Tubulointerstitial nephritis in primary Sjögren syndrome: clinical manifestations and response to treatment

BACKGROUND: Primary Sjögren syndrome (pSS) is a common autoimmune condition which primarily affects epithelial tissue, often including the kidney causing either tubulointerstitial nephritis (TIN) or more rarely, an immune complex related glomerulonephritis. METHODS: We describe the clinical, biochemical and histological characteristics of 12 patients with pSS related TIN and their response to treatment with antiproliferative agents. All 12 patients were investigated and treated at the UCL Centre for Nephrology in London. RESULTS: All patients had TIN demonstrated via needle biopsy; immunophenotyping showed that the interstitial infiltrate was predominantly a CD4+ T-cell infiltrate. Urinary acidification testing demonstrated distal renal tubular acidosis in 8 patients. Proximal tubular dysfunction was present in 5 patients. All but 1 patient were treated with antiproliferative agents and most also with a reducing course of steroids. In the treated patients, there was a significant improvement in the serum creatinine and measured GFR. CONCLUSION: Patients with pSS TIN have significant renal impairment and other functional tubular defects. There is a mononuclear lymphocytic infiltrate on renal biopsy and this appears to be mainly a CD4+ T-cell infiltrate. Treatment with mycophenolate (and corticosteroids) improves the renal function in patients with pSS TIN

Iron status and anaemia of chronic disease in HIV-infected African women in Mangaung, Bloemfontein

Background: Anaemia occurs widely among people living with HIV/AIDS. The aim of this study was to investigate the effect of HIV status on ironstatus, more specifically to investigate the nutritional health of women between 25 and 44 years of age.Methods: An epidemiological study was undertaken in Mangaung, a black residential community of Bloemfontein in the Free State (South Africa).A random sample consisted of 500 women in two age groups (25–34 [n = 273] and 35–44 years [n = 215]). Blood specimens were collected in ethyldimethylacetic acid collection tubes according to standard procedures. Respondents fasted overnight, abstained from exercise and avoided consuming alcohol and caffeine for 24 hours prior to collection of the blood specimens. All specimens were taken in the morning. A full blood count was performed using a Coulter Microdiff 18 Cell Counter. The metabolic variables haematocrit (Hct), haemoglobin (Hb), serum iron, ferritin and transferrin were determined. The red blood cell count was performed to calculate the mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC). Age and HIV-status groups were described and compared by nonparametric methods. A p-value lower than 0.05 was considered significant. HIV-infected and -uninfected groups were compared by 95% confidence intervals for the difference in the percentage of women with parameters below or above the normal range.Results: Sixty-one per cent of the younger women and 38% of the older women were HIV infected. The percentage with serum ferritin levels below20 μg/L was higher in HIV-uninfected women, ranging from 0% in older HIV-infected women to 10.4% in younger HIV-uninfected women. A largepercentage of women had elevated transferrin values, ranging from 23.9% in older HIV-infected women to 44.8% in older HIV-uninfected women.A large percentage of women had anaemia of chronic disease, with HIV-infected women afflicted more often.Conclusion: The results of the study indicate that prevalence of HIV infection in Mangaung is high, especially among women between 25 and34 years of age. Although the parameters of iron status on average did not indicate iron deficiency in the different age and HIV-status groups, a large percentage of women did have anaemia of chronic disease, with HIV-infected women afflicted more often. Knowledge of the HIV status of a patient is of paramount importance in evaluating laboratory results of iron levels to determine future treatment or nutritional recommendations. HIV-infected and -uninfected individuals might not be comparable regarding their laboratory results to interpret iron store depletion, with consequences for further therapeutic actions in these two groups. The progression rate to AIDS might also be enhanced by certain interventions.Keywords: iron; HIV; nutrition; women; South Afric

Evaluation of energy and macronutrient intake of black women in Bloemfontein: A cross-sectional study

There is growing evidence that urbanization of black South Africans is associated with changes in the structure of dietary intake. The urban diet is more diverse than the rural diet, and includes more animalfoods, refined carbohydrates and fats, posing a potential risk to the health of urbanized populations. The objective of this cross-sectional study was to determine the macronutrient intake of non-pregnant,pre-menopausal black women living in Bloemfontein in South Africa. A representative group of 500 participants was randomly selected to participate. Women were divided into two age groups. Youngerwomen were 25 - 34 years old and older women 35 - 44 years old. Macronutrient intake was determined using a validated Quantitative Food Frequency Questionnaire (QFFQ). Median macronutrient intake was compared with the Dietary Reference Intakes (DRI) as applicable. Median energy, macronutrient and cholesterol intake of younger and older women was compared using non-parametric 95% confidenceintervals (CI’s). P-value less than 0.05 was considered significant. Median energy distribution of macronutrients was determined and compared with standard references. After being screened foreligibility, four pregnant women were excluded from the study, and 496 women qualified for participation. Median total energy, protein and carbohydrate intakes of all women exceeded the DRI. Median intakes of fibre were low, while median fat intakes were high. Younger women had significantly higher intakes of total fat (p = 0.034), saturated fat (p = 0.046) and PUFA (p = 0.015). Median energy distribution was 12% protein (both age groups), 32% fat (younger women) and 31% fat (older women) and 51% carbohydrates (younger women) and 53% carbohydrates (older women). The high median energy and macronutrient intakes may pose a potential risk for the development of chronic lifestyle diseases. The main focus of intervention should be to improve the quality of the diet, by decreasing fat intake and replacing this with fruit and vegetables. The benefits of a low glycaemic index and high fibre diet need to be emphasized

Nutritional status of undergraduate healthcare students at the University of the Free State

Objectives: This study aimed to evaluate the lifestyle habits of South African students preparing for careers in health care that could influence the efficacy of their counselling practices on risk factors for noncommunicable diseases (NCDs) as future healthcare professionals.Design: Cross-sectional descriptive study.Setting and subjects: One hundred and sixty-one students (median age 21.5 years, 75.8% women) enrolled in the Faculty of Health Sciences at the University of the Free State.Outcome measures: Anthropometry was measured and structured questionnaires administered to assess dietary and lifestyle habits.Results: Many students were at risk of NCDs, with 19.8% being overweight or obese (body mass index > 25 kg/m2), 11.8% had a waist circumferences above gender-specific cut-off points, 98.1% consumed < 3 servings of vegetables/day, 58.4% consumed < 2 servings of fruit/day, 83% consumed < 2 servings of dairy products/day, 60% did not eat a beta-carotenerich fruit or vegetable daily, 31% did not eat a vitamin C-rich fruit or vegetable daily, 62% never consumed legumes, 43% reported a high intake of fats and sweets, 11% smoked a median of 3.5 cigarettes/day and 63% consumed a median of three drinks of alcohol/day on a median of four days (95% weekend days) per month. Fifty-nine per cent were active and 39% were very active owing to busy class schedules, but only 32% participated in formal exercise and sports.Conclusion: The poor dietary and lifestyle habits of most participants highlight the need to not just educate, but better empower these students to deal with the growing public health problem of obesity and related NCDs in the country.Keywords: students, healthcare professionals, diet, anthropometry, lifestyl

Leukemia-associated Rho guanine-nucleotide exchange factor is not critical for RhoA regulation, yet is important for platelet activation and thrombosis in mice.

BACKGROUND: RhoA is an important regulator of platelet responses downstream of Gα13 , yet we still know little about its regulation in platelets. Leukemia-associated Rho guanine-nucleotide exchange factor (GEF [LARG]), a RhoA GEF, is highly expressed in platelets and may constitute a major upstream activator of RhoA. To this end, it is important to determine the role of LARG in platelet function and thrombosis. METHODS AND RESULTS: Using a platelet-specific gene knockout, we show that the absence of LARG results in a marked reduction in aggregation and dense-granule secretion in response to the thromboxane mimetic U46619 and proteinase-activated receptor 4-activating peptide, AYPGKF, but not to adenosine diphosphate. In a ferric chloride thrombosis model in vivo, this translated into a defect, under mild injury conditions. Importantly, agonist-induced RhoA activation was not affected by the absence of LARG, although basal activity was reduced, suggesting that LARG may play a housekeeper role in regulating constitutive RhoA activity. CONCLUSIONS: LARG plays an important role in platelet function and thrombosis in vivo. However, although LARG may have a role in regulating the resting activation state of RhoA, its role in regulating platelet function may principally be through RhoA-independent pathways, possibly through other Rho family members

Prevalence of diabetes mellitus in the rural southern Free State

Background: A worldwide increase in the prevalence of diabetes mellitus (DM) has been reported and an even further increase is expected as a result of lifestyle changes. The objectives of this study were to determine the prevalence of DM in the rural southern Free State and to investigatethe contribution of risk factors such as age, physical activity, body mass index (BMI), waist-to-hip ratio and waist circumference to the developmentof impaired fasting glucose (IFG) or DM.Methods: Fasting venous plasma glucose (FVPG) levels were obtained from a total of 552 participants from Springfontein (n = 195), Trompsburg (n = 162) and Philippolis (n = 180). Participants were between 25 and 64 years of age, with 28.1% male (mean age 47.3 years) and 71.9% female (mean age 46 years). Anthropometric status was determined using standardised techniques. Levels of physical activity were determined using a 24-hour recall of physical activity as well as frequency of performing certain activities. Relative risks (RR) as well as 95% confidence intervals (95%CI) were used to distinguish significant risk factors for having IFG or DM.Results: In the study population the prevalence of DM was 7.6% (5.2% in men and 8.6% in women) and that of IFG was 6.3% (4.5% in men and 7.1% in women). The majority of nondiabetic (34%), IFG (55%) and DM (61%) participants were between the ages of 51 and 60 years. Age was found to be a statistically significant risk factor for having IFG or DM in participants older than 40 years of age (RR 2.3; 95% CI [1.22; 4.34]). Crude measurements (not age- and gender-adjusted) of waist circumference (RR 3.23; 95% CI [1.82; 5.74]), BMI (RR 2.32; 95% CI [1.43; 3.78]) and waist-to-hip ratio (RR 2.51; 95% CI [1.55; 4.07]) were statistically significant risk factors for having IFG or DM. Physical inactivity in men ≥ 40 years was also a statistically significant risk factor (RR 3.23; 95% CI [1.15; 9.05]) for having IFG or DM.Conclusions: In this study, 37.5% of diabetics were newly discovered. A high waist circumference, BMI and waist-to-hip-ratio were associated withan increased risk for developing IFG or DM, with a high waist circumference being the most significant general risk factor. Physically inactive men(≥ 40 years) were also at a higher risk of having IFG or DM. Follow-up FVPG and glucose tolerance tests should be performed on participants in the IFG group. A need for intervention regarding the identification and treatment of DM in these rural areas has been identified.Keywords: impaired fasting glucose; diabetes; risk factors; rura

Cassini in situ observations of long duration magnetic reconnection in Saturn’s magnetotail

Magnetic reconnection is a fundamental process in solar system and astrophysical plasmas, through which stored magnetic energy associated with current sheets is converted into thermal, kinetic and wave energy1, 2, 3, 4. Magnetic reconnection is also thought to be a key process involved in shedding internally produced plasma from the giant magnetospheres at Jupiter and Saturn through topological reconfiguration of the magnetic field5, 6. The region where magnetic fields reconnect is known as the diffusion region and in this letter we report on the first encounter of the Cassini spacecraft with a diffusion region in Saturn’s magnetotail. The data also show evidence of magnetic reconnection over a period of 19?h revealing that reconnection can, in fact, act for prolonged intervals in a rapidly rotating magnetosphere. We show that reconnection can be a significant pathway for internal plasma loss at Saturn6. This counters the view of reconnection as a transient method of internal plasma loss at Saturn5, 7. These results, although directly relating to the magnetosphere of Saturn, have applications in the understanding of other rapidly rotating magnetospheres, including that of Jupiter and other astrophysical bodies

The age-dependent associations of white matter hyperintensities and neurofilament light in early- and late-stage Alzheimer's disease

Neurofilament light (NFL) is an emerging marker of axonal degeneration. This study investigated the relationship between white matter hyperintensities (WMHs) and plasma NFL in a large elderly cohort with, and without, cognitive impairment. We used the Alzheimer's Disease Neuroimaging Initiative and included 163 controls, 103 participants with a significant memory concern, 279 with early mild cognitive impairment (EMCI), 152 with late mild cognitive impairment (LMCI), and 130 with Alzheimer's disease, with 3T MRI and plasma NFL data. Multiple linear regression models examined the relationship between WMHs and NFL, with and without age adjustment. We used smoking status, history of hypertension, history of diabetes, and BMI as additional covariates to examine the effect of vascular risk. We found increases of between 20% and 41% in WMH volume per 1SD increase in NFL in significant memory concern, early mild cognitive impairment, late mild cognitive impairment, and Alzheimer's disease groups (p < 0.02). Marked attenuation of the positive associations between WMHs and NFL were seen after age adjustment, suggesting that a significant proportion of the association between NFL and WMHs is age-related. No effect of vascular risk was observed. These results are supportive of a link between WMH and axonal degeneration in early to late disease stages, in an age-dependent, but vascular risk-independent manner

Digital habits of pulmonary rehabilitation service-users following the COVID-19 pandemic

Objective: We previously demonstrated low levels of digital literacy amongst pulmonary rehabilitation service-users prior to the COVID-19 pandemic. We aimed to identify whether the pandemic accelerated digital literacy in this population, resulting in greater acceptance of remote web-based pulmonary rehabilitation programme models. Methods: We surveyed digital access and behaviours and pulmonary rehabilitation delivery preferences of service-users referred to pulmonary rehabilitation in 2021 (cohort 2021) and propensity score-matched them to a cohort who completed the survey in 2020 (cohort 2020). Results: There were indicators that digital access and confidence were better amongst the Cohort 2021 but no difference was seen in the proportion of patients choosing remote web-based pulmonary rehabilitation as an acceptable method of receiving pulmonary rehabilitation. Conclusion: In an unselected cohort of service-users, remote web-based pulmonary rehabilitation was considered acceptable in only a minority of patients which has implications on healthcare commissioning and delivery of pulmonary rehabilitation

Fragmentation and disk formation in high-mass star formation: The ALMA view of G351.77-0.54 at 0.06" resolution

Aims: We resolve the small-scale structure around the high-mass hot core region G351.77-0.54 to investigate its disk and fragmentation properties. Methods: Using ALMA at 690GHz with baselines exceeding 1.5km, we study the dense gas, dust and outflow emission at an unprecedented spatial resolution of 0.06" ([email protected]). Results: Within the inner few 1000AU, G351.77 fragments into at least four cores (brightness temperatures between 58 and 197K). The central structure around the main submm source #1 with a diameter of ~0.5" does not show additional fragmentation. While the CO(6-5) line wing emission shows an outflow lobe in the north-western direction emanating from source #1, the dense gas tracer CH3CN shows a velocity gradient perpendicular to the outflow that is indicative of rotational motions. Absorption profile measurements against the submm source #2 indicate infall rates on the order of 10^{-4} to 10^{-3}M_sun/yr which can be considered as an upper limit of the mean accretion rates. The position-velocity diagrams are consistent with a central rotating disk-like structure embedded in an infalling envelope, but they may also be influenced by the outflow. Using the CH_3CN(37_k-36_k) k-ladder with excitation temperatures up to 1300K, we derive a gas temperature map of source #1 exhibiting temperatures often in excess of 1000K. Brightness temperatures of the submm continuum never exceed 200K. This discrepancy between gas temperatures and submm dust brightness temperatures (in the optically thick limit) indicates that the dust may trace the disk mid-plane whereas the gas could be tracing a hotter gaseous disk surface layer. In addition, we conduct a pixel-by-pixel Toomre gravitational stability analysis of the central rotating structure. The derived high Q values throughout the structure confirm that this central region appears stable against gravitational instability