Sex work, drug use, HIV infection, and spread of sexually transmitted infections in Moscow, Russian Federation

Rates of HIV-1 infection are growing rapidly, and the epidemic of sexually transmitted infections is continuing at an alarming rate, in the Russian Federation. We did a cross-sectional study of sexually transmitted infections, HIV infection, and drug use in street youth at a juvenile detention facility, adults at homeless detention centres, and women and men at a remand centre in Moscow. 160 (79%) women at the remand centre were sex workers. 91 (51%) homeless women had syphilis. At least one bacterial sexually transmitted infection was present in 97 (58%) female juvenile detainees, 120 (64%) women at the remand centre, and 133 (75%) homeless women. HIV seroprevalence was high in women at the remand centre (n=7 [4%]), adolescent male detainees (5 [3%]), and homeless women (4 [2%]). In view of the interaction between sexually transmitted infections and HIV infection, these findings of high prevalence of sexually transmitted infections show that these disenfranchised populations have the potential to make a disproportionately high contribution to the explosive growth of the HIV epidemic unless interventions targeting these groups are implemented in the Russian Federation.     

Fear Assessment in Inflammatory Rheumatic diseases (FAIR) questionnaire: a cross-cultural adaptation and validation to the Turkish language

In chronic inflammatory rheumatic diseases (CIRD), it is important to understand patients’ fears towards their disease in order to improve patient-physician dialog, to raise the quality of care offered, and to optimize treatment adherence. In this study, we aimed to translate the Fear Assessment in Inflammatory Rheumatic diseases (FAIR) questionnaire into Turkish and evaluate its psychometric properties in patients with CIRD. One hundred fifteen patients filled the provided socio-demographic information form, FAIR-Tr questionnaire, Hospital Anxiety and Depression Scale (HADS), and Beck’s Hopelessness Scale (BHS). For the analysis of short-term reliability, 50 patients re-filled the FAIR-Tr questionnaire 1 week later. Internal consistency was evaluated with Cronbach’s α coefficient and test-retest reliability was evaluated with intraclass correlation coefficients (ICC). Construct validity analysis was investigated based on the correlation with HADS and BHS. All patients found FAIR-Tr easily understandable and acceptable. FAIR-Tr internal consistency (Cronbach’s α?=?0.93) and test-retest reliability (ICC?=?0.91) were excellent. Psychometric validation was proved upon observing high correlation with HADS (Anxiety, r?=?0.77; Depression, r?=?0.70) and moderate correlation with BHS (r?=?0.65). FAIR-Tr is a questionnaire that has excellent internal consistency and test-retest reliability. The successful correlation with HADS and BHS supported its psychometric validity in terms of evaluating the fear in CIRD cases. We think that FAIR-Tr is a specific scale that can help to evaluate the disease- and treatment-related fears of the Turkish patients with CIRD and may be useful in both routine practice and clinical studies.     

Anatomical accuracy of brain connections derived from diffusion MRI tractography is inherently limited

Tractography based on diffusion-weighted MRI (DWI) is widely used for mapping the structural connections of the human brain. Its accuracy is known to be limited by technical factors affecting in vivo data acquisition, such as noise, artifacts, and data undersampling resulting from scan time constraints. It generally is assumed that improvements in data quality and implementation of sophisticated tractography methods will lead to increasingly accurate maps of human anatomical connections. However, assessing the anatomical accuracy of DWI tractography is difficult because of the lack of independent knowledge of the true anatomical connections in humans. Here we investigate the future prospects of DWI-based connectional imaging by applying advanced tractography methods to an ex vivo DWI dataset of the macaque brain. The results of different tractography methods were compared with maps of known axonal projections from previous tracer studies in the macaque. Despite the exceptional quality of the DWI data, none of the methods demonstrated high anatomical accuracy. The methods that showed the highest sensitivity showed the lowest specificity, and vice versa. Additionally, anatomical accuracy was highly dependent upon parameters of the tractography algorithm, with different optimal values for mapping different pathways. These results suggest that there is an inherent limitation in determining long-range anatomical projections based on voxel-averaged estimates of local fiber orientation obtained from DWI data that is unlikely to be overcome by improvements in data acquisition and analysis alone.The creation of a comprehensive map of the connectional neuroanatomy of the human brain would be a fundamental achievement in neuroscience. However, despite the numerous efforts to date (for a historical review, see ref. 1), creating this map remains a challenge. A major limitation is that the current gold-standard technique for mapping structural connections, which requires the injection of axonal tracers, cannot be used in humans. The introduction of diffusion-weighted MRI (DWI) (2–4) and the subsequent advent of diffusion tensor MRI (DTI) (5) opened the possibility of exploring the structural properties of white matter in the living human brain (6). Local DWI measures are used clinically for the early detection of stroke and for the characterization of neurological disorders such as multiple sclerosis, epilepsy, and brain gliomas, among others (7). In addition, tractography approaches (8–12) that can infer structural brain connectivity based on brain-wide local DWI measurement have been developed (for reviews, see refs. 13 and 14). The success of DWI tractography as a method for studying fiber trajectories has led to a systematic characterization of large white-matter pathways of the living human brain (e.g., ref. 15), and now it is used routinely to provide a structural explanation for aspects of human brain function (16).A major limitation of DWI tractography is that its characterization of axonal pathways is based on indirect information and numerous assumptions. Local white matter orientation profiles are based on the statistical displacement profile (i.e., diffusion propagator) of water molecules in brain tissue on the coarse scale of a voxel, and fiber trajectories are inferred based on the adjacency of similar diffusion profiles. This approach differs fundamentally from conventional tract-tracing approaches in animals, which involve the physical transport of traceable molecules through the cells’ axoplasm over a large distance. Because these molecules occupy positions within the axon, it sometimes is possible to reconstruct the trajectory of individual neurons through the white matter (e.g., ref. 17). Given the inherent coarseness of DWI tractography, it can be argued that the prospect of using this method to reconstruct complex axonal pathways accurately in the human brain, in a manner similar to that used for molecular tracers in animals, is likely to be intrinsically problematic. Indeed, the limitations of DWI tractography techniques have been noted since their inception (8), and the anatomical accuracy of results from tractography based on the tensor model has been shown to be mixed (18). This inaccuracy has been attributed to two main factors. The first relates to the assumptions underlying tractography algorithms. For example, it has long been recognized that a simple tensor model (19) of local diffusion leads to problems in certain white matter regions where fibers cross within individual voxels. As a remedy, high angular resolution diffusion imaging (HARDI) methods (e.g., refs. 20–24) have been developed to enable better characterization of the diffusion displacement profile and to improve the accuracy of tractography. The second factor limiting accuracy stems from the low quality of clinical DWI data because of various sources of noise. Eddy current distortions, subject motion, physiological noise (see ref. 25 for a review), and susceptibility artifacts from echo planar imaging (EPI) (26) all lead to poor local characterization of diffusion and, consequently, to incorrect tractography results. Continuing advances in sequence design, MRI gradient hardware, and postprocessing correction schemes have overcome many of the initial problems (27) and have led to the belief that further acquisition improvements will result in more precise mapping of structural connections in the human brain (28). In fact, the assumption underlying many recent initiatives to map structural brain connectivity from DWI data is that improved image data quality and sophisticated diffusion modeling approaches will result in anatomically accurate maps of white matter connections (29). The goal of the present study is to investigate the validity of this assumption.To achieve this goal, we acquired high angular resolution DWI data from a normal adult rhesus macaque brain, ex vivo, at a spatial resolution of 250 microns (isotropic). This dataset is ideal for exploring the limits of DWI tractography because of its high signal-to-noise ratio (SNR) (for SNR computation, see SI Materials and Methods) and the almost complete absence of experimental confounds and artifacts such as those originating from patient motion, noise, cardiac pulsation, and EPI distortion that are typically encountered in in vivo studies. Using the axonal tracer results from a well-known atlas (17) as reference, we measured the sensitivity (i.e., the ability to detect true connections) and specificity (i.e., the ability to avoid false connections) of several DWI tractography implementations representative of the current state of the art. This approach allowed us to investigate whether sophisticated diffusion modeling techniques, when applied to DWI data of exceptional quality, would yield accurate maps of axonal connections.     

Mitochondrial serine protease HTRA2 p.G399S in a kindred with essential tremor and Parkinson disease

Essential tremor is one of the most frequent movement disorders of humans and can be associated with substantial disability. Some but not all persons with essential tremor develop signs of Parkinson disease, and the relationship between the conditions has not been clear. In a six-generation consanguineous Turkish kindred with both essential tremor and Parkinson disease, we carried out whole exome sequencing and pedigree analysis, identifying HTRA2 p.G399S as the allele likely responsible for both conditions. Essential tremor was present in persons either heterozygous or homozygous for this allele. Homozygosity was associated with earlier age at onset of tremor (P < 0.0001), more severe postural tremor (P < 0.0001), and more severe kinetic tremor (P = 0.0019). Homozygotes, but not heterozygotes, developed Parkinson signs in the middle age. Among population controls from the same Anatolian region as the family, frequency of HTRA2 p.G399S was 0.0027, slightly lower than other populations. HTRA2 encodes a mitochondrial serine protease. Loss of function of HtrA2 was previously shown to lead to parkinsonian features in motor neuron degeneration (mnd2) mice. HTRA2 p.G399S was previously shown to lead to mitochondrial dysfunction, altered mitochondrial morphology, and decreased protease activity, but epidemiologic studies of an association between HTRA2 and Parkinson disease yielded conflicting results. Our results suggest that in some families, HTRA2 p.G399S is responsible for hereditary essential tremor and that homozygotes for this allele develop Parkinson disease. This hypothesis has implications for understanding the pathogenesis of essential tremor and its relationship to Parkinson disease.Essential tremor is one of the most frequent movement disorders in humans (1). It is characterized primarily by postural or kinetic tremor of the arms and hands, but head, legs, voice, and other regions of the body may also be affected (2). The worldwide prevalence is 0.9%, increasing to more than 4% in elderly populations (1). Familial essential tremor is genetically heterogeneous. Genetic linkage studies of multiply affected families revealed three genomic regions segregating with the condition, on chromosomes 3q13 [ETM1; Online Mendelian Inheritance in Man (OMIM) 190300], 2p22-24 (ETM2; OMIM 602134), and 6p23 (ETM3; OMIM 611456) (3–5). No clearly causal mutations have been identified in these regions, although the common variant DRD3 p.S9G in the ETM1 region has been proposed as a risk factor and HS1BP3 p.A265G in the ETM2 region appeared in two multiply affected families (6, 7). Genomewide association studies of essential tremor reported associations with common variants in an intron of LINGO1 and in an intron of SLC1A2 (8–10). Recently, DNAJC13 p.N855S, which had been identified in Parkinson disease patients, was also found in two unrelated patients with essential tremor (11). Nonsense mutation p.Q290X in the RNA-binding protein FUS was identified by whole exome sequencing in a large family with essential tremor (ETM4; OMIM 614782) (12). Screening other subjects with essential tremor for FUS revealed two rare missense variants, suggesting that mutations in FUS explain a subset of cases with the condition (13, 14).In this study, we examined a six-generation family segregating essential tremor, and in multiple relatives, essential tremor as a feature of Parkinson disease. We carried out whole exome sequencing of genomic DNA from three severely affected family members and subsequent pedigree analysis to identify the genetic basis of essential tremor and Parkinson disease in the family.     

Evaluation of choroidal thickness and choroidal vascularity index during pregnancy

ObjectiveTo assess the choroidal structural characteristics in the first and third trimesters in pregnant women using enhanced depth imaging optical coherence tomography and binarization method.DesignProspective study.ParticipantsTwenty-five eyes of 25 pregnant women in the first trimester (group 1) and 25 eyes of 25 pregnant women in the third trimester (group 2) were examined. Healthy age-matched 25 participants were enrolled as a control group (group 3).MethodsThe choroidal thickness (CT) was measured at 3 points; subfoveal, 1500 μm nasal to the fovea, and 1500 μm temporal to the fovea. Total choroidal area, luminal area, stromal area, stroma/lumen ratio, and choroidal vascularity index (CVI) were measured by Image-J software.ResultsThe mean subfoveal and nasal CT were statistically significantly increased in group 1 compared with controls (p = 0.005 and p = 0.004, respectively). The mean temporal CT was statistically significantly increased in group 1 compared with groups 2 and 3 (group 1 vs group 2, p = 0.043; group 1 vs group 3, p = 0.011). The mean total choroidal area, stromal area, and luminal area were significantly increased in groups 1 and 2 compared with control group (p < 0.001, p < 0.001, p < 0.001, and p < 0.001, p = 0.002, p = 0.002, respectively). There were no statistically significant differences among groups in terms of mean stroma/lumen ratio and CVI (p = 0.148 and p = 0.312, respectively).ConclusionsThere was a significant increase in subfoveal, temporal, and nasal CT in the first trimester. Total choroidal, stromal, and luminal areas were significantly increased in the first and third trimesters.     

Secondary infertility due to use of low-dose finasteride

Herein, we present an unusual case of secondary infertility after prolonged use of low-dose finasteride for androgenetic alopecia in a 40-year-old man. We detected sperm DNA damage in the patient. Despite such a long-term use, we observed that impairment in semen parameters and sperm DNA fragmentation index regressed after the drug was discontinued. Consequently, pregnancy occurred and resulted in live birth.     

Physical Activity Benefits the Skeleton of Children Genetically Predisposed to Lower Bone Density in Adulthood

Both genetics and physical activity (PA) contribute to bone mineral density (BMD), but it is unknown if the benefits of physical activity on childhood bone accretion depend on genetic risk. We, therefore, aimed to determine if PA influenced the effect of bone fragility genetic variants on BMD in childhood. Our sample comprised US children of European ancestry enrolled in the Bone Mineral Density in Childhood Study (N = 918, aged 5 to 19 years, and 52.4% female). We used a questionnaire to estimate hours per day spent in total, high‐, and low‐impact PA. We calculated a BMD genetic score (% BMD lowering alleles) using adult genome‐wide association study (GWAS)‐implicated BMD variants. We used dual‐energy X‐ray absorptiometry to estimate femoral neck, total hip, and spine areal‐BMD and total body less head (TBLH) bone mineral content (BMC) Z‐scores. The BMD genetic score was negatively associated with each bone Z‐score (eg, TBLH‐BMC: estimate = –0.03, p = 1.3 × 10^?6). Total PA was positively associated with bone Z‐scores; these associations were driven by time spent in high‐impact PA (eg, TBLH‐BMC: estimate = 0.05, p = 4.0 × 10^?10) and were observed even for children with lower than average bone Z‐scores. We found no evidence of PA‐adult genetic score interactions (p interaction > 0.05) at any skeletal site, and there was no evidence of PA‐genetic score–Tanner stage interactions at any skeletal site (p interaction > 0.05). However, exploratory analyses at the individual variant level revealed that PA statistically interacted with rs2887571 (ERC1/WNT5B) to influence TBLH‐BMC in males (p interaction = 7.1 × 10^?5), where PA was associated with higher TBLH‐BMC Z‐score among the BMD‐lowering allele carriers (rs2887571 AA homozygotes: estimate = 0.08 [95% CI 0.06, 0.11], p = 2.7 × 10^?9). In conclusion, the beneficial effect of PA on bone, especially high‐impact PA, applies to the average child and those genetically predisposed to lower adult BMD (based on GWAS‐implicated BMD variants). Independent replication of our exploratory individual variant findings is warranted. © 2016 American Society for Bone and Mineral Research.     

Hospital Charges for Pediatric Heart Failure-Related Hospitalizations from 2000 to 2009

Scarce data exist regarding costs of pediatric heart failure-related hospitalizations (HFRH) or how costs have changed over time. Pediatric HFRH costs, due to advances in management, will have increased significantly over time. A retrospective analysis of Healthcare Cost and Utilization Project Kids’ Inpatient Database was performed on all pediatric HFRH. Inflation-adjusted charges are used as a proxy for cost. There were a total of 33,189 HFRH captured from 2000 to 2009. Median charges per HFRH rose from $35,079 in 2000 to $72,087 in 2009 (p < 0.0001). The greatest median charges were incurred in patients on extracorporeal membrane oxygenation ($442,134 vs $53,998) or ventricular assist devices ($462,647 vs $55,151). Comorbidities, including sepsis ($207,511 vs $48,995), renal failure ($180,624 vs $52,812), stroke ($198,260 vs $54,974) and respiratory failure ($146,200 vs $48,797), were associated with greater charges (p < 0.0001). Comorbidities and use of mechanical support increased over time. After adjusting for these factors, later year remained associated with greater median charges per HFRH (p < 0.0001). From 2000 to 2009, there has been an almost twofold increase in pediatric HFRH charges, after adjustment for inflation. Although comorbidities and use of mechanical support account for some of this increase, later year remained independently associated with greater charges. Further study is needed to understand potential factors driving these higher costs over time and to identify more cost-effective therapies in this population.     

Effect of octenidine dihydrochloride on viability of protoscoleces in hepatic and pulmonary hydatid diseases

BACKGROUND: Use of effective scolicidal agents during puncture, aspiration or injection of a scolicidal agent and reaspiration (PAIR) and surgery for hydatid cysts are essential to reduce the recurrence rate. In this in vitro study, we tried to determine the scolicidal property of a new agent, octenidine dihydrochloride, and of various agents in different concentrations and exposure times. MATERIAL AND METHODS: Echinococcus granulosus protoscoleces were obtained from six patients with liver (n=3) and lung (n=3) hydatid cysts. Various concentrations of octenidine dihydrochloride (0.1%, 0.01% and 0.001% diluted form), povidone iodine (10%, 1% and 0.1% diluted) and 20% saline were used in this study. Viability of protoscoleces was determined with dye-uptake (0.1% eosin) and flame cell activity. RESULTS: Octenidine dihydrochloride 0.1% had strong scolicidal effect in 15 min and octenidine dihydrochloride 0.01% in 30 min. Sixty percent of protoscoleces lost viability at 5 min with octenidine dihydrochloride 0.1%. Viability ratio decreased to 20% at 10 min, and all of them died at 15 min. Povidone iodine 10% and 1% had strong scolicidal effects after 15- and 30 min of exposure, respectively. Saline 20% killed all the protoscoleces in 30-min exposure. CONCLUSION: Because of the rapid and strong scolocidal effectiveness of octenidine dihydrochloride on protoscoleces, it may be used as a scolocidal agent during both perioperative and in the PAIR method.