Slower Rate Of Progression Research Articles

Longitudinal Assessment of the Doppler-Estimated Maximum Gradient in Patients With Congenital Valvar Aortic Stenosis Pre- and Post-Balloon Valvuloplasty.

Aortic stenosis has been reported to manifest a slow rate of progression in mild disease, with a greater likelihood of progression in patients with moderate-severe disease. The natural history of the Doppler-estimated maximum gradient (DEMG) in patients after balloon aortic valvuloplasty (BAVP) has not previously been studied on a large scale. A retrospective review was performed of 360 patients from 1984 to 2012 with aortic stenosis, providing a total of 2059 echocardiograms both before and after BAVP. Patients were excluded if they had an intervention within the first 30 days of life. The relationships between the aortic stenosis DEMG and several predictors (age at initial study, body surface area, valve morphology, and initial DEMG) were explored using linear mixed effect models. Patients with a unicommissural aortic valve had a significantly higher rate of progression compared with those with a bicommissural aortic valve (0.81 and 0.45 mm Hg/year; P<0.001). The median rate of progression in the post-BAVP group was significantly lower than the median pre-BAVP rate of progression (n=34; pre-BAVP 3.97 [1.69-8.7] mm Hg/year; post-BAVP 0.40 [-1.80 to 3.88] mm Hg/year; P<0.008). When adjusted for body surface area, there was no significant increase in the DEMG (-0.03 mm Hg/m2 per year; P<0.001). There is a statistically significant increase in the DEMG over time in patients with aortic stenosis. After balloon dilation, the DEMG rate of change is reduced compared with that pre-dilation. Given the effect of body surface area on DEMG progression, more frequent observation should be made during periods of rapid somatic growth.

Variations in Progression and Regression of Precancerous Lesions of the Uterine Cervix on Cytology Testing Among Women of Different Races

Although not incorporated into current cervical cancer screening guidelines, racial differences are known to persist in both occurrence of and outcomes related to cervical cancer. To compare the differences in progression and regression of precancerous lesions of the uterine cervix on cervical cytologic analysis among women of different races who adhered to cervical cancer screening recommendations and follow-up. Retrospective cohort study comparing differences in precancerous lesion diagnoses for patients receiving adequate evaluation according to the American Society for Colposcopy and Cervical Pathology guidelines. The authors fit Markov multistate models to estimate self-reported race-specific expected wait times and hazard ratios for each possible regression and progression and compared a race model with an intercept-only model using a likelihood ratio test. The sample included 5472 women receiving a Papanicolaou test between January 2006 and September 2016, contributing a total of 24,316 person-years of follow-up. Of 21 hazard ratios tested for significance, the following 4 hazard ratios (95% CIs) were statistically significant: atypical squamous cells of undetermined significance (ASC-US) progression to low-grade squamous intraepithelial lesion (LSIL) for Hispanic patients (0.72; 95% CI, 0.54-0.96); LSIL regression to ASC-US for Hispanic patients (1.55; 95% CI, 1.04-2.31), LSIL regression to ASC-US for Asian patients (1.91; 95% CI, 1.08-3.36), and high-grade squamous intraepithelial lesion regression to LSIL for black patients (0.39; 95% CI, 0.16-0.96). There is an observed trend that all racial groups other than white had a slower rate of progression from ASC-US to LSIL, with Hispanics having demonstrated the slowest rate from ASC-US to LSIL. Hispanics also demonstrated the fastest rate from LSIL to HSIL when compared with all other race categories. In regressions, blacks had the slowest rate of regression from HSIL to LSIL, and Asians had the fastest rate from LSIL to ASC-US. The Hispanic group demonstrated the fastest expected progression (17.6 months; 95% CI, 11.5-25.5), as well as the fastest regression (27.6 months; 95% CI, 21.5-35.6), and the black group has the slowest expected times for both progression (28.1 months; 95% CI, 14.6-47.2) and regression (49 months; 95% CI, 29.1-86.2). The number of visits (1 vs ≥2) in the study was differentially distributed both by race (P=.033) and by last diagnosis (P<.001). Variations in precancerous lesions of the uterine cervix are not uniform across races.

Abstract 2503: Metabolomics identifies a caveolin-1-associated plasma glycosphingolipid and sphingomyelin signature that differentiates aggressive from indolent prostate cancer in an active surveillance cohort

Abstract Purpose: To identify a plasma signature that can distinguish aggressive from indolent prostate cancer in patients on active surveillance based on metabolomics profiling. Introduction: The slow growth rate and low likelihood of disease progression in low-risk prostate cancer patients have led to the widely implemented active surveillance (AS) strategy. Given tumor heterogeneity, a clinical challenge is how to expand the pool of patients eligible for AS safely. Consequently, additional markers able to identify patients at increased risk of disease progression are needed. We previously identified plasma caveolin-1 (CAV1) as predictive of aggressive prostate cancer in an AS cohort. Complementary in vitro and in vivo studies demonstrated that CAV1 mediates major reprogramming of lipid metabolism, collectively suggesting that dysregulated lipid biogenesis may be associated with aggressive prostate cancer. Experimental Procedures: An integrated approach was utilized which included multi-assay untargeted metabolomics to characterize alterations in the metabolome and lipidome of conditioned media from prostate cancer cell lines following overexpression of CAV1 (LNCaP) or CAV1 siRNA knockdown (PC3M). In parallel, sera from PBCre+PTENloxp/loxp;PBCav-1+ and PBCre+PTENloxp/loxp;PBCav-1- mice were collected for metabolomics analysis to further delineate signatures related to CAV1-associated aggressive prostate cancer. We further conducted untargeted metabolomic analysis on plasma samples (n=16 per group) prospectively collected from patients with early stage prostate cancer undergoing AS who exhibited early progression (defined as upgrading of Gleason score (GS) and/or increased tumor volume on surveillance biopsy within 18 months after start of AS) or indolent disease (did not progress for a minimum of 5 years after start of AS). Patients were matched with respect to age, clinical stage, prostate-specific antigen, and GS on baseline biopsy at start of AS. We evaluated plasma samples collected at baseline (start of AS) and after 12 months. Results: Analysis of conditioned media identified a metabolomics signature with major alterations in lipid composition highlighted by CAV1-mediated elevations in lipid-raft associated sphingomyelins and glycosphingolipids. This signature was observed in patients who had early progression but not in patients with indolent disease. Importantly, this signature was observed at baseline and at least 18 months prior to disease progression on surveillance biopsy. Conclusions: We have identified a plasma-derived lipid signature that differentiates aggressive versus indolent prostate cancer in an active surveillance cohort. Our findings highlight the potential utility of altered lipid profiles as additional risk markers for aggressive prostate cancer. Citation Format: Johannes Fahrmann, Jody Vykoukal, Spyridon Basourakos, Jianxiang Wang, Jennifer Dennison, Eunice Murage, Jeri Kim, Timothy C. Thompson, Samir Hanash. Metabolomics identifies a caveolin-1-associated plasma glycosphingolipid and sphingomyelin signature that differentiates aggressive from indolent prostate cancer in an active surveillance cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2503. doi:10.1158/1538-7445.AM2017-2503

European Glaucoma Society Terminology and Guidelines for Glaucoma, 4th Edition - Chapter 3: Treatment principles and optionsSupported by the EGS Foundation

### 3.1 - General Principles of Glaucoma Treatment The purpose of this chapter is to give a summary overview and it is not meant to be an all-inclusive text Figure...

Clinical Psychology Training: Accreditation and Beyond.

Beginning with efforts in the late 1940s to ensure that clinical psychologists were adequately trained to meet the mental health needs of the veterans of World War II, the accreditation of clinical psychologists has largely been the province of the Commission on Accreditation of the American Psychological Association. However, in 2008 the Psychological Clinical Science Accreditation System began accrediting doctoral programs that adhere to the clinical science training model. This review discusses the goals of accreditation and the history of the accreditation of graduate programs in clinical psychology, and provides an overview of the evaluation procedures used by these two systems. Accreditation is viewed against the backdrop of the slow rate of progress in reducing the burden of mental illness and the changes in clinical psychology training that might help improve this situation. The review concludes with a set of five recommendations for improving accreditation.

Nutritional strategies and gut microbiota composition as risk factors for necrotizing enterocolitis in very-preterm infants

Background: The pathophysiology of necrotizing enterocolitis (NEC) remains poorly understood.Objective: We assessed the relation between feeding strategies, intestinal microbiota composition, and the development of NEC.Design: We performed a prospective nationwide population-based study, EPIPAGE 2 (Etude Epidémiologique sur les Petits Ages Gestationnels), including preterm infants born at <32 wk of gestation in France in 2011. From individual characteristics observed during the first week of life, we calculated a propensity score for the risk of NEC (Bell's stage 2 or 3) after day 7 of life. We analyzed the relation between neonatal intensive care unit (NICU) strategies concerning the rate of progression of enteral feeding, the direct-breastfeeding policy, and the onset of NEC using general linear mixed models to account for clustering by the NICU. An ancillary propensity-matched case-control study, EPIFLORE (Etude Epidémiologique de la flore), in 20 of the 64 NICUs, analyzed the intestinal microbiota by culture and 16S ribosomal RNA gene sequencing.Results: Among the 3161 enrolled preterm infants, 106 (3.4%; 95% CI: 2.8%, 4.0%) developed NEC. Individual characteristics were significantly associated with NEC. Slower and intermediate rates of progression of enteral feeding strategies were associated with a higher risk of NEC, with an adjusted OR of 2.3 (95% CI: 1.2, 4.5; P = 0.01) and 2.0 (95% CI: 1.1, 3.5; P = 0.02), respectively. Less favorable and intermediate direct-breastfeeding policies were associated with higher NEC risk as well, with an adjusted OR of 2.5 (95% CI: 1.1, 5.8; P = 0.03) and 2.3 (95% CI: 1.1, 4.8; P = 0.02), respectively. Microbiota analysis performed in 16 cases and 78 controls showed an association between Clostridium neonatale and Staphylococcus aureus with NEC (P = 0.001 and P = 0.002).Conclusions: A slow rate of progression of enteral feeding and a less favorable direct-breastfeeding policy are associated with an increased risk of developing NEC. For a given level of risk assessed by propensity score, colonization by C. neonatale and/or S. aureus is significantly associated with NEC. This trial (EPIFLORE study) was registered at clinicaltrials.gov as NCT01127698.

Low renal replacement therapy incidence among slowly progressing elderly chronic kidney disease patients referred to nephrology care: an observational study

BackgroundElderly patients with advanced chronic kidney disease (CKD) have a high risk of death before reaching end-stage kidney disease. In order to allocate resources, such as advanced care nephrology where it is most needed, it is essential to know which patients have the highest absolute risk of advancing to renal replacement therapy (RRT).MethodsWe included all nephrology-referred CKD stage 3b-5 patients in Sweden 2005–2011 included in the Swedish renal registry (SRR-CKD) who had at least two serum creatinine measurements one year apart (+/− 6 months). We followed these patients to either initiation of RRT, death, or September 30, 2013. Decline in estimated glomerular filtration rate (eGFR) (%) was estimated during the one-year baseline period. The patients in the highest tertile of progression (>18.7% decline in eGFR) during the initial year of follow-up were classified as “fast progressors”. We estimated the cumulative incidence of RRT and death before RRT by age, eGFR and progression status using competing risk models.ResultsThere were 2119 RRT initiations (24.2%) and 2060 deaths (23.5%) before RRT started. The median progression rate estimated during the initial year was −8.8% (Interquartile range [IQR] - 24.5–6.5%). A fast initial progression rate was associated with a higher risk of RRT initiation (Sub Hazard Ratio [SHR] 2.24 (95% confidence interval [CI] 2.00–2.51) and also a higher risk of death before RRT initiation (SHR 1.27 (95% CI 1.13–1.43). The five year probability of RRT was highest in younger patients (<65 years) with fast initial progression rate (51% in CKD stage 4 and 76% in stage 5), low overall in patients >75 years with a slow progression rate (7, 13, and 25% for CKD stages 3b, 4 and 5 respectively), and slightly higher in elderly patients with a fast initial progression rate (28% in CKD stage 4 and 47% in CKD stage 5) or with diabetic kidney disease.ConclusionsThe 5-year probability of RRT was low among referred slowly progressing CKD patients >75 years of age because of the competing risk of death.

Effect of vitamin A supplementation in category-I Pulmonary Tuberculosis patients in a Medical College in India: a rapid assessment analysis

Background: Tuberculosis is one of the major health problems affecting the global population causing immense morbidity and mortality. Studies have shown that a good antioxidant status of the body has immune protective role against tuberculosis and may be associated with a decreased risk of the disease and slower rate of progression. Objective of the study was planned to evaluate the beneficial effects of Vitamin A as add on therapy to the standard drug therapy in patients with sputum positive pulmonary tuberculosis. Methods: The study was done in a Tuberculosis clinic, Department of Internal Medicine, Stanley Medical College for duration of 6 months. All the newly diagnosed sputum positive pulmonary tuberculosis patients (18-55 years) attending the outpatient were taken for the study purpose. A Phase III, prospective, open, two arm parallel group, outpatient, randomized, active controlled study was done. Results: After two weeks of therapy, the number of patients with negative sputum smear was higher in the study group than the control group. Vitamin A supplementation resulted in an earlier elimination of tubercle bacilli from the sputum. Conclusions: This study shows that vitamin A as add on therapy to the existing standard therapy improves the clinical response and decreases the disease activity to a greater extent than with routine standard therapy alone.

Single-nucleotide polymorphism rs948854 in human galanin gene and multiple sclerosis: a gender-specific risk factor.

We performed comparative analyses of the genotype distribution and allelic frequencies of the rs948854 polymorphism (G/A) in the galanin gene's promoter in patients with multiple sclerosis (MS) and in healthy matched controls. In total 111 patients and 115 control subjects were included. The analyses revealed that the presence of the minor allele (G) increased susceptibility to MS in men (OR = 2.49, P = 0.008) but not in women. The presence of the G allele in men was also significantly associated with the late onset of MS. Furthermore, rs948854 polymorphism affected the rate of MS progression depending on the sex of the patients. In woman (typically slowly progressing), the percentage of patients with the slow (<0.5 EDSS score per year) progression rate was significantly reduced (χ2 = 5.7, P = 0.017) in the minor allele carriers group (52.6%), in comparison with the wild-type carriers (83.9%). In men (typically quickly progressing), the number of patients with fast progression rate (≥0.75 EDSS score per year) tended to increase in the minor allele carriers group (50%) compared with number of patients with the wild-type carriers (31.3%). These data demonstrate for the first time an association between rs948854 polymorphism and multiple sclerosis and, further, that this association is sex specific. They also point to diagnostic and prognostic benefits of genetic screening of patients with multiple sclerosis. © 2016 Wiley Periodicals, Inc.

Committee Opinion No.675: Management of Vulvar Intraepithelial Neoplasia.

Vulvar intraepithelial neoplasia (VIN) is an increasingly common problem, particularly among women in their 40s. Although spontaneous regression has been reported, VIN should be considered a premalignant condition. Immunization with the quadrivalent or 9-valent human papillomavirus vaccine, which is effective against human papillomavirus genotypes 6, 11, 16, and 18, and 6, 11, 16, 18, 31, 33, 45, 52, and 58, respectively, has been shown to decrease the risk of vulvar high-grade squamous intraepithelial lesion (HSIL) (VIN usual type) and should be recommended for girls aged 11-12 years with catch-up through age 26 years if not vaccinated in the target age. There are no screening strategies for the prevention of vulvar cancer through early detection of vulvar HSIL (VIN usual type). Detection is limited to visual assessment with confirmation by histopathology when needed. Treatment is recommended for all women with vulvar HSIL (VIN usual type). Because of the potential for occult invasion, wide local excision should be performed if cancer is suspected, even if biopsies show vulvar HSIL. When occult invasion is not a concern, vulvar HSIL (VIN usual type) can be treated with excision, laser ablation, or topical imiquimod (off-label use). Given the relatively slow rate of progression, women with a complete response to therapy and no new lesions at follow-up visits scheduled 6 months and 12 months after initial treatment should be monitored by visual inspection of the vulva annually thereafter.

Interaction between migration behaviour and estuarine mortality in cultivated Atlantic salmon Salmo salar smolts.

Migration behaviour and estuarine mortality of cultivated Atlantic salmon Salmo salar smolts in a 16 km long estuary were studied using two methods: (1) acoustic telemetry and (2) group tagging in combination with trap nets. Progression rates of surviving individuals through the estuary were relatively slow using both methods [0·38 LT (total length) s-1 v. 0·25 LT s-1 ]. In 2012, the progression rate was slow from the river to the estuary (0·55 LT s-1 ) and the first part of the estuary (0·31 LT s-1 ), but increased thereafter (1·45-2·21 LT s-1 ). In 2013, the progression rate was fast from the river to the estuary (4·31 LT s-1 ) but was slower thereafter (0·18-0·91 LT s-1 ). Survival to the fjord was higher in 2012 (47%) compared to 2013 (6%). Fast moving individuals were more likely to migrate successfully through the estuary compared to slower moving individuals. Adult recapture of coded-wire-tagged S. salar was generally low (0·00-0·04%). Mortality hot spots were related to topographically distinct areas such as the river outlet (in 2012) or the sill separating the estuary and the fjord (in 2013). At the sill, an aggregation of cod Gadus morhua predating on cultivated smolts was identified. The results indicate that slow progression rates through the estuary decreases the likelihood of smolts being detected outside the estuary. The highly stochastic and site-specific mortality patterns observed in this study highlight the complexity in extrapolating mortality patterns of single release groups to the entire smolt run of wild S. salar.

Phylogeny, ecology, morphological evolution, and reclassification of the diatom orders Surirellales and Rhopalodiales

The Surirellales and Rhopalodiales are large, widespread, and morphologically diverse groups of raphid pennate diatoms (Bacillariphyta) whose raphe, a structure that facilitates active motility, opens internally into a siliceous canal. We collected 202 representatives of the lineage and sequenced genes from the nuclear, plastid, and mitochondrial genomes to infer phylogenetic relationships as a basis for comparative study of ecology and morphological evolution as well as reclassification. The lineage was ancestrally marine, and we report the first evidence for a ‘stepping stone’ model of marine–freshwater transitions in which freshwater invasions were preceded by adaptation to intermediate brackish habitats. Phylogenetic comparative analyses also showed that the shift from an apical (e.g., Entomoneis) to transapical major axis of development (e.g., Surirella) did not have to proceed through subcircular intermediate forms (i.e., Campylodiscus). Rather, subcircular forms evolved both within lineages with longer apical axis or longer transapical axis. We also used the inferred phylogeny as a basis for genus-level reclassification of the lineage. Campylodiscus now includes the fastuosoid members of Surirella and Campylodiscus, but excludes other marine Campylodiscus which are now classified as Coronia. Surirella includes the Surirella striatula clade, Surirella Pinnatae group, and species formerly classified as Cymatopleura. We resurrected the genus Iconella to accommodate Stenopterobia and the robustoid members of Surirella and Campylodiscus. We broadened Epithemia to include members of the paraphyletic genus Rhopalodia. Finally, we discuss the challenges of constructing a classification that best leverages available phylogenetic data, while minimizing disruption to the research community and recognizing practical considerations stemming from the slow rate of progress on systematic studies of understudied organisms.

Long term survival in persons with hemophilia and chronic hepatitis C: 40 year outcomes of a large single center cohort.

We studied the course of chronic HCV infections in a cohort of 222 persons with hemophilia (PWH) and von Willebrand disease followed at our center since 1973. Twenty two (10%) developed end stage liver disease (ESLD). Forty years after HCV infection, cumulative incidence of ESLD was 12.3% and overall survival was 45.5%. Those who were infected with HCV only (n = 100) had a survival of 75.2%, while those infected with HIV (n = 122) had a survival of 24% (P < 0.001). Survivals were significantly longer for those infected with HCV at younger age (< 15 years) compared to those infected over age 30 years (P = 0.014). Cause specific deaths for ESLD and bleeding were 8.8% and 8.3% respectively. For HIV negative subjects, the annual hazard of death from ESLD and bleeding was near zero for the first 10 years, and then rose slowly over the next 20 years to 0.4/100py for ESLD and 0.2/100py for bleeding. Sixty subjects completed 79 treatment episodes. Sustained viral response rates increased from 7/21 (33%) between 1990 and 2001, to 17/29 (58%) between 2002 and 2011, and to 27/29 (93%), since 2012 with the advent of the directly acting antiviral agents. These results confirm the very slow ESLD progression rate in HIV negative PWH. However, the risk of death from both ESLD and bleeding increases steadily with longer duration of HCV infection. More aggressive surveillance to detect those with early fibrosis is needed now that curative treatment is possible in >95% of individuals. Am. J. Hematol. 91:E335-E340, 2016. © 2016 Wiley Periodicals, Inc.

Sequential Right and Left Ventricular Assessment in Posttetralogy of Fallot Patients with Significant Pulmonary Regurgitation.

The natural history of right ventricular (RV) and left ventricular (LV) size and function among adults with tetralogy of Fallot (TOF) repair and hemodynamically significant pulmonary regurgitation (PR) is not known. The main aim of this study was to determine changes in RV and LV size and function over time in an adult population with TOF repair and hemodynamically significant pulmonary regurgitation. Forty patients with repaired TOF and hemodynamically significant PR were included. These patients were identified on the basis of having more than one CMR between January 2008 and 2015. Patients with a prosthetic pulmonary valve or any cardiac intervention between CMR studies were excluded. Rate of progression (ROP) of RV dilation was determined for both indexed right ventricular end-systolic volume (RVESVi) and indexed right ventricular end-diastolic volume (RVEDVi), and calculated as the difference between the last and first volumes divided by the number of years between CMR#1 and CMR#2. Subjects were also divided into two groups based on the distribution of the ROP of RV dilation: Group I-rapid ROP (>50th percentile) and Group II-slower ROP (≤50th percentile). The interval between CMR#1 and CMR#2 was 3.9 ± 1.7 years (range 1-8 years). We did find a significant change in RVEDVi and RVESVi over this time period, although the magnitude of change was small. Nine patients (23%) had a reduction in right ventricular ejection fraction (RVEF) by greater than 5%, 13 patients (33%) had an increase in RVEDVi by greater than 10 mL/m2 and seven patients (18%) had an increase in RVESVi by greater than 10 mL/m2 . Median ROP for RVEDVi was 1.8 (range -10.4 to 21.8) mL/(m2 year); RVESVi 1.1 (range -5.8 to 24.5) mL/(m2 year) and RVEF -0.5 (range -8 to 4)%/year. Patients with a rapid ROP had significantly larger RV volumes at the time of CMR#1 and lower RVEF as compared to the slow ROP group. There was no overall significant change in LVEDVi, LVESVi, or LVEF over this time period. We have demonstrated, in a small population of patients with hemodynamically significant PR, that there is a small increase in RV volumes and decrease in RVEF over a mean 4-year period. We believe it to be reasonable practice to perform CMR at least every 4 years in asymptomatic patients with repaired TOF and hemodynamically significant PR. We found that LV volumes and function remained stable during the study period, suggesting that significant progressive LV changes are less likely to occur over a shorter time period. Our results inform a safe standardized approach to monitoring adults with hemodynamically significant PR post TOF repair and assist in planning allocation of this expensive and limited resource.

Diagnosis and management of periodontal disease in children and adolescents: A brief review

Periodontal disease when occurring in children leads to premature tooth loss, affecting the quality of life. Thus, screening pediatric and adolescent patients early, for periodontal disease is deemed imperative to its early management for improved prognosis. Chronic periodontitis (CP) has slow rate of progression, whereas aggressive periodontitis (AP) affecting children and young adults has rapid rate of progression. The management of AP in particular is affected by bacterial virulence of Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis in plaque leading to rapid attachment and bone loss around the affected teeth. Nonsurgical treatment, use of appropriate antimicrobial therapy, and surgical correction of defects is required to mitigate disease followed by a comprehensive supportive periodontal therapy. This review visits the current understanding of periodontal disease, its management in pediatric and adolescent patients.

Activation of autophagy in peripheral blood mononuclear cells in amyotrophic lateral sclerosis

Introduction. Accumulation of intracellular protein aggregates is one of the key processes in pathogenesis of amyotrophic lateral sclerosis (ALS). Autophagy is a complex process during which cell components and organelles are transferred inside lysosomes and are degraded. Autophagy disturbance was found to take place in various neurodegenerative diseases. Autophagy alteration can be observed not only in the central nervous system but also in peripheral blood mononuclear cells (PBMCs). Protein LC3 is the key marker of autophagy. Objective. To determine protein LC3 concentration in PBMCs of ALS patients and to analyze the relationship between this parameter and clinical characteristics of the disease. Materials and methods. The study involved 66 patients with definite ALS and 15 healthy volunteers. Past medical history was elicited in all patients; neurological examination and the pulmonary function test were performed. PBMCs were isolated from blood of patients and healthy volunteers. The cells were lysed and subjected to Western blot analysis using anti-LC3 antibodies. Results. The LC3-I level in PBMCs of ALS patients was increased compared to that in the control group (p<0.001). The LC3-I/LC3-II level was elevated in patients with the lumbosacral form of ALS (stage II ALS and the slow rate of disease progression). The tendency towards increased LC3-II level was observed for the bulbar form and stage III ALS. Conclusions. The results demonstrated for the first time that PBMCs of ALS patients tend to exhibit a higher level of autophagy activity compared to healthy volunteers.

Dividing the Pie

The authors are the first to study the factors determining labor’s share of income on the level of the individual firm, employing an unusually informative panel data set. The empirical examination is concerned with Switzerland, which stands out as one of the very few developed countries with a stable labor share. Broadly confirming results from previous cross-country and industry-level studies, the authors find that the main factor decreasing the labor share between 2001 and 2010 was the increase in the firm’s share of workers using information and communication technology. The main reasons why Switzerland’s labor share remained almost constant are the counteracting effects of a relatively slow rate of technological progress in 1980 to 1995 and sectoral reallocation toward industries with above-average labor shares.

Becker Muscular Dystrophy in a 2-Year-Old Boy caused by a Novel Missense Mutation p.Arg145Pro in the Dystrophin Gene

Background: X-linked dystrophinopathy, resulting from mutations in the dystrophin gene, is the most common cause of inherited myopathy in males. On the molecular level, Becker muscular dystrophy (BMD) is caused by deletions, point mutations, or duplications in the dystrophin gene. Although the genetic defect and the impaired formation of dystrophin are already present from birth, males with Duchenne muscular dystrophy (DMD) or the milder BMD are born with normal muscle function and develop progressive muscle weakness as they age. In BMD, the pattern of symptom development resembles that of DMD, but with a later, and much slower rate of progression.

Burden of chronic kidney disease in Peru: a population-based study

Abstract Background Chronic kidney disease's (CKD) silent progression, association with other chronic diseases, and high treatment costs make it a global public health concern, especially in low-income and middle-income countries (LMIC) where health-care resources are constrained. Understanding CKD epidemiology in these countries is key to addressing CKD burden and will guide disease surveillance, screening, prevention, and resource allocation. In keeping, this study serves as one of the early descriptions of the CKD burden in Peru. Methods In this cross-sectional study, we collected baseline demographic data and biological samples to measure markers for CKD, serum creatinine, and urine protein, from 404 participants who were a random subsample of the ongoing CRONICAS cohort study in Lima and Tumbes, Peru. Participants were identified via a single-stage sampling method and stratified by sex and age (35–44; 45–54; 55–64; and ≥65 years). Inclusion required full-time residence in the area, the ability to understand study procedures, and informed consent. Selection of participants continued until age and sex strata were filled. Trained fieldworkers went door-to-door to enrol selected participants and receive written informed consent. We used Poisson regression to identify possible factors associated with CKD. CKD was defined as estimated glomerular filtration rate (eGFR) 2 or proteinuria (protein-creatinine ratio) ≥150 mg/g creatinine, or both, based on the latest Kidney Disease Improving Global Outcomes (KDIGO) guideline. Findings Participants' median age was 54·8 years (IQR 44·9–64·8). Of the 404 participants, 68 (16·8%) met the study's CKD criteria: 60 (14·9%) with proteinuria, four (1%) with eGFR 2 , and four (1%) with both. CKD prevalence was higher in Lima than Tumbes (20·7% vs 12·9%, p=0·04). Among participants with CKD, the prevalence of diabetes and hypertension was 19·1% (n= 13) and 42·7% (29), respectively. After multivariable adjustment, CKD was associated with older age, female sex, the highest wealth tertile (although all wealth strata were below the poverty line), living in Lima, diabetes, and hypertension. Interpretation This study has identified a high prevalence of CKD in our Lima and Tumbes sample groups. Our findings highlight the burden of CKD, much of which is likely occult, and suggest that expanded strategies to measure actual CKD burden through nationwide surveillance efforts are needed. In light of the few therapeutic options to slow CKD progression and low rates of access to health care and insurance in Peru, such expanded surveillance strategies may identify more disease and, therefore, help to prevent disease progression and secondary morbidity. Funding The CKD study was funded by University of Pennsylvania. The CRONICAS Cohort Study was supported by the National Heart, Lung, and Blood Institute (project number 268200900033C-1-0-1). ERF was supported by WCMC and JHBSPH.

Echocardiographic and Biohumoral Characteristics in Patients With AL and TTR Amyloidosis at Diagnosis

Few studies have analyzed the clinical and echocardiographic differences between light-chain (AL) and transthyretin (TTR) amyloidosis. The aim of the present research was to compare, in a real-world setting, the clinical and echocardiographic profiles of these kinds of amyloidosis, at the time of diagnosis, using new-generation echocardiography. Seventy-nine patients with AL and 48 patients with TTR amyloidosis were studied. According to the criterion of mean left ventricular (LV) thickness >12 mm, 45 AL (C-AL) and all TTR patients had cardiac amyloidotic involvement, whereas 34 AL patients did not. TTR patients had increased right ventricular (RV) and LV chambers with increased RV and LV wall thickness and reduced LV ejection fraction and fractional shortening. Furthermore, TTR patients showed lower N-terminal pro Brain Natriuretic Peptide concentrations and New York Heart Association functional class when compared with C-AL. Our data show that at time of first diagnosis, TTR patients have a more advanced amyloidotic involvement of the heart, despite less severe symptoms and biohumoral signs of heart failure. We can hypothesize that we observed different diseases at different stages. In fact, AL amyloidosis is a multiorgan disease with quick progression rate, that becomes rapidly symptomatic, whereas TTR amyloidosis might have a slow progression rate and might remain poorly symptomatic for a greater amount of time.