Multimodal Chronic Pain Therapy for Adults via Smartphone: Randomized Controlled Clinical Trial.

BACKGROUND: Combination therapies delivered remotely via the internet or mobile devices are increasingly being used to improve and promote the self-management of chronic conditions. However, little is known regarding the long-term effects of these interventions. OBJECTIVE: The aim of this study is to evaluate the effectiveness of a multimodal intervention program that measures associated variables such as catastrophizing, pain acceptance, and quality of life using a mobile device in people with chronic pain in an outpatient setting. METHODS: A randomized controlled clinical trial was performed using parallel treatment groups. A total of 209 patients with chronic musculoskeletal pain were randomly assigned to one of the two study arms. The intervention group received a standard web-based psychosocial therapy-type program of activities through a smartphone for 6 weeks. The control group only had access to the Find out more section of the app, which contained audiovisual material for pain management based on a self-help approach. The primary outcome was catastrophizing measured using the Pain Catastrophizing Scale (PCS). Secondary outcomes were pain acceptance measured using the Chronic Pain Acceptance Questionnaire and health-related quality of life measured using the EuroQol Visual Analogue Scale. Assessments were conducted at baseline (T1), after treatment (T2), and at the 3-month follow-up (T3). The variations between the different phases were assessed using the percentage change rescaled with log base 2. The Cohen d was calculated based on the results of the linear mixed model. The investigators of the study who evaluated the results were not involved in patient recruitment and were blinded to the group assignment. RESULTS: Positive effects were found in the intervention group (T2-T1) in catastrophizing between the baseline and posttreatment phases (P<.001) and in helplessness (-0.72 vs 0.1; P=.002), rumination (-1.59 vs -0.53; P<.001), acceptance (0.38 vs 0.05; P=.001), and quality of life (0.43 vs -0.01; P=.002), although no significant changes were found for magnification (0.2 vs 0.77; P=.14) and satisfaction with health (0.25 vs -0.27; P=.13). Three months after treatment, significant differences were observed in the intervention group for the outcome variable of catastrophizing (PCS; -0.59 vs 0.2; P=.006) and the PCS subscales of helplessness (-0.65 vs 0.01; P=.07), rumination (1.23 vs -0.59; P=.04), and magnification (0.1 vs 0.86; P=.02). CONCLUSIONS: The results of our study suggest that app-based mobile multidimensional treatments for adults with chronic pain improve catastrophizing, quality of life, and psychological flexibility immediately after treatment and that the effects are maintained for the primary outcome of catastrophizing for at least 3 months following treatment. Moreover, they promote self-management and can be used to complement face-to-face pain treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04509154; https://clinicaltrials.gov/ct2/show/NCT04509154.

Intrahepatic angiopoietin-2 correlates with chronic hepatitis C progression and is induced in hepatitis C virus replicon systems.

BACKGROUND & AIMS: Chronic hepatitis C (CHC) is a major cause of cirrhosis and hepatocellular carcinoma and angiogenesis is closely related to the pathogenesis and progression of different chronic liver diseases (CLD). Thus, the intrahepatic expression of angiopoietins 1 and 2 (Ang1 and Ang2), as relevant mediators of pathological angiogenesis in several CLD, was investigated. In addition, the differential influence of structural and non-structural genomic regions of HCV on the expression of angiopoietins and the possible signalling involved were studied. METHODS: Ang1 and Ang2 expression was evaluated by western blotting and enzyme-linked immunosorbent assay (ELISA) in liver homogenates of CHC patients (n=47) and uninfected subjects (n=8). Their association with disease progression (according to METAVIR classification) was assessed by Spearman's correlation. Statistical differences among the expression of angiopoietins at different CHC stages were calculated by Mann-Whitney U-test. Finally, the in vitro expression of Angiopoietins in HCV replicons (complete or non-structural subgenomic) and the main signalling pathways involved were also examined. RESULTS: Ang2 levels were significantly higher in the liver of CHC patients compared to controls and significantly correlated with inflammation and fibrosis. Accordingly, an increased expression of Ang2 was found in all HCV replicons tested. Interestingly, the inhibition of MEK and PI3K signalling pathways exerted differential effects on Ang2 expression concerning to the genomic region of HCV. CONCLUSIONS: Hepatitis C virus induces Ang2 expression in hepatocytes through different signalling routes which may lead to the disregulation of vascular homeostasis in the liver. Thus, pharmacologic intervention on Ang2 signalling might constitute an important therapeutic tool.

Aneurysmal Degeneration in Patients with Type B Aortic Dissection.

BACKGROUND: The optimal management of type B aortic dissection (TBAD) remains controversial in the era of endovascular therapies. This study reports the outcomes and complication rates of different treatment paradigms for TBAD. METHODS: A retrospective review was undertaken of all patients with TBAD from June 2006 to June 2012. Demographics, hospital course, and follow-up visits were analyzed. Patients who underwent surgical interventions were compared to those with medical therapy. Survival rates and predictors of outcome were determined using the Kaplan-Meier method with Cox proportional hazards. RESULTS: Of 261 consecutive patients who were hospitalized during this period with a confirmed thoracic dissection, 134 (51%) had TBAD. Sixty-two (46%) were women, and the mean age was 66.4 ± 14.9. Median follow-up was 22.4 (0, 184) months. Thirty-five patients underwent surgical intervention with 20 thoracic endovascular aortic repair (TEVAR) and open surgery in 15. The overall 30-day mortality was 7%, and cumulative survival rates at 1, 3, and 5 years were 85% (95% confidence interval [CI], 79-91), 68% (95% CI, 59-78), and 57% (95% CI, 47-69) with no difference between medical versus surgical groups (P = 0.8) and TEVAR versus open surgery group (P = 1.0). Sixty-six (50%) patients developed aneurysmal expansion, which required surgical intervention in 26 (hazard ratios [HR], 0.99; P = 0.96). Malperfusion and rupture only occurred in 5 (HR, 1.57; P = 0.54) and 5 (HR, 3.64; P = 0.01) patients, respectively. Multivariate analysis for overall survival found renal insufficiency (HR, 2.6; P = 0.004) and age (HR, 1.06; P < 0.0001) and rupture (HR 3.3, P = 0.04) were independent predictors of mortality. Intramural hematoma was not a significant predictor of survival (HR, 0.49; P = 0.11). CONCLUSIONS: Medical therapy remains the mainstay of treating TBAD with low morbidity. Surgical interventions are indicated in selected patients with malperfusion or aneurysmal expansion with comparable survival rates.

Advancing disability-inclusive climate research and action, climate justice, and climate-resilient development.

Globally, more than 1 billion people with disabilities are disproportionately and differentially at risk from the climate crisis. Yet there is a notable absence of climate policy, programming, and research at the intersection of disability and climate change. Advancing climate justice urgently requires accelerated disability-inclusive climate action. We present pivotal research recommendations and guidance to advance disability-inclusive climate research and responses identified by a global interdisciplinary group of experts in disability, climate change, sustainable development, public health, environmental justice, humanitarianism, gender, Indigeneity, mental health, law, and planetary health. Climate-resilient development is a framework for enabling universal sustainable development. Advancing inclusive climate-resilient development requires a disability human rights approach that deepens understanding of how societal choices and actions-characterised by meaningful participation, inclusion, knowledge diversity in decision making, and co-design by and with people with disabilities and their representative organisations-build collective climate resilience benefiting disability communities and society at large while advancing planetary health.

Preliminary evidence of sustained expression of angiopoietin-2 during monocyte differentiation in chronic hepatitis C.

BACKGROUND: Monocytes are essential precursors of antigen-presenting cells, such as macrophages and dendritic cells, and contribute to the pathogenesis of chronic inflammatory diseases and cancer. AIMS: As Tie2-expressing monocytes (TEMs) are increased in the peripheral blood of patients with chronic hepatitis C (CHC), we aimed to examine the expression of Tie2 and angiopoietins (Ang1 and Ang2) during monocyte differentiation and maturation in CHC. METHODS: The expression of Tie2, CD11b, CD80, CD83, CD86 and MHC-II was measured by flow cytometry in peripheral blood monocytes and monocytes-derived cells (Mo-DCs) from nine healthy subjects and eight CHC patients whose HCV infection was unresolved after combination therapy. Ang1 and Ang2 levels were measured in cellular supernatants by ELISA. RESULTS: Mo-DCs from CHC patients expressed differential patterns of maturation markers compared with controls--primarily with regard to CD80. Tie2 was downregulated during monocyte differentiation in controls and CHC patients, whereas Ang1 expression was constant. However, Ang2 levels fell significantly during the differentiation of control monocytes, in contrast with those from CHC patients in whom Ang2 expression remained stable throughout differentiation. CONCLUSIONS: Altered expression of the Ang/Tie2 system in monocytes and Mo-DCs from CHC patients might account for the inflammatory and angiogenic disorders that are related to CHC. An increased understanding of Ang/Tie2 system regulation might be helpful in designing strategies to prevent CHC progression.

NGS Custom Panel Implementation in Patients with Non-Syndromic Autism Spectrum Disorders in the Clinical Routine of a Tertiary Hospital.

Autism spectrum disorder (ASD) is a set of neurodevelopmental disorders characterized by deficiencies in communication, social interaction, and repetitive and restrictive behaviors. The discovery of genetic involvement in the etiology of ASD has made this condition a strong candidate for genome-based diagnostic tests. Next-generation sequencing (NGS) is useful for the detection of variants in the sequence of different genes in ASD patients. Herein, we present the implementation of a personalized NGS panel for autism (AutismSeq) for patients with essential ASD over a prospective period of four years in the clinical routine of a tertiary hospital. The cohort is composed of 48 individuals, older than 3 years, who met the DSM-5 (The Diagnostic and Statistical Manual of Mental Disorders) diagnostic criteria for ASD. The NGS customized panel (AutismSeq) turned out to be a tool with good diagnostic efficacy in routine clinical care, where we detected 12 "pathogenic" (including pathogenic, likely pathogenic, and VUS (variant of uncertain significance) possibly pathogenic variations) in 11 individuals, and 11 VUS in 10 individuals, which had previously been negative for chromosomal microarray analysis and other previous genetic studies, such as karyotype, fragile-X, or MLPA/FISH (Multiplex Ligation dependent Probe Amplification/Fluorescence in situ hybridization) analysis. Our results demonstrate the high genetic and clinical heterogeneity of individuals with ASD and the current difficulty of molecular diagnosis. Our study also shows that an NGS-customized panel might be useful for diagnosing patients with essential/primary autism and that it is cost-effective for most genetic laboratories.

Vitrified blastocysts from Preimplantation Genetic Diagnosis (PGD) as a source for human Embryonic Stem Cell (hESC) derivation.

Embryos diagnosed as abnormal in Preimplantation Genetic Diagnosis (PGD) cycles are useful for the establishment of human Embryonic Stem Cells (hESC) lines with genetic disorders. These lines can be helpful for drug screening and for the development of new treatments. Vitrification has proved to be an efficient method to preserve human blastocysts. One hundred and three abnormal or undiagnosed vitrified blastocysts from the PGD programme at Institut Universitari Dexeus were donated for human embryonic stem cell derivation. The overall survival rate after warming was 70.6 %. Our results showed better survival rates when blastocysts have not started the hatching process (initial/expanded 87.8 %, hatching 68.3 % and hatched 27.3 %). Thirty-five blastocysts and 12 partially surviving embryos were seeded. One hESC line with the multiple exostoses type 2 paternal mutation was obtained.

Multimodal Interventions to Improve the Management of Chronic Non-Malignant Pain in Primary Care Using Participatory Research.

BACKGROUND: The use of diverse therapies combined with a multidisciplinary approach and prevention initiatives for patients with chronic non-malignant pain (CNMP) can improve health and have a positive impact on psychotropic drug use and the self-management of pain. PURPOSE: This purpose of this study has been two-fold: to conduct a literature review with a view to selecting best evidence recommendations for CNMP and to prioritize self-care recommendations using a participatory methodology for the analysis and selection of interventions. METHODS: A qualitative, descriptive, and documentary method based on participatory action research was used. FINDINGS: Based on the study results, a multimodal psychosocial intervention program has been designed for CNMP that includes psychoeducational therapy, pharmacological therapy, physical exercise, and health assets. DISCUSSION: The findings are consistent with previous studies underlining the need to invest in resources for the management of CNMP, including strategies for good differential diagnoses and pharmacological treatments combined with non-pharmacological treatments to confer greater well-being for people living with pain who want to participate in their own recovery.

The hepatitis B virus X protein induces paracrine activation of human hepatic stellate cells.

UNLABELLED: Chronic hepatitis B virus (HBV) infection is a major cause of liver fibrosis, eventually leading to cirrhosis and hepatocellular carcinoma. Although the involvement of the X protein of HBV (HBx) in viral replication and tumor development has been extensively studied, little is known about its possible role in the development of fibrosis. In this work we show that expression of HBx in hepatocytes results in paracrine activation and proliferation of hepatic stellate cells (HSCs), the main producers of extracellular matrix proteins in the fibrotic liver. Both human primary HSCs and rat HSCs exposed to conditioned medium from HBx-expressing hepatocytes showed increased expression of collagen I, connective tissue growth factor, alpha smooth muscle actin, matrix metalloproteinase-2, and transforming growth factor-beta (TGF-beta), together with an enhanced proliferation rate. We found that HBx induced TGF-beta secretion in hepatocytes and that the activation of HSCs by conditioned medium from HBx-expressing hepatocytes was prevented by a neutralizing anti-TGF-beta antibody, indicating the involvement of this profibrotic factor in the process. CONCLUSION: Our results propose a direct role for HBx in the development of liver fibrosis by the paracrine activation of stellate cells and reinforce the indication of antiviral treatment in patients with advanced HBV-related chronic liver disease and persistent liver replication.

Thiamine deficiency impairs common eider (Somateria mollissima) reproduction in the field.

The Baltic Sea population of the common eider (Somateria mollissima) has declined dramatically during the last two decades. Recently, widespread episodic thiamine (vitamin B1) deficiency has been demonstrated in feral birds and suggested to contribute significantly to declining populations. Here we show that the decline of the common eider population in the Baltic Sea is paralleled by high mortality of the pulli a few days after hatch, owing to thiamine deficiency and probably also thereby associated abnormal behaviour resulting in high gull predation. An experiment with artificially incubated common eider eggs collected in the field revealed that thiamine treatment of pulli had a therapeutic effect on the thiamine status of the brain and prevented death. The mortality was 53% in untreated specimens, whereas it was only 7% in thiamine treated specimens. Inability to dive was also linked to brain damage typical for thiamine deficiency. Our results demonstrate how thiamine deficiency causes a range of symptoms in the common eider pulli, as well as massive die-offs a few days after hatch, which probably are the major explanation of the recent dramatic population declines.

Generation of integration-free induced pluripotent stem cell lines derived from two patients with X-linked Alport syndrome (XLAS).

Skin biopsies were obtained from two male patients with X-linked Alport syndrome (XLAS) with hemizygous COL4A5 mutations in exon 41 or exon 46. Dermal fibroblasts were extracted and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53 shRNA. The generated induced Pluripotent Stem Cell (iPSC) lines AS-FiPS2-Ep6F-28 and AS-FiPS3-Ep6F-9 were free of genomically integrated reprogramming genes, had the specific mutations, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro. These iPSC lines offer a useful resource to study Alport syndrome pathomechanisms and drug testing.

Mild cognitive impairment (MCI) and dementia in a sample of adults in the city of Bogotá.

The low prevalence of dementia described in communities is likely due to the low sensitivity of screening tests and an absence of evaluation by specialists. OBJECTIVE: To estimate the prevalence of mild cognitive impairment (MCI) and dementia in adults older than 50 years. METHODS: A two-phase, cross-sectional study was conducted by specialists to evaluate cognition and associated demographic risk factors in 1,235 independent community-dwelling adults from Bogotá. In Phase I, screening was performed using the MMSE and MoCA tests. In Phase II, after application of a comprehensive neuropsychological battery with neurologic and psychiatric evaluations, a cognitive diagnosis was established by consensus. RESULTS: The prevalence found for MCI was 34% and for dementia was 23%. MCI was associated with incomplete high school, OR=1.74 (95%CI=1.23-2.45), and with an age of 70-79 years, OR=1.93 (95%CI=1.47-2.53). A total of 73% of MCI cases were amnestic. Dementia was associated with incomplete primary education, OR=8.98 (95%CI=5.56-14.54), complete primary education, OR=6.23 (95%CI=3.70-10.47), and age older than eighty years, OR=3.49 (95%CI=2.23-5.44). CONCLUSION: The prevalence of dementia found was greater than the rates reported in previous studies. Low educational level was the main risk factor for cognitive impairment and should be considered in strategic planning for the local health system.

A baixa prevalência de demência relatada em comunidades deve ser devida ao emprego de testes de rastreio de baixa sensibilidade e à falta da avaliação por especialistas. OBJETIVO: Estimar a prevalência de comprometimento cognitivo leve (CCL) e demência em adultos com idade superior a 50 anos. MÉTODOS: Um estudo transversal de duas fases realizado por especialistas, avaliando a cognição e os fatores de risco demográficos associados, com 1.235 adultos autônomos da comunidade em Bogotá. Em uma Fase I, foram realizados os testes de rastreio MEEM e MoCA. Na Fase II, após uma ampla bateria neuropsicológica com avaliações neurológicas e psiquiátricas, foi estabelecido um diagnóstico cognitivo por consenso. RESULTADOS: A prevalência encontrada de CCL foi de 34% e de demência, de 23%. CCL foi associado a ensino médio incompleto, OR=1,74 (IC 95%=1,23-2,45) e idade entre 70-79 anos, OR=1,93 (IC 95%=1,47-2,53). Entre os casos de CCL, 73% eram amnésticos. A demência foi associada a ensino fundamental incompleto, OR=8,98 (IC 95%=5,56-14,54), ensino fundamental completo, OR=6,23 (IC 95%=3,70-10,47) e idade superior a oitenta anos, OR=3,49 (IC 95%=2,23-5,44). CONCLUSÃO: A prevalência de demência encontrada é maior do que a relatada em estudos prévios. O baixo nível educacional foi o principal fator de risco para declínio cognitivo e deve ser considerado no planejamento estratégico do nosso sistema de saúde.

Integration-free induced pluripotent stem cells derived from a patient with autosomal recessive Alport syndrome (ARAS).

A skin biopsy was obtained from a 25-year-old female patient with autosomal recessive Alport syndrome (ARAS) with the homozygous COL4A3 mutation c.345delG, p.(P166Lfs*37). Dermal fibroblasts were derived and reprogrammed by nucleofection with episomal plasmids carrying OCT3/4, SOX2, KLF4 LIN28, L-MYC and p53shRNA. The generated induced Pluripotent Stem Cell (iPSC) clone AS FiPS1 Ep6F-2 was free of genomically integrated reprogramming genes, had the specific homozygous mutation, a stable karyotype, expressed pluripotency markers and generated embryoid bodies which were differentiated towards the three germ layers in vitro. This iPSC line offers a useful resource to study Alport syndrome pathomechanisms and drug testing.

Interferon-related genetic markers of necroinflammatory activity in chronic hepatitis C.

INTRODUCTION: Chronic hepatitis C (CHC) is a major cause of liver disease worldwide which often leads to progressive liver inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). CHC displays heterogeneous progression depending on a broad set of factors, some of them intrinsic to each individual such as the patient's genetic profile. This study aims to evaluate the contribution of certain genetic variants of crucial interferon alpha and lambda signaling pathways to the hepatic necroinflammatory activity (NIA) grade of CHC patients. METHODS: NIA was evaluated in 119 CHC patients by METAVIR scale and classified as low (NIA = 0-2, n = 80) or high grade (NIA = 3, n = 39). In a candidate gene approach, 64 SNPs located in 30 different genes related to interferon pathways (IL-28B, IFNAR1-2, JAK-STAT and OAS1-3, among others) were genotyped using the Illumina GoldenGate® Genotyping Assay. Statistical association was determined by logistic regression and expressed as OR and 95% CI. Those SNPs significantly associated were further adjusted by other covariates. RESULTS: Seven SNPs located in IL-28B (rs12979860), JAK1 (rs11576173 and rs1497056), TYK2 (rs280519), OAS1 (rs2057778), SOCS1 (rs33932899) and RNASEL (rs3738579) genes were significantly related to severe NIA grade (p<0.05). Regarding to clinical variables, elevated NIA was notably associated with aspartate aminotransferase (AST) serum levels >40 IU/L (p<0.05) but not with other clinical factors. Multivariate logistic regression analysis of these factors reflected that AST (>40 IU/L), TYK2 rs280519 (G allele) and RNASEL rs3738579 (G allele) were factors independently associated with elevated NIA (p<0.05). AST concentration showed a moderate AUC value (AUC = 0.63), similar to TYK2 (rs280519) and RNASEL (rs3738579) SNPs (AUC = 0.61, both) in the ROC_AUC analysis. Interestingly, the model including all significant variables reached a considerable predictive value (AUC = 0.74). CONCLUSION: The identified genetic variants in interferon signaling pathways may constitute useful prognostic markers of CHC progression. Further validation in larger cohorts of patients is needed.

Comparative study of human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) as a treatment for retinal dystrophies.

Retinal dystrophies (RD) are major causes of familial blindness and are characterized by progressive dysfunction of photoreceptor and/or retinal pigment epithelium (RPE) cells. In this study, we aimed to evaluate and compare the therapeutic effects of two pluripotent stem cell (PSC)-based therapies. We differentiated RPE from human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs) and transplanted them into the subretinal space of the Royal College of Surgeons (RCS) rat. Once differentiated, cells from either source of PSC resembled mature RPE in their morphology and gene expression profile. Following transplantation, both hESC- and hiPSC-derived cells maintained the expression of specific RPE markers, lost their proliferative capacity, established tight junctions, and were able to perform phagocytosis of photoreceptor outer segments. Remarkably, grafted areas showed increased numbers of photoreceptor nuclei and outer segment disk membranes. Regardless of the cell source, human transplants protected retina from cell apoptosis, glial stress and accumulation of autofluorescence, and responded better to light stimuli. Altogether, our results show that hESC- and hiPSC-derived cells survived, migrated, integrated, and functioned as RPE in the RCS rat retina, providing preclinical evidence that either PSC source could be of potential benefit for treating RD.

Conocimientos, actitudes y prácticas sobre donación y trasplante de córneas en comunidades rurales y urbanas de Honduras / Knowledge, attitudes and practices about corneal donation and transplantation in rural and urban communities in Honduras

Introducción: aproximadamente 600 personas urgen de trasplante de córnea en Honduras. La mayor dificultad para este procedimiento es que no se cuenta con banco de ojo en el país. Además, los estudios de conocimiento sobre donación y trasplante, son escasos. Objetivo: conocer las actitudes y prácticas de la población rural versus la urbana sobre la donación y trasplante de córnea, según conocimientos y factores sociodemográficos, con el fin de diseñar un plan de acción para concientizar la importancia de una conducta donante positiva para el beneficio del paciente con ceguera corneal. Metodología: estudio descriptivo realizado entre mayo y septiembre del 2019 en Comayagua, Intibucá y Francisco Morazán. Con una muestra de 350 personas por departamento, para un total de 1050 participantes mayores de 18 años y de ambos sexos. Se realizó entrevista por investigadores, bajo la escala de Likert, previamente validado. Variables agrupadas en demográficas, socio personales, laborales, conocimiento, creencias y aptitudes. Se analizaron los datos mediante razón de probabilidades y productos cruzados. Los resultados se expresaron en porcentajes, frecuencias y odd ratio. Resultados: 74.86% manifestó una actitud donante positiva, el 67.55% donaría a cualquier persona que lo necesitase, 48% conocía acerca de las características requeridas para el donante y. menos del 10% sabía qué es la córnea. Los factores negativos para la donación son la procedencia rural, la parentela y el desempleo en Intibucá y motivos religiosos en el área rural de Comayagua y población urbana de Francisco Morazán. Conclusiones: Es importante superar las limitaciones impuestas por la desinformación, para ello es necesario impulsar una cultura de donación a través de la creación de estrategias comunicativas de educación, con el fin de mejorar la salud visual y la demanda poblacional...(AU)

Widespread episodic thiamine deficiency in Northern Hemisphere wildlife.

Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiamine-dependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.

Predicción temporal de CD4+ en 80 pacientes con manejo antirretroviral a partir de valores de leucocitos / CD4+ temporal prediction in 80 patients with antiretroviral management from leukocyte counts

Objetivo: establecer una metodología predictiva de aplicación clínica de recuentos de CD4+ en rangos de interés clínico a partir del recuento absoluto de leucocitos. Metodología: a partir de los valores secuenciales de leucocitos y linfocitos CD4+ de 9 pacientes, se observaron patrones matemáticos que posteriormente fueron aplicados en un estudio ciego con 71 casos para confirmar su capacidad predictiva, midiendo porcentajes de especificidad y sensibilidad. Resultados: se determinaron cinco patrones matemáticos que predicen en el 99% de los casos los distintos recuentos de CD4+ a partir de recuentos de leucocitos con valores de especificidad y sensibilidad del 99%. Conclusiones: los patrones matemáticos encontrados entre recuento de leucocitos y CD4+ sugieren que este fenómeno prácticamente es determinista.

Objective: To establish a predictive methodology of CD4+ counts for clinical application in ranges of clinical interest based on the absolute leukocyte count. Methodology: From sequential values of leukocytes and CD4+ lymphocytes of nine patients, mathematical patterns were observed and applied in a blind study with 71 cases to confirm their predictive capacity, measuring percentages of specificity and sensitivity. Results: Five mathematical patterns were determined that predict 99% of the cases in which CD4+ counts are obtained from leukocyte counts with specificity and sensitivity values of 99%. Conclusions: The mathematical patterns found between leukocytes and CD4 counts suggest that this phenomenon is practically deterministic.

Effects of facility characteristics on departures from assisted living: results from a national study.

PURPOSE: Assisted living is an increasingly important residential setting for the frail elderly person. How often and why residents leave such facilities are important issues for consumers, for clinicians advising frail patients on their options for living arrangements, and for policymakers. This research investigated the impact of facility and individual characteristics on residents' departures from assisted living. DESIGN AND METHODS: This research is based on data on 1,483 residents in a nationally representative sample of 278 assisted living facilities (ALFs). Analyses of these data from 1998 and 1999 especially focused on those residents who left a study ALF between baseline and follow-up data collection. Multinomial logit models were estimated to investigate the impact of facility and individual factors on residents' status at follow-up. RESULTS: Over three quarters of those leaving their baseline ALF did so because they needed more care. The multivariate analyses indicated that poorer functional status and being married affected residents' relative odds of death before follow-up. Moving to another setting, other than a nursing home, was more likely for residents in for-profit ALFs. Functional status, cognitive status, and the presence of a full-time RN affected residents' odds of moving from an ALF to a nursing home. IMPLICATIONS: Both facility-level and individual-level factors affected residents' relative odds of leaving an ALF. The findings with the most potentially interesting policy implications are those concerning the factors that affected residents' relative likelihoods of entering a nursing home.