Increasing heterosexual transmission of HIV‐1 subtype C in Inland Central Western Brazil

The molecular epidemiology of HIV‐1 in Brazil is complex and heterogeneous because several subtypes co‐circulate with some important regional differences. This study evaluated HIV‐1 subtypes amongst pregnant women living in the metropolitan area and in the interior cities from central western Brazil. From June 2008 to June 2010, 86.9% of confirmed cases of HIV‐1 infection amongst pregnant women (172 out of 198 cases) were recruited in Goiania/Goias state. The HIV‐1 pol gene was sequenced after nested‐PCR. HIV‐1 subtypes were assigned by REGA, phylogenetic, and bootscan analyses. The median age of participants was 26 years (15–41 years range); 58.7% of participants were diagnosed during prenatal care and 51.7% of participants came from >50 interior cities within Goias state. Amongst the 131 HIV‐1 pol sequences, 64.9% were subtype B, 13.0% were BF1 recombinant, 11.4% were subtype C, 7.6% were subtype F1, and 2.3% were BC recombinant. According to the HIV‐1 diagnosis date (1994–2010), a significant increase in subtype C and a decrease of BF1 mosaics were observed over time. All subtype C patients lived in interior cities where the highest prevalence of subtype C outside southern Brazil was observed (18.4%). Phylogenetic analysis revealed multiple independent introductions of the Brazilian subtype C clade from the southern/southeastern regions of Brazil. The HIV‐1 epidemic in women from central western Brazil infected by the heterosexual route is characterized by an unexpectedly high prevalence of subtype C viruses highly related to those circulating in southern/southeastern Brazil. These findings highlight the importance of molecular surveillance programs outside large metropolitan regions in Brazil. J. Med. Virol. 85:396–404, 2013. © 2012 Wiley Periodicals, Inc.     

The nonsense mutation stop+4 model correlates with motor changes in Duchenne muscular dystrophy

The aim was to assess 3-year longitudinal data using 6MWT in 26 ambulant boys affected by DMD carrying nonsense mutations and to compare their results to other small mutations. We also wished to establish, within the nonsense mutations group, patterns of change according to several variables. Patients with nonsense mutations were categorized according to the stop codon type newly created by the mutation and also including the adjacent 5′ (upstream) and 3′ (downstream) nucleotides. No significant difference was found between nonsense mutations and other small mutations (p > 0.05) on the 6MWT. Within the nonsense mutations group, there was no difference in 6MWT when the patients were subdivided according to: Type of stop codon, frame status of exons involved, protein domain affected. In contrast, there was a difference when the stop codon together with the 3′ adjacent nucleotide (“stop+4 model”) was considered (p < 0.05) with patients with stop codon TGA and 3′ adjacent nucleotide G (TGAG) having a more rapid decline. Our finding suggest that the stop+4 model may help in predicting functional changes. This data will be useful at the time of interpreting the long term follow up of patients treated with Ataluren that are becoming increasingly available.     

The effects of Sarconesiopsis magellanica larvae (Diptera: Calliphoridae) excretions and secretions on fibroblasts

Sarconesiopsis magellanica is a necrophagous blowfly which is relevant in both forensic and medical sciences. Previous studies regarding this species have led to understanding life-cycle, population and reproduction parameters, as well as identifying and characterising proteolytic enzymes derived from larval excretions and secretions (ES). As other studies have shown that ES proteolytic activity plays a significant role in wound healing and fibroblasts play a relevant role in granulation tissue formation during such healing, the present study was aimed at analysing the biological effect of S. magellanica larval ES on fibroblasts. ES were obtained from third-instar larvae and added to fibroblast cells at three concentrations (10, 5 and 1 μg/mL) to evaluate their behaviour. MTT assays were used for analysing cell proliferation and viability, whilst cell adhesion was measured by optical density with 10% SDS. Fibroblast migration and morphology was recorded by microscopic observation. ES did not affect fibroblast viability and induced an increase in cell proliferation; cell adhesion became reduced, whilst cell migration through extracellular matrix increased. ES also induced a decreased cell surface and morphological alterations. Changes in all the above-mentioned parameters were reduced when ES were incubated at 60 °C, probably due to protease denaturation. These results suggested that the proteases contained in S. magellanica larval ES contributed towards granulation tissue formation, increased cell migration and promoted cell proliferation. All these data support carrying out further experiments aimed at validating S. magellanica usefulness in larval therapy.     

Hepatitis C cure improved patient‐reported outcomes in patients with and without liver fibrosis in a prospective study at a large urban medical center

Patient‐reported outcomes (PROs) are important measures of quality of life. Direct‐acting antiviral (DAA) drugs for hepatitis C virus (HCV) improved PROs in clinical trials. We prospectively evaluated the impact of DAA‐based HCV cure on PROs and liver‐related outcomes in real‐world patients at a large urban medical center. The short form (SF)‐36 and three additional validated instruments were used. F3‐4 fibrosis was defined as > 9.6 kPa by transient elastography (TE); S2‐3 steatosis was defined as > 270 dB/m by TE‐controlled attenuation parameter (CAP). Data were analysed by paired and unpaired t tests. Patients (n = 16) who did not achieve a sustained virologic response at 12 weeks (SVR12) were excluded. The study achieved its primary endpoint and showed a significant 30% improvement in the SF‐36 vitality score, measured baseline to SVR12: 63 versus 82, P < .001 (n = 111). Scores in 24 of 25 PRO domains improved at SVR12 (P < .05). Nearly all gains exceeded 5%, indicating their clinical significance. Transaminase values and liver stiffness improved (decreased) significantly, baseline to SVR12 (P < .005), but steatosis was unchanged (P = .58). Patients with baseline F0‐2 fibrosis and those with F3‐F4 fibrosis both improved in 22 domains. Patients with baseline S0‐S1 steatosis improved in more domains (23) than patients with S2‐S3 steatosis (19). At baseline, patients with F3‐F4 fibrosis and patients with S2‐3 steatosis had worse scores in certain PRO domains than patients with F0‐2 fibrosis or S0‐S1 steatosis, but this difference resolved by SVR12. HCV cure led to meaningful gains in PROs, and these findings may encourage patients to seek treatment.     

Defluoridation efficiency of a green composite reactive material derived from lateritic soil and gastropod shell

In the bid to exploit the synergy in mixed metal matrix that enhances substrate binding affinity, a composite reactive material (GLT) was prepared using lateritic soil and Gastropod shell as precursors. The defluoridation efficiency of the GLT was studied in laboratory grade fluoride contaminated water and groundwater matrix. Using experimental evidences, insight into the underlying defluoridation mechanisms of GLT was provided. The monolayer adsorption capacity (q_m, mg/g) of the GLT (43.7 mg/g) was higher than that of any of the precursors (i.e. lateritic soil (q_{m =} 2.8 mg/g) and Gastropod shell (q_m = 19.8 mg/g)), which confirmed the synergistic effect of the constituents of the composite. Premised on the results of kinetic analysis, the Gibbs (?G) free energy value of formation of insoluble metal fluoride and the results of the evaluation of the effects of water chemistry on the fluoride removal efficiency of the GLT, mechanism of the defluoridation process was found to be a combination of adsorption (via ion exchange or outer sphere complexation) and precipitation reaction. Relative to the performance of the GLT in laboratory grade water, the GLT was also effective in groundwater but the value of the Langmuir monolayer adsorption capacity (q_m mg/g) was lower in the groundwater system (29.76 mg/g) than in the laboratory grade water system (43.7 mg/g). The leached constituents of the GLT enhanced the values of the pH, electrical conductivity and the total dissolved solids of the treated water.     

Characteristics of Homeless Adults with Serious Mental Illness Served by a State Mental Health Transitional Shelter

Specialized transitional shelters are available in various cities to provide assistance to homeless individuals with serious mental illness. Little is known about the population using such shelters. The authors conducted a retrospective chart review to collect demographic, social, and clinical data of residents in a state-operated mental health transitional shelter in Massachusetts. A total of 74 subjects were included. Schizophrenia-spectrum disorders were present in 67.6 % of the sample and mood disorders in 35.1 %. Substance use disorders were documented in 44.6 %. Chronic medical illness (mostly hypertension, dyslipidemia, asthma, and diabetes) was found in 82.4 %. The co-occurrence of a psychiatric and substance use disorder and chronic medical illness was found in 36.5 %. The majority (75.7 %) of patients had a history of legal charges. Homeless individuals with serious mental illness served by specialized transitional shelters represent a population with complex psychiatric, medical and social needs.     

Evaluation of systemic microvascular endothelial function using laser speckle contrast imaging

ObjectiveThe aim of this study was to compare cutaneous microvascular function in young healthy subjects (n = 50) with that of cardiometabolic diseased patients (n = 50) using laser speckle contrast imaging (LSCI) coupled with transdermal iontophoretic delivery of acetylcholine (ACh) and post-occlusive reactive hyperemia (PORH).MethodsCutaneous blood flow was assessed in the forearm using LSCI at rest, during PORH and during iontophoresis of ACh with increasing anodal currents of 30, 60, 90, 120, 150 and 180 μA during 10-second intervals spaced 1 min apart.ResultsEndothelium-dependent skin microvascular vasodilator responses induced by both ACh and PORH were significantly reduced in cardiometabolic diseased patients compared to healthy subjects. Vasodilator responses induced by ACh were significantly higher in young women than in young men. Iontophoresis charges up to 1.5 mC do not induce nonspecific effects on skin microvascular flux.ConclusionLSCI appears to be a promising noninvasive technique for evaluating systemic microvascular endothelial function.