Early development of the glucocorticoid stress response in poison frog tadpoles.

In vertebrates, the glucocorticoid response through the hypothalamic-pituitary-adrenal (HPA) axis controls many essential functions, including behavior, metabolism, and ontogenetic transitions. However, there are tradeoffs associated with high levels of glucocorticoids, including reduced growth rate and lowered immunity. These tradeoffs drive variation in the timing of the development of the HPA axis across taxa. In anurans (frogs and toads), corticosterone has critical roles in development and behavior, and concentrations can fluctuate in response to environmental stressors. Given the role of corticosterone in ontogenetic changes and behaviors, we hypothesized that species with immediate habitat transitions and challenges would develop an HPA axis early in development. To test this hypothesis, we studied tadpoles of the dyeing poison frog ( Dendrobates tinctorius ), a species in which tadpoles hatch terrestrially and are transported to pools of water by their parent. We measured the excretion rate and whole-body concentration of corticosterone and the corticosterone response to adrenocorticotropic hormone (ACTH). We found no significant differences in excretion rates and whole-body concentration of corticosterone, nor physiological response to ACTH injection across tadpole development. These findings indicate that the glucocorticoid response is developed early in ontogeny. These findings generally differ from those found in other species of tadpoles, which may suggest the unique ecological pressures of D. tinctorius has shaped the development of its HPA axis. More broadly, this study illustrates how life history strategies and tradeoffs of glucocorticoids impact the timing of the development of the HPA axis. Highlights: The timing of HPA axis development differs across species. We studied the HPA axis across tadpole development in Dendrobates tinctorius . No difference in corticosterone concentration across development.No difference in corticosterone response to ACTH across development.Results suggest an early developed HPA axis is essential for their life history.

Development and Validation of Performance-Based Assessment of Daily Living Tasks in Age-Related Macular Degeneration.

Purpose: To establish the reliability and validity of five performance-based activities of daily living task tests (ADLTT), to correlate structure to function, to evaluate the impact of visual impairment (VI) on age-related macular degeneration (AMD), and to develop new outcome measures. Methods: A multidisciplinary team developed five ADLTTs: (1) reading test (RT); (2) facial expression (FE) recognition; (3) item search (IS) task; (4) money counting (MC) task; and (5) making a drink (MD), tested with binocular and monocular vision. ADLTTs were tested for known-group (i.e., difference between AMD group and controls) and convergent (i.e., correlation to other measures of visual function), validity metrics, and test-retest reliability in 36 patients with VI (visual acuity (logMAR VA > 0.4) in at least one eye caused by AMD versus 36 healthy controls without VI. Results: Compared to controls, AMD patients had a slower reading speed (-77.41 words/min; P < 0.001); took longer to complete MC using monocular worse eye and binocular vision (15.13 seconds and 4.06 seconds longer compared to controls, respectively; P < 0.001); and MD using monocular worse eye vision (9.37 sec; P = 0.033), demonstrating known-group validity. Only RT and MC demonstrated convergent validity, showing correlations with VA, contrast sensitivity, and microperimetry testing. Moderate to good test-retest reliability was observed for MC and MD (interclass correlation coefficient = 0.55 and 0.77; P < 0.001) using monocular worse eye vision. Conclusions: Real-world ADL functioning associated with VI-related AMD can be assessed with our validated ADLTTs, particularly MC and MD. Translational Relevance: This study validates visual function outcome measures that are developed for use in future clinical practice and clinical trials.

Proteomic profiling reveals ACSS2 facilitating metabolic support in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by genomic aberrations in oncogenes, cytogenetic abnormalities, and an aberrant epigenetic landscape. Nearly 50% of AML cases will relapse with current treatment. A major source of therapy resistance is the interaction of mesenchymal stroma with leukemic cells resulting in therapeutic protection. We aimed to determine pro-survival/anti-apoptotic protein networks involved in the stroma protection of leukemic cells. Proteomic profiling of cultured primary AML (n = 14) with Hs5 stroma cell line uncovered an up-regulation of energy-favorable metabolic proteins. Next, we modulated stroma-induced drug resistance with an epigenetic drug library, resulting in reduced apoptosis with histone deacetylase inhibitor (HDACi) treatment versus other epigenetic modifying compounds. Quantitative phosphoproteomic probing of this effect further revealed a metabolic-enriched phosphoproteome including significant up-regulation of acetyl-coenzyme A synthetase (ACSS2, S30) in leukemia-stroma HDACi treated cocultures compared with untreated monocultures. Validating these findings, we show ACSS2 substrate, acetate, promotes leukemic proliferation, ACSS2 knockout in leukemia cells inhibits leukemic proliferation and ACSS2 knockout in the stroma impairs leukemic metabolic fitness. Finally, we identify ACSS1/ACSS2-high expression AML subtype correlating with poor overall survival. Collectively, this study uncovers the leukemia-stroma phosphoproteome emphasizing a role for ACSS2 in mediating AML growth and drug resistance.

Future-proofing genomic data and consent management: a comprehensive review of technology innovations.

Genomic information is increasingly used to inform medical treatments and manage future disease risks. However, any personal and societal gains must be carefully balanced against the risk to individuals contributing their genomic data. Expanding our understanding of actionable genomic insights requires researchers to access large global datasets to capture the complexity of genomic contribution to diseases. Similarly, clinicians need efficient access to a patient's genome as well as population-representative historical records for evidence-based decisions. Both researchers and clinicians hence rely on participants to consent to the use of their genomic data, which in turn requires trust in the professional and ethical handling of this information. Here, we review existing and emerging solutions for secure and effective genomic information management, including storage, encryption, consent, and authorization that are needed to build participant trust. We discuss recent innovations in cloud computing, quantum-computing-proof encryption, and self-sovereign identity. These innovations can augment key developments from within the genomics community, notably GA4GH Passports and the Crypt4GH file container standard. We also explore how decentralized storage as well as the digital consenting process can offer culturally acceptable processes to encourage data contributions from ethnic minorities. We conclude that the individual and their right for self-determination needs to be put at the center of any genomics framework, because only on an individual level can the received benefits be accurately balanced against the risk of exposing private information.

Anterior enterocele after cystectomy: case report and review of the literature.

PURPOSE: Anterior enterocele is a rare but potentially serious complication after cystectomy with heterogeneous treatment options. METHODS: Here we report on the management of a 71-year-old patient with recurrence of anterior enterocele after cystectomy and provide a systematic review of the literature using the PubMed/MEDLINE database. RESULTS: The 71-year-old patient with recurrence of anterior enterocele after cystectomy was successfully treated with colpocleisis and anterior colporrhaphy at the Department of Gynecology and Gynecological Oncology, University Hospital Bonn. The use of a synthetic mesh was not needed. At 16-month follow-up postoperatively, the patient was asymptomatic and had no signs of recurrence. n = 14 publications including n = 39 patients were identified for the systematic review including case reports and reviews. The median duration of developing an anterior enterocele after cystectomy was 9 months (range 3 months to 8 years). Patients had a median age of 71 years (range 44-84). In all cases, a surgical approach was described using a wide variety of surgical procedures. In total, 36% of all patients developed a recurrence with an average time period of 7 months after primary surgery. A rare complication represents a vaginal evisceration with the need of urgent surgery. Furthermore, the occurrence of a fistula is a possible long-term complication. CONCLUSION: Anterior enterocele after cystectomy is a rare complication requiring an individual and interdisciplinary treatment.

Methods of Evaluating EEG Reactivity in Adult Intensive Care Units: A Review.

PURPOSE: EEG reactivity (EEG-R) has become widely used in intensive care units for diagnosing and prognosticating patients with disorders of consciousness. Despite efforts toward standardization, including the establishment of terminology for critical care EEG in 2012, the processes of testing and interpreting EEG-R remain inconsistent. METHODS: A review was conducted on PubMed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria consisted of articles published between January 2012, and November 2022, testing EEG-R on adult intensive care unit patients. Exclusion criteria included articles focused on highly specialized stimulation equipment or animal, basic science, or small case report studies. The Quality In Prognostic Studies tool was used to assess risk of bias. RESULTS: One hundred and five articles were identified, with 26 variables collected for each. EEG-R testing varied greatly, including the number of stimuli (range: 1-8; 26 total described), stimulus length (range: 2-30 seconds), length between stimuli (range: 10 seconds-5 minutes), frequency of stimulus application (range: 1-9), frequency of EEG-R testing (range: 1-3 times daily), EEG electrodes (range: 4-64), personnel testing EEG-R (range: neurophysiologists to nonexperts), and sedation protocols (range: discontinuing all sedation to no attempt). EEG-R interpretation widely varied, including EEG-R definitions and grading scales, personnel interpreting EEG-R (range: EEG specialists to nonneurologists), use of quantitative methods, EEG filters, and time to detect EEG-R poststimulation (range: 1-30 seconds). CONCLUSIONS: This study demonstrates the persistent heterogeneity of testing and interpreting EEG-R over the past decade, and contributing components were identified. Further many institutional efforts must be made toward standardization, focusing on the reproducibility and unification of these methods, and detailed documentation in the published literature.

Clinical experience with shear wave elastography (SWE) for assessing healthy uterus in a transabdominal approach.

Aim of the study was to evaluate the diagnostic performance and feasibility of transabdominal ultrasound shear wave elastography (SWE) in assessing sonoelastographic features of the uterus. Twenty-seven premenopausal women were enrolled between 2021 and 2022. Transabdominal SWE measured myometrial stiffness in various uterine segments. Additionally, tissue stiffness of the quadriceps femoris muscle and autochthonous back muscle was measured. Statistical analysis employed non-parametric tests, t test, and a robust mixed linear model. Stiffness values of the uterus and the two investigated muscle types exhibited a similar spectrum: 6.38 ± 2.59 kPa (median 5.61 kPa; range 2.76-11.31 kPa) for the uterine myometrium, 7.22 ± 1.24 kPa (6.82 kPa; 5.11-9.39 kPa) for the quadriceps femoris musle, and 7.43 ± 2.73 kPa (7.41 kPa; 3.10-13.73 kPa) for the autochthonous back muscle. A tendency for significant differences in myometrial stiffness was observed concerning the type of labor mode (mean stiffness of 9.17 ± 1.35 kPa after vaginal birth vs. 3.83 ± 1.35 kPa after Caesarian section, p = 0.01). No significant differences in myometrial stiffness were observed concerning age, BMI, previous pregnancies, uterine flexion and menstrual cycle phase. Transabdominal SWE of uterine stiffness seems to be a fast and practicable method in a clinical setting. Uterine stiffness appears to be largely independent of various factors, except for the mode of delivery. However, further studies are needed to validate these results.

Idelalisib-Induced Pneumonitis in Chronic Lymphocytic Leukemia.

Idelalisib, a phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, effectively treats relapsed chronic lymphocytic leukemia (CLL). While this targeted approach offers a therapeutic edge, particularly in B-cell malignancies, it is associated with complications such as pneumonitis. This report details idelalisib-induced pneumonitis, highlighting the importance of early diagnosis and tailored treatment in achieving a favorable patient outcome.

Associations Between Genetically Predicted Iron Status and Cardiovascular Disease Risk: A Mendelian Randomization Study.

BACKGROUND: Mendelian randomization (MR) studies suggest a causal effect of iron status on cardiovascular disease (CVD) risk, but it is unknown if these associations are confounded by pleiotropic effects of the instrumental variables on CVD risk factors. We aimed to investigate the effect of iron status on CVD risk controlling for CVD risk factors. METHODS AND RESULTS: Iron biomarker instrumental variables (total iron-binding capacity [n=208 422], transferrin saturation [n=198 516], serum iron [n=236 612], ferritin [n=257 953]) were selected from a European genome-wide association study meta-analysis. We performed 2-sample univariate MR of each iron trait on CVD outcomes (all-cause ischemic stroke, cardioembolic ischemic stroke, large-artery ischemic stroke, small-vessel ischemic stroke, and coronary heart disease) from MEGASTROKE (n=440 328) and CARDIoGRAMplusC4D (Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus the Coronary Artery Disease Genetics) (n=183 305). We then implemented multivariate MR conditioning on 7 CVD risk factors from independent European samples to evaluate their potential confounding or mediating effects on the observed iron-CVD associations. With univariate MR analyses, we found higher genetically predicted iron status to be associated with a greater risk of cardioembolic ischemic stroke (transferrin saturation: odds ratio, 1.17 [95% CI, 1.03-1.33]; serum iron: odds ratio, 1.21 [95% CI, 1.02-1.44]; total iron-binding capacity: odds ratio, 0.81 [95% CI, 0.69-0.94]). The detrimental effects of iron status on cardioembolic ischemic stroke risk remained unaffected when adjusting for CVD risk factors (all P<0.05). Additionally, we found diastolic blood pressure to mediate between 7.1 and 8.8% of the total effect of iron status on cardioembolic ischemic stroke incidence. Univariate MR initially suggested a protective effect of iron status on large-artery stroke and coronary heart disease, but controlling for CVD factors using multivariate MR substantially diminished these associations (all P>0.05). CONCLUSIONS: Higher iron status was associated with a greater risk of cardioembolic ischemic stroke independent of CVD risk factors, and this effect was partly mediated by diastolic blood pressure. These findings support a role of iron status as a modifiable risk factor for cardioembolic ischemic stroke.

Bladder instillations vs onabotulinumtoxinA injection for interstitial cystitis/bladder pain syndrome: a randomized clinical trial.

BACKGROUND: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is an unpleasant sensation related to the bladder with lower urinary tract symptoms lasting more than 6 weeks, unrelated to an otherwise identifiable cause. The etiology is likely multifactorial including urothelial abnormalities, neurogenic pain upregulation, and potentially bladder and vaginal microbiome alterations. Despite treatment effectiveness of both bladder instillations and intradetrusor onabotulinumtoxinA injection for this condition, a head-to-head comparison has not been performed. OBJECTIVE: To compare the efficacy of bladder instillations and intradetrusor onabotulinumtoxinA injection for treatment of IC/BPS. STUDY DESIGN: Patients with O'Leary-Sant (OLS) questionnaire scores of ≥6, meeting clinical criteria for IC/BPS, and desiring procedural management were randomized to bladder instillations or intradetrusor onabotulinumtoxinA injection. The primary outcome was the difference in OLS scores at 2 months posttreatment between groups. Secondary outcomes included evaluation of sexual function, physical/mental health status, pain, patient satisfaction, treatment perception, retreatment, and adverse event rates. RESULTS: Forty-seven patients were analyzed with 22 randomized to bladder instillations and 25 to onabotulinumtoxinA injection. There were no differences in demographic and clinical characteristics between groups. From baseline to 2 months posttreatment, there was a decrease in OLS subscales in all patients (Interstitial Cystitis Symptom Index [ICSI] -6.3 (confidence interval [CI] -8.54, -3.95), P<.0001; Interstitial Cystitis Problem Index [ICPI] -5.9 (CI -8.18, -3.57), P<.0001). At 2 months posttreatment, patients in the onabotulinumtoxinA group had significantly lower OLS scores compared to those in the bladder instillation group (ICSI 6.3±4.5 [onabotulinumtoxinA] vs 9.6±4.2 [instillation], P=.008; ICPI 5.9±5.1 [onabotulinumtoxinA] vs 8.3±4.0 [instillation], P=.048). The difference in OLS scores between groups did not persist at 6 to 9 months posttreatment. There were no statistically significant differences between baseline and posttreatment time points for the remaining questionnaires. Eight percent of patients who received onabotulinumtoxinA injection experienced urinary retention requiring self-catheterization. Patients who underwent onabotulinumtoxinA injection were significantly less likely to receive retreatment within 6 to 9 months compared to patients who received bladder instillations (relative risk 13.6; 95% CI, 1.92-96.6; P=.0002). There were no differences between groups regarding patient satisfaction, perception of treatment convenience, or willingness to undergo retreatment. CONCLUSION: Both onabotulinumtoxinA injection and bladder instillations are safe, effective treatments for patients with IC/BPS, with significant clinical improvement demonstrated at 2 months posttreatment. Our findings suggest that intradetrusor onabotulinumtoxinA injection is a more effective procedural treatment for this condition than bladder instillation therapy and associated with decreased rates of retreatment.

A metabarcoding assessment of the diet of the insectivorous bats of Madeira Island, Macaronesia.

Understanding the trophic structure of species assemblages is crucial in order to comprehend how syntropic species coexist in space and time. Bats are the second most taxonomically diverse group of mammals and display a wide range of dietary strategies. Due to their ability to disperse over water, ca. 60% of all extant bat species occur on islands and for the most part their interspecific ecological interactions are poorly known. Using DNA metabarcoding, this study offers the first insights into the diet of Macaronesian bats by providing a holistic overview of prey consumed by all 3 bat species found on Madeira Island (Pipistrellus maderensis, Nyctalus leisleri verrucosus, and Plecotus austriacus) and investigating both interspecific (between P. maderensis and N. l. verrucosus) and intraspecific (between female and male N. l. verrucosus) dietary differences. We identified a total of 110 species of arthropod prey in the diet of the 3 bat species, including multiple agriculture and forestry pest species, a human disease-relevant species, and numerous taxa not previously recorded on the island. Lepidoptera was the primary prey order for all 3 bat species. The diet composition of P. maderensis and N. l. verrucosus differed significantly, with P. maderensis consuming more Diptera and multiple prey taxa not found in the diet of N. l. verucosus. Moreover, male N. l. verrucosus exhibited a broader niche breadth than females. This study is among the first to use DNA metabarcoding to evaluate the diet of insular bats and thus greatly advances knowledge regarding the trophic ecology and pest suppression services of these poorly-known mammals.

Temporal and spatial analysis of over 7,000 measles cases outbreak from 2018 to 2019 in the Brazilian Amazon.

OBJECTIVE: This study aimed to present a temporal and spatial analysis of the 2018 measles outbreak in Brazil, particularly in the metropolitan city of Manaus in the Amazon region, and further introduce a new tool for spatial analysis. METHODS: We analyzed the geographical data of the residences of over 7,000 individuals with measles in Manaus during 2018 and 2019. Spatial and temporal analyses were conducted to characterize various aspects of the outbreak, including the onset and prevalence of symptoms, demographics, and vaccination status. A visualization tool was also constructed to display the geographical and temporal distribution of the reported measles cases. RESULTS: Approximately 95% of the included participants had not received vaccination within the past decade. Heterogeneity was observed across all facets of the outbreak, including variations in the incubation period and symptom presentation. Age distribution exhibited two peaks, occurring at one year and 18 years of age, and the potential implications of this distribution on predictive analysis were discussed. Additionally, spatial analysis revealed that areas with the highest case densities tended to have the lowest standard of living. CONCLUSION: Understanding the spatial and temporal spread of measles outbreaks provides insights for decision-making regarding measures to mitigate future epidemics.

Systematic analysis of RNA-binding proteins identifies targetable therapeutic vulnerabilities in osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor with a strong tendency to metastasize, limiting the prognosis of affected patients. Genomic, epigenomic and transcriptomic analyses have demonstrated the exquisite molecular complexity of this tumor, but have not sufficiently defined the underlying mechanisms or identified promising therapeutic targets. To systematically explore RNA-protein interactions relevant to OS, we define the RNA interactomes together with the full proteome and the transcriptome of cells from five malignant bone tumors (four osteosarcomata and one malignant giant cell tumor of the bone) and from normal mesenchymal stem cells and osteoblasts. These analyses uncover both systematic changes of the RNA-binding activities of defined RNA-binding proteins common to all osteosarcomata and individual alterations that are observed in only a subset of tumors. Functional analyses reveal a particular vulnerability of these tumors to translation inhibition and a positive feedback loop involving the RBP IGF2BP3 and the transcription factor Myc which affects cellular translation and OS cell viability. Our results thus provide insight into potentially clinically relevant RNA-binding protein-dependent mechanisms of osteosarcoma.

The prevalence patterns and risk factor profiles of poor muscle health and its associated components in multiethnic older Asians: The PIONEER study.

BACKGROUND: We aim to determine the multiethnic patterns of the prevalence and associated factors of poor muscle health and its associated components in older Chinese, Malays, and Indian Asian adults. METHODS: We included 2199 participants (mean age ± SD: 72.9 ± 8.3 years; 54.3% female) from the baseline assessment of the Population Health and Eye Disease Profile in Elderly Singaporeans (PIONEER; 2017-2022) cohort study. Poor muscle health was defined as the presence of either low muscle mass (DEXA), or low muscle strength (handgrip strength), or low physical performance (gait speed). Its components include poor muscle function (low muscle strength and/or low physical performance without low muscle mass), pre-sarcopenia (low muscle mass only), and any sarcopenia (low muscle mass with low muscle strength and/or low physical performance). Sociodemographic, clinical, and lifestyle factors were assessed using biochemistry, clinical tests, and validated questionnaires. Regression models were utilized to evaluate the independent risk factors of poor muscle health and its components. RESULTS: The national census-adjusted prevalence of poor muscle health (88%) was similar across the three ethnic groups. However, Chinese individuals had higher prevalence of pre-sarcopenia and any sarcopenia, and a lower prevalence of poor muscle function compared with Indians or Malays. We observed ethnic differences in modifiable risk factors (low physical activity, diabetes, osteoporosis, and obesity) of poor muscle health and its components. Although obesity was protective of pre-sarcopenia (RRR = 0.19, 95% CI: 0.11, 0.36) and any sarcopenia (RRR = 0.29, 95% CI: 0.18, 0.47) in the overall population and across ethnic groups, it was associated with 1.7 times (95% CI: 1.07, 2.67) the likelihood of poor muscle function in the entire population. CONCLUSIONS: Almost 90% of community dwelling Singaporean aged ≥60 years have poor muscle health across the three ethnic groups with ethnic disparities in modifiable risk factors, highlighting an urgent need for community-wide targeted interventions to promote muscle health.

Integrating Palliative Care Into the Management of Genitourinary Malignancies.

Palliative care (PC) plays a critical role in managing the difficulties associated with genitourinary malignancies. Its primary aim is to improve the overall health of patients, provide support to both patients and their caregivers, and help individuals to navigate the complex decisions about treatment and end-of-life care. PC takes a holistic approach to patient care, recognizing that genitourinary malignancies affect multiple aspects of a person's life. By addressing physical, emotional, social, and spiritual needs, PC aims to provide comprehensive support that is consistent with the patient's values and preferences. The goal is to optimize comfort, minimize distress, and enhance the patient's quality of life throughout the course of the illness. PC is not a one-off intervention, but an ongoing source of support. This article aims to provide a thorough overview of the critical elements involved in addressing the challenges posed by genitourinary cancers, emphasizing the importance of palliative interventions. We will highlight the multifaceted aspects of care and explore strategies to optimize the overall well-being of patients throughout the course of treatment for genitourinary malignancies.

Prevalence, associated risk factors; and patient and economic impact of multiple sensory impairment in a multi-ethnic elderly population in Singapore: the PIONEER study.

BACKGROUND: To determine the prevalence, risk factors; and impact on patient health and economic outcomes across the laterality spectrum of multiple sensory impairment (MSI) in a multi-ethnic older Asian population. METHODS: In this population-based study of Singaporeans aged ≥ 60 years, MSI was defined as concomitant vision (visual acuity > 0.3 logMAR), hearing (pure-tone air conduction average > 25 dB), and olfactory (score < 12 on the Sniffin' Sticks test) impairments across the spectrum of laterality (any, unilateral, combination [of unilateral and bilateral], and bilateral). RESULTS: Among 2,057 participants (mean ± SD 72.2 ± 0.2 years; 53.1% female), the national census-adjusted prevalence rates of any, unilateral, combination, and bilateral MSI were 20.6%, 1.2%, 12.2%, and 7.2%, respectively. Older age, male gender, low socioeconomic status (SES), and smoking (all p < 0.05) were independently associated with higher likelihood of any MSI. Compared to those with no sensory loss, those with MSI had significantly decreased mobility (range 5.4%-9.2%), had poor functioning (OR range 3.25-3.45) and increased healthcare costs (range 4-6 folds) across the laterality spectrum. Additionally, bilateral MSI had a significant decrease in HRQoL (5.5%, p = 0.012). CONCLUSIONS: MSI is a highly prevalent medical condition, with 1 in 5; and almost 1 in 10 community-dwelling older Asians having any and bilateral MSI, respectively, with a higher likelihood in men, smokers, and those with low SES. Critically, MSI has a substantial negative impact on patient health and economic outcomes across the laterality spectrum. Sensory testing is critical to detect and refer individuals with MSI for management to improve their functional independence and QoL.

Extending the diabetic retinopathy screening intervals in Singapore: methodology and preliminary findings of a cohort study.

BACKGROUND: The Diabetic Retinopathy Extended Screening Study (DRESS) aims to develop and validate a new DR/diabetic macular edema (DME) risk stratification model in patients with Type 2 diabetes (DM) to identify low-risk groups who can be safely assigned to biennial or triennial screening intervals. We describe the study methodology, participants' baseline characteristics, and preliminary DR progression rates at the first annual follow-up. METHODS: DRESS is a 3-year ongoing longitudinal study of patients with T2DM and no or mild non-proliferative DR (NPDR, non-referable) who underwent teleophthalmic screening under the Singapore integrated Diabetic Retinopathy Programme (SiDRP) at four SingHealth Polyclinics. Patients with referable DR/DME (> mild NPDR) or ungradable fundus images were excluded. Sociodemographic, lifestyle, medical and clinical information was obtained from medical records and interviewer-administered questionnaires at baseline. These data are extracted from medical records at 12, 24 and 36 months post-enrollment. Baseline descriptive characteristics stratified by DR severity at baseline and rates of progression to referable DR at 12-month follow-up were calculated. RESULTS: Of 5,840 eligible patients, 78.3% (n = 4,570, median [interquartile range [IQR] age 61.0 [55-67] years; 54.7% male; 68.0% Chinese) completed the baseline assessment. At baseline, 97.4% and 2.6% had none and mild NPDR (worse eye), respectively. Most participants had hypertension (79.2%) and dyslipidemia (92.8%); and almost half were obese (43.4%, BMI ≥ 27.5 kg/m2). Participants without DR (vs mild DR) reported shorter DM duration, and had lower haemoglobin A1c, triglycerides and urine albumin/creatinine ratio (all p < 0.05). To date, we have extracted 41.8% (n = 1909) of the 12-month follow-up data. Of these, 99.7% (n = 1,904) did not progress to referable DR. Those who progressed to referable DR status (0.3%) had no DR at baseline. CONCLUSIONS: In our prospective study of patients with T2DM and non-referable DR attending polyclinics, we found extremely low annual DR progression rates. These preliminary results suggest that extending screening intervals beyond 12 months may be viable and safe for most participants, although our 3-year follow up data are needed to substantiate this claim and develop the risk stratification model to identify low-risk patients with T2DM who can be assigned biennial or triennial screening intervals.

Treatment of menopausal skin - A narrative review of existing treatments, controversies, and future perspectives.

Menopause is a state of estrogen deficiency that affects numerous estrogen-dependent tissues in the female body. Skin is one of the most affected organs. Many consider menopausal skin changes to be merely an aesthetic problem; however, they can significantly affect women's quality of life. Currently, there are no approved effective treatments to prevent or alleviate skin changes associated with estrogen deficiency. Standard systemic hormone replacement therapy used to treat menopausal symptoms may be effective to some degree for skin treatment. In addition, compounded bioidentical hormone replacement therapy, selective estrogen receptor modulators, and phytoestrogens could also be used for skin treatment, although this is only hypothetical due to lack of data. Many questions therefore remain unanswered. On the other hand, topical, low-dose estrogen that would act only on the skin without systemic effects could be a possible option, as could be skin-only acting topical phytoestrogens. Such topical products without systemic effects could play a role in the treatment of menopausal skin. However, they are not currently approved because there is insufficient data on their safety and efficacy. A healthy lifestyle could have a positive effect on the menopausal skin. In this review, we provide an overview of the characteristics of menopausal skin, an outlook on the future treatment of menopausal skin with estrogens and other approaches, and the associated controversies and speculations. Overall, the importance of menopausal skin changes should not be neglected, and high-quality research is needed to gain new insights into the treatment of menopausal skin.

More With Less: Single-Incision Sling Insertion Techniques.

STUDY OBJECTIVE: To demonstrate reproducible procedures for efficient single-incision sling insertion and troubleshooting. DESIGN: Narrated video footage with stepwise demonstration of single-incision sling insertion technique with anchor system. SETTING: The mesh midurethral sling is a highly effective and safe procedure that is considered the gold standard for surgical treatment of stress urinary incontinence. Retropubic and transobturator approaches for midurethral slings have similar subjective cure rates with differing surgical risk profiles [1,2]. The retropubic route has a higher risk of injury to the bladder, nerves, and vascular structures, whereas the obturator approach carries a risk of groin or thigh pain [3-5]. Use of a single-incision sling decreases these risks and allows flexibility to perform the procedure without sedation or general anesthesia. Recent literature demonstrates similar subjective and objective success and safety of single-incision slings compared with both retropubic and transobturator approaches, although long-term data are forthcoming [5]. INTERVENTIONS: We demonstrate a stepwise approach for the insertion of a single-incision sling using a helical trocar. Easily reproducible procedures for setup and sling anchor management allow for efficient placement without assistance. In addition, we outline hand positioning, trocar management, and anchor deployment with troubleshooting techniques for potential placement difficulties. Finally, we review methods for sling tensioning to prevent complications such as voiding dysfunction and mesh or suture exposures. CONCLUSION: Given that single-incision slings are more likely to be performed under local anesthesia and are less invasive with decreased recovery time, it has the potential to become the preferred approach in the future. This video demonstrates clear and detailed steps to facilitate successful placement of the single-incision mesh midurethral sling.