The high comorbidity burden of the hepatitis C virus infected population in the United States

<p>Abstract</p> <p>Background</p> <p>Chronic hepatitis C (HCV) disease can be complicated with comorbid conditions that may impact treatment eligibility and outcomes. The aim of the study was to systematically review comorbidities and symptoms in an HCV infected population, specifically assessing comorbidities associated with HCV anti-viral treatment and disease, as well as comparing comorbidities between an HCV infected and uninfected control population.</p> <p>Methods</p> <p>This was a retrospective cohort study within a United States medical claims database among patients with chronic HCV designed to estimate the two-year period prevalence of comorbidities. Patients with two HCV diagnosis codes, 24 months of continuous health insurance coverage, and full medical and pharmacy benefits were included.</p> <p>Results</p> <p>Among a chronic HCV cohort of 7411 patients, at least one comorbid condition was seen in almost all patients (> 99%) during the study period. HCV-infected patients reported almost double the number of comorbidities compared to uninfected controls. Of the 25 most common comorbidities, the majority of the comorbidities (n = 22) were known to be associated with either HCV antiviral treatment or disease. The five most frequent comorbidities were liver disease [other] (37.5%), connective tissue disease (37.5%), abdominal pain (36.1%), upper respiratory infections (35.6%), and lower respiratory disease (33.7%). Three notable comorbidities not known to be associated with antiviral treatment or disease were benign neoplasms (24.3%), genitourinary symptoms & ill-defined conditions (14.8%), and viral infections (13.8%).</p> <p>Conclusions</p> <p>This US medically insured HCV population is highly comorbid. Effective strategies to manage these comorbidities are necessary to allow wider access to HCV treatment and reduce the future burden of HCV disease and its manifestations.</p

The Transmembrane Isoform of Plasmodium falciparum MAEBL Is Essential for the Invasion of Anopheles Salivary Glands

Malaria transmission depends on infective stages in the mosquito salivary glands. Plasmodium sporozoites that mature in midgut oocysts must traverse the hemocoel and invade the mosquito salivary glands in a process thought to be mediated by parasite ligands. MAEBL, a homologue of the transmembrane EBP ligands essential in merozoite invasion, is expressed abundantly in midgut sporozoites. Alternative splicing generates different MAEBL isoforms and so it is unclear what form is functionally essential. To identify the MAEBL isoform required for P. falciparum (NF54) sporozoite invasion of salivary glands, we created knockout and allelic replacements each carrying CDS of a single MAEBL isoform. Only the transmembrane form of MAEBL is essential and is the first P. falciparum ligand validated as essential for invasion of Anopheles salivary glands. MAEBL is the first P. falciparum ligand experimentally determined to be essential for this important step in the life cycle where the vector becomes infectious for transmitting sporozoites to people. With an increasing emphasis on advancing vector-based transgenic methods for suppression of malaria, it is important that this type of study, using modern molecular genetic tools, is done with the agent of the human disease. Understanding what P. falciparum sporozoite ligands are critical for mosquito transmission will help validate targets for vector-based transmission-blocking strategies

Leishmania major Survival in Selective Phlebotomus papatasi Sand Fly Vector Requires a Specific SCG-Encoded Lipophosphoglycan Galactosylation Pattern

Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. In “selective” sand flies, Leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (LPG), which exhibits species- and strain-specific modifications of the dominant phosphoglycan (PG) repeat units. For the “selective” fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications (scGal) of PG repeats play key roles in parasite binding. We probed the specificity and properties of this scGal-LPG PAMP (Pathogen Associated Molecular Pattern) through studies of natural isolates exhibiting a wide range of galactosylation patterns, and of a panel of isogenic L. major engineered to express similar scGal-LPG diversity by transfection of SCG-encoded β1,3-galactosyltransferases with different activities. Surprisingly, both ‘poly-scGal’ and ‘null-scGal’ lines survived poorly relative to PpapJ-sympatric L. major FV1 and other ‘mono-scGal’ lines. However, survival of all lines was equivalent in P. duboscqi, which naturally transmit L. major strains bearing ‘null-scGal’-LPG PAMPs. We then asked whether scGal-LPG-mediated interactions were sufficient for PpapJ midgut survival by engineering Leishmania donovani, which normally express unsubstituted LPG, to express a ‘PpapJ-optimal’ scGal-LPG PAMP. Unexpectedly, these “L. major FV1-cloaked” L. donovani-SCG lines remained unable to survive within PpapJ flies. These studies establish that midgut survival of L. major in PpapJ flies is exquisitely sensitive to the scGal-LPG PAMP, requiring a specific ‘mono-scGal’ pattern. However, failure of ‘mono-scGal’ L. donovani-SCG lines to survive in selective PpapJ flies suggests a requirement for an additional, as yet unidentified L. major-specific parasite factor(s). The interplay of the LPG PAMP and additional factor(s) with sand fly midgut receptors may determine whether a given sand fly host is “selective” or “permissive”, with important consequences to both disease transmission and the natural co-evolution of sand flies and Leishmania

Homemade oral supplement: a proposal for the nutritional recovery of children and adolescents with cancer

Objective The aim of this study was to evaluate the impact of homemade oral supplements on the nutritional recovery of patients with mild or severe malnutrition or at nutritional risk. Methods Eight recipes of homemade oral supplements containing 30% to 35% of the total energy expenditure were proposed. The patients with severe malnutrition (group B) received the oral supplement for 2 weeks and the others for 4 weeks (group A). Oral supplementation with homemade supplements was compared with oral supplementation with store-bought supplements, investigated earlier with a protocol with the same design. Results Homemade oral supplements contain much lower amounts of certain micronutrients but are five times cheaper than store-bought supplements. In group A, 88% of the patients taking homemade oral supplements and 84% of the patients taking store-bought supplements responded positively to supplementation. In group B, 22% of the patients taking homemade oral supplements and 25% of the patients taking store-bought supplements recovered. The difference was not significant. The impact of store-bought supplementation on the triceps skinfold thicknesses and arm circumferences of the patients in group A was greater than that obtained with homemade supplements. In group B, the effect on triceps skinfold thickness was not significant (p=0.16). Patients taking homemade or store-bought oral supplements presented similar protein and energy intakes and improvements in nutritional status. Only the body composition of patients in group A taking store-bought oral supplements was better. Conclusion The results obtained by this study suggest that the therapeutic use of homemade oral supplements is an alternative capable of promoting the nutritional recovery of cancer patients, especially those who cannot afford store-bought supplements.Objetivo Avaliar o impacto do suplemento oral artesanal na recuperação do estado nutricional de pacientes com desnutrição leve, grave e com risco nutricional. Métodos Propuseram-se oito receitas de suplementos visando ofertar entre 30,0% e 35,0% do gasto energético total. Os pacientes com desnutrição grave (grupo B) receberam o suplemento oral por duas semanas, e os demais pacientes (grupo A), por quatro semanas. Para a comparação dos resultados obtidos com o emprego do suplemento oral artesanal, foram utilizados dados referentes a um protocolo anterior, com o mesmo desenho, entretanto, com a utilização de suplemento oral industrializado. Resultados O suplemento oral artesanal fica muito aquém no que diz respeito a alguns micronutrientes, entretanto é cinco vezes mais barato do que a preparação com o suplemento oral industrializado. Os pacientes do grupo A com suplemento oral artesanal apresentaram 88,0% de resposta positiva na semana de avaliação, enquanto os com suplemento oral industrializado tiveram 84,0%. No grupo B, foram recuperados 22,0% dos pacientes com suplemento oral artesanal e 25,0% do grupo com suplemento oral industrializado, não apresentando, portanto, diferença significante. Comparando o impacto do industrializado com o do artesanal na prega cutânea tricipital e circunferência do braço, verificou-se que o suplemento oral industrializado no grupo A apresentou melhores resultados que o suplemento oral artesanal, e no grupo B, esse efeito observado na prega cutânea não foi significante (p=0,16). Os consumos de energia e de proteína, assim como a evolução nutricional, foram semelhantes entre suplemento oral industrializado e suplemento oral artesanal. Apenas a composição corpórea no grupo A com suplemento oral industrializado apresentou melhores resultados. Conclusão Os resultados apresentados neste estudo sugerem que o emprego da terapia com suplemento artesanal seja uma opção capaz de auxiliar na recuperação nutricional de pacientes oncológicos e uma opção para populações financeiramente desfavorecidas.Hospital Samaritano de São PauloInstituto Adriana GarófoloUniversidade Federal de São Paulo (UNIFESP) Departamento de Pediatria Instituto de Oncologia PediátricaUniversidade Federal de São Paulo (UNIFESP) Departamento de PediatriaUNIFESP, Depto. de Pediatria Instituto de Oncologia PediátricaUNIFESP, Depto. de PediatriaSciEL

Association between perineal trauma and pain in primiparous women

Objective To identify the association between perineal trauma and pain in 473 primiparous women. Method Cross-sectional study in which pain was measured by the numerical pain scale (0 to 10 - 0 being no pain and 10 maximal pain). Results The prevalence and mean intensity of pain were 33.0% and 4.7 points (standard deviation = 2.0) in the numeric scale, respectively. Episiotomy represented the most frequent trauma (46.7%). The occurrence and intensity of the pain were associated with perineal trauma and postpartum time. Having perineal trauma tripled the chance of pain. Each hour elapsed following the birth reduced the chance of pain by 4.8%. Conclusion Primiparous women are subject to a high frequency of perineal trauma, with episiotomy being the most prominent. Perineal pain affects approximately one-third of primiparous women and is associated with the postpartum time and perineal traumas

Muscle-Specific Adaptations, Impaired Oxidative Capacity and Maintenance of Contractile Function Characterize Diet-Induced Obese Mouse Skeletal Muscle

BACKGROUND:The effects of diet-induced obesity on skeletal muscle function are largely unknown, particularly as it relates to changes in oxidative metabolism and morphology. PRINCIPAL FINDINGS:Compared to control fed mice, mice fed a high fat diet (HFD; 60% kcal: fat) for 8 weeks displayed increased body mass and insulin resistance without overt fasting hyperglycemia (i.e. pre-diabetic). Histological analysis revealed a greater oxidative potential in the HFD gastrocnemius/plantaris (increased IIA, reduced IIB fiber-type percentages) and soleus (increased I, IIA cross-sectional areas) muscles, but no change in fiber type percentages in tibialis anterior muscles compared to controls. Intramyocellular lipid levels were significantly increased relative to control in HFD gastrocnemius/plantaris, but were similar to control values in the HFD soleus. Using a novel, single muscle fiber approach, impairments in complete palmitate and glucose oxidation (72.8+/-6.6% and 61.8+/-9.1% of control, respectively; p<0.05) with HFD were detected. These reductions were consistent with measures made using intact extensor digitorum longus and soleus muscles. Compared to controls, no difference in succinate dehydrogenase or citrate synthase enzyme activities were observed between groups in any muscle studied, however, short-chain fatty acyl CoA dehydrogenase (SCHAD) activity was elevated in the HFD soleus, but not tibialis anterior muscles. Despite these morphological and metabolic alterations, no significant difference in peak tetanic force or low-frequency fatigue rates were observed between groups. CONCLUSIONS:These findings indicate that HFD induces early adaptive responses that occur in a muscle-specific pattern, but are insufficient to prevent impairments in oxidative metabolism with continued high-fat feeding. Moreover, the morphological and metabolic changes which occur with 8 weeks of HFD do not significantly impact muscle contractile properties