Seed germination is a physiological process regulated by multiple factors. Abscisic acid (ABA) can inhibit seed germination to improve seedling survival under conditions of abiotic stress, and this process is often regulated by light signals. Constitutive Photomorphogenic 1 (COP1) is an upstream core repressor of light signals, and is involved in several ABA responses. Here, we demonstrate that COP1 is a negative regulator of the ABA-mediated inhibition of seed germination. Disruption of COP1 enhanced Arabidopsis seed sensitivity to ABA and increased ROS levels. In seeds, ABA induced the translocation of COP1 to the cytoplasm, resulting in enhanced ABA-induced ROS levels. Genetic evidence indicated that HY5 and ABI5 act downstream of COP1 in the ABA-mediated inhibition of seed germination. ABA-induced COP1 cytoplasmic localization increased HY5 and ABI5 protein levels in the nucleus, leading to increased expression of ABI5 target genes and ROS levels in seeds. Together, our results reveal that ABA-induced cytoplasmic translocation of COP1 activates the HY5-ABI5 pathway to promote the expression of ABA-responsive genes and the accumulation of ROS during ABA-mediated inhibition of seed germination. These findings enhance the role of COP1 in the ABA signal transduction pathway. This article is protected by copyright. All rights reserved.

Keywords: ABA; COP1; HY5-ABI5 pathway; Hormones; Oxidative stress; Seed germination.

pH is one of the important environmental factors that affect the growth, development and pathogenicity of postharvest pathogen. The transcription factor PacC dominates the pH signal pathway. PacC in Trichothecium roseum showed three typical conserved zinc finger domains and closest homology to Fusarium graminearum. T. roseum increased the environmental pH both in vitro and in vivo. Expression patterns of TrpacC under different pH showed that at increasing pH from 3 to 5, the wild-type (WT) strain induced the expression of TrPacC in parallel to increased fungal growth; however, TrPacC expression decline at higer pH than 5, while fungal growth continued to increase. Development of a ΔTrPacC mutant down-regulated the expression of TrbrlA, TrabaA and TrwetA, reduced sporulation and delayed spore germination, resulting in smaller spores and sparse hyphae. ΔTrPacC mutant was sensitive to ionic stress, oxidative stress and cell wall integrity stress compared to the WT strain, especially the ionic stress. In addition, ∆TrPacC mutant showed reduced pathogenicity to muskmelon and tomato fruits. Taken together, T. roseum is an alkalinizing fungus, and the acidic environment could induce TrPacC expression. TrPacC positively regulates fungal growth and development as well as pathogenicity showing effect on fungal response to different stresses.

In this work, the hydroxyapatite nanoparticle doped with trivalent dysprosium ions were synthesized by co-precipitation method. The characterization techniques like X-Ray diffraction (XRD), Transmission Electron Microscopy (TEM), Energy Dispersive X-Ray Spectroscopy (EDX) were carried to determine the crystalline and structural properties. The Rietveld structural refinement of the XRD patterns confirmed the purity of the phase formation of the synthesized nanoparticles. The photoluminescence emission spectra exhibited intense emissions in the blue region at 450 nm and 476 nm along with less intense yellow emission at 573 nm which can be attributed to the magnetic dipole and electric dipole transitions of dysprosium respectively. In order to evaluate the color tunability of the emitted light CIE chromaticity coordinate values were calculated. The intense blue emissions from the synthesized sample were found to be favourable for bioimaging. The images obtained from the fluorescence microscopy revealed that the dysprosium doped hydroxyapatite nanoparticles are potential bioimaging probes in human cells.

Keywords: Dysprosium; N2a cells; hydroxyapatite nanoparticles; imaging.

Problem: High school teenagers are facing significant challenges during the COVID-19 pandemic. Teenagers are at risk of experiencing physical, mental, and social health problems due to the COVID-19 pandemic. This narrative review aims to explore the impact of COVID-19 on the emergence of mental health problems in high school adolescents.

Methods: This study employed a narrative review method. We conducted a systematic search using PRISMA on three databases: Medline, PubMed, and ScienceDirect. A total of 40 articles met the inclusion and exclusion criteria set based on the research objectives.

Findings: The study uncovered that high school adolescents had an increased risk of experiencing mental health problems, namely psychological distress, worry, loneliness, anxiety, depression, traumatic symptoms, other psychological disorders, suicide risk, sleep disorders, and psychosocial functioning. Anxiety, depression, and psychological stress were the most discussed mental health problems among high school adolescents during the COVID-19 pandemic.

Conclusions: There is a need for efforts to identify health problems and intervene in mental health problems early in high school adolescents. Schools, mental health workers, and the government (e.g., policy stakeholders) need to implement the recommendations given as a follow-up effort for mental health services for high school youth.

Keywords: COVID-19; adolescent; high school; mental health.

Background: Dynamic changes in metabolites may affect liver disease progression, and provide new methods for predicting liver damage.

Methods: We used ultra-performance liquid chromatography mass spectroscopy to assess serum metabolites in healthy controls (HC), and patients with acute hepatitis E (AHE) or hepatitis E virus acute liver failure (HEV-ALF).

Results: The principal component analysis, partial least squares discriminant analysis, and discriminant analysis of orthogonal projections to latent structures models illustrated significant differences in the metabolite components between AHE patients and HCs, or between HEV-ALF and AHE patients. In pathway enrichment analysis, we further identified two altered pathways, including linoleic acid metabolism and phenylalanine, tyrosine and tryptophan biosynthesis, when comparing AHE patients with HCs. Linoleic acid metabolism and porphyrin and chlorophyll metabolism pathways were significantly different in HEV-ALF when compared with AHE patients. The discriminative performances of differential metabolites showed that taurocholic acid, glycocholic acid, glycochenodeoxycholate-3-sulfate, and docosahexaenoic acid could be used to distinguish HEV-ALF from AHE patients. The serum levels of glycocholic acid, taurocholic acid, deoxycholic acid glycine conjugate, and docosahexaenoic acid were associated with prognosis of HEV-ALF patients.

Conclusions: Dynamic changes in serum metabolites were associated with AHE infection and severity. The identified metabolites can be used to diagnose and predict the prognosis of HEV-ALF. This article is protected by copyright. All rights reserved.

Keywords: Acute hepatitis E; Acute liver failure; Diagnose and prognosis; Serum metabolites; UPLC−MS.

Background: Flexible work-life policies for medical school faculty are necessary to support career progress, advancement, retention, and job satisfaction. Objective: Our objective was to perform a 10-year follow-up descriptive assessment of the availability of flexible work-life policies for faculty in medical schools in the Big Ten Conference. Design: In this descriptive study, a modified objective scoring system was used to evaluate the flexibility of faculty work-life policies at 13 medical schools in the Big Ten Conference. Policy information was obtained from institutional websites and verified with the human resources offices. Scores from the 2011 study and 2020 were compared. Results: Michigan State and Ohio State Universities offered the most flexible policies (score 17.75/22) with the Universities of Maryland and Minnesota following (score 16/22). The largest delta scores, indicating more flexible policies in the past decade, were at University of Minnesota (5.25) and University of Michigan (5). Policies for parental leave and part-time faculty varied widely. Most schools earned an additional point in the newly added category of "flexible scheduling and return-to-work policies." Nearly every institution reported dedicated lactation spaces and improved childcare options. Limitations : Limitations included missing policy data and interpretation bias in reviewing the policy websites, unavailable baseline data for schools that joined the Big Ten after the 2011 study, and unavailable baseline data for the additional category of return-to-work policies. Conclusions: While progress has been made, every institution should challenge themselves to review flexibility in work-life policies for faculty. It is important to advance a healthy competition with the goal to achieve more forward-thinking policies that improve retention, recruitment, and advancement of faculty. Big Ten institutions can continue to advance their policies by providing greater ease of access to options, further expansion of parental leave and childcare support, and offering more flexible policies for part-time faculty.

Keywords: academic employment; burnout; gender equity; lactation support; wellness; work-life.

Introduction: Although several studies have investigated the prognostic significance of the radiographic appearance of stage IA lung adenocarcinoma, the prognostic impact of solid component size or consolidation-to-tumor ratio (CTR) of part-solid nodules (PSNs) still remains controversial. This study aimed to clarify the combined prognostic impact of the mentioned radiographic features of PSNs and compare it with that of pure solid nodules in the current TNM classification.

Methods: We retrospectively investigated 1014 patients with clinical stage IA (TNM eighth edition) adenocarcinoma who underwent curative resection. Overall survival (OS) and pathologic characteristics of pure solid nodules, solid-dominant PSNs (CTR > 0.5), and ground-glass opacity (GGO)-dominant PSNs (CTR ≤ 0.5) were compared according to T category.

Results: Patients with pure solid nodules (297 cases) had significantly shorter OS compared with those with PSNs (717 cases) (p < 0.001) but a marginal difference compared with those with solid-dominant PSNs (286 cases) (p = 0.051). No significant difference in OS was found according to T category in those with GGO-dominant PSNs (431 cases). Patients with cT1b and T1c solid-dominant PSNs had significantly worse prognosis compared with those with other PSNs and had comparable prognosis with those with cT1b pure solid nodules (p = 0.892). Higher frequency of nodal and lymphovascular involvement and pathologic upstaging was observed with T category progression in solid-dominant PSNs.

Conclusions: An hierarchy of prognosis and pathologic malignant characteristics was observed according to T category in patients with solid-dominant PSNs but not in those with GGO-dominant PSNs, suggesting the importance of classifying PSNs on the basis of solid component size and CTR for accurate prognostic comparison with pure solid nodules.

Keywords: Ground-glass opacity; High-resolution computed tomography; Lung adenocarcinoma; Part-solid nodule; Prognosis.

Introduction: Women experiencing intimate partner violence (IPV) do not tend to go very frequently to formal support services. The objective of this study is to identify barriers related to the accessibility, acceptability, equity, appropriateness and effectiveness of IPV services from the perspective of the professionals working in the IPV public services.

Methods: A qualitative study was carried out in the Madrid region based on 13 semi-structured interviews of young women who had survived IPV as well as 17 interviews with professionals. A thematic content analysis was performed, guided by the dimensions proposed by the World Health Organization (WHO) for friendly services for young people.

Results: From the perspective of the young women and professionals, barriers were identified for all the dimensions of the WHO's friendly services for young people: accessibility: lack of information and support from the social setting, scarce dissemination of the services, economic cost, non-adapted schedules, inadequate locations or lack of services in settings close to young people; acceptability: lack of protocols to guarantee confidentiality, lack of speed in the provision of services or their referral, unwelcoming environments or unsympathetic professional malpractice; equity: discriminatory professional attitudes towards groups with different social status and lack of protocols to ensure the care of these groups; appropriateness: unmet needs and lack of multidisciplinary teams; and effectiveness: shortage of time, resources, competent professionals, protocols and coordination.

Conclusions: Strategies are needed to make the necessary changes to promote friendly services for the care of young people exposed to IPV. Additionally, it must be emphasized that resources are needed to raise awareness and disseminate IPV services, as well as to train professionals in this area.

Patient or public contribution: This paper is based on professionals' perspectives of public IPV-related services of different areas such as Psychology, Social Work, Nursing, Psychiatry, Social Education and young women exposed to IPV. They either work in the public administration at the local, regional or state level or in NGOs in Spain.

Keywords: friendly services; intimate partner violence; young women.

Inducing gamma oscillations with non-invasive light flicker has been reported to impact Alzheimer's disease-related pathology. However, it is unclear which signaling pathways are involved in reducing amyloid load. Here, we found that gamma frequency light flicker increased anchoring of amyloid precursor protein (APP) to the plasma membrane for non-amyloidogenic processing, and then physically interacted with KCC2, a neuron-specific K⁺ -Cl^- cotransporter, suggesting that it is essential to maintain surface GABA_A receptor α1 levels and reduce β-amyloid (Aβ) production. Stimulation with such light flicker limited KCC2 internalization and subsequent degradation via both tyrosine phosphorylation and ubiquitination, leading to an increase in surface-KCC2 levels. Specifically, PKC-dependent phosphorylation of APP on a serine residue was induced by gamma frequency light flicker, which was responsible for maintaining plasma membrane levels of full-length APP, leading to its reduced trafficking to endosomes and inhibiting the β-secretase cleavage pathway. The activated PKC from the gamma frequency light flicker subsequently phosphorylated serine of KCC2 and stabilized it onto the cell surface, which contributed to the upregulation of surface GABA_A receptor α1 levels. Together, these data indicate that enhancement of APP trafficking to the plasma membrane via light flicker plays a critical modulatory role in reduction of Aβ load in Alzheimer's disease.

Keywords: Alzheimer's disease; GABAA receptor α1; KCC2; amyloid precursor protein trafficking; gamma frequency light flicker; β-amyloid.

The early detection of hepatocellular carcinoma (HCC) is critical to improving outcomes since advanced HCC has limited treatment options. Current guidelines recommend HCC ultrasound surveillance every 6 months in high-risk patients however the sensitivity for detecting early stage HCC in clinical practice is poor. Blood-based biomarkers are a promising direction since they are more easily standardized and less resource intensive. Combining of multiple biomarkers is more likely to achieve the sensitivity required for a clinically useful screening algorithm and the longitudinal trajectory of biomarkers contains valuable information that should be utilized. We propose a multivariate parametric empirical Bayes (mPEB) screening approach that defines personalized thresholds for each patient at each screening visit to identify significant deviations that trigger additional testing with more sensitive imaging. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) trial provides a valuable source of data to study HCC screening algorithms. We study the performance of the mPEB algorithm applied to serum $\alpha$ -fetoprotein, a widely used HCC surveillance biomarker, and des- $\gamma$ carboxy prothrombin, an HCC risk biomarker that is FDA approved but not used in practice in the United States. Using cross-validation, we found that the mPEB algorithm demonstrated moderate but improved sensitivity compared to alternative screening approaches. Future research will validate the clinical utility of the approach in larger cohort studies with additional biomarkers.

Keywords: biomarkers; early detection; empirical Bayes; longitudinal screening history; numeric optimization.

Objectives: This project aimed to enhance the identification of patients at-risk for prediabetes or diabetes within a dental school patient population by introduction of a modified screening tool and related training of dental residents and students.

Methods: The American Diabetes Association Risk Tool (ADART) was modified by addition of three diabetes-linked oral health questions. Of the 1477 dental patients screened, 551 (37.3%) indicated an at-risk status using the modified tool. A subset of 138 patients received follow-up chairside HbA1c blood testing conducted by dental residents and students. Data was analysed to determine a) the influence of the modifications on the tool's discrimination strength and b) change in the tool's predictive value.

Results: The addition of the 3 oral health questions to the 7-item ADART resulted in a 9.4% increase in identification of patients at-risk for pre-diabetes/diabetes. The predictive value of the tool remained stable. Residents and students successfully incorporated the new screening activities within their assigned clinics.

Conclusions: This project demonstrates that screening for risk for prediabetes/diabetes is both prudent and practical in the dental setting. Dental personnel, including trainees, can successfully incorporate enhanced screening methods within their traditional activities. Further, screening tools used in the dental setting might be enhanced by inclusion of certain oral health variables associated with diabetes. These findings add to emerging knowledge on the importance of screening for prediabetes/diabetes in dental settings and have particular relevance and application to institutional practice.

Keywords: comprehensive dental care; diabetes mellitus, type 2; interprofessional practice; practice transformation; primary health care; risk assessment; scope of practice.

Wnt/β-catenin is an evolutionarily conserved, complex developmental signal pathway that regulates embryogenesis, cell fate, tissue homeostasis, injury repair, and the pathogenesis of human diseases. Mounting evidence demonstrates that Wnt/β-catenin signaling plays a key role in early nephrogenesis. It is relatively silent in normal adult kidneys but reactivated in a wide variety of animal models of nephropathies and in human kidney diseases. Activation of Wnt/β-catenin after acute kidney injury contributes to proper repair and regeneration of damaged renal tubules. However, sustained activation of this signal cascade is closely related to the development and progression of fibrotic chronic kidney disease. In this paper, we systematically review the components and mechanisms of Wnt/β-catenin signaling and its role in kidney repair and fibrosis after injury. A better delineation of the mechanisms of this pathway will provide novel targets and new strategies for designing effective treatment of various kidney diseases.

The global survival rates for childhood cancers are high: approximately 80% of affected children will survive. Nevertheless, the burden of treatment for survivors is also high as three-quarters experience late effects of varying severity following cancer treatment. The aims of this study were to evaluate the treatment-related late effects of patients with childhood solid tumour in northern Finland and to report their survival rates. Our study included 104 patients treated for malignant solid tumours, excluding central nervous system tumours and lymphomas, between 1990 and 2015. Information regarding the type of late effects as well as other clinical data were obtained from the patients' medical records. Late effects were observed in 65 (63%) patients, and almost half (40%) of the patients displayed more than one late effect. The most common late effect was hearing loss (n = 20). The 5-year survival rate in our study was 75%. Conclusion: Our results highlight the importance of long-term follow-up for childhood cancer survivors. As survivors age and survival rates improve, late effects and their impact on patient health as well as the value of surveillance must be considered. What is Known: • Up to three-quarters of childhood cancer survivors experience treatment-related late effects. What is New: • The 5-year survival rate and the prevalence of late effects amongst childhood solid tumour patients treated in northern Finland are in line with findings from previous studies.

Keywords: Childhood; Late effects; Solid tumours; Survival.

Mental health comorbidities are prevalent among young Black gay, bisexual, and other men who have sex with men (YB-GBMSM) living with HIV and can adversely impact HIV-related outcomes. We conducted a cross-sectional survey study with 100 YB-GBMSM recruited from two HIV care centers in Atlanta, and constructed multivariable logistic and linear regression models to examine correlates of depression, anxiety, trauma symptoms, and general well-being. In adjusted models, full-time employment was associated with fewer depressive symptoms, while HIV stigma and substance use were associated with higher levels of depressive symptoms. Younger age and full-time employment were negatively associated with severe anxiety, while HIV stigma was positively associated with severe anxiety and trauma symptoms. Trust in physicians, lower HIV stigma, full-time employment, and lack of substance use were associated with higher average general well-being scores. In conclusion, we found high frequency of depressive, anxiety, and trauma-related symptoms among this sample of YB-GBMSM living with HIV. Unemployment, substance use, and HIV stigma emerged as particularly salient correlates of psychological morbidity, suggesting a need for structural and community-level interventions to address mental health in this population.

Keywords: African American; Depression; HIV; Mental health; Sexual and gender minorities.

Introduction: Jejunal gastrointestinal stromal tumours (GIST) are rare mesenchymal tumours. Acute massive overt bleeding from jejunal GIST is very rare and poses both diagnostic and therapeutic challenges in emergent conditions.

Methods: A case series with retrospective analysis of prospectively maintained database of patients presenting with acute massive overt bleeding secondary to histologically proven jejunal GIST was done. Clinical characteristics, endoscopic and imaging diagnostic features, histological findings, surgical procedures and outcomes in these patients were studied.

Results: Three patients were included in this case series. Mean age of presentation was 49.0 years with two male and one female patient. All three patients presented with melena and hemodynamic instability, resuscitated with adequate blood transfusions. Routine endoscopic assessment were inconclusive. Multiphasic Computed Tomographic Angiography (CTA) revealed hypodense hypervascular mass in jejunum in all three patients. One patient was unresponsive to blood transfusion and underwent emergency exploratory laparotomy. One patient underwent laparoscopic resection and reconstruction. Mean length of hospital stay was 5.3 days. Histopathological examination confirmed jejunal GIST in all three patients with microscopically negative resection margins. Two patients were disease free till 18-month follow-up and the one patient lost to follow-up after 1 year.

Conclusion: Multiphasic CTA is a single-step diagnostic tool for localisation of bleed and assessment of tumour characteristics in emergent conditions. Surgical resection is the mainstay of treatment for both control of bleed and to provide oncologically clear resection margins.

Keywords: Bleeding; Computed tomography; Gastrointestinal stromal tumour; Jejunum; Surgery.

In order to reduce the transmission of pathogens, and COVID-19, WHO and NHS England recommend hand washing (HW) and/or the use of hand sanitizer (HS). The planetary health consequences of these different methods of hand hygiene have not been quantified. A comparative life cycle assessment (LCA) was carried out to compare the environmental impact of the UK population practising increased levels of hand hygiene during the COVID-19 pandemic for 1 year. Washing hands with soap and water was compared to using hand sanitizer (both ethanol and isopropanol based sanitizers were studied). The isopropanol-based HS had the lowest environmental impact in 14 out of the 16 impact categories used in this study. For climate change, hand hygiene using isopropanol HS produced the equivalent of 1060 million kg CO₂, compared to 1460 million for ethanol HS, 2300 million for bar soap HW, and 4240 million for liquid soap HW. For both the ethanol and isopropanol HS, the active ingredient was the greatest overall contributing factor to the environmental impact (83.24% and 68.68% respectively). For HW with liquid soap and bar soap, there were additional contributing factors other than the soap itself: for example tap water use (28.12% and 48.68% respectively) and the laundering of a hand towel to dry the hands (10.17% and 17.92% respectively). All forms of hand hygiene have an environmental cost, and this needs to be weighed up against the health benefits of preventing disease transmission. When comparing hand sanitizers to handwashing with soap and water, this study found that using isopropanol based hand sanitizer is better for planetary health. However, no method of hand hygiene was ideal; isopropanol had a greater fossil fuel resource use than ethanol based hand sanitizer. More research is needed to find hand hygiene sources which do not diminish planetary health, and environmental impact is a consideration for public health campaigns around hand hygiene.

Keywords: Carbon footprint; Environment; Hand gel; Hand sanitizer; Industrial ecology; Planet; Planetary health.

Introduction: Automated external defibrillators (AEDs) increase survival after out-of-hospital cardiac arrest. However, the effect of AEDs for in-hospital cardiac arrest (IHCA) remains uncertain. This study aims to describe the distribution and use of AEDs in Danish hospitals and investigate whether early rhythm analysis is associated with return of spontaneous circulation (ROSC).

Methods: All Danish public hospitals with a cardiac arrest team were included and sent a questionnaire on the in-hospital distribution of AEDs and manual defibrillators. Further, we collected data on IHCAs including rhythm analysis, device type, cardiac arrest team arrival, and ROSC from the national database on IHCA (DANARREST).

Results: Of 46 hospitals, 93% had AEDs and 93% had manual defibrillators. AEDs were often placed in wards or non-clinical areas, whereas manual defibrillators were often placed in areas with high-risk patients. We identified 3,204 IHCAs. AEDs were used in 13% of IHCAs. After adjustment for confounders, chance of ROSC was higher if the first rhythm analysis was performed before the arrival of the cardiac arrest team (RR: 1.28 (95% CI: 1.12-1.46)). The relative risk of ROSC was 1.09 (0.84-1.41) when analyzing with an AED before cardiac arrest team arrival and 1.19 (1.00-1.41) when using a manual defibrillator. However, there was no significant effect modification for AED vs manual defibrillator (p = 0.26).

Conclusion: AEDs are widely distributed in Danish hospitals but less commonly used for IHCAs compared to manual defibrillators. Rhythm analysis before arrival of the cardiac arrest team was associated with ROSC without significant effect modification of device type.

Keywords: Automated external defibrillator; Defibrillation; In-hospital cardiac arrest; Return of spontaneous circulation.

Aims: The CRASH study examined severe hypoglycemia (SH) experiences among people with diabetes (PWD) and caregivers across eight countries. Here we report findings from the Japan cohort, with references to data from the United Kingdom (UK) cohort.

Materials and methods: Adults with type 1 (T1DM) or insulin-treated type 2 diabetes mellitus (T2DM) and caregivers (not necessarily related) were recruited from online patient panels. Participants who had experienced at least one SH event in the past 3 years were eligible for study inclusion. Participants completed an online survey regarding their experience with SH, its treatment, and actions during and after an event.

Results: Of the 9367 PWD and caregivers from the online patient panels, 8475 participants were ineligible and a total of 53 Japanese participants (35 T1DM, 9 T2DM, 9 caregivers) completed the survey. Most SH incidents occurred at home and were unattended by a healthcare provider. For T1DM, 29% of Japan PWD and 13% of the UK PWD called an ambulance during an SH event; of these, 90% (Japan) and 50% (UK) were transported to hospital. Glucagon use was low (3% Japan and 10% UK for T1DM). Japanese respondents reported emotional impacts of SH, including feeling scared (86% T1DM, 56% T2DM), unprepared (63% T1DM, 78% T2DM), and helpless (60% T1DM, 33% T2DM). Despite the emotional burden, most PWD did not immediately discuss their SH event with a healthcare provider, with the majority (75% T1DM, 71% T2DM) waiting until their next doctor's appointment.

Conclusion: Conversations around SH between healthcare providers and PWD appear to be insufficient in Japan. An emotional burden of SH was reported by PWD and caregivers. Education regarding the prevention of SH and available treatment options may reduce SH events and improve treatment preparation, while alleviating PWD concerns.

Keywords: Caregivers; Diabetes; Emotional burden; Glucagon; Japan; Severe hypoglycemia.

Objectives: Efforts to achieve zero transmission of HIV to infants born to women living with HIV in sub-Saharan African are undermined by high rates of loss to follow-up in prevention of vertical transmission (PVT) programmes. The fear of HIV status disclosure through the discovery of pill bottles at home is a major contributor. Injectable antiretroviral therapy (ART) has proved to be efficacious in clinical trials and is discreet, offering a potential solution. We investigated the knowledge and willingness to use injectable ART among women who were lost to follow-up from the PVT programme in Uganda.

Methods: Women were traced by nurse counsellors and knowledge and opinions relating to injectable ART, including willingness to use it when it becomes available, were collected. Generalized linear models were used to determine predictors of willingness to use injectable ART.

Conclusions: Among 1023 women registered between 2017 and 2019 under the PVT programmes in Kampala and Wakiso districts, Uganda, 385 (38%) were lost to follow-up from care and 22% of these (83/385) were successfully traced and interviewed. Only 25% (21/83) had heard of injectable ART. Over half (55%, 46/83) were very willing to use injectable ART, 40% (33/83) were somewhat willing and four (5%) were not willing. Those who associated ART tablets with disclosure risk were more willing to consider injectable ART (adjusted odds ratio = 4.21; 95% confidence interval: 1.45-12.19; p = 0.008). We report high willingness to use injectable ART associated with fears that ART tablets were a potential source of HIV status disclosure. Injectable ART could be a solution for women who have challenges with disclosure.

Keywords: HIV/AIDS; PVT programme; injectable ART; loss to follow-up; nursing; pregnant.

Introduction: Atrial tachycardias (AT) in patients with congenital heart disease (CHD) are significantly contributing to morbidity and mortality. Aim of this study was to evaluate the long-term course of CHD patients requiring repeat ablation procedures (RAP) of AT.

Patients and methods: All 144 patients with CHD who had undergone ablation of AT at our center between January 2003 and October 2018 were enrolled. Patients were classified according to complexity of CHD: complex CHD (cCHD), moderate CHD (mCHD) and simple CHD (sCHD).

Results: A total of 101 RAP were performed in 64 patients. One RAP was performed in n=40, two in n=13, three in n=10 and 5 in n=1. Acute success rate was 82% (83/101) and was not associated with complexity of CHD (p=1.0). Number of procedures was lower in patients with sCHD than in patients with mCHD and cCHD (sCHD 1.3±0.6, mCHD 1.8±1.0 and cCHD 1.8±1.1, p=0.04). RAP were most frequent in patients after Fontan palliation or Atrial switch procedure (2.0±1.1 (n=41) vs. 1.6±0.9 all others, p=0.016) and in patients with multiple unstable AT´s (2.5±1.1 (n=11) vs. 1.7±1.0, p=0.008). Major complications occurred in 4/101 procedures. Complete follow-up was available in 125 patients. Since last RAP 73% of the patients were in sinus/atrial rhythm and 34/125 patients (27%) with AT recurrence did not require re-ablation with mean follow-up of 52±40 months.

Conclusions: Recurrences after ablation of AT in CHD patients were frequent. After RAP promising long-term results could be achieved. Data encourage repetitive ablation procedures in this patient population. This article is protected by copyright. All rights reserved.

Keywords: Atrial switch procedure; Atrial tachyarrhythmia; Catheter ablation; Congenital heart disease; Fontan procedure; Intraatrial re-entrant tachycardia.

Background: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorders in females of reproductive age, with a prevalence of 20%-33% in the general population. Interleukin (IL)-34 is a recently explored proinflammatory cytokine and is an important modulator in different disease types. However, the function of IL-34 in PCOS has yet to be investigated.

Objective: The purpose of this study was to determine the IL-34 serum level in women with PCOS and to compare it to that of a relatively healthy control group. Focusing on its relationship with IL-6, TNF-α, and IL-1β and homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride, and low-density lipoprotein cholesterol (LDL-C).

Materials and methods: In this study, blood samples were obtained from 100 women with PCOS and 100 healthy control women for the purpose of estimating their serum levels of IL-34, IL-6, TNF-α, and IL-1β using the enzyme-linked immunosorbent assay technique.

Results: Serum levels of IL-34, IL-6, TNF-α, and IL-1β were all higher in PCOS women than in healthy controls, and the difference was highly statistically significant. Serum IL-34 concentration was positively correlated with IL-6, TNF-α, and IL-1β concentration. Additionally, serum concentrations of IL-34 were positively correlated with HOMA-IR, triglyceride, and LDL-C.

Conclusion: When compared to normal women, IL-34, IL-6, TNF-α, and IL-1β levels were highly statistically significant in PCOS, and these high levels were associated with other cytokines (IL-6, TNF-α, and IL-1β), HOMA-IR, triglyceride, and LDL-C.

Keywords: PCOS; interleukin 34; polycystic ovary syndrome.

Infertility randomized controlled trials (RCTs) are often too small to detect realistic treatment effects. Large observational studies have been proposed as a solution. However, this strategy threatens to weaken the evidence base further, because non-random assignment to treatments makes it impossible to distinguish effects of treatment from confounding factors. Alternative solutions are required. Power in an RCT can be increased by adjusting for prespecified, prognostic covariates when performing statistical analysis, and if stratified randomization or minimization has been used, it is essential to adjust in order to get the correct answer. We present data showing that this simple, free and frequently necessary strategy for increasing power is seldom employed, even in trials appearing in leading journals. We use this article to motivate a pedagogical discussion and provide a worked example. While covariate adjustment cannot solve the problem of underpowered trials outright, there is an imperative to use sound methodology to maximize the information each trial yields.

Keywords: RCTs; covariate adjustment; infertility; research methods; statistics.

Purpose: Epilepsy with centrotemporal spikes (ECTS) is the most common epilepsy syndrome in children and usually presents with cognitive dysfunctions. However, little is known about the processing speed dysfunction and the associated neuroimaging mechanism in ECTS. This study aims to investigate the brain functional abnormality of processing speed dysfunction in ECTS patients by using the ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) and resting-state functional magnetic resonance imaging (rs-fMRI).

Methods: This prospective study recruited twenty-eight ECTS patients who underwent the ¹⁸F-FDG PET, rs-fMRI, and neuropsychological examinations. Twenty children with extracranial tumors were included as PET controls, and 20 healthy children were recruited as MRI controls. The PET image analysis investigated glucose metabolism by determining standardized uptake value ratio (SUVR). The MRI image analysis explored abnormal functional connectivity (FC) within the cortical-striatal circuit through network-based statistical (NBS) analysis. Correlation analysis was performed to explore the relationship between SUVR, FC, and processing speed index (PSI).

Results: Compared with healthy controls, ECTS patients showed normal intelligence quotient but significantly decreased PSI (P = 0.04). PET analysis showed significantly decreased SUVRs within bilateral caudate, putamen, pallidum, left NAc, right rostral middle frontal gyrus, and frontal pole of ECTS patients (P < 0.05). Rs-fMRI analysis showed absolute values of 20 FCs were significantly decreased in ECTS patients compared with MRI controls, which connected 16 distinct ROIs. The average SUVR of right caudate and the average of 20 FCs were positively correlated with PSI in ECTS patients (P = 0.034 and P = 0.005, respectively).

Conclusion: This study indicated that ECTS patients presented significantly reduced PSI, which is closely associated with decreased SUVR and FC of cortical-striatal circuit. Caudate played an important role in processing speed dysfunction.

Clinical trial registration: NCT04954729; registered on July 8, 2021, public site, https://clinicaltrials.gov/ct2/show/NCT04954729.

Keywords: Epilepsy; Positron emission tomography (PET); Processing speed; Resting-state functional magnetic resonance imaging (Rs-fMRI).