The emergence of obesity in type 1 diabetes.

Obesity, a chronic low-grade inflammatory disease represented by multifactorial metabolic dysfunctions, is a significant global health threat for adults and children. The once-held belief that type 1 diabetes is a disease of people who are lean no longer holds. The mounting epidemiological data now establishes the connection between type 1 diabetes and the subsequent development of obesity, or vice versa. Beyond the consequences of the influx of an obesogenic environment, type 1 diabetes-specific biopsychosocial burden further exacerbates obesity. In the course of obesity management discussions, recurring challenges surfaced. The interplay between weight gain and escalating insulin dependence creates a vicious cycle from which patients struggle to break free. In the absence of weight management guidelines and regulatory approval for this population, healthcare professionals must navigate the delicate balance between benefits and risks. The gravity of this circumstance highlights the importance of bringing these topics to the forefront. In this Review, we discuss the changing trends and the biopsychosocial aspects of the intersection between type 1 diabetes and obesity. We highlight the evidence supporting the therapeutic means (i.e., exercise therapy, nutritional therapy, adjunct pharmacotherapy, and bariatric surgery) and directions for establishing a more robust and safer evidence-based approach.

Skin cancer and HIV.

The risk of skin cancer in persons living with HIV (PLWH) is an evolving subject area shaped by the use of antiretroviral therapy. Keratinocyte carcinomas, including basal cell carcinoma and squamous cell carcinoma, have a high incidence in the general population as well as in PLWH. PLWH may have a higher risk of squamous cell carcinoma when compared to the general population. In addition, Merkel cell carcinoma and sebaceous carcinoma exhibit higher incidence rates in PLWH. Data on melanoma risk are varied. Risks of skin cancer may be influenced by vigilant surveillance, photosensitivity, and immune status. Screening for skin cancer is generally recommended, although national guidelines vary in specific recommendations. Treatments range from topical therapies to surgeries to immune checkpoint inhibitors, with Mohs micrographic surgery playing an important role. Data on immune checkpoint inhibitors suggest safe and efficacious use in PLWH, although larger trials are warranted. The dynamic interplay among HIV, antiretroviral use and immunosuppression, and the risk and treatment of skin cancer underscores the importance of rigorous research studies and screening and treatment guidelines specific to this population.

Biomarkers of Hepatic Dysfunction and Cardiovascular Risk.

PURPOSE OF REVIEW: The objective of this manuscript is to examine the current literature on non-alcoholic fatty liver disease (NAFLD) biomarkers and their correlation with cardiovascular disease (CVD) outcomes and cardiovascular risk scores. RECENT FINDINGS: There has been a growing appreciation for an independent link between NAFLD and CVD, culminating in a scientific statement by the American Heart Association in 2022. More recently, studies have begun to identify biomarkers of the three NAFLD phases as potent predictors of cardiovascular risk. Despite the body of evidence supporting a connection between hepatic biomarkers and CVD, more research is certainly needed, as some studies find no significant relationship. If this relationship continues to be robust and readily reproducible, NAFLD and its biomarkers may have an exciting role in the future of cardiovascular risk prediction, possibly as risk-enhancing factors or as components of novel cardiovascular risk prediction models.

Mycoplasma genitalium in Singapore is associated with Chlamydia trachomatis infection and displays high macrolide and Fluoroquinolone resistance rates.

BACKGROUND: Mycoplasma genitalium is an emerging sexually transmitted infection, with increasing rates of resistance to fluroquinolones and macrolides, the recommended treatments. Despite this, M. genitalium is not part of routine screening for Sexually Transmitted Infections (STIs) in many countries and the prevalence of infection and patterns of disease remain to be determined in many populations. Such data is of particular importance in light of the reported rise in antibiotic resistance in M. genitalium isolates. METHODS: Urine and urethral swab samples were collected from the primary public sexual health clinic in Singapore and tested for C. trachomatis (CT) or N. gonorrhoeae (NG) infection and for the presence of M. genitalium. Antibiotic resistance in M. genitalium strains detected was determined by screening for genomic mutations associated with macrolide and fluroquinolone resistance. RESULTS: We report the results of a study into M. genitalium prevalence at the national sexual health clinic in Singapore. M. genitalium was heavily associated with CT infection (8.1% of cases), but present in only of 2.4% in CT negative cases and not independently linked to NG infection. Furthermore, we found high rates of resistance mutations to both macrolides (25%) and fluoroquinolones (37.5%) with a majority of resistant strains being dual-resistant. Resistance mutations were only found in strains from patients with CT co-infection. CONCLUSIONS: Our results support targeted screening of CT positive patients for M. genitalium as a cost-effective strategy to reduce the incidence of M. genitalium in the absence of comprehensive routine screening. The high rate of dual resistance also highlights the need to ensure the availability of alternative antibiotics for the treatment of multi-drug resistant M. genitalium isolates.

Following the Status of Visual Cortex Over Time in Patients With Macular Degeneration Reveals Atrophy of Visually Deprived Brain Regions.

Purpose: Previous research has shown atrophy of visual cortex can occur in retinotopic representations of retinal lesions resulting from eye disease. However, the time course of atrophy cannot be established from these cross-sectional studies, which included patients with longstanding disease of varying severity. Our aim, therefore, was to measure visual cortical structure over time in participants after onset of unilateral visual loss resulting from AMD. Methods: Inclusion criteria were onset of acute unilateral neovascular AMD with bilateral dry AMD based on clinical examination. Therefore, substantial loss of unilateral visual input to cortex was relatively well-defined in time. Changes in cortical anatomy were assessed in the occipital lobe as a whole, and in cortical representations of the lesion and intact retina, the lesion and intact projection zones, respectively. Whole brain, T1-weighted magnetic resonance imaging was taken at diagnosis (before antiangiogenic treatment to stabilize the retina), during the 3- to 4-month initial treatment period, with a long-term follow-up approximately 5 (range 3.8-6.1 years) years later. Results: Significant cortical atrophy was detected at long-term follow-up only, with a reduction in mean cortical volume across the whole occipital lobe. Importantly, this reduction was explained by cortical thinning of the lesion projection zone, which suggests additional changes to those associated with normal aging. Over the period of study, antiangiogenic treatment stabilized visual acuity and central retinal thickness, suggesting that the atrophy detected was most likely governed by long-term decreased visual input. Conclusions: Our results indicate that consequences of eye disease on visual cortex are atrophic and retinotopic. Our work also raises the potential to follow the status of visual cortex in individuals over time to inform on how best to treat patients, particularly with restorative techniques.

Gender Differences in Factors Associated With Anal Intercourse Among Heterosexual Adolescents in Singapore.

Using a cross-sectional survey, we examined the gender differences in prevalence of and factors associated with anal sex among adolescents attending the only public STI clinic in Singapore. Data were collected from 1035 sexually active adolescents aged 14 to 19 and analyzed using Poisson regression. Prevalence of anal intercourse was 28%, with significantly more females (32%) than males (23%) ever engaged in it. On multivariate analysis, the factors associated with anal intercourse for both genders were oral sex and the nonuse of contraception at last sex. For males, anal intercourse was associated with younger age of sexual debut and greater perceived external control. Among females, it was associated with higher rebellious scores and lack of confidence to resist peer pressure to engage in sex. Consistent condom use for anal sex was 22% and 8% for males and females, respectively. STI prevention programs for adolescents should address anal sex, be gender-specific, and take into consideration individual personality characteristics.

A prospective study on the use of teledermatology in psychiatric patients with chronic skin diseases.

BACKGROUND: To compare the use of live interactive teledermatology versus conventional face-to-face consultation in long-term, institutionalised psychiatric patients with chronic skin diseases. METHODS: All institutionalised psychiatric patients at the Institute of Mental Health with follow-up appointments at the National Skin Centre were assessed for eligibility and invited to participate. Recruited patients were first seen by a dermatologist via videoconferencing, and then by another dermatologist in person, within 1 week. Clinical outcome measures were then assessed by a third independent dermatologist. The following outcome measures were assessed for each paired patient visit: inter-physician clinical assessment, diagnosis, management plan, adverse events and total patient turnaround time (PTAT) for each consultation. RESULTS: There were a total of 13 patients (mean age, 64.6 years; range 44-80) with 27 patient visits. All were male patients with chronic schizophrenia. The predominant skin condition was chronic eczema and its variants (62%), followed by cutaneous amyloidosis (23%) and psoriasis (15%). The level of complete and partial agreement between the teledermatology and face-to-face consultation was 100% for history-taking and physical examination and 96% for the investigations, diagnosis, management plan and the treatment prescribed. The PTAT for teledermatology was 23 min, compared to 240 min for face-to-face consultations. No adverse events were reported. CONCLUSION: Teledermatology was as effective as face-to-face consultation and reduced the PTAT by 90%, resulting in increased patient convenience, operational efficiency and reduced manpower need. Our study supports the safe and cost-effective use of teledermatology for the follow-up of chronic skin conditions in psychiatric patients.

Assessment of psychosocial impact of genital warts among patients in Singapore.

UNLABELLED: Background Genital warts (GW) are a common sexually transmissible infection (STI) among young adults and are associated with poor quality of life (QoL). We investigated the functional and psychosocial effect of GW on Singaporean patients and evaluated for any variations in QoL between genders. METHODS: Patients with GW completed a standard questionnaire containing the Short Form-36 (SF-36) health survey and the Cuestionario Específico para Condiloma Acuminado in a cross-sectional survey. QoL deficits were determined by comparing the SF-36 scores with local population norms. Variations in SF-36 (norm-based) scores among patients with different characteristics were examined using multiple linear regressions. All data analyses were performed for male and female patients separately. RESULTS: The mean age of male (n=100) and female patients (n=80) was 31 years. The typical patient profile was male, ethnic Chinese, single, tertiary education level and presenting with recurrent warts and a history of prior STIs. Compared with the general population, male patients had similar or better functioning and wellbeing, whereas female patients had lower levels of productivity, mental health and general health. Among male patients, individuals afflicted with their first episode of GW and currently with a partner had better QoL. In contrast, for females, tertiary education, older age and being a nonsmoker were positively associated with better QoL. CONCLUSIONS: Patients with GW have a significant psychosocial burden, with differences in certain aspects of QoL between genders. We hope that with active intervention, we will be able to mitigate the associated negative impact to QoL.

Syphilitic uveitis in a Singaporean population.

PURPOSE: To report the presentations of syphilitic uveitides in Singapore. METHODS: Retrospective noncomparative observational case series of 18 eyes from 12 patients with ocular syphilis between 2004 and 2009. RESULTS: Patients were mainly male (91.7%). Median age was 49.5 (24-84) years. Initial visual acuity varied from 6/6 to counting fingers (CF) and was ≥6/12 in 7 eyes (38.8%). Blurring of vision (n = 11, 61.1%) was the most common presenting complaint. Anterior uveitis and panuveitis were both most common (n = 6, 33.3%). Treponemal and nontreponemal serologies were positive in 12 (100.0%) and 10 (83.3%) patients, respectively. Patients were treated systematically with penicillin therapy by infectious disease physicians. CONCLUSIONS: Ocular syphilis is seeing a worldwide resurgence. Although anterior uveitis and panuveitis were most common in this study, there was a large spectrum of ocular manifestations. Syphilitic uveitides can potentially cause severe loss of vision but are effectively treated by an appropriate regimen of penicillin.

Experience with the implementation of a web-based teledermatology system in a nursing home in Singapore.

We introduced a web-based teledermatology system, the distributed personal health information management system (DPHIMS), into a nursing home in Singapore. The introduction was conducted in two phases. Five staff nurses in Phase 1 and nine nurse aides in Phase 2 performed the data entry and uploaded digital images of the resident's skin condition. By the end of Phase 2, there were 50 residents registered with DPHIMS. The average age of the participants was 82 years and 84% were women. There were 31 first-time referral requests registered in the system during Phase 2. The average time taken to complete a referral request was 86 minutes. The average time taken by the dermatologist to prepare and submit a diagnosis/treatment report was 11 minutes. An online survey form was given to the nurses and the dermatologists to gauge their level of satisfaction and their experience of using DPHIMS. All the nurses said they would readily recommend DPHIMS to other nurses. Overall, the dermatologists felt that DPHIMS was helpful in obtaining specialist care for the residents. However, some skin conditions required a face-to-face consultation. Thus a mixture of face-to-face consultations and consultations via teledermatology may be necessary to provide complete diagnosis and treatment to patients. Our experience suggests that understanding and addressing the organizational concerns is as important as solving the technical problems.

Sexually transmissible infection management practices among primary care physicians in Singapore.

BACKGROUND: Primary care physicians manage a significant number of sexually transmissible infections (STI); however, there has not been a survey to assess the standard of medical care, completeness of notifications, provision of counselling and contact tracing by primary care physicians in Singapore. METHODS: An anonymous postal survey was conducted in which 1557 questionnaires were mailed out to general practitioners (GP), and government primary care and emergency department doctors. RESULTS: In all, 736 questionnaires (47.3%) were returned, and the majority of respondents were graduates from the local medical school, worked in solo or group practices and were males. One hundred and thirty doctors (17.7%) indicated they had received training attachments or postings in dermato-venereology departments. Almost one-third (30.8%) had been working as doctors for fewer than 10 years and 87.8% reported that they managed STI in their practice. Almost half did not investigate genital discharge patients, and one-third would still use ciprofloxacin to treat discharges. In the management of ulcers, over half indicated that they would order syphilis serology, and a significant minority would use parenteral penicillin. Most doctors provided history taking, screening for other STI, testing for HIV infection and STI counselling. A small minority of doctors undertook contact tracing, and there was incomplete notification of many STI. CONCLUSIONS: Overall medical management of STI by primary care physicians was acceptable. Skills in contact tracing and reminders on disease notification are areas that need particular attention.

Convection in vibrated annular granular beds.

The response to vibration of a granular bed, consisting of a standard cylindrical geometry but with the addition of a dissipative cylindrical inner wall, has been investigated both experimentally (using positron emission particle tracking) and numerically (using hard sphere molecular dynamics simulation). The packing fraction profiles and granular temperature distributions (in both vertical and horizontal directions) were determined as a function of height and distance from the axis. The two sets of results were in reasonable agreement. The molecular dynamics simulations were used to explore the behavior of the granular bed in the inner wall-outer wall coefficient of restitution phase space. It was observed that one could control the direction of the toroidal convection rolls by manipulating the relative dissipation at the inner and outer walls via the coefficients of restitution, and with several layers of grains it was seen that double convection rolls could also be formed, a result that was subsequently confirmed experimentally.

Molecular basis of mitomycin C resistance in streptomyces: structure and function of the MRD protein.

Mitomycin C (MC) is a potent anticancer agent. Streptomyces lavendulae, which produces MC, protects itself from the lethal effects of the drug by expressing several resistance proteins. One of them (MRD) binds MC and functions as a drug exporter. We report the crystal structure of MRD and its complex with an MC metabolite, 1,2-cis-1-hydroxy-2,7-diaminomitosene, at 1.5 A resolution. The drug is sandwiched by pi-stacking interactions of His-38 and Trp-108. MRD is a dimer. The betaalphabetabetabeta fold of the MRD molecule is reminiscent of methylmalonyl-CoA epimerase, bleomycin resistance proteins, glyoxalase I, and extradiol dioxygenases. The location of the binding site is identical to the ones in evolutionarily related enzymes, suggesting that the protein may have been recruited from a different metabolic pathway.

The functional implications of the dimerization of the catalytic subunits of the mammalian brain platelet-activating factor acetylhydrolase (Ib).

The mammalian brain contains significant amounts of the cytosolic isoform Ib of the platelet-activating factor acetylhydrolase (PAF-AH), a unique type of PLA2. This oligomeric protein complex contains three types of subunits: two homologous (63% identity) 26 kDa catalytic subunits (alpha(1) and alpha(2)) which harbor all the PAF-AH activity, and the 45 kDa beta-subunit (LIS1), a product of the causal gene for Miller-Dieker lissencephaly. During fetal development, the preferentially expressed alpha(1)-subunit forms a homodimer, which binds to a homodimer of LIS1, whereas in adult organisms alpha(1)/alpha(2) and alpha(2)/alpha(2) dimers, also bound to dimeric LIS1, are the prevailing species. The consequences of this "switching" are not understood, but appear to be of physiological significance. The alpha(1)- and alpha(2)-subunits readily associate with very high affinity to form homodimers. The nature of the interface has been elucidated by the 1.7 A resolution crystal structure of the alpha(1)/alpha(1) homodimer (Ho et al., 1997). Here, we examined the functional consequences of the dimerization in both types of alpha-subunits. We obtained monomeric protein in the presence of high concentrations (>50 mM) of Ca2+ ions, and we show that it is catalytically inactive and less stable than the wild type. We further show that Arg29 and Arg22 in one monomer contribute to the catalytic competence of the active site across the dimer interface, and complement the catalytic triad of Ser47, Asp192 and His195, in the second monomer. These results indicate that the brain PAF-acetylhydrolase is a unique PLA2 in which dimerization is essential for both stability and catalytic activity.