Dome-Shaped Osteotomy for Revision of Failed Closing-Wedge High Tibial Osteotomy

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Ethnic inequality, multimorbidity and psychosis: can a syndemic framework resolve disputed evidence?

Syndemic theory is described as population-level clustering or co-occurrence of health conditions in the context of shared aetiologies that interact and can act synergistically. These influences appear to act within specific places of high disadvantage. We suggest ethnic inequality in experiences and outcomes of multimorbidity, including psychosis, may be explained through a syndemic framework. We discuss the evidence for each component of syndemic theory in relation to psychosis, using psychosis and diabetes as an exemplar. Following this, we discuss the practical and theoretical adaptations to syndemic theory in order to apply it to psychosis, ethnic inequality and multimorbidity, with implications for research, policy, and practice

Understanding psychosis complexity through a syndemic framework: A systematic review.

Psychotic conditions pose significant challenges due to their complex aetiology and impact on individuals and communities. Syndemic theory offers a promising framework to understand the interconnectedness of various health and social problems in the context of psychosis. This systematic review aims to examine existing literature on testing whether psychosis is better understood as a component of a syndemic. We conducted a systematic search of 7 databases, resulting in the inclusion of five original articles. Findings from these studies indicate a syndemic characterized by the coexistence of various health and social conditions, are associated with a greater risk of psychosis, adverse health outcomes, and disparities, especially among ethnic minorities and deprived populations. This review underscores the compelling need for a new paradigm and datasets that can investigate how psychosis emerges in the context of a syndemic, ultimately guiding more effective preventive and care interventions as well as policies to improve the health of marginalised communities living in precarity

Obesity-induced hypoadiponectinaemia: the opposite influences of central and peripheral fat compartments

$\textbf{Background and Aims:}$ The substantial reduction in adiponectin concentration among obese individuals seems to depend on fat distribution and is a marker of metabolic and adipose tissue dysfunction. We aimed to: (i) address whether abdominal fat from different compartments (visceral, deep subcutaneous abdominal and superficial subcutaneous abdominal) and gluteofemoral fat are independently associated with blood adiponectin concentration; and (ii) investigate whether abdominal (proxied by waist circumference) and gluteofemoral fat (proxied by hip circumference) accumulation causally determine blood adiponectin concentration. $\textbf{Methods:}$ To investigate the independent association of abdominal and gluteofemoral fat with adiponectin concentration, we used multivariable regression and data from 30-year-old adults from the 1982 Pelotas Birth Cohort ($n$ = 2,743). To assess the causal role of abdominal and gluteofemoral fat accumulation on adiponectin concentration, we used Mendelian randomization and data from two consortia of genome-wide association studies—the GIANT ($n$ > 210 000) and ADIPOGen consortia ($n$ = 29 347). $\textbf{Results:}$ In the multivariable regression analysis, all abdominal fat depots were negatively associated with adiponectin concentration, specially visceral abdominal fat [men: $\beta$ = -0.24 standard unit of log adiponectin per standard unit increase in abdominal fat; 95% confidence interval (CI) = -0.31, -0.18; $P$ = 8*10$^{-13}$; women: $\beta$ = -0.31; 95% CI = -0.36, -0.25; $P$ = 7*10$^{-27}$), whereas gluteofemoral fat was positively associated with adiponectin concentration (men: $\beta$ = 0.13 standard unit of log adiponectin per standard unit increase in gluteofemoral fat; 95% CI = 0.03, 0.22; $P$ = 0.008; women: $\beta$ = 0.24; 95% CI = 0.17, 0.31; $P$ = 7*10$^{-11}$). In the Mendelian randomization analysis, genetically-predicted waist circumference was inversely related to blood adiponectin concentration ($\beta$ = -0.27 standard unit of log adiponectin per standard unit increase in waist circumference; 95% CI = -0.36, -0.19; $P$ = 2*10$^{-11}$), whereas genetically-predicted hip circumference was positively associated with blood adiponectin concentration ($\beta$ = 0.17 standard unit of log adiponectin per standard unit increase in hip circumference; 95% CI = 0.11, 0.24; $P$ = 1*10$^{-7}$). $\textbf{Conclusions:}$ These results support the hypotheses that there is a complex interplay between body fat distribution and circulating adiponectin concentration, and that whereas obesity-induced hypoadiponectinaemia seems to be primarily attributed to abdominal fat accumulation, gluteofemoral fat accumulation is likely to exert a protective effect.The study ‘Pelotas Birth Cohort, 1982’ is conducted by Postgraduate Program in Epidemiology at Universidade Federal de Pelotas with the collaboration of the Brazilian Public Health Association (ABRASCO). From 2004 to 2013, the Wellcome Trust supported the 1982 birth cohort study. The International Development Research Center, World Health Organization, Overseas Development Administration, European Union, National Support Program for Centers of Excellence (PRONEX), the Brazilian National Research Council (CNPq) and the Brazilian Ministry of Health supported previous phases of the study. M.C.B. receives financial support from the Brazilian National Research Council (CNPq) [144749/2014-9, 201498/2014-6 (Science Without Borders Program), and 163291/2015-2] and Coordenac¸~ao de Aperfeic¸oamento de Pessoal de Nıvel Superior (CAPES). K.K.O. is supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/1 and MC_UU_12015/2]

Obesity-induced hypoadiponectinaemia: the opposite influences of central and peripheral fat compartments

$\textbf{Background and Aims:}$ The substantial reduction in adiponectin concentration among obese individuals seems to depend on fat distribution and is a marker of metabolic and adipose tissue dysfunction. We aimed to: (i) address whether abdominal fat from different compartments (visceral, deep subcutaneous abdominal and superficial subcutaneous abdominal) and gluteofemoral fat are independently associated with blood adiponectin concentration; and (ii) investigate whether abdominal (proxied by waist circumference) and gluteofemoral fat (proxied by hip circumference) accumulation causally determine blood adiponectin concentration. $\textbf{Methods:}$ To investigate the independent association of abdominal and gluteofemoral fat with adiponectin concentration, we used multivariable regression and data from 30-year-old adults from the 1982 Pelotas Birth Cohort ($n$ = 2,743). To assess the causal role of abdominal and gluteofemoral fat accumulation on adiponectin concentration, we used Mendelian randomization and data from two consortia of genome-wide association studies—the GIANT ($n$ > 210 000) and ADIPOGen consortia ($n$ = 29 347). $\textbf{Results:}$ In the multivariable regression analysis, all abdominal fat depots were negatively associated with adiponectin concentration, specially visceral abdominal fat [men: $\beta$ = -0.24 standard unit of log adiponectin per standard unit increase in abdominal fat; 95% confidence interval (CI) = -0.31, -0.18; $P$ = 8*10$^{-13}$; women: $\beta$ = -0.31; 95% CI = -0.36, -0.25; $P$ = 7*10$^{-27}$), whereas gluteofemoral fat was positively associated with adiponectin concentration (men: $\beta$ = 0.13 standard unit of log adiponectin per standard unit increase in gluteofemoral fat; 95% CI = 0.03, 0.22; $P$ = 0.008; women: $\beta$ = 0.24; 95% CI = 0.17, 0.31; $P$ = 7*10$^{-11}$). In the Mendelian randomization analysis, genetically-predicted waist circumference was inversely related to blood adiponectin concentration ($\beta$ = -0.27 standard unit of log adiponectin per standard unit increase in waist circumference; 95% CI = -0.36, -0.19; $P$ = 2*10$^{-11}$), whereas genetically-predicted hip circumference was positively associated with blood adiponectin concentration ($\beta$ = 0.17 standard unit of log adiponectin per standard unit increase in hip circumference; 95% CI = 0.11, 0.24; $P$ = 1*10$^{-7}$). $\textbf{Conclusions:}$ These results support the hypotheses that there is a complex interplay between body fat distribution and circulating adiponectin concentration, and that whereas obesity-induced hypoadiponectinaemia seems to be primarily attributed to abdominal fat accumulation, gluteofemoral fat accumulation is likely to exert a protective effect.The study ‘Pelotas Birth Cohort, 1982’ is conducted by Postgraduate Program in Epidemiology at Universidade Federal de Pelotas with the collaboration of the Brazilian Public Health Association (ABRASCO). From 2004 to 2013, the Wellcome Trust supported the 1982 birth cohort study. The International Development Research Center, World Health Organization, Overseas Development Administration, European Union, National Support Program for Centers of Excellence (PRONEX), the Brazilian National Research Council (CNPq) and the Brazilian Ministry of Health supported previous phases of the study. M.C.B. receives financial support from the Brazilian National Research Council (CNPq) [144749/2014-9, 201498/2014-6 (Science Without Borders Program), and 163291/2015-2] and Coordenac¸~ao de Aperfeic¸oamento de Pessoal de Nıvel Superior (CAPES). K.K.O. is supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/1 and MC_UU_12015/2]

Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that infects approximately 10–20 million people worldwide and causes an aggressive neoplasia (adult T-cell leukemia/lymphoma - ATL). Therapeutic approaches for the treatment of ATL have variable effectiveness and poor prognosis, thus requiring strategies to identify novel compounds with activity on infected cells. In this sense, we initially screened a small series of 25 1,2,3-triazole derivatives to discover cell proliferation inhibitors and apoptosis inducers in HTLV-1-infected T-cell line (MT-2) for further assessment of their effect on viral tax activity through inducible-tax reporter cell line (Jurkat LTR-GFP). Eight promising compounds (02, 05, 06, 13, 15, 21, 22 and 25) with activity ≥70% were initially selected, based on a suitable cell-based assay using resazurin reduction method, and evaluated towards cell cycle, apoptosis and Tax/GFP expression analyses through flow cytometry. Compound 02 induced S phase cell cycle arrest and compounds 05, 06, 22 and 25 promoted apoptosis. Remarkably, compounds 22 and 25 also reduced GFP expression in an inducible-tax reporter cell, which suggests an effect on Tax viral protein. More importantly, compounds 02, 22 and 25 were not cytotoxic in human hepatoma cell line (Huh-7). Therefore, the discovery of 3 active and non-cytotoxic compounds against HTLV-1-infected cells can potentially contribute, as an initial promising strategy, to the development process of new drugs against ATL

A mass accuracy sensitive probability based scoring algorithm for database searching of tandem mass spectrometry data

<p>Abstract</p> <p>Background</p> <p>Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) has become one of the most used tools in mass spectrometry based proteomics. Various algorithms have since been developed to automate the process for modern high-throughput LC-MS/MS experiments.</p> <p>Results</p> <p>A probability based statistical scoring model for assessing peptide and protein matches in tandem MS database search was derived. The statistical scores in the model represent the probability that a peptide match is a random occurrence based on the number or the total abundance of matched product ions in the experimental spectrum. The model also calculates probability based scores to assess protein matches. Thus the protein scores in the model reflect the significance of protein matches and can be used to differentiate true from random protein matches.</p> <p>Conclusion</p> <p>The model is sensitive to high mass accuracy and implicitly takes mass accuracy into account during scoring. High mass accuracy will not only reduce false positives, but also improves the scores of true positive matches. The algorithm is incorporated in an automated database search program MassMatrix.</p

Cell walls of the dimorphic fungal pathogens Sporothrix schenckii and Sporothrix brasiliensis exhibit bilaminate structures and sloughing of extensive and intact layers

This work was supported by the Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), grants E-26/202.974/2015 and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), grants 229755/2013-5, Brazil. LMLB is a senior research fellow of CNPq and Faperj. NG acknowledged support from the Wellcome Trust (Trust (097377, 101873, 200208) and MRC Centre for Medical Mycology (MR/N006364/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

LHC and lepton flavour violation phenomenology of a left-right extension of the MSSM

We study the phenomenology of a supersymmetric left-right model, assuming minimal supergravity boundary conditions. Both left-right and (B-L) symmetries are broken at an energy scale close to, but significantly below the GUT scale. Neutrino data is explained via a seesaw mechanism. We calculate the RGEs for superpotential and soft parameters complete at 2-loop order. At low energies lepton flavour violation (LFV) and small, but potentially measurable mass splittings in the charged scalar lepton sector appear, due to the RGE running. Different from the supersymmetric 'pure seesaw' models, both, LFV and slepton mass splittings, occur not only in the left- but also in the right slepton sector. Especially, ratios of LFV slepton decays, such as Br(${\tilde\tau}_R \to \mu \chi^0_1$)/Br(${\tilde\tau}_L \to \mu \chi^0_1$) are sensitive to the ratio of (B-L) and left-right symmetry breaking scales. Also the model predicts a polarization asymmetry of the outgoing positrons in the decay $\mu^+ \to e^+ \gamma$, A ~ [0,1], which differs from the pure seesaw 'prediction' A=1$. Observation of any of these signals allows to distinguish this model from any of the three standard, pure (mSugra) seesaw setups.Comment: 43 pages, 17 figure