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[Background] Previous studies linked disease-progression variables such as age at onset or survival to both genetic, and non-genetic factors in Parkinson's disease (PD) patients., [Objective] The aim of this study was to assess how genetic and non genetic factors act as modifiers of age at onset and survival and in a cohort of 753 PD patients, and to determine how these variables interact to define the overall risk., [Methods] We analyzed the effect of gender, tobacco, alcohol, type of PD (genetic, gPD or idiopathic, iPD) and three genetic variants rs5848- GRN, rs1042522- TP53 and APOE. We studied two cohorts (PPMI and IPDGC) to replicate positive results., [Results] Regarding age at onset, male smokers PD had a significantly lower mean age compared to non-smoker (p = 0.001). APOE-Ɛ4 carriers had a younger onset-age compared to non-carriers (p = 0.03) in the Spanish cohort, but these results were not replicated in the other cohorts. Concerning survival, PD patients with an early onset (below 50 years) had an increased survival rate (p < 0.001)., [Conclusions] Our study showed how several genetic and non-genetic risk factors influenced the age at onset and survival in PD., Irene Rosas was supported by a grant from Fundación Jose Luis Castaño-SEQC. Sergio Pérez-Oliveira is supported by Fundación Parkinson Asturias-Obra Social Cajastur. This study was supported by grant PI 15/00878 (Fondos Feder) to VA.

Traumatic events and violence are widespread public health problems. They do not have limits related to age, sex or socioeconomic level. The prevalence of mental disorders and sociodemographic characteristics were compared in the context of traumatic events and types of violence in the general population.Observational prevalence study with a secondary information source, in the general population aged 13 to 65 years, selected at random. The interview was conducted using the Compositum International Diagnosis Interview which generates psychiatric diagnoses according to the DSM-IV. The variables included were traumatic events grouped into five categories: related to armed conflict, sexual violence, interfamily violence, other types of violence, traumas and some mental disorders. The prevalence of mental disorders was compared in the five categories of traumatic events. Statistical significance was defined as a p value of0.05.Sexual and interfamily violence were more prevalent in women (p0.05). In those under age 13, major depression related to armed conflict had a prevalence of 48.3%, with a significant difference from the other trauma groups (p=0.015). All prevalences for childhood-onset disorders showed significantly different prevalences compared with the group for violence related to armed conflict (p0.05) and suicidal ideation was higher in the sexual violence group (p=0.006).High prevalences of mental disorders were found in people who had been exposed to traumatic events and violence. In those who experienced traumatic events related to armed conflict and sexual violence, higher prevalences of certain mental disorders were detected.

Smoking can play a key role in SARS-CoV-2 infection and in the course of the disease. Previous studies have conflicting or inconclusive results on the prevalence of smoking and the severity of the coronavirus disease (COVID-19).Observational, multicenter, retrospective cohort study of 14,260 patients admitted for COVID-19 in Spanish hospitals between February and September 2020. Their clinical characteristics were recorded and the patients were classified into a smoking group (active or former smokers) or a non-smoking group (never smokers). The patients were followed up to one month after discharge. Differences between groups were analysed. A multivariate logistic regression and Kapplan Meier curves analysed the relationship between smoking and in-hospital mortality.The median age was 68.6 (55.8-79.1) years, with 57.7% of males. Smoking patients were older (69.9 (59.6-78.0 years)), more frequently male (80.3%) and with higher Charlson index (4 (2-6)) than non-smoking patients. Smoking patients presented a worse evolution, with a higher rate of admission to the intensive care unit (ICU) (10.4 vs. 8.1%), higher in-hospital mortality (22.5 vs. 16.4%) and readmission at one month (5.8 vs. 4.0%) than in non-smoking patients. After multivariate analysis, smoking remained associated with these events.Active or past smoking is an independent predictor of poor prognosis in patients with COVID-19. It is associated with higher ICU admissions and in-hospital mortality.El tabaquismo puede tener un papel importante en la infección por SARS-CoV-2 y en el curso de la enfermedad. Los estudios previos muestran resultados contradictorios o no concluyentes sobre la prevalencia de fumar y la severidad en la enfermedad por coronavirus (COVID-19).Estudio de cohortes observacional, multicéntrico y retrospectivo de 14.260 pacientes que ingresaron por COVID-19 en hospitales españoles desde febrero a septiembre de 2020. Se registraron sus características clínicas y se clasificaron en el grupo con tabaquismo si tabaquismo activo o previo o en el grupo sin tabaquismo si nunca habían fumado. Se realizó un seguimiento hasta un mes después del alta. Se analizaron las diferencias entre grupos. La relación entre tabaquismo y mortalidad intrahospitalaria se valoró mediante una regresión logística multivariante y curvas de Kapplan Meier.La mediana de edad fue 68,6 (55,8–79,1) años, con un 57,7% de varones. El grupo con tabaquismo presentó mayor edad (69,9 (59,6–78,0 años)), predominio masculino (80,3%) y mayor índice de Charlson (4 (2−6)). La evolución fue peor en estos pacientes, con una mayor tasa de ingreso en UCI (10,4 vs 8,1%), mayor mortalidad intrahospitalaria (22,5 vs 16,4%) y reingreso al mes (5,8 vs 4,0%) que el grupo sin tabaquismo. Tras el análisis multivariante, el tabaquismo permanecía asociado a estos eventos.El tabaquismo de forma activa o pasada es un factor predictor independiente de mal pronóstico en los pacientes con COVID-19, estando asociada a mayor probabilidad de ingreso en UCI y a mayor mortalidad intrahospitalaria.

In Europe, gastric adenocarcinoma (GADC) is commonly regarded as a disease of the elderly. This study aims to assess the proportion, characteristics, and survival of patients diagnosed with GADC under the age of 60.This is a retrospective, multicentric, and analytical study conducted at four tertiary Spanish hospitals. All patients diagnosed with GADC between 2008 and 2015 were included. Demographic, clinical, endoscopic, histologic, and survival data were retrieved. A multivariate analysis was performed to compare GADC in young (age≤60 years) and elderly patients.A total of 1374 patients with GADC were included. The mean age was 74 years (SD:11.1); 62.2% were males. There were 177 patients under the age of 60 (12.9%, 95% CI: 11.2-14.8%). GADC was frequently encountered as a metastatic disease in both young and elderly patients (Stage IV: 45.7% and 41%, respectively). In the multivariate analysis, alcohol abuse, ASA functional status I-II, diffuse subtype, neoadjuvant, and palliative therapy were independently associated (P0.05) with age ≤60 years. No differences were found in 2-year survival (GADC ≤60: 39% vs. 35%, P=0.45). Curative-intent surgery, TNM stage I-II, body mass index30kg/mOne out of eight cases of GADC were diagnosed under the age of 60. Metastatic disease was frequent at diagnosis and overall survival was poor regardless of age. Factors associated with localized disease correlated with improved survival in younger patients. Our results underline the need for early diagnosis strategies in our country.

Missed gastric cancer (MGC) is poorly documented in Mediterranean populations.(1) To assess the rate, predictors and survival of MGC. (2) To compare MGC and non-MGC tumors.This is a retrospective-cohort study conducted at four centers. MGC was defined as cancer detected within three years after negative esophagogastroduodenoscopy. Gastric adenocarcinomas diagnosed between 2008-2015 were included. Patients with no follow-up were excluded.During the study period 123,395 esophagogastroduodenoscopies were performed, with 1374 gastric cancers being diagnosed (1.1%). A total of 1289 gastric cancers were finally included. The overall rate of MGC was 4.7% (61/1289, 3.7-6%). A negative esophagogastroduodenoscopy in MGC patients was independently associated with PPI therapy (p 0.001), previous Billroth II anastomosis (p = 0.002), and lack of alarm symptoms (p 0.001). The most frequent location for MGC was the gastric body(52.4%). MGCs were smaller than non-MGCs (31 vs 41 mm, p = 0.047), more often flat or depressed (p = 0.003) and less likely to be encountered as advanced disease. Overall 2-year survival was similar between MGC (34.1%) and Non-MGC (35.3 %) (p = 0.59).MGC accounted for nearly five percent of newly-diagnosed gastric adenocarcinomas. Overall survival was poor and not different between MGC and non-MGC.

Introduction Autologous haematopoietic stem cell transplantation (AHSCT) is an accepted treatment in refractory Crohn's disease (CD). Material and methods Data on patients with refractory CD subjected to AHSCT are collected at the Hospital Universitario Ramon y Cajal in Madrid and the results obtained are described retrospectively. Results Seven patients in total have received AHSCT due to refractory CD in our centre. Three patients (43%) presented with clinical and endoscopic remission; one patient (14%) clinical improvement without remission and three patients (43%) remained active with the need to restart treatment in the assessment of the initial response to the AHSCT (after six months). Symptoms recurred in five of the seven patients (71%) and all of them had to restart medical treatment after an average of 13.8 months (range: 3–30 months). Only one patient needed surgery after the AHSCT. At the end of the follow-up, after a mean of 48 months (range: 17–78 months), 5/7 (71%) of the patients were in clinical remission with or without treatment. Conclusion AHSCT may be a promising therapeutic option for patients with refractory CD. Its usefulness lies in the fact that it can produce clinical remission without treatment in some patients, but also that it can make the disease treatable, obtaining a response to certain treatments in patients who had previously lost it.

Backgound: Traditional anthropometrics such as body mass index (BMI) or waist circumference (WC) do not fully capture the complex biology of body fat (BF) in the elderly. The Clinica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) index, based on BMI, is proposed as a better indicator of BF. However, its relation with BMI is not clear. The aim was to compare the agreement between CUN-BAE, BMI, and WC in those aged &ge, 50 years. Methods: A cross-sectional sample of 3153 Caucasian healthy adults was taken from the MCC-Spain study. The Pearson&rsquo, s correlation and its 95% confidence interval (CI), adiposity distribution, and Kappa Index (95%CI) were calculated. Results: The correlation of CUN-BAE with WC is 0.18 (95%CI 0.14&ndash, 0.21) and that with BMI is moderate (r 0.58, 95%CI 0.55&ndash, 0.60), but both increased strongly by sex. Agreement (normal weight/overweight/obesity) of CUN-BAE with BMI is 7% and with WC is 18%. Conclusions: The correlation and the degree of agreement of CUN-BAE with BMI and WC are low in individuals aged over 50, but it is higher by sex. Thus, this different criterion of obesity may have clinical applications. More studies with a gold standard are needed to evaluate the CUN-BAE in elderly adults.

The aim of this study is to analyse the percentage of hypovitaminosis D, as well as its relationship with the various parameters of calcium-phosphate metabolism. A case control study was conducted on 366 patients, divided into two groups: Group 1: 127 non-stone-forming patients, and Group 2: 239 calcium stone forming. A study was performed on calcium-phosphate metabolism and urinary lithogenic factors. The percentage of vitamin D deficiency (25-OH-vitamin D levels

Idarucizumab is a monoclonal antibody that rapidly reverses the anticoagulant effect of dabigatran. The experience with this drug in the setting of gastrointestinal bleeding is scarce. We present the case of an 84-year-old male with known history of non-valvular atrial fibrillation anticoagulated with dabigatran who presented to the emergency room with melena. During his stay in the emergency department he suddenly worsened with hemodynamic derangement and massive melena so idarucizumab was administered. Gastroscopy and colonoscopy were performed without identifying a bleeding source. After the administration of idarucizumab, the patient did not presented signs of ongoing bleeding. Anticoagulation was resumed on the sixth day and no rebleeding or thromboembolic events have been recorded after six months of follow-up. This case and the limited information available in the literature suggest that idarucizumab can be useful and safe in cases of severe gastrointestinal bleeding with recent intake of dabigatran.

A recent study showed that Arab-Berbers GG homozygous at rs2421947(C/G) in the dynamin 3 gene (DNM3) had 12.5 years earlier age at onset of leucine-rich repeat kinase 2 (LRRK2)-associated Parkinson's disease (PD) (L2PD). We explored whether this variant modulates the L2PD age at onset in Spain.We genotyped rs2421947 in 329 participants (210 L2PD patients, 119 L2PD nonmanifesting p.G2019S carriers), and marker rs356219 (A/G) in the α-synuclein gene (SNCA).By Kaplan Meier and Cox regression analyses, we did not find an association of the DNM3 polymorphism with L2PD age at onset. However, we found an association of the SNCA marker with up to an 11 years difference in the L2PD median age at onset (58 years for GG carriers vs 69 years for AA).Our results indicate that SNCA rs356219 but not dynamin 3 DNM3 rs2421947 modifies the penetrance of the mutation G2019S in the Spanish population by influencing the L2PD age at onset. These findings suggest that different genetic modifiers may influence the L2PD age at onset in different populations. © 2018 International Parkinson and Movement Disorder Society.

The need for endoscopic investigation in patients with iron deficiency without anemia (ID) is not established.Data from patients with ID (serum ferritin ≤20 ng/mL, normal hemoglobin) studied with upper and lower endoscopies were retrospectively analyzed. Patients evaluated for iron deficiency anemia (IDA) served as controls, matched by sex and age in the proportion of 2:1. The groups were compared for the presence, type, location and age distribution of endoscopic findings.Altogether 109 patients (55% women; mean age 59.6 ± 13.5 years; aged50 years [27.5%]; 50-69 years [43.1%]; ≥70 years [29.4%]) were included in the ID group and 218 matched controls in the IDA group. Lesions were found in a similar proportion of patients (53.2% in the ID group vs 49.1% in the IDA group, P = 0.48) irrespective of age (P = 0.92). The colonoscopy diagnostic yield was low in both the ID and IDA subgroups of aged50 years (6.3% vs 4.2%, P = 0.76). Multivariate analysis revealed a significant relationship between age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.06) and male sex (OR 2.28, 95% CI 1.18-4.39) with a positive colonoscopy. Malignancy was significantly less frequent in the ID group (1.8% vs 14.2%, P0.05).The prevalence of gastrointestinal lesions in patients with and without anemia was similar but malignancy was eight times less frequent in the ID group. Systematic endoscopic evaluation in patients with ID is therefore questionable.

To assess the value of baseline clinical and imaging biomarkers in a cohort of asymptomaticThirty-two asymptomatic carriers ofThree carriers, asymptomatic at baseline, had converted to PD at 4-year evaluation. Twenty-three participants were fully evaluated. PD converters had lower striatal DaT binding at baseline than nonconverters (Semiquantitative DaT-SPECT could be used to predict early conversion to PD in asymptomatic carriers of the

Background: Mycophenolate (MF) is effective as induction and maintenance treatment in patients with lupus nephritis (LN). This study evaluates the efficacy and safety of MF in patients with refractory and relapsing LN. Methods: Data were retrospectively obtained for 85 patients (35 refractory and 50 relapsing) from 11 nephrology departments in Spain. The primary endpoints were the incidence and cumulative number of renal responses and relapses and their relationship with baseline clinical and analytical data. The secondary endpoint was the appearance of side effects. Results: The main clinical and analytical variables were similar both in refractory and relapsing LN. Most of the patients had received cyclophosphamide, and all of them switched to MF. 74 patients (87%) achieved a response (69% partial, 31% complete). Age at starting MF, gender, pathological classification, body mass index, blood pressure, baseline renal function, and proteinuria were not associated with achieving response. After stopping MF, 3 of 19 patients (15.7%) relapsed, all at 6 months of follow-up. No differences were found between clinical and analytical variables and number of relapses. Side effects were unremarkable, except for 1 patient, who died of thrombocytopenia and ovarian hemorrhage. Conclusions: Switching to MF from other immunosuppressive treatments is effective and safe in refractory and relapsing LN.

Background/Purpose: Psoriasis is a multisystem disease which has been related to vitamin-D deficiency through chronic inflammation. This psoriasis-related inflammatory state and vitamin-D deficiency may induce bone mineral density loss. The purpose of this study is to assess the relationship of psoriasis with bone mineral density, by comparing psoriatic patients with healthy controls and patients with osteopenia/osteoporosis. Methods: A total of 185 subjects were studied; 58 psoriatic patients who had not been under systemic or biological treatment were included. Age, gender, body mass index, phosphocalcic metabolic parameters and hip and lumbar (L4) bone mineral density data were collected. These variables were compared with those collected in 61 healthy controls and 67 patients with osteopenia/osteoporosis. Results: Psoriatic patients showed worse hip and lumbar spine bone mineral density levels than healthy controls (P = 0.001) and better levels than osteoporotic patients (P < 0.001). Multivariate analysis demonstrated a negative association of age and a positive association of body mass index in hip bone mineral density in psoriatic patients. Limitations: The main limitations are those of cross-sectional studies, such as a lack of follow up period, and a male predominance in the psoriatic group, which is corrected employing a multivariate analysis with an adjusted model for confounding factors. Conclusions: Bone mineral density levels in psoriatic patients are situated halfway between healthy controls and patients with osteopenia/osteoporosis. In addition, the higher body mass index in patients with psoriasis appears to confer a protective effect against further development of lower bone mineral density.

Objective: To ascertain in a cross-sectional study whether substantia nigra (SN) echogenicity, olfaction, and dopamine transporter (DaT)-SPECT are reliable premotor biomarkers in a cohort of asymptomatic carriers of the LRRK2 G2019S mutation (AsG2019S+). Methods: These biomarkers were evaluated in 49 AsG2019S+ patients, and we also studied olfaction and SN echogenicity in 29 patients with G2019S-associated Parkinson disease (PD-G2019S), 47 relatives who were noncarriers of the LRRK2 G2019S mutation (AsG2019S−), 50 patients with idiopathic Parkinson disease (iPD), and 50 community controls. Results: Eighty-five percent of unaffected mutation carriers (AsG2019S+) showed pathologic SN hyperechogenicity, with a similar proportion observed among both PD-G2019S and iPD cases, and 41% of AsG2019S− also showing increased SN echogenicity. The proportion of hyposmic individuals was not statistically different in patients with PD-G2019S (50%) and iPD (82%), but hyposmia was significantly less common in both AsG2019S+ (26%) and AsG2019S− (28%). In AsG2019S+ cases, reduced striatal uptake in DaT-SPECT was observed in 43.7%. Conclusions: Independently of age at examination, the most frequently altered premotor biomarker in LRRK2 G2019S-associated PD was SN hyperechogenicity, whereas abnormal DaT-SPECT predominated in older, unaffected mutation carriers.

The aim of this study was to analyze the presence of lithogenic metabolic factors in the blood and urine of patients with osteopenia versus osteoporosis. This is a cross-sectional study including 67 patients who were divided into two groups according to the presence of either osteopenia or osteoporosis as measured by bone densitometry: group 1—40 patients with osteopenia (22 men and 18 women) and group 2—27 patients with osteoporosis (13 men and 14 women). Metabolic studies were performed on the blood and urine; statistical analysis was performed comparing means and conducting linear correlation and multivariate analyses with SPSS. Statistical significance was considered to be p ≤ 0.05. The mean age of patients in group 1 was 52.9 ± 12.8 years versus 50.3 ± 11.4 in group 2; the difference was not statistically significant. In group 2, higher levels of osteocalcin, β-crosslaps, urinary calcium, fasting urine calcium/creatinine, 24 h urine calcium/creatinine and 24 h oxaluria were observed compared to group 1. In the multivariate analysis, only the β-crosslaps and urinary calcium were independently associated with osteoporosis. It would be advisable to determine the urinary calcium levels in patients with osteoporosis since altered levels may necessitate modifying the diagnostic and therapeutic approach to osteoporosis.

To analyze the presence of phosphocalcic metabolism disorders in patients with osteopenia-osteoporosis without nephrolithiasis with respect to a control group.A cross-sectional study was conducted in patients with osteopenia-osteoporosis without nephrolithiasis (n = 67) in lumbar spine or femur and in a control group (n = 61) with no lithiasis or bone disorders. Blood bone markers, phosphocalcic metabolism, fasting urine, 24-h urine lithogenic risk factors, and densitometry were recorded in both groups. SPSS 20.0 was used for statistical analysis.In comparison with the controls, significantly higher blood calcium (9.27 ± 0.36 vs. 9.57 ± 0.38, p = 0.0001), intact parathormone (45.6 ± 14.9 vs. 53.8 ± 18.9, p = 0.008), and alkaline phosphatase (61.9 ± 20.9 vs. 70.74 ± 18.9, p = 0.014) levels were found in patients with osteopenia-osteoporosis. In the 24-h urine test, citrate (1010.7 ± 647.8 vs. 617.6 ± 315.8, p = 0.0001) and oxalate (28.21 ± 17.65 vs. 22.11 ± 16.49, p = 0.045) levels were significantly lower in osteopenia-osteoporosis patients than in controls, with no significant difference in calcium (187.3 ± 106.9 vs. 207.06 ± 98.12, p = 0.27) or uric acid (540.7 ± 186.2 vs. 511.9 ± 167.06, p = 0.35) levels. Patients with osteopenia-osteoporosis had significantly higher levels of lithogenic risk factors associated with bone remodeling, including significantly increased β-crosslaps and osteocalcin values and higher β-crosslaps/osteocalcin ratios.Patients with osteopenia-osteoporosis without nephrolithiasis showed phosphocalcic metabolism disorders as well as lower urinary citrate and higher β-crosslaps/osteocalcin and fasting calcium/creatinine ratios, which would increase the risk of nephrolithiasis. Hence, prospective studies are warranted to evaluate the long-term risks.

The aim of this study is to assess the presence of substantia nigra (SN) hypoechogenicity in a cohort of Friedreich's ataxia (FRDA) patients and its possible association with restless syndrome (RLS). Fourteen genetically confirmed FRDA patients and 14 sex- and age-matched healthy controls underwent transcranial sonography examination to evaluate the area of echogenicity of the SN. Both groups were clinically assessed with the essential and additional diagnostic criteria for RLS established by the International RLS Study Group. Ataxia was evaluated using the Scale for the Assessment and Rating of Ataxia. We did not find significant differences between the mean sum area of SN echogenicity in FRDA patients and in controls. Only one patient in the FDRA group and two control subjects showed SN hypoechogenicity. Two out of the 14 FDRA patients and one of the controls fulfilled diagnostic criteria for RLS. The areas of SN echogenicity in the two FRDA patients with RLS were the lowest found in this group. We conclude that our data do not support the notion that SN hypoechogenicity is related to FRDA itself, although it might be associated with RLS.

Calcium lithiasis is the most frequently diagnosed renal lithiasis and is associated with a high percentage of patients with metabolic disorders, such as hypercalciuria, hypocitraturia, and hyperoxaluria. The present study included 50 patients with recurrent calcium lithiasis. We conducted a random urine test during nocturnal fasting and a 24-h urine test, and examined calcium, oxalate, and citrate. A study of the linear correlation between the metabolites was performed, and the receiver operator characteristic (ROC) curves were analyzed in the random urine samples to determine the cutoff values for hypercalciuria (excretion greater than 200 mg), hyperoxaluria (excretion greater than 40 mg), and hypocitraturia (excretion less than 320 mg) in the 24-h urine. Linear relationships were observed between the calcium levels in the random and 24-h urine samples (R = 0.717, p = 0.0001), the oxalate levels in the random and 24-h urine samples (R = 0.838, p = 0.0001), and the citrate levels in the random and 24-h urine samples (R = 0.799, p = 0.0001). After obtaining the ROC curves, we observed that more than 10.15 mg/dl of random calcium and more than 16.45 mg/l of random oxalate were indicative of hypercalciuria and hyperoxaluria, respectively, in the 24-h urine. In addition, we found that the presence of less than 183 mg/l of random citrate was indicative of the presence of hypocitraturia in the 24-h urine. Using the proposed values, screening for hypercalciuria, hyperoxaluria, and hypocitraturia can be performed with a random urine sample during fasting with an overall sensitivity greater than 86 %.

Androgenetic alopecia (AGA) and benign prostatic hyperplasia are both androgen-dependent entities that respond to the blocking of 5-alpha-reductase.The objective of this study was to determine whether prostatic volumes and urinary flow changes were higher in patients with early-onset AGA than in healthy control subjects.This was an observational case-control study of 87 men: 45 with early-onset AGA diagnosed in the dermatology department and 42 control subjects. End-point variables were prostatic volume, measured by transrectal ultrasound, and urinary flow, measured by urinary flowmetry. A hormone study was performed on all participants, and the International Prostate Symptom Score and International Index of Erectile Function score were determined.The groups did not significantly differ in mean age (cases, 52.7 years vs control subjects, 49.8 years; P = .12). Patients with AGA had significantly higher mean prostate volume (29.65 vs 20.24 mL, P.0001), International Prostate Symptom Score (4.93 vs 1.23, P.0001), and prostate-specific antigen value (1.53 vs 0.94 ng/mL, P.0001) and significantly lower maximum urinary flow (14.5 vs 22.45 mL/s, P.0001) versus control subjects. Binary logistic regression analysis showed a strong association between the presence of AGA and benign prostatic hyperplasia after adjusting for age, urinary volume, urination time, International Prostate Symptom Score, abdominal obesity, glucose levels, systolic blood pressure, insulin levels, fibrinogen, and C-reactive protein (odds ratio = 5.14, 95% confidence interval 1.23-47.36, P = .041).The study of larger sample sizes would facilitate stratified analyses according to the Ebling type of androgenetic alopecia.There is a relationship between the presence of AGA and prostate growth-associated urinary symptoms, likely attributable to their pathophysiological similarity. This study suggests that early-onset AGA may be an early marker of urinary/prostatic symptomatology. Future studies may clarify whether treatment of patients with AGA may benefit the concomitant benign prostatic hypertrophy, which would be present at an earlier stage in its natural evolution.

The frequency and penetrance of the LRRK2 G2019S mutation varies considerably in different Parkinson disease (PD) populations. This information is essential both for clinical purposes and genetic counseling. The objective of this study was to estimate the prevalence and penetrance of the G2019S mutation of the LRRK2 gene in a small region in northern Spain (Cantabria). The G2019S mutation was tested in 367 consecutive patients with PD attended as outpatients in a tertiary Hospital in Northern Spain, and 126 at-risk family members of probands were also investigated for G2019S mutation and disease status. The gene penetrance was estimated in terms of cumulative age-specific incidence of PD by the Kaplan-Meier method. Thirty-two PD patients (8.7%) carried the G2019S mutation. Penetrance estimation of the G2019S mutation was 2% at 50 years, 12% at 60 years, 26% at 70 years, and 47% at 80 years. The frequency of the G2019S mutation of the LRRK2 gene in PD patients from Cantabria is among the highest reported so far after North African Arabs and Ashkenazi Jews. At the age of 80 years only one-half of G2019S mutation carriers manifest motor symptoms of PD. © 2011 Movement Disorder Society

Objective Low serum uric acid (UA) levels have been associated with a worse cognitive function later in life and also with a higher risk and faster progression of Parkinson's disease (PD). Here we studied whether serum UA levels and the genetic variants related to its variability are associated with the presence of dementia in a cohort of patients with PD. Methods The study included 343 PD patients, which were examined for the presence of dementia according to the MDS Task Force criteria (level 1). The predominant PD phenotype and UPDRS-III and Hoehn-Yahr scales were recorded. Serum UA levels were determined in each participant. Genotyping of SLC2A9 rs734553, ABCG2 rs2231142, SLC17A1 rs1183201, SLC22A11 rs17300741, SLC22A12 rs505802, GCKR rs780094, PDZK1 rs12129861, LRRC16A + SCGN rs742132, and SLC16A9 rs12356193 was carried out by Taqman analysis. For each subject we calculated a cumulative genetic risk score (GRS), defined as the total number of risk alleles (range 2–15) associated to lower serum UA levels. Results 72 out of 343 PD patients (21%) presented dementia. Serum UA levels were not different between PD patients with or without dementia. No significant association was detected between any single SNP and the risk of PD-dementia. When we analyzed the combined effect of the eight SNPs using the cumulative GRS no significant association between the number of risk alleles and the risk of PD was observed. Conclusions Our data suggest that serum UA levels have not a significant impact on the risk of dementia in PD.

A 78-year-old man with hyperuricemia treated with allopurinol presents with asymptomatic nodules on both hands. What is the most likely diagnosis?

The antitumoral effect of cisplatin [cis-diamminodichloroplatinum(II)] in mammals is related to its binding to DNA components. However, there is a lack of specific chemical methods to selectively detect those adducts formed in vivo at low concentrations. In this work, a new sensitive and selective method of determining cisplatin-DNA adducts based on the use of element-selective mass spectrometry is proposed, and the method is then applied to detect cisplatin adducts induced in vivo in somatic cells of Drosophila melanogaster. The bioanalytical strategy proposed here allows the determination of the most important DNA adduct formed between adjacent guanine units of the same DNA strand with cisplatin, and it is based on the coupling of capillary liquid chromatography (cap-LC) to inductively coupled plasma mass spectrometry (ICP-MS). This set-up allows the simultaneous monitoring of the Pt (from the drug) and P (from the DNA components) present in these adducts, once they have been cleaved by enzymatic hydrolysis of the DNA samples. Using this instrumental set-up, the adducts of cisplatin formed in vivo when D. melanogaster flies are exposed to different cisplatin concentrations can be detected and their concentration determined. The results obtained show a direct correlation between the concentration of cisplatin adducts, the induced genotoxic damage (measured as DNA strand breaks using the Comet assay) and the cisplatin concentration. [figure: see text] The work illustrates the complementary use of bioanalytical and biological information to study cisplatin interactions with DNA is vivo at biologically relevant concentrations of the drug.

Human immunodeficiency virus type 1 (HIV-1) BF intersubtype recombinant viruses are common in Argentina and Uruguay, where CRF12_BF and related recombinants are frequently found, and, in a lower proportion, in Brazil. Full-length genome sequences have been characterized in several of these recombinant viruses. Here, we analyze six newly derived near full-length genome sequences of BF recombinant viruses, three from Chile, one from Venezuela and two from Spain. Five of them had known epidemiological links to Argentina. Genomes were amplified by PCR from plasma RNA or from peripheral blood mononuclear cells’ DNA. Mosaic structures and phylogenetic relationships were analyzed by bootscanning, neighbour-joining phylogenetic trees and by examination of subtype signature nucleotides. One virus from Spain had a mosaic structure fully coincident with CRF12_BF. The others had unique mosaic structures, except the viruses from two Chilean sisters infected vertically from the same mother, who showed identical recombination patterns. Each of the unique recombinants had one to six breakpoints coincident with CRF12_BF and three also had two or three breakpoints coincident with a previously characterized unique recombinant from Argentina (A025) related to CRF12_BF. A phylogenetic tree of concatenated subtype F segments supported the relationship of five recombinants with CRF12_BF. In trees of partial subtype F and B segments, four recombinants clustered with A025. The examination of CRF12_BF signature amino acids and nucleotides supported the common ancestry of all the analyzed viruses. Based on these results, a model of generation of HIV-1 BF recombinants of Argentinean ancestry by successive rounds of recombination along diverse lineages deriving from a common BF recombinant ancestor related to CRF12_BF is proposed.

We recently reported the finding of phylogenetically related HIV-1 BG intersubtype recombinant and G subtype nonrecombinant viruses circulating among injecting drug users in the region of Galicia in northwestern Spain. Here, we report the characterization of near full-length genome sequences of nine of these viruses (seven BG recombinant and two of nonrecombinant G subtype), obtained from epidemiologically unlinked individuals. Bootscan analysis reveals that six recombinant viruses share an identical mosaic structure, with two intersubtype breakpoints delimiting a B subtype segment comprising most of Env gp120 and the external portion of Env gp41, with the remaining portions of the genome being of subtype G, thus mimicking a pseudotype virion structure. The seventh BG recombinant virus exhibits breakpoints in env coincident with the other BG viruses but contains additional B subtype segments in gag and pol. In phylogenetic trees of complete genomes and of the B subtype segment of env, all seven BG viruses group in a monophyletic cluster. G subtype portions of the BG viruses group uniformly with the newly derived nonrecombinant G subtype viruses of Galicia in bootscan analysis, which points to the locally circulating G subtype strain as parental of the recombinants. These results allow us to define a new HIV-1 circulating recombinant form (CRF14_BG), the first reported to originate in Western Europe.

Recurrent kidney stones are associated with bone mineral density loss, altered bone remodeling markers, hypercalciuria and increased in fasting calcium/creatinine ratio. The objective was to determine biochemical alterations in urine in patients with osteopenia/osteoporosis without calcium kidney stones compared with patients with calcium kidney stones. This is a cross-sectional study including 142 patients who were divided in two groups: Group 1 (patients with recurrent calcium kidney stones) and Group 2 (patients with osteopenia/osteoporosis in the lumbar spine or hip). Analyses of bone mineral density, calcium–phosphorous and bone metabolism and lithogenic risk factors in fasting urine samples and 24-h urine samples were performed. Statistical analysis was carried out with SPSS 17.0. A p ≤ 0.05 was considered statistically significant. Patients in Group 2 presented greater loss of bone mineral density and more elevated alkaline phosphatase, iPTH, phosphorous and β-crosslaps levels, as compared to patients in Group 1. However, Group 1 presented greater urine calcium, oxalate and uric acid and a higher proportion of hypocitraturia, hypercalciuria and hyperoxaluria, as compared to Group 2. Multivariate analysis revealed that advanced age and β-crosslaps levels are risk factors for bone mineral density loss, while low urinary calcium excretion was protective against bone demineralization. Patients with osteopenia/osteoporosis without lithiasis present some urinary biochemical alterations. This would explain the lack of lithogenic activity, although low calcium excretion in 24-h urine samples is a protective factor against the loss of bone mineral density.

Resistance to carbapenems is considered to represent a serious threat to public health at the global level, since these antibiotics are one of the last therapeutic options for the treatment of multidrug-resistant bacteria. Molecular characterization of outbreaks due to resistant bacteria provides information that can be used in the design of infection control strategies.To describe the molecular characteristics of an outbreak of carbapenem-resistant Klebsiella pneumoniae that occurred in a tertiary care hospital in Medellín in 2010-2011.Eighty-four isolates were obtained from a collection of strains associated with the hospital outbreak, of which 32 were from patients infected at that time and 52 were carriers. Identification and susceptibility of the isolates was performed using Vitek2®. Carbapenemases were detected using a modified Hodge test and polymerase chain reaction. Genetic relationships between the isolates were evaluated using pulsed field gel electrophoresis and multiple locus sequence typing.All the isolates analyzed were multidrug resistant; molecular analysis revealed that all harbored bla KPC-3 . The genetic analysis showed that 58/64 of the isolates from both infected and colonized patients were closely related (Dice similarity index80%) and belonged to the ST258 lineage.Using molecular typing techniques it was possible to confirm the occurrence of an outbreak caused by K. pneumoniae ST258, a carrier of bla KPC-3 with a multidrug-resistant profile which had been associated with a previous outbreak in another hospital in the city of Medellín. ST258 is a high risk clone at the global level, demonstrating the potential for dissemination of resistance in this country. Implementation of molecular tools in support of epidemiological surveillance is useful for evaluating the spread of microorganisms of public health significance.

Objective To analyze differences in bone remodeling markers, lithogenic factors and bone densitometry among the 3 groups of patients (controls, patients with relapsing calcium renal lithiasis, and patients with loss of bone mineral density without lithiasis). Material and Methods This is a cross-sectional study including 203 patients who were divided in 3 groups: group 1 (controls), group 2 (patients with relapsing calcium renal lithiasis), and group 3 (patients with osteopenia and/or osteoporosis in the lumbar spine or hip). Bone densitometry, calcium-phosphorous and bone metabolism analysis, and analysis of lithogenic risk factors in fasting urine samples and 24-hour urine samples were performed. Statistical analysis was performed with SPSS 17.0. A P ≤.05 was considered statistically significant. Results Patients in group 2 presented greater calcium excretion and a lower citrate excretion in 24-hour urine samples as compared with the other 2 groups. The proportion of hypercalciuria and hypocitraturia was higher in group 2. In addition, patients in group 2 presented a lower loss of bone mineral density as well as altered bone remodeling markers as compared with those in group 1. Patients in group 3 also presented alterations in urine calcium and citrate excretion with respect to the control group, with elevated fasting calcium and citrate levels and calcium-to-citrateratio. Conclusion Lithogenic risk factors are altered in patients with osteopenia and/or osteoporosis without renal lithiasis although to a lesser extent than patients with calcium renal lithiasis.

BACKGROUND: Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined. OBJECTIVE: To evaluate the prevalence and time of onset of nonmotor symptoms (NMS) in LRRK2-PD patients. METHODS: The presence of hyposmia and of neuropsychiatric, dysautonomic and sleep disturbances was assessed in 33 LRRK2-G2019S-PD patients by standardized questionnaires and validated scales. Thirty-three IPD patients, matched for age, gender, duration of parkinsonism and disease severity and 33 healthy subjects were also evaluated. RESULTS: University of Pennsylvania Smell Identification Test (UPSIT) scores in LRRK2-G2019S-PD were higher than those in IPD (23.5±6.8 vs 18.4±6.0; p = 0.002), and hyposmia was less frequent in G2019S carriers than in IPD (39.4% vs 75.8%; p = 0.01). UPSIT scores were significantly higher in females than in males in LRRK2-PD patients (26.9±4.7 vs 19.4±6.8; p

The commonest known cause of Parkinson's disease (PD) is the G2019S mutation of the LRRK2 gene, but this mutation is not sufficient for causing PD, and many carriers of the mutation never develop PD symptoms during life. Differences at the expression level of certain genes, resulting from either genetic variations or environmental interactions, might be one of the mechanisms underlying differential risks for developing both idiopathic and genetic PD. To identify the genes involved in PD pathogenesis, we compared genome-wide gene expression (RNA-seq) in peripheral blood of 20 PD patients carrying the G2019S mutation of the LRRK2 gene, 20 asymptomatic carriers of the mutation, 20 subjects with idiopathic PD, 20 controls and 7 PD patients before and after initiating dopaminergic therapy. We identified 13 common genes (. ADARB2, CEACAM6, CNTNAP2, COL19A1, DEF4, DRAXIN, FCER2, HBG1, NCAPG2, PVRL2, SLC2A14, SNCA, and TCL1B) showing significant differential expression between G2019S-associated PD and asymptomatic carriers and also between idiopathic PD and controls but not between untreated and treated patients. Some of these genes are functionally involved in the processes known to be involved in PD pathogenesis, such as Akt signaling, glucose metabolism, or immunity. We consider that these genes merit further attention in future studies as potential candidate genes involved in both idiopathic and LRRK2-G2019S-associated forms of PD., This work was supported by the grant PI11/00228 form Instituto de Salud Carlos III. Bioinformatic analyses were performed on the Altamira Supercomputer at the University of Cantabria.

A healthy man presents with a tender subcutaneous nodule on his hand that appeared after cleaning his aquarium. What is the most likely diagnosis?

Molecular mutation spectra induced by N-ethyl-N-nitrosourea have been obtained in several organisms and test systems, frequently showing different results. In Drosophila melanogaster this spectrum has been analyzed in post-meiotic stages, resulting in good agreement between the adduct spectrum and mutational events, the majority being GC→AT transitions (61%). However, when collecting data about in vivo ENU-induced mutations in mouse germ cell stages mostly damage at A:T sites (89%) was observed. In this work we analyze the molecular spectrum induced with ENU in pre-meiotic repair-active male germ cells of D.melanogaster, using the specific locus test (SLT) with the vermilion locus as target. Results show that the most mutagenic sites in spermatogonial stem cells of Drosophila are A:T pairs (85%), with AT→TA transversions (50%) and AT

The white-ivory somatic assay of Drosophila melanogaster was developed to detect genotoxic agents which induce loss of a tandem duplication. Although the mechanism of this loss is not known, some suggestions point to intrachromosomal recombination as the main reversion mechanism. Since the few papers published to date on this assay present controversial methodologies, prior to a larger study of chemicals with different mechanisms of action, we have carried out an analysis to optimize some conditions of this assay. For this purpose, we have used three different strains and four well characterized mutagenic chemicals: N-ethyl-N-nitrosourea (ENU), methyl methane-sulfonate (MMS), ethyl methanesulfonate (EMS) and hexamethyl phosphoramide (HMPA). The results obtained allow us to conclude that: (i) the best strain for this assay is C(1)DX,y,f Dp(1:1:1)w i ,y 2 , although the use of strain FM6,l(1)66a / Dp(1:1:1:1)wi,y2;st / st could be considered for some mechanistical studies; (ii) developmental reasons make it necessary to use as estimate of reversion frequency the proportion of eyes showing at least one spot; (iii) reversion frequency cannot be used as estimate of mutation efficiency, neither can spot size evaluate time of spot induction; (iv) the four chemicals clearly induce loss of the wi duplication; according to their activities they rank ENU HMPA , MMS ≈ EMS .

Low serum uric acid (UA) levels have been associated with increased Parkinson's disease (PD) risk and accelerated disease progression. We analyzed the effect of polymorphisms in 9 genes influencing serum UA concentration on the risk of PD.We genotyped SLC2A9 rs734553, ABCG2 rs2231142, SLC17A1 rs1183201, SLC22A11 rs17300741, SLC22A12 rs505802, GCKR rs780094, PDZK1 rs12129861, LRRC16A+SCGN rs742132, and SLC16A9 rs12356193 in 1061 PD patients and 754 controls. For each subject we calculated a cumulative genetic risk score (GRS), defined as the total number of PD-risk alleles (range, 2-15) associated to lower serum UA levels. Serum UA levels were measured in a subgroup of 365 PD cases and 132 controls.Serum UA levels were significantly lower in men with PD than in controls. Subjects (both men and women) carrying more than 9 risk alleles (third GRS tertile) had a 1.5 higher risk of developing PD than subjects with less than 8 risk alleles (first GRS tertile). An inverse correlation was observed between higher GRS and lower serum UA concentration in both men and women.Genetic variability influencing serum UA levels might modify susceptibility to PD.

Objective To establish cutoff points for markers of bone remodeling that allow for screening of patients at risk for serious lithogenic activity. Materials and Methods We conducted a cross-sectional study with 182 patients (aged between 25 and 60 years) divided into 3 groups: group 1, 56 patients without lithiasis; group 2, 67 patients with light calcium lithiasis; and group 3, 59 patients with severe calcium lithiasis. The criteria for inclusion in and exclusion from the study were established, and light and severe lithogenic activity were defined. Metabolic variables in blood and urine, along with bone densitometry, were studied for the groups. Statistical analysis of the results and preparation of receiver operating characteristic curves to establish optimal cutoff points were performed. Results The patients in group 3 showed the greatest bone mineral density loss and the highest values for markers of bone remodeling, together with increased 24-hour calciuria. Using the receiver operating characteristic curves developed and based on statistical significance ( P = .0001), the following cutoff points for severe lithogenic activity, with a sensitivity between 75% and 85%, were established: β-crosslaps >0.331 ng/mL; osteocalcin >13.2 ng/mL; β-crosslaps/osteocalcin >0.024; 24-hour calciuria >306.6 mg; and fasting urine calcium/creatinine >0.105. Conclusion Patients with calcium lithiasis and elevated values for osteocalcin, β-crosslaps, β-crosslaps/osteocalcin, 24-hour calciuria, and fasting urine calcium/creatinine may present a high risk of severe lithogenic activity.

The objective of this study is to analyze the alterations in bone mineral density and bone and calcium–phosphorus metabolism in patients with calcium nephrolithiasis. We designed a study with 182 patients who were distributed among three groups: group O, 56 patients without nephrolithiasis; group A, 67 patients with calcium nephrolithiasis and mild lithogenic activity; and group B, 59 patients with calcium nephrolithiasis and severe lithogenic activity. Metabolic parameters of blood and urine that were related to calcium–phosphorous and bone metabolism and bone densitometry were assessed in all patients. A comparative study was performed on the variables of bone and calcium–phosphorus metabolism and bone densitometry as well as the presence or absence of osteopenia/osteoporosis. The patients in group B had a greater loss of bone mineral density, measured by the T-score, than the patients in groups O and A. Moreover, the proportion of patients in group B with osteopenia/osteoporosis was statistically significantly higher than the proportion of patients in groups O and A. We observed higher values of calciuria, fasting calcium/creatinine ratio, and 24-h calcium/creatinine among the patients in group B compared to the other two groups. Calciuria, citraturia, and fasting calcium/creatinine were independent factors that showed a relationship with severe lithogenic activity compared to the control group, and β-crosslaps is an independent factor that has a relationship with severe lithogenic activity as compared to mild lithogenic activity. Patients with calcium lithiasis and severe lithogenic activity have a greater loss in bone mineral density and therefore a greater risk of osteopenia/osteoporosis.

Recent genome-wide association studies of Parkinson's disease have nominated 3 new susceptibility loci (PARK16-18) and confirmed 2 known risk genes (MAPT and SNCA) in populations of European ancestry. We sought to replicate these findings. We genotyped single-nucleotide polymorphisms in each of these genes/loci in 1445 Parkinson's disease patients and 1161 controls from northern Spain. Logistic regression was used to test for association between genotype and Parkinson's disease under an additive model, adjusting for sex, age, and site. We also performed analyses stratified by age at onset. Single-nucleotide polymorphisms in MAPT (rs1800547; P = 3.1 × 10(-4) ) and SNCA (rs356219; P = 5.5 × 10(-4) ) were significantly associated with Parkinson's disease. However, none of the markers in PARK16-18 associated with Parkinson's disease in the overall sample, or in any age stratum, with P values ranging from .09 to .88. Although our data further validate MAPT and SNCA as Parkinson's disease susceptibility genes, we failed to replicate PARK16, PARK17, and PARK18. Potential reasons for the discordance between our study and previous genome-wide association studies include effects of population structure, power, and population-specific environmental interactions. Our findings suggest that additional studies of PARK16-18 are necessary to establish the role of these loci in modifying risk for Parkinson's disease in European-derived populations. © 2011 Movement Disorder Society.

Several studies have analyzed the relationship between androgenetic alopecia and cardiovascular disease (mainly heart disease). However few studies have analyzed lipid values in men and women separately. This case-control study included 300 patients consecutively admitted to an outpatient clinic, 150 with early onset androgenetic alopecia (80 males and 70 females) and 150 controls (80 males and 70 females) with other skin diseases. Female patients with androgenic alopecia showed significant higher triglycerides values (123.8 vs 89.43 mg/dl, p = 0.006), total cholesterol values (196.1 vs 182.3 mg/dl, p = 0.014), LDL-C values (114.1 vs 98.8 mg/dl, p = 0.0006) and lower HDL-C values (56.8 vs 67.7 mg/dl, p

Background Chronic inflammation was found to play an important role in the development of cardiovascular risk factors. Recently a case-control study found that lichen planus was associated with dyslipidemia in a large series of patients. However, no data were presented about lipid values, glucose levels, or blood pressure. Objective The objective of this case-control study was to evaluate cardiovascular risk factors included in Adult Treatment Panel III criteria for metabolic syndrome in men and women with lichen planus and in healthy controls. Patients and Methods This case-control study included 200 patients, 100 with lichen planus (50 men and 50 women) and 100 controls consecutively admitted to the outpatient clinic in Dermatology departments in Granada, Spain. Results Analysis of metabolic syndrome parameters revealed a higher significant prevalence of dyslipidemia in patients with lichen planus. No significant differences were observed in glucose levels, abdominal obesity, or blood pressure. Elevated levels of C-reactive protein, erythrocyte sedimentation rate, and fibrinogen were noted in patients with lichen planus. Adjusted odds ratio for dyslipidemia in patients with lichen planus was 2.85 (95% confidence interval, 1.33-5.09; P =.001). Conclusion Chronic inflammation in patients with lichen planus may explain the association with dyslipidemia. Lipid levels screening in men or women with lichen planus may be useful to detect individuals at risk and start preventive treatment against the development of cardiovascular disease.

Low circulating levels of sex hormone-binding globulin (SHBG) are a strong predictor of the risk of type 2 diabetes. Androgenetic alopecia (AGA) has been related to an increase in cardiovascular risk, but the mechanism of this association has not been elucidated. AGA can be associated with low levels of SHBG and insulin resistance, which could be related to hyperglycemia and type 2 diabetes.The objective of this study was to evaluate SHBG and blood glucose levels in men and women with early-onset AGA and control subjects to determine whether low levels of SHBG are associated with hyperglycemia.This case-control study included 240 patients consecutively admitted to the outpatient clinic (Dermatology Department of San Cecilio University Hospital, Granada, Spain), 120 with early-onset AGA (60 men and 60 women) and 120 control subjects (60 men and 60 women) with skin diseases other than alopecia.Of patients with AGA, 39.1% presented with hyperglycemia (110 mg/dL) versus 12.5% of controls (P0.0001). AGA patients with hyperglycemia or diabetes presented lower significant levels of SHBG than alopecic patients without hyperglycemia or type 2 diabetes, respectively. Patients with AGA and hyperglycemia presented significantly lower levels of SHBG than controls with hyperglycemia (22.3 vs 39.4 nmol/L for AGA patients and controls, respectively, P = .004). No significant differences in SHBG levels were noticed between patients and controls without hyperglycemia. Binary logistic regression showed a strong association between lower SHBG levels and glucose levels greater than 110 mg/dL in patients with AGA even after additional adjustment for sex, abdominal obesity, and free testosterone (odds ratio = 3.35; 95% confidence interval = 1.9-5.7; P.001).The study of a wider sample of AGA patients would confirm these findings and would permit analysis of the pathogenic mechanisms underlying the increase in cardiovascular risk in patients with AGA.An association between early-onset AGA, hyperglycemia/diabetes, and low levels of SHBG was observed in the current study. Low levels of SHBG could be a marker of insulin resistance and hyperglycemia/diabetes in patients with AGA.

Highly diverse HIV-1 genetic forms are circulating in Cuba, including subtypes B and G and two recombinant forms of African origin (CRF18_cpx and CRF19_cpx). Here we phylogenetically analyze pol sequences from a large collection of recent samples from Cuba, corresponding to 425 individuals from all Cuban provinces, which represents approximately 12% of prevalent infections in the country. RNA from plasma was used to amplify a pol segment by reverse transcription-polymerase chain reaction; phylogenetic analyses were performed with neighbour-joining trees and bootscanning. The distribution of genetic forms was subtype B, 41.2%; CRF19_cpx, 18.4%; BG recombinants, 11.6%; CRF18_cpx, 7.1%; subtype C, 6.1%; subtype G, 3.8%; B/CRF18 recombinants, 2.6%; subtype H, 2.1%; B/CRF19 recombinants, 1.7%; and others, 5.4%. Seventy-five (17.6%) viruses were recombinant between genetic forms circulating in Cuba. In logistic regression analyses, adjusting by gender and region, subtype B was more prevalent (OR 5.0, 95% CI 2.0-12.3) and subtype G less prevalent (OR 0.1, 95% CI 0.0-0.5) among men who have sex with men (MSM) than among heterosexuals. Within the main genetic forms of Cuba there were phylogenetic subclusters, several of which correlated with risk exposure or region. BG recombinants formed three phylogenetically related subclusters, corresponding to three different mosaic structures; most of these recombinants were from MSM from Havana City, among whom they have expanded recently, reaching 31% HIV-1 infections diagnosed in 2003. This study confirms the high HIV-1 diversity and frequent recombination in Cuba and reveals the recent expansion of diverse related BG recombinant forms in this country.

Circulating recombinant forms (CRFs) represent a substantial proportion of HIV-1 isolates in the global pandemic. Characterization of HIV-1 genetic forms, including CRFs, may be relevant to studies on molecular epidemiology, recombination, superinfection, vaccine development, and antiretroviral therapy. This study analyzes near complete genomes of 4 epidemiologically unlinked viruses from Cuba, originally characterized as D/A intersubtype recombinants in pol and env segments. The genomes of 3 viruses exhibited virtually coincident mosaic structures, with multiple segments of subtypes A, D, and G and uniform phylogenetic clustering with each other along the genome. These results allow us to define a new CRF (CRF19_cpx). The 4th analyzed Cuban virus was recombinant between CRF19_cpx and CRF18_cpx (which also circulates in Cuba). CRF19_cpx exhibited homology to an AG intersubtype recombinant virus from Cameroon (CM53392) along approximately 5 kb and clustered with a subtype D virus from Gabon (G109) in gag. Four other viruses from central or west Africa were also phylogenetically related to CRF19_cpx in env fragments. These results allow us to define CRF19_cpx as a second novel CRF of African origin circulating in Cuba, to identify putative representative viruses of its parental strains, and to characterize a unique CRF18/CRF19 recombinant virus.

There are few data on drug resistance-associated mutations in the former Soviet Union since, studies have usually been focused on the env or gag genes for subtype information. This study examines the prevalence and patterns of resistance-associated mutations to reverse transcriptase and protease inhibitors (RTI, PRI) in 278 HIV-1-infected treatment-naive subjects from countries of Eastern Europe, and defines characteristic polymorphisms of RT and PR sequences in HIV-1 subtype A viruses. Blood samples were collected between 1997 and 2004. Plasma RNA was used for PR-RT amplification by reverse transcription coupled with nested PCR and sequencing. Phylogenetic analysis was done with neighbor-joining trees and bootscanning. Analysis of drug resistance mutations, with Stanford University HIV Drug Resistance Database's algorithm, resulted in an overall prevalence of 12.9% resistance to RTI and 3.9% to PRI. The most frequent substitutions in the RT region were at positions 62 and 236. V77I substitution in PR was found in 47.8% of samples. Polymorphisms in subtype A sequences were identified. This is the first study reporting the prevalence and patterns of both PRI and RTI resistance-associated mutations in naive HIV-1 infected patients from the former Soviet Union. These data underline the importance of genotypic resistance testing of chronically HIV-1-infected patients before initiating treatment, in order to select the most suitable drug regimen. J. Med. Virol. 77:337–344, 2005. © 2005 Wiley-Liss, Inc.

Background: Analysis of partial pol and env sequences have indicated a high diversity of HIV-1 genetic forms in Cuba, including two potential novel circulating recombinant forms (CRF): U pol /H env and D pol /A env . Objectives: To determine whether U pol /H env recombinant viruses from Cuba, detected in 7% of samples, represent a novel HIV-1 CRF, and to identify non-Cuban viruses related to this recombinant form. Methods: Near full-length genome amplification was carried out by nested polymerase chain reaction in four overlapping DNA segments of two epidemiologically unlinked viruses in uncultured peripheral blood mononuclear cells. The sequences were analysed phylogenetically. Recombinant structures and phylogenetic relationships were analysed by bootscanning and by maximum likelihood. Searches for related viruses in databases were initially based on sequence homology and sharing of signature nucleotides. Results: Both Cuban viruses clustered uniformly in bootscans all along the genome with each other and with a virus from Cameroon, CM53379, indicating that all three represent the same recombinant form. Their genome comprised multiple segments clustering with subtypes A1, F, G, H and K, as well as segments failing to cluster with recognized subtypes. The newly defined CRF, designated CRF18―cpx, was phylogenetically related in partial segments to CRF13―cpx, CRF04―cpx and 36 additional viruses, most of them from Central Africa. One of the viruses from Cameroon, sequenced in the near full-length genome, was a CRF18―cpx/subtype G secondary recombinant. Conclusions: A novel HIV-1 complex circulating recombinant form (CRF18―cpx) has been identified that is circulating in Cuba and Central Africa.