Discussion Abounds on the Potential Carcinogenic Risks Associated With the Use of UV Curing Lamps for Permanent Nail Polish. / Controversias sobre los riesgos procarcinogénicos asociados al uso de lámparas ultravioleta polimerizadoras para el esmaltado permanente de uñas.

BACKGROUND: Controversy has recently broken out over the potential carcinogenic risk associated with exposure to UV lamps for permanent nail polish. The new LED-based polymerization devices, and their potential biological effect has not been analyzed to this date. OBJECTIVE: To evaluate the emission power and its potential biological effects on the skin of 2 types of UV LED and fluorescent curing lamps under normal use conditions compared to doses of sunlight exposure. MATERIAL AND METHODS: The emission spectrum (290nm to 450nm) of curing lamps and the Sun at noon on an average summer day in mid-latitude Spain was analyzed. The effective biological irradiance potential for erythema, non-melanoma skin cancer, DNA damage, photoimmunosuppression and permanent pigmentation was also characterized. RESULTS: The high-energy UVA-visible irradiance emitted by these devices was similar to the one coming from the Sun in that spectral range while the effective biological doses were lower or similar to those also coming from the Sun. The total UV and high-energy visible dose per manicure session corresponded to that obtained from 3.5min to 6min exposures to the Sun at noon in the summer days at our latitudes. CONCLUSIONS: The exposure times and doses received with the common use of artificial lamp nail drying correspond to sunlight exposures of 3min to 5min in the central hours of the day. This represents a very low carcinogenic potential compared to sunlight exposure, although similar regarding immunosuppressive potential. Photoprotective measures would further minimize the risks.

Discussion Abounds on the Potential Carcinogenic Risks Associated With the Use of UV Curing Lamps for Permanent Nail Polish.

BACKGROUND: Controversy has recently broken out over the potential carcinogenic risk associated with exposure to UV lamps for permanent nail polish. The new LED-based polymerization devices, and their potential biological effect has not been analyzed to this date. OBJECTIVE: To evaluate the emission power and its potential biological effects on the skin of 2 types of UV LED and fluorescent curing lamps under normal use conditions compared to doses of sunlight exposure. MATERIAL AND METHODS: The emission spectrum (290nm to 450nm) of curing lamps and the Sun at noon on an average summer day in mid-latitude Spain was analyzed. The effective biological irradiance potential for erythema, non-melanoma skin cancer, DNA damage, photoimmunosuppression and permanent pigmentation was also characterized. RESULTS: The high-energy UVA-visible irradiance emitted by these devices was similar to the one coming from the Sun in that spectral range while the effective biological doses were lower or similar to those also coming from the Sun. The total UV and high-energy visible dose per manicure session corresponded to that obtained from 3.5min to 6min exposures to the Sun at noon in the summer days at our latitudes. CONCLUSIONS: The exposure times and doses received with the common use of artificial lamp nail drying correspond to sunlight exposures of 3min to 5min in the central hours of the day. This represents a very low carcinogenic potential compared to sunlight exposure, although similar regarding immunosuppressive potential. Photoprotective measures would further minimize the risks.

Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.

Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection. Inducing the expression of latent genomes within resting CD4(+) T cells is the primary strategy to clear this reservoir. Although histone deacetylase inhibitors such as suberoylanilide hydroxamic acid (also known as vorinostat, VOR) can disrupt HIV-1 latency in vitro, the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Here we isolated the circulating resting CD4(+) T cells of patients in whom viraemia was fully suppressed by antiretroviral therapy, and directly studied the effect of VOR on this latent reservoir. In each of eight patients, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4(+) cells (mean increase, 4.8-fold). This demonstrates that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in humans, provides proof-of-concept for histone deacetylase inhibitors as a therapeutic class, and defines a precise approach to test novel strategies to attack and eradicate latent HIV infection directly.

Risk of End-Stage Renal Disease in HIV-Positive Potential Live Kidney Donors.

New federal regulations allow HIV-positive individuals to be live kidney donors; however, potential candidacy for donation is poorly understood given the increased risk of end-stage renal disease (ESRD) associated with HIV infection. To better understand this risk, we compared the incidence of ESRD among 41 968 HIV-positive participants of North America AIDS Cohort Collaboration on Research and Design followed for a median of 5 years with the incidence of ESRD among comparable HIV-negative participants of National Health and Nutrition Examination III followed for a median of 14 years. We used risk associations from multivariable Cox proportional hazards regression to derive cumulative incidence estimates for selected HIV-positive scenarios (no history of diabetes, hypertension, AIDS, or hepatitis C virus coinfection) and compared these estimates with those from similarly selected HIV-negative scenarios. For 40-year-old HIV-positive individuals with health characteristics that were similar to those of age-matched kidney donors, viral load <400 copies/mL, and CD4+ count ≥500 cells/µL, the 9-year cumulative incidence of ESRD was higher than that of their HIV-negative peers, yet still low: 2.5 versus 1.1 per 10 000 among white women, 3.0 versus 1.3 per 10 000 among white men, 13.2 versus 3.6 per 10 000 among black women, and 15.8 versus 4.4 per 10 000 among black men. HIV-positive individuals with no comorbidities and well-controlled disease may be considered low-risk kidney donor candidates.

Core Content for Undergraduate Medical Education in Spain: Recommendations of the Instructors' Group of the Spanish Academy of Dermatology and Venereology (AEDV).

BACKGROUND: Skin problems are among the most frequent reasons for seeking medical attention in primary care. In recent years, as a result of the process of adapting medical curricula to the requirements of the European Higher Education Area, the amount of time students spend learning the concepts of dermatology has been reduced in many universities. MATERIAL AND METHODS: In order to reach a consensus on core content for undergraduate education in dermatology, we sent a survey to the 57 members of the instructors' group of the Spanish Academy of Dermatology and Venereology (AEDV), asking their opinions on what objectives should be set for a dermatology course in Spain. A total of 131 previously selected objectives were listed. We then applied the Delphi method to achieve consensus on which ones the respondents considered important or very important (score≥4 on a Likert scale). RESULTS: Nineteen responses (33%) were received. On the second round of the Delphi process, 68 objectives achieved average scores of at least 4. The respondents emphasized that graduates should understand the structure and functions of the skin and know about bacterial, viral, and fungal skin infections, the most common sexually transmitted diseases (STDs), and the 4 main inflammatory dermatoses. Students should also learn about common complaints, such as itching and bald patches; the management of dermatologic emergencies; purpura and erythema nodosum as signs of internal disease; and the prevention of STDs and skin cancer. During clinical clerkships students should acquire the communication skills they will need to interview patients, write up a patient's medical history, and refer the patient to a specialist. CONCLUSIONS: The AEDV's group of instructors have defined their recommendations on the core content that medical faculties should adopt for the undergraduate subject of dermatology in Spain.

Clinical malaria diagnosis in pregnancy in relation to early perinatal mother-to-child transmission of HIV: a prospective cohort study.

OBJECTIVES: We prospectively investigated fever symptoms and maternal diagnosis of malaria in pregnancy (MIP) in relation to child HIV infection among 2368 pregnant HIV-positive women and their infants, followed up from pregnancy until 6 weeks post-delivery in Tanzania. METHODS: Doctors clinically diagnosed and treated MIP and fever symptoms during prenatal health care. Child HIV status was determined via DNA polymerase chain reaction (PCR). Multivariable logistic regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for HIV mother-to-child transmission (MTCT) by the 6th week of life. RESULTS: Mean gestational age at enrolment was 22.2 weeks. During follow-up, 16.6% of mothers had at least one MIP diagnosis, 15.9% reported fever symptoms and 8.7% had both fever and MIP diagnosis. Eleven per cent of HIV-exposed infants were HIV-positive by 6 weeks. The RR of HIV MTCT was statistically similar for infants whose mothers were ever vs. never clinically diagnosed with MIP (RR 1.24; 95% CI 0.94-1.64), were diagnosed with one vs. no clinical MIP episodes (RR 1.07; 95% CI 0.77-1.48) and had ever vs. never reported fever symptoms (RR 1.04; 95% CI 0.78-1.38) in pregnancy. However, the HIV MTCT risk increased by 29% (95% CI 4-58%) per MIP episode. Infants of women with at least two vs. no MIP diagnoses were 2.1 times more likely to be HIV infected by 6 weeks old (95% CI 1.31-3.45). CONCLUSIONS: Clinical MIP diagnosis, but not fevers, in HIV-positive pregnant women was associated with an elevated risk of early HIV MTCT, suggesting that malaria prevention and treatment in pregnant HIV-positive women may enhance the effectiveness of HIV prevention in MTCT programmes in this setting. Future studies using a laboratory-confirmed diagnosis of malaria are needed to confirm this association.

Micronutrient supplementation and T cell-mediated immune responses in patients with tuberculosis in Tanzania.

Limited studies exist regarding whether incorporating micronutrient supplements during tuberculosis (TB) treatment may improve cell-mediated immune response. We examined the effect of micronutrient supplementation on lymphocyte proliferation response to mycobacteria or T-cell mitogens in a randomized trial conducted on 423 patients with pulmonary TB. Eligible participants were randomly assigned to receive a daily dose of micronutrients (vitamins A, B-complex, C, E, and selenium) or placebo at the time of initiation of TB treatment. We found no overall effect of micronutrient supplements on lymphocyte proliferative responses to phytohaemagglutinin or purified protein derivatives in HIV-negative and HIV-positive TB patients. Of HIV-negative TB patients, the micronutrient group tended to show higher proliferative responses to concanavalin A than the placebo group, although the clinical relevance of this finding is not readily notable. The role of nutritional intervention in this vulnerable population remains an important area of future research.

[The syndrome of Capgras: converging models]. / Het syndroom van Capgras: convergerende modellen.

BACKGROUND: Various theories have been proposed concerning the syndrome of Capgras. AIM: To search for a concept that is common to the various theories relating to the aetiology of the syndrome of Capgras. METHODS: We begin by describing a new case of Capgras syndrome that we encountered recently, and thereafter we searched the literature using PubMed and PsycINFO. RESULTS: Various explanatory models converge in that they all assign a central role to a changed affect. A sensation of 'alienation' at a conscious or subconscious level, together with inadequate evaluation of beliefs, seems plausible. All models demonstrate some form of 'splitting' i.e. the separate processing of information in time, anatomy or mental representation. CONCLUSION: Although there is no conclusive evidence to support any one of the hypotheses, the models display striking similarities. They complement each other.

[Pyoderma gangrenosum: a report of 15 cases and review of the literature]. / Pioderma gangrenoso: Presentación de 15 casos y revisión de la literatura.

BACKGROUND: Pyoderma gangrenosum is a condition that is included among the neutrophilic dermatoses. Given its low incidence, few studies have addressed its epidemiology or treatment. OBJECTIVE: To describe the epidemiological and clinical characteristics of patients with pyoderma gangrenosum along with our experience of treating the condition in a referral hospital in Malaga, Spain. MATERIAL AND METHODS: A retrospective, observational study was undertaken in the Department of Dermatology at Hospital Clínico Universitario Virgen de la Victoria in Malaga, Spain between January 2000 and December 2009 and included all patients diagnosed with pyoderma gangrenosum. RESULTS: The incidence of pyoderma gangrenosum in our reference population is 3.26 cases per million inhabitants per year. The most frequent concomitant systemic disease was ulcerative colitis (5 cases, 33%). In 4 patients with that disease, pyoderma gangrenosum appeared during a flare-up. In 80% of cases, patients were not referred to a dermatologist during the initial phase of pyoderma gangrenosum, and most referrals were from gastroenterology or general surgery (4 patients each, 52%). CONCLUSIONS: Patients with pyoderma gangrenosum are often referred to dermatologists by other specialists after a varying period of time has elapsed without achieving an accurate diagnosis. In these patients, especially those between 20 and 40 years of age, it is essential to rule out concomitant disease. Adalimumab is a good treatment option for pyoderma gangrenosum.

The impact of HIV/HCV co-infection on health care utilization and disability: results of the ACTG Longitudinal Linked Randomized Trials (ALLRT) Cohort.

HIV/hepatitis C virus (HCV) co-infection places a growing burden on the HIV/AIDS care delivery system. Evidence-based estimates of health services utilization among HIV/HCV co-infected patients can inform efficient planning. We analyzed data from the ACTG Longitudinal Linked Randomized Trials (ALLRT) cohort to estimate resource utilization and disability among HIV/HCV co-infected patients and compare them to rates seen in HIV mono-infected patients. The analysis included HIV-infected subjects enrolled in the ALLRT cohort between 2000 and 2007 who had at least one CD4 count measured and completed at least one resource utilization data collection form (N = 3143). Primary outcomes included the relative risk of hospital nights, emergency department (ED) visits, and disability days for HIV/HCV co-infected vs HIV mono-infected subjects. When controlling for age, sex, race, history of AIDS-defining events, current CD4 count and current HIV RNA, the relative risk of hospitalization, ED visits, and disability days for subjects with HIV/HCV co-infection compared to those with HIV mono-infection were 1.8 (95% CI: 1.3-2.5), 1.7 (95% CI: 1.4-2.1), and 1.6 (95% CI: 1.3-1.9) respectively. Programs serving HIV/HCV co-infected patients can expect approximately 70% higher rates of utilization than expected from a similar cohort of HIV mono-infected patients.

Incidence rate of and factors associated with loss to follow-up in a longitudinal cohort of antiretroviral-treated HIV-infected persons: an AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) analysis.

PURPOSE: Examine incidence and factors associated with loss to follow-up (LTFU) in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) cohort. METHOD: ALLRT is a prospective cohort of HIV-infected persons randomized to antiretroviral (ARV) regimens/strategies in ACTG trials and followed long-term after the trial ends. Person-years were calculated from ALLRT entry until loss to follow-up (LTFU; defined using off-study reasons or ≥ 3 consecutive missed visits), death/ severe debilitation/site closures, or June 2009 (censored). Poisson regression was used to examine LTFU factors separately among participants who were ARV naïve or ARV experienced at trial entry. RESULTS: Among 4,630 participants (22,524 person-years), 1,140 were lost to follow-up, 237 died, 29 were severely debilitated, and 443 were at sites that closed. The LTFU incidence was 5.5 and 4.2 per 100 person-years among previously ARV-naïve and ARV-experienced participants, respectively. In both groups, age ≤ 50, site location, being off ARVs, and viral load ≥ 400 copies/mL were associated with a higher risk of LTFU. Among ARV-naïve participants, male sex, education <16 years, intravenous drug use, and cigarette smoking were also associated with LTFU. CONCLUSION: Knowledge of differential LTFU can help researchers identify participants at risk of LTFU in longitudinal HIV cohorts and design retention strategies, thereby limiting study bias. The identified factors should be included in inverse probability of weighting models to account for LTFU.

[Typical and atypical antipsychotics: Is there a difference in their influence on neurocognition?]. / Typische en atypische antipsychotica bij patiënten met schizofrenie: is er verschil in invloed op neurocognitie?

BACKGROUND: Neurocognitive dysfunction is a core feature of schizophrenia and is related to the functional outcome of the illness. It has been suggested that the so-called atypical antipsychotics may have a more favourable influence on neurocognition than the older, typical antipsychotics and thus also on the functional outcome. AIM: To review the recent scientific literature concerning the effects of antipsychotics on neurocognition. METHOD: The literature was reviewed systematically via the most important databases. RESULTS: Meta-analyses suggest that atypical antipsychotics have moderate, positive effects on neurocognition and in that respect are more beneficial than typical antipsychotics. Recent studies, however, challenge this finding. CONCLUSION: The reported positive, cognitive effects of atypical antipsychotics are slight, particularly compared to the severity of neurocognitive dysfunction found in schizophrenia. In clinical practice there seem to be no convincing reason for attaching much weight to any differential effects that typical or atypical antipsychotics may have on neurocognition.

[The current challenge of imported leprosy in Spain: a study of 7 cases]. / Lepra importada y su dificultad en el medio actual: a propósito de 7 casos.

BACKGROUND: although the foci of leprosy once present in Spain are now under control and almost inactive, isolated cases are still occasionally diagnosed. Meanwhile, population migration has brought about an increase in the incidence of cases corresponding to individuals from countries where leprosy is endemic, leading to changes in the epidemiology of this disease. OBJECTIVES: the aim of this paper was to describe the clinical, epidemiologic, dermatologic, microbiologic, and therapeutic characteristics of cases of leprosy in our department in the last 5 years. MATERIAL AND METHODS: we report the cases of imported leprosy seen in our department between 2004 and 2009. RESULTS: seven patients with leprosy (3 men and 4 women; age range, 26-80 years) were diagnosed; 2 were cases of tuberculoid leprosy, 2 borderline tuberculoid leprosy, and 3 indeterminate. All patients acquired the disease in South American or South African countries, but were residing in Spain at the time of diagnosis. One patient was a Spaniard, from Malaga, who had worked as a missionary in Venezuela for 25 years. The presence of the bacterium by either Ziehl-Neelsen stain or bacilloscopy could not be demonstrated in any of the patients. CONCLUSIONS: we would like to draw attention to the changes we have observed in the characteristics of cases of leprosy seen in our department, the majority of which are imported. It is important to maintain a clinical suspicion of leprosy in cases of granulomatous dermatitis, particularly in patients from countries where the disease is endemic.

The efficacy of SMS text messages to compensate for the effects of cognitive impairments in schizophrenia.

BACKGROUND AND AIMS: Many people with schizophrenia have severe cognitive impairments that hamper their activities. The effect of pharmacological and behavioural interventions on cognitive functioning has been demonstrated, but even after successful intervention considerable impairments can remain. Therefore, we sought for alternative ways to help patients cope with the effects of their cognitive impairments. In the present study, we have evaluated the efficacy of short message service (SMS) text messages to compensate for the effects of cognitive impairments in schizophrenia in daily life. DESIGN: A waiting list controlled trial was conducted: patients were quasi-randomly assigned to an A-B-A (baseline-intervention-follow-up) condition or an A-A-B-A condition that included an additional 7-week waiting list. The waiting list was included to control for the effect of time on relevant outcome. METHOD: Sixty-two people with schizophrenia or related psychotic disorders were included in the study. All patients showed impaired goal-directed behaviour in daily life-situations. Patients were prompted with SMS text messages to improve their everyday functioning. The primary outcome measure was the percentage of goals achieved. RESULTS: The overall percentage of goals achieved increased with prompting, while performance dropped to baseline level after withdrawing the prompts. Keeping appointments with mental health workers and carrying out leisure activities increased with prompting, while medication adherence and attendance at training sessions remained unchanged. A majority of the patients enjoyed receiving the SMS text messages. DISCUSSION: Prompting can significantly improve achievement of a number of relevant goals. For other goals, combining prompting with interventions that enhance motivation seems indicated.

Bisphenol A induces coronary endothelial cell necroptosis by activating RIP3/CamKII dependent pathway.

Epidemiological studies link long term exposure to xenoestrogen Bisphenol-A to adverse cardiovascular effects. Our previous results show that BPA induces hypertension by a mechanism involving CamKII activation and increased redox stress caused by eNOS uncoupling. Recently, CamKII sustained activation has been recognized as a central mediator of programmed cell death in cardiovascular diseases, including necroptosis. However, the role of necroptosis in cardiac response to BPA had not yet been explored. Mice exposed to BPA for 16 weeks showed altered heart function, electrical conduction, and increased blood pressure. Besides, a stress test showed ST-segment depression, indicative of cardiac ischemia. The hearts exhibited cardiac hypertrophy and reduced vascularization, interstitial edema, and large hemorrhagic foci accompanied by fibrinogen deposits. BPA initiated a cardiac inflammatory response, up-regulation of M1 macrophage polarization, and increased oxidative stress, coinciding with the increased expression of CamKII and the necroptotic effector RIP3. In addition, cell death was especially evident in coronary endothelial cells within hemorrhagic areas, and Evans blue extravasation indicated a vascular leak in response to Bisphenol-A. Consistent with the in vivo findings, BPA increased the necroptosis/apoptosis ratio, the expression of RIP3, and CamKII activation in endothelial cells. Necrostatin-1, an inhibitor of necroptosis, alleviated BPA induced cardiac dysfunction and prevented the inflammatory and hemorrhagic response in mice. Mechanistically, silencing of RIP3 reversed BPA-induced necroptosis and CamKII activation in endothelial cells, while inhibition of CamKII activation by KN-93 had no effect on RIP3 expression but decreased necroptotic cell death suggesting that BPA induced necroptosis is mediated by a RIP 3/CamKII dependent pathway. Our results reveal a novel pathogenic role of BPA on the coronary circulation. BPA induces endothelial cell necroptosis, promotes the weakening of coronary vascular wall, which caused internal ventricular hemorrhages, delaying the reparative process and ultimately leading to cardiac dysfunction.

The predictive value of measures of social cognition for community functioning in schizophrenia: implications for neuropsychological assessment.

The objective of this study was to examine the unique contribution of social cognition to the prediction of community functioning and to explore the relevance of social cognition for clinical practice. Forty-six schizophrenia patients and 53 healthy controls were assessed with tests of social cognition [emotion perception and Theory of Mind (ToM)], general cognition, and, within the patient sample, psychiatric symptoms. Community functioning was rated by nurses or family members. Social cognition was a better predictor of community functioning than general cognition or psychiatric symptoms. When the contributions of emotion perception and ToM were examined separately, only ToM contributed significantly to the prediction of community functioning. Independent living skills were poor in patients with impaired social cognition. In controls, social cognition was not related to community functioning. ToM was the best predictor of community functioning in schizophrenia. However, to fully understand a patient's strengths and weaknesses, assessment of social cognition should always be combined with assessment of general cognition and psychiatric symptoms.

Amicrobial pustulosis of the folds associated with Hashimoto's thyroiditis.

Neutrophilic dermatoses comprise a wide spectrum of diseases characterized histologically by the presence of an aseptic neutrophilic infiltrate in the skin. The neutrophilic infiltrate may move from the epidermis to the dermis and the subcutis, resulting in distinct clinicopathological conditions. There have been a few reports on a peculiar pustular dermatosis involving the cutaneous flexures and arising in patients with autoimmune diseases or immunological abnormalities. We report a patient who developed amicrobial pustulosis of the folds soon after she was diagnosed with Hashimoto's thyroiditis (HT). To our knowledge, the association of APF with HT is a novel finding that has not previously been described. We believe that this combination is not just coincidental, but may share similar immunopathological mechanisms.

Evidence of higher intramyocellular fat among normal and overweight Indians with prediabetes.

BACKGROUND: The rise in prevalence rates of Type 2 Diabetes among Indians is well recognized. The research focus has been primarily to understand the changes in insulin sensitivity and beta cell dysfunction among Indians with Type 2 Diabetes. However, no data are available on the role of peripheral tissue, in particular intramyocellular lipid (IMCL) content and its impact on glucose homeostasis among Indians with prediabetes. METHODS: 28 male subjects (20-40 year) were studied. 13 with prediabetes (BMI ranging from 25.4 ± 2.9 kg/m2) and 15 controls (BMI ranging from 24.6 ± 2.8 kg/m2) were recruited. Body composition by dual energy X-ray absorptiometry (DXA), insulin sensitivity, insulin secretion rates were derived using the minimal model of C-peptide secretion and kinetics rates and skeletal muscle strength of the lower limb (quadriceps) was assessed using Isokinetic dynamometry. From muscle biopsy samples of the vastus lateralis, IMCL fat content (Oil red O staining) was determined. RESULTS: The prediabetes group were older compared to controls (P < 0.01), but had similar BMI. The muscle to fat ratio, plasma Insulin, C peptide, HOMA-IR and HOMA % B were also comparable between the groups. IMCL fat content (%) was significantly higher in the prediabetes group compared to controls (7.0 ± 0.7% vs. 2.0 ± 0.3%, P < 0.01). This difference persisted even after controlling for age. Overall the IMCL fat content (%) was positively and significantly associated with HbA1c (r = 0.76, P < 0.01). HOMA-IR was significantly correlated with central (android, trunk) adiposity (kg) (r = 0.71, P < 0.01) but not with IMCL (%). CONCLUSIONS: This is the first direct evidence of existence of significantly higher lipid levels within skeletal muscle cells among normal and overweight young Indians with prediabetes. However, there was no association between IMCL and HOMA-IR among the prediabetes group.

Parathyroid hormone-related protein promotes inflammation in the kidney with an obstructed ureter.

Parathyroid hormone-related protein (PTHrP) promotes fibrogenesis in the acutely damaged kidney. Considering the relation between fibrosis and inflammation, we studied transgenic mice that overexpress PTHrP in the proximal tubule. When unilateral ureteric obstruction was induced in these transgenic mice, we found that they had more renal tubulointerstitial damage, leukocyte influx, and expression of proinflammatory factors than their control littermates. Reversal of PTHrP constitutive overexpression in these transgenic mice or treatment of control mice with the PTHrP antagonist (7-34) decreased this inflammatory response. Losartan, which abolished obstruction-induced endogenous PTHrP upregulation, also decreased the latter response but less effectively in transgenic mice. The PTHrP fragment (1-36) induced nuclear factor-kappaB (NF-kappaB) activation and proinflammatory cytokine overexpression in mouse cortical tubule cells in culture as well as migration of the macrophage cell line Raw 264.7. All these effects were decreased by PTHrP (7-34) and NF-kappaB or extracellular signal-regulated kinase (ERK) activation inhibitors. Our findings suggest a critical role of PTHrP in the renal inflammatory process that results from ureteral obstruction and indicate that ERK-mediated NF-kappaB activation seems to be an important mechanism whereby PTHrP triggers renal inflammation.

Fetal sex modifies the effect of maternal macronutrient intake on the incidence of small-for-gestational-age births: a prospective observational cohort study.

Background: Maternal macronutrient intake is likely to play a pivotal role in fetoplacental growth. Male fetuses grow faster and their growth is more responsive to maternal size. Objective: We assessed the role of fetal sex in modifying the effect of maternal macronutrient intake on the risk of small-for-gestational-age (SGA) birth. Design: This was a prospective, observational cohort study of 2035 births from an urban South Asian Indian population. Maternal intakes of total energy and macronutrients were recorded by validated food-frequency questionnaires. The interaction of trimester 1 macronutrient intake with fetal sex was tested on the outcome of SGA births. Results: The prevalence of SGA was 28%. Trimester 1 macronutrient composition was high in carbohydrate and low in fat (means ± SDs-carbohydrate: 64.6% ± 5.1%; protein: 11.5% ± 1.1%; and fat: 23.9% ± 4.4% of energy). Higher carbohydrate and lower fat consumption were each associated with an increased risk of SGA [adjusted OR (AOR) per 5% of energy (95% CI): carbohydrate: 1.15 (1.01, 1.32); fat: 0.83 (0.71, 0.97)] specifically among male births (males: n = 1047; females: n = 988). Dietary intake of >70% of energy from carbohydrate was also associated with increased risk (AOR: 1.67; 95% CI: 1.00, 2.78), whereas >25% of energy from fat intake was associated with decreased risk (AOR: 0.61; 95% CI: 0.41, 0.90) of SGA in male births. Conclusions: Higher carbohydrate and lower fat intakes early in pregnancy were associated with increased risk of male SGA births. Therefore, we speculate that fetal sex acts as a modifier of the role of maternal periconceptional nutrition in optimal fetoplacental growth.