electrophoresis fragment analysis. Using the multiple fluorescence quantitative PCR kit as a reference, Chi-square test was used to analyze the diagnostic effect of multiple PCR-capillary electrophoresis fragment analysis, and the consistency was analyzed by Kappa value. Results: The total HPV infection rate was 45.85%(199/434), including 35.48% (154/434) of high-risk HPV (HR-HPV), 3.92% (17/434) of low-risk HPV (LR-HPV), 6.45% (28/434) of HR-HPV and LR-HPV mixed infection, 27.88% (121/434) of single type HPV and 17.97% (78/434) of multi type HPV. HPV52 (9.68%, 42/434), HPV16 (6.91%, 30/434), and HPV58 (6.91%, 30/434) are common HPV subtypes. The positive rate of physical examination was 45.40% (79/174), which was slightly lower than that of patients 46.15% (120/260), there was no significant difference (χ2=0.024,P>0.05). The highest infection rate in the 17-30 age group was 54.76% (46/84), and there was no statistical difference among the age groups(χ2=4.123,P>0.05). The sensitivity and specificity of multiplex PCR capillary electrophoresis fragment analysis were 92.96% and 94.04%, respectively, and Kappa value was 0.870, with the multiplex fluorescent quantitative PCR as the reference. Conclusion: HPV infection may appear younger, and the positive rate of HR-HPV infection is the highest, with HPV52, 16, 58 as the main infection subtypes. The detection results of multiplex PCR capillary electrophoresis fragment analysis method are highly consistent with those of multiplex fluorescent quantitative PCR method, which is suitable for HPV DNA typing.

Spectrum of cutaneous granulomatous lesions: A 5-year experience in a tertiary care centre in Sarawak.

INTRODUCTION: Granulomatous skin lesions can have various histopathological features leading to diagnostic confusion. The study aimed to determine the frequency and pattern of different granulomatous skin lesions. MATERIALS AND METHODS: This was a 5-year retrospective study done between April 2017 and March 2022 at Dermatology Department, Sarawak General Hospital. Subjects with a clinicopathological diagnosis of granulomatous diseases were included in the analysis. RESULTS: A total of 1718 skin biopsies were done during the study periods, with 49 (2.8%) confirmed granulomatous skin lesions. Most patients were aged 40-60 with a male predominance of 51%. Most of the skin biopsy samples were taken from the upper limb (36%). In this study, epitheloid granuloma was the commonest subtype (21, 43%) followed by suppurative granuloma (12, 24%), tuberculoid granuloma (8, 16%) and foreign body granuloma (5, 10%). The commonest aetiology of granulomatous skin lesions in our study was infections (30, 61%) followed by foreign body inoculation (8, 16%). Fungal infection was the most common infective cause, followed by cutaneous tuberculosis. CONCLUSION: The major cause of granulomatous dermatoses in developing countries is still infections, fungal and tuberculosis being the leading causes.

Efficacy and safety of adjunctive treatment with perampanel in epilepsy patients.

INTRODUCTION: Epilepsy is a neurological disease with high global prevalence. Almost one-third of epilepsy patients continue having seizures despite adequate treatment. Perampanel has been widely used in the Western countries as an adjunctive therapy for both generalized and focal seizures. Owing to its high cost, the use of perampanel is limited in our country. MATERIALS AND METHODS: We conducted a descriptive, retrospective study among epilepsy patients treated with perampanel. We aimed to assess the efficacy and safety of perampanel as an adjunctive in our hospital. RESULTS AND CONCLUSIONS: From our cohort of 25 patients, most of the patients were either on one or three anti-seizure medications (ASMs) prior to initiation of perampanel. Perampanel was added in 88% of them due to persistent seizures. Twenty-two (88%) patients experienced reduction in seizure frequency. 12% experienced mild side effects, which were leg cramps, hyponatremia and drowsiness. Only 1 patient stopped perampanel due to its side effects. CONCLUSION: Perampanel is a well-tolerated ASM that should be widely used as an adjunctive. More studies with regards to its efficacy and safety involving more centres are encouraged in Malaysia.

Factors related to prehospital delay and decision delay among acute stroke patients in a district hospital, Malaysia.

INTRODUCTION: Time is the greatest challenge in stroke management. This study aimed to examine factors contributing to prehospital delay and decision delay among stroke patients. MATERIALS AND METHODS: A cross-sectional study involving acute stroke patients admitted to Seri Manjung Hospital was conducted between August 2019 and October 2020 via faceto- face interview. Prehospital delay was defined as more than 120 minutes taken from recognition of stroke symptoms till arrival in hospital, while decision delay was defined as more than 60 minutes taken from recognition of stroke symptoms till decision was made to seek treatment. RESULTS: The median prehospital delay of 102 enrolled patients was 364 minutes (IQR 151.5, 1134.3) while the median for decision delay was 120 minutes (IQR 30.0, 675.0). No history of stroke (adj. OR 4.15; 95% CI 1.21, 14.25; p=0.024) and unaware of thrombolysis service (adj. OR 17.12; 95% CI 1.28, 229.17; p=0.032) were associated with higher odds of prehospital delay, while Indian ethnicity (adj. OR 0.09; 95% CI 0.02, 0.52; p=0.007) was associated with lower odds of prehospital delay as compared to Malay ethnicity. On the other hand, higher National Institutes of Health Stroke Scale (NIHSS) score (adj. OR 0.86; 95% CI 0.78, 0.95; p=0.002) was associated with lower odds of decision delay. CONCLUSION: Public awareness is crucial to shorten prehosital delay and decision delay for better patients' outcomes in stroke. Various public health campaigns are needed to improve the awareness for stroke.

Characteristics of electroencephalogram changes and correlation with seizures in hospitalised patients.

INTRODUCTION: Electroencephalogram (EEG) is an important investigational tool that is widely used in the hospital settings for numerous indications. The aim was to determine factors associated with abnormal EEG and its clinical correlations in hospitalised patients. MATERIALS AND METHODS: Patients with at least one EEG recording were recruited. The EEG and clinical data were collated. RESULTS: Two hundred and fifty patients underwent EEG and 154 (61.6%) were found to have abnormal EEG. The abnormal changes consist of theta activity (79,31.6%), delta activity (20, 8%), focal discharges (41,16.4%) and generalised discharges (14, 5.6%). Older patients had 3.481 higher risk for EEG abnormalities, p=0.001. Patients who had focal seizures had 2.240 higher risk of having EEG abnormalities, p<0.001. Low protein level was a risk for EEG abnormalities, p=0.003. CONCLUSION: This study emphasised that an abnormal EEG remains a useful tool in determining the likelihood for seizures in a hospital setting. The risk factors for EEG abnormality in hospitalised patients were age, focal seizures and low protein level. The EEG may have an important role as part of the workup in hospitalised patients to aid the clinician to tailor their management in a holistic manner.

Intravenous thrombolysis for multi-ethnic Asians with acute ischaemia stroke in Malaysian public primary stroke centres versus acute stroke ready hospitals: Comparison of real-world clinical outcomes.

INTRODUCTION: Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator is beneficial in acute ischaemic stroke (AIS). We aim to compare the realworld clinical outcomes and service efficiency of IVT in Malaysian primary stroke centres (PSCs) versus acute stroke ready hospitals (ASRHs). MATERIALS AND METHODS: We conducted a multi-centre cohort study involving 5 PSCs and 7 ASRHs in Malaysia. Through review of medical records of AIS patients who received IVT from 01 January 2014 to 30 June 2021, real-world data was extracted for analysis. Univariate and multivariate regression models were employed to evaluate the role of PSCs versus ASRHs in post-IVT outcomes and complications. Statistical significance was set at p<0.05. RESULTS: A total of 313 multi-ethnic Asians, namely 231 from PSCs and 82 from ASRHs, were included. Both groups were comparable in baseline demographic, clinical, and stroke characteristics. The efficiency of IVT delivery (door-toneedle time), functional outcomes (mRS at 3 months post- IVT), and rates of adverse events (intracranial haemorrhages and mortality) following IVT were comparable between the 2 groups. Notably, 46.8% and 48.8% of patients in PSCs and ASRHs group respectively (p=0.752) achieved favourable functional outcome (mRS≤1 at 3 months post-IVT). Regression analyses demonstrated that post-IVT functional outcomes and adverse events were independent of the role of PSCs or ASRHs. CONCLUSION: Our study provides real-world evidence which suggests that IVT can be equally safe, effective, and efficiently delivered in ASRHs. This may encourage the establishment of more ASRHs to extend the benefits of IVT to a greater proportion of stroke populations and enhance the regional stroke care.

[Imaging classification and analysis of the diagnosis and treatment of infected pancreatic necrosis:a report of 126 cases].

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ2 test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ2=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ2=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.

[Analysis on the clinical features of sarcoid uveitis].

Objective: To analyze the clinical features of patients with sarcoid uveitis. Methods: This was a retrospective case series study. The medical records of 19 086 patients with uveitis admitted to the Department of Ophtalmology, The First Affiliated Hospital of Chongqing Medical University from April 2008 to December 2019 were collected. The general data, medical history, treatment, diagnosis, follow-up, ophthalmic and other auxiliary examinations were retrospectively analyzed. The paired sample Wilcoxon signed rank test was used to compare the best corrected visual acuity (BCVA) of the affected eye at the first visit to the BCVA of the affected eye at the corresponding last visit. Results: A total of 51 patients (97 eyes) with sarcoid uveitis were included, including 15 males (29.4%) and 36 females (70.6%), with a male/female ratio of 1/2.4. There were 46 patients (88 eyes) with presumed sarcoidosis and 5 patients (9 eyes) with definite sarcoidosis. The age of onset was 48 (40, 55) years and 90.2% of patients (46 cases) were involved in both eyes, while 88.2% of the patients (45 cases) were chronic, and only 11.8% (6 cases) showed acute inflammatory response. Anterior uveitis was the most common type (50.5%, 49 eyes). Ophthalmoscopy revealed retinal vasculitis in only 2 eyes (2.1%) and fundus fluorescence angiography (FFA) revealed diffuse vascular leakage of fluorescein in 64 eyes (66.0%). Thirty-one patients (59 eyes) were followed up for≥3 months. Cataract was the most common ocular complication, accounting for 44.1% (26 eyes), and the inflammatory response was controlled in 45 eyes (76.3%) treated with combination of corticosteroids and immunosuppressive agents. The patients were followed up for 21.5 (13.7, 29.3) months. Among 31 patients (59 eyes) followed up for≥3 months, BCVA was≥0.8 in 25 eyes (42.3%) and<0.3 in 15 eyes (25.4%) at the last follow-up, BCVA of 59 affected eyes of 31 patients was better than that at the first visit, the difference was statistically significant (Z=-2.76, P=0.006). Conclusions: Uveitis associated with sarcoidosis or presumed ocular sarcoidosis mainly manifests as a bilateral, chronic anterior uveitis with a subclinical retinal vasculitis. FFA shows subclinical retinal vasculitis in most patients. Glucocorticoid therapy in combination with other immunosuppressive agents can control inflammatory responses and improve visual acuity in most patients.

[Reversible bilateral blindness associated with alcoholic ketoacidosis: a case report].

A 51-year-old male with a history of chronic alcoholism presented to the emergency department with an abrupt onset of complete bilateral blindness lasting for one hour. Funduscopic examination yielded unremarkable findings. Systemic evaluations revealed the presence of severe ketoacidosis. The patient spontaneously regained light perception after experiencing total blindness for 3 hours; however, he subsequently developed hypothermia and entered a state of shock. Following treatment with sodium bicarbonate and aggressive fluid resuscitation, his condition stabilized, and there was a rapid improvement in his visual acuity. The diagnosis of alcoholic ketoacidosis was established based on the patient's history of chronic alcohol abuse, physical examination findings, and blood analysis results.

Cost-effectiveness analyses of denosumab for osteoporosis: a systematic review.

This paper systematically reviewed and assessed all retrievable pharmacoeconomic studies on denosumab for the treatment of osteoporosis. Denosumab was more cost-effective in patients with older age, prior fracture experience, lower BMD T-scores, and more risk factors. ESCEO-IOF guidelines were more applicable to improve the quality of pharmacoeconomic studies in osteoporosis. INTRODUCTION: There are many pharmacoeconomic studies on denosumab for osteoporosis. However, the corresponding reviews are outdated or incomplete and need to be updated and refined. This article aims to systematically review and evaluate all retrievable pharmacoeconomic studies of denosumab for osteoporosis. METHODS: A systematic literature search was performed utilizing PubMed, EMBASE(Ovid), Proquest(EconLit), Chongqing VIP, WanFang Database, and Chinese National Knowledge Infrastructure to identify full-text articles published before September 2021. The quality of full-text articles was evaluated by the Consolidated Health Economic Evaluation Reporting Standards(CHEERS) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases International Osteoporosis Foundation guideline(ESCEO-IOF). RESULTS: In total, 21 full-text articles were eligible for inclusion. Denosumab for postmenopausal osteoporosis was not dominant compared to zoledronate and teriparatide. However, denosumab was dominant compared with strontium ranelate, raloxifene, and ibandronate in patients over 65 years. The probabilities of denosumab being cost-effective or dominant were more than 85% compared with no treatment and risedronate in patients aged over 70 years. Compared to alendronate, the highest rate of denosumab dominance occurred in patients aged 65 to 75 years, at about 65%. Most of the articles had higher CHEERS scores than ESCEO-IOF scores (converted into percentages). CONCLUSIONS: The cost-effectiveness of denosumab for the treatment of osteoporosis was influenced by multiple factors. Generally, denosumab was more cost-effective in patients with older age, prior fracture experience, lower BMD T-scores, and more risk factors. ESCEO-IOF guidelines were more applicable to improve the transparency, generalization, and quality of pharmacoeconomic studies in osteoporosis.

Schlafen2 is a regulator of quiescence in adult murine hematopoietic stem cells.

Even though hematopoietic stem cells (HSC) are characterized by their ability to self-renew and differentiate, they primarily reside in quiescence. Despite the immense importance of this quiescent state, its maintenance and regulation is still incompletely understood. Schlafen2 (Slfn2) is a cytoplasmic protein known to be involved in cell proliferation, differentiation, quiescence, interferon response, and regulation of the immune system. Interestingly, Slfn2 is highly expressed in primitive hematopoietic cells. In order to investigate the role of Slfn2 in the regulation of HSC we have studied HSC function in the elektra mouse model, where the elektra allele of the Slfn2 gene contains a point mutation causing loss of function of the Slfn2 protein. We found that homozygosity for the elektra allele caused a decrease of primitive hematopoietic compartments in murine bone marrow. We further found that transplantation of elektra bone marrow and purified HSC resulted in a significantly reduced regenerative capacity of HSC in competitive transplantation settings. Importantly, we found that a significantly higher fraction of elektra HSC (as compared to wild-type HSC) were actively cycling, suggesting that the mutation in Slfn2 increases HSC proliferation. This additionally caused an increased amount of apoptotic stem and progenitor cells. Taken together, our findings demonstrate that dysregulation of Slfn2 results in a functional deficiency of primitive hematopoietic cells, which is particularly reflected by a drastically impaired ability to reconstitute the hematopoietic system following transplantation and an increase in HSC proliferation. This study thus identifies Slfn2 as a novel and critical regulator of adult HSC and HSC quiescence.

A bibliometric analysis of primary ovarian insufficiency from 2010 to 2020.

OBJECTIVE: This study aimed to carry out a bibliometric analysis of primary ovarian insufficiency (POI) from 2010 to 2020 and to reveal the research status and hotspots in the future. METHOD: A total of 3087 articles and reviews related to POI published from 2010 to 2020 retrieved from the Web of Science Core Collection were used for bibliometric analysis. CiteSpace and VOSviewer were adopted to analyze countries and regions, organizations, authors, journals, keywords and co-cited references. RESULTS: The number of publications about POI increased year by year. The USA produced the largest number of publications and the most influence in this field. The main research directions of POI can be roughly divided into four aspects according to the analysis of keywords and co-cited references: genetic research of POI; stem cell therapy for patients with POI; prediction of ovarian function; and fertility preservation of cancer patients. Genetic research and stem cell therapy may become research hotspots in the future. CONCLUSION: This study might be the first bibliometric study to analyze publications of POI from multiple indicators, in order to provide new opinions for the research trends and possible hotspots of POI.

[A time-series study on the association of ambient temperature with daily outpatient visits of eczema in Huizhou city].

Objective: To explore the impact of environmental temperature exposure on eczema visits. Methods: Eczema clinic data from January 1, 2016 to December 31, 2019 were collected from the Huizhou Dermatology Hospital, and data on meteorological factors (average daily temperature and relative humidity) for the same period were derived from 86 meteorological stations of the Guangdong Provincial Climate Center. A distributed lag nonlinear model (DLNM) was used to assess the lagged effect of environmental temperature exposure on eczema, and a natural smooth spline function was used to control the nonlinear confounding of humidity. Results: There were 254 053 eczema outpatient visits at the Huizhou Dermatology Hospital within four years, with an average of 173.89 visits per day. The relationship between daily average temperature and the number of visits was non-linear (U shape). The risk of eczema increased by 2.20% (1.19%-3.21%) for every 1 ℃ decrease for the low temperature, and increased by 2.35% (1.24%-3.5%) for every 1 ℃ increase for the high temperature. The effect of high temperature was greater than that of low temperature. In all cases, 1.60% (0.44%-2.68%) of eczema outpatient visits were attributed to low temperature and the attributable number was 4 065 (1 128-6 798), while 6.33% (1.40%-10.87%) of eczema outpatient visits were due to high temperature and the attributable number was 16 082 (3 557-27 616). Conclusion: Both high temperature and low temperature are associated with increased risk of eczema.

[Oxidative stress in psychosis: a new target for intervention?] / Oxidatieve stress bij psychotische stoornissen: een nieuw target voor interventie?

BACKGROUND: Oxidative stress is a state of imbalance between reactive oxidants and anti-oxidants. Oxidative stress and a disrupted redox regulation in the brain might contribute to the pathophysiology of psychotic disorders and could serve as interesting new targets for clinical intervention. Advanced glycation end products (AGEs) in the skin can be measured non-invasively and indicate cumulative oxidative stress. AIM: To investigate cross-sectional and longitudinal differences in AGE-levels in patients with recent onset psychosis (patients) and healthy controls (controls). To investigate association of AGE-levels and brain volume in psychosis. METHOD: An autofluorescence measurement of AGEs in the skin was performed in patients and controls. AGEs were compared in patients and controls. Furthermore, the association between AGEs and volumes of the amygdala, hippocampus and total cortical gray matter was investigated in patients. RESULTS: AGEs in the skin were elevated by 15% (or 0.66 standard deviations) in patients (n = 86) compared to controls (n = 135) (p < 0.001). An indication of a higher AGE-accumulation rate (p = 0.07) was found in patients (n = 66) compared to controls (n = 160). We found a negative association between AGEs in the skin and hippocampus volume (standardized beta= 0.27; p = 0.03) in patients (n = 46). CONCLUSION: Findings of a high level of AGEs in the skin indicate excessive oxidative stress in patients with recent onset psychosis.

Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST).

BACKGROUND: The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. AIMS: The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. METHODS: iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. BASELINE RESULTS: A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and < 2500 ventricular premature contractions during 24-hour Holter monitoring. There were no statistically significant differences between the two groups in any of the baseline characteristics. The study is currently well underway, with the last participants expected to finish in 2021. CONCLUSION: iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856).

Subthalamic deep brain stimulation induces finely-tuned gamma oscillations in the absence of levodopa.

Finely-tuned gamma (FTG) oscillations can be recorded from cortex or the subthalamic nucleus (STN) in patients with Parkinson's disease (PD) on dopaminergic medication, and have been associated with dyskinesias. When recorded during deep brain stimulation (DBS) on medication the FTG is entrained to half the stimulation frequency. We investigated whether these characteristics are shared off medication by recording local field potentials (LFP) from the STN from externalised DBS leads in 14 PD patients after overnight withdrawal of medication. FTG was induced de-novo by DBS in the absence of dyskinesias in a third of our cohort. The FTG could outlast stimulation or arise only after DBS ceased. FTG frequencies decreased during and across consecutive DBS blocks, but did not shift with changing stimulation frequency off medication. Together with the sustained after-effects this argues against simple entrainment by DBS in the off medication state. We also found significant coherence between STN-LFP and electroencephalogram (EEG) signals at FTG frequencies. We conclude that FTG is a network phenomenon that behaves differently in the off medication state, when it is neither associated with dyskinesias nor susceptible to entrainment.

Atomic Ionization by Scalar Dark Matter and Solar Scalars.

We calculate the cross sections of atomic ionization by absorption of scalar particles in the energy range from a few eV to 100 keV. We consider both nonrelativistic particles (dark matter candidates) and relativistic particles that may be produced inside the Sun. We provide numerical results for atoms relevant for direct dark matter searches (O, Na, Ar, Ca, Ge, I, Xe, W and Tl). We identify a crucial flaw in previous calculations and show that they overestimated the ionization cross sections by several orders of magnitude due to violation of the orthogonality of the bound and continuum electron wave functions. Using our computed cross sections, we interpret the recent data from the Xenon1T experiment, establishing the first direct bounds on coupling of scalars to electrons. We argue that the Xenon1T excess can be explained by the emission of scalars from the Sun. Although our finding is in a similar tension with astrophysical bounds as the solar axion hypothesis, we establish direct limits on scalar DM for the ∼1-10 keV mass range. We also update axio-ionization cross sections. Numerical data files are provided.