Characterization and Investigation of Risk Factors for Late-Relapsing Hepatitis After Yellow Fever.

BACKGROUND: Late-relapsing hepatitis after yellow fever (LHep-YF) during the convalescent phase of the disease has been described during recent yellow fever (YF) outbreaks in Brazil. LHep-YF is marked by a rebound in liver enzymes and nonspecific clinical manifestations around 46-60 days after YF symptom onset. METHODS: Here we have characterized the clinical course and risk factors for LHep-YF using data from a representative cohort of patients who survived YF in Brazil, 2017-2018. A total of 221 YF-positive patients were discharged from the infectious disease reference hospital in Minas Gerais and were followed up at 30, 45, and 60 days post-symptom onset. RESULTS: From 46 to 60 days post-symptom onset, 16% of YF patients (n = 36/221) exhibited a rebound of aminotransferases (aspartate aminotransferase or alanine aminotransferase >500 IU/L), alkaline phosphatase, and total bilirubin levels. Other etiologies of liver inflammation such as infectious hepatitis, autoimmune hepatitis, and metabolic liver disease were ruled out. Jaundice, fatigue, headache, and low platelet levels were associated with LHep-YF. Demographic factors, clinical manifestations, laboratory tests, ultrasound findings, and viral load during the acute phase of YF were not associated with the occurrence of LHep-YF. CONCLUSIONS: These findings provide new data on the clinical course of Late-relapsing hepatitis during the convalescent phase of YF and highlight the need for extended patient follow-up after acute YF.

High-dimensional single-cell analysis reveals the immune characteristics of COVID-19.

Coronavirus disease 2019 (COVID-19), driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a global pandemic in March 2020. Pathogenic T cells and inflammatory monocytes are regarded as the central drivers of the cytokine storm associated with the severity of COVID-19. In this study, we explored the characteristic peripheral cellular profiles of patients with COVID-19 in both acute and convalescent phases by single-cell mass cytometry (CyTOF). Using a combination of algorithm-guided data analyses, we identified peripheral immune cell subsets in COVID-19 and revealed CD4+ T-cell depletion, T-cell differentiation, plasma cell expansion, and the reduced antigen presentation capacity of innate immunity. Notably, COVID-19 induces a dysregulation in the balance of monocyte populations by the expansion of the monocyte subsets. Collectively, our results represent a high-dimensional, single-cell profile of the peripheral immune response to SARS-CoV-2 infection.

Physical function and health-related quality of life in the convalescent phase in surgically treated patients with malignant pleural mesothelioma.

PURPOSE: According to reports, patients with lung cancer have decreased pulmonary function and exercise capacity after surgery. However, to date, physical function and health-related quality of life (HRQOL) after surgery for malignant pleural mesothelioma (MPM) have not been evaluated in detail in the convalescent phase. This study aimed to assess physical function and HRQOL of MPM patients following pleurectomy/decortication (P/D) in the convalescent phase. METHODS: The study included 16 male MPM patients who underwent P/D between September 2014 and August 2016. Physical function was assessed based on handgrip and knee extensor strengths, the six-minute walk distance (6MWD), and pulmonary function, including forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). HRQOL was assessed using the Medical Outcome Study 36-item Short Form Health Survey (SF-36). The assessment was performed preoperatively, postoperatively, and 1-year after surgery. RESULTS: The 6MWD, FVC, and FEV1 values 1-year postoperatively improved significantly compared with baseline (P < 0.05 all). Additionally, the scores of six of the eight SF-36 domains were significantly improved 1 year after P/D: physical functioning, body pain, general health, vitality, social functioning, and mental health (all P < 0.05). 6MWD, FVC, and FEV1 were correlated with vitality, mental health, and physical functioning (P < 0.05 all). CONCLUSIONS: Patients with MPM who underwent P/D showed improved physical function and HRQOL compared with postoperative values in the convalescent phase. Physicians, nurses, and rehabilitation staff should note these findings, which may provide insight into the development of customized rehabilitation strategies in the convalescent phase for such patients.

Comprehensive Characterization of Cellular Immune Responses Following Ebola Virus Infection.

The West African Ebola virus disease (EVD) outbreak was the largest EVD outbreak in history. However, data on lymphocyte dynamics and the antigen specificity of T cells in Ebola survivors are scarce, and our understanding of EVD pathophysiology is limited. A case of EVD survival in which the patient cleared Ebola virus (EBOV) infection without experimental drugs allowed for the detailed examination of lymphocyte dynamics. We demonstrate the persistence of T-cell activation well beyond viral clearance and detect EBOV-specific T cells. Our study provides significant insights into lymphocyte specificity during the recovery phase of EVD and may inform novel strategies to treat EVD.

Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia.

We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.

Uveitis and Systemic Inflammatory Markers in Convalescent Phase of Ebola Virus Disease.

We report a case of probable Zaire Ebola virus-related ophthalmologic complications in a physician from the United States who contracted Ebola virus disease in Liberia. Uveitis, immune activation, and nonspecific increase in antibody titers developed during convalescence. This case highlights immune phenomena that could complicate management of Ebola virus disease-related uveitis during convalescence.

Rehabilitation for Cerebrovascular Disease: Current and new methods in Japan.

Rehabilitation is treated as an independent subject in Japanese Guidelines for the Management of Stroke 2009, formulated primarily by 5 academic societies, namely The Japan Stroke Society, The Japan Neurosurgical Society, Societas Neurologica Japonica, Japanese Society of Neurological Therapeutics, and The Japanese Association of Rehabilitation Medicine. Rehabilitation is discussed in terms of "procedures for stroke rehabilitation" and "rehabilitation for main disorders and problems." Rehabilitation should be carried out based on these criteria. As one approach that should be pursued in stroke rehabilitation, we recommend the treatment concept of incorporating intensive rehabilitation intervention simultaneously to the extent possible to encourage functional compensation ability, which we call intensive neurorehabilitation. For example, the patient receives preconditioning to improve the brain's plasticity, followed by intensive and active rehabilitation. Following this approach, positive results have been achieved in pioneering and systematic tests, which focused on using low-frequency rTMS (repetitive transcranial magnetic stimulation) and intensive training with patients who are paralyzed in the upper limbs.

Adipocytokine profile in children with Kawasaki disease at a mean follow-up period of 5.5 years: A study from North India.

BACKGROUND: Kawasaki disease (KD) is an acute self-limited vasculitis with a predilection for coronary arteries. Children with KD may have altered lipid metabolism and abnormal lipid profiles that may last for prolonged periods. However, there is a paucity of literature on the role of adipocytokines in KD. AIM: To estimate the levels of adipocytokines (adiponectin, leptin and resistin) during the convalescent phase of KD. METHODS: Twenty children, who had KD at least three years earlier, were enrolled in this study. In addition, 20 healthy controls were also enrolled. Clinical and laboratory profiles of patients were obtained from hospital records. Serum adiponectin, leptin and resistin levels were estimated by enzyme-linked immunosorbent assay. RESULTS: Mean age of the patients in the study group was 10.15 ± 3 years and the male: female ratio was 1.5:1. Median serum resistin levels in patients with KD (27.77 ng/mL; [IQR: 18.66, 48.90]) were decreased compared to controls (21.20 ng/mL; [IQR: 14.80, 27.00]) (P = 0.04). Median serum leptin levels in cases and controls were 1.83 ng/mL; (IQR: 1.13, 3.80), and 1.10 ng/mL; (IQR: 0.41, 2.88), respectively (P = 0.09). Median serum adiponectin levels were similar in both cases (12.20 µg/mL; [IQR: 9.76, 17.97]) and controls (13.95 µg/mL; [IQR: 11.17, 22.58]); (P = 0.18). There was no significant difference in all 3 adipocytokines between children with (4/20) and without coronary artery abnormalities (16/20). CONCLUSION: Serum resistin levels were significantly elevated in patients with KD during the convalescent phase compared to controls. Serum leptin levels appeared to be higher in patients with KD, although the difference was not statistically significant. Adiponectin levels were similar in both cases and controls. Raised resistin and leptin levels may partially explain lipid perturbations observed during the convalescent phase of KD.

Limited Variation between SARS-CoV-2-Infected Individuals in Domain Specificity and Relative Potency of the Antibody Response against the Spike Glycoprotein.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is arranged as a trimer on the virus surface, composed of three S1 and three S2 subunits. Infected and vaccinated individuals generate antibodies against spike, which can neutralize the virus. Most antibodies target the receptor-binding domain (RBD) and N-terminal domain (NTD) of S1; however, antibodies against other regions of spike have also been isolated. The interhost variability in domain specificity and relative neutralization efficacy of the antibodies is still poorly characterized. To this end, we tested serum and plasma samples collected from 85 coronavirus disease 2019 (COVID-19) convalescent subjects. Samples were analyzed using seven immunoassays that employ different domains, subunits, and oligomeric forms of spike to capture the antibodies. Samples were also tested for their neutralization of pseudovirus containing SARS-CoV-2 spike and of replication-competent SARS-CoV-2. While the total amount of anti-spike antibodies produced varied among convalescent subjects, we observed an unexpectedly fixed ratio of RBD- to NTD-targeting antibodies. The relative potency of the response (defined as the measured neutralization efficacy relative to the total level of spike-targeting antibodies) also exhibited limited variation between subjects and was not associated with the overall amount of antispike antibodies produced. These studies suggest that host-to-host variation in the polyclonal response elicited against SARS-CoV-2 spike in early pandemic subjects is primarily limited to the quantity of antibodies generated rather than their domain specificity or relative neutralization potency. IMPORTANCE Infection by SARS-CoV-2 elicits antibodies against various domains of the spike protein, including the RBD and NTD of subunit S1 and against subunit S2. The antibody responses of different infected individuals exhibit different efficacies to inactivate (neutralize) the virus. Here, we show that the observed variation in the neutralizing activity of the antibody responses in COVID-19 convalescent subjects is caused by differences in the amounts of antibodies rather than their recognition properties or the potency of their antiviral activity. These findings suggest that COVID-19 vaccine strategies that focus on enhancing the overall level of the antibodies will likely elicit a more uniformly efficacious protective response.

Kinetics of the neutralising antibody response in patients with hand, foot, and mouth disease caused by EV-A71: A longitudinal cohort study in Zhengzhou during 2017-2019.

BACKGROUND: Hand, foot, and mouth disease (HFMD) caused by enterovirus A71 (EV-A71) poses a serious threat to children's health. Kinetics of the neutralising antibody (NAb) response in EV-A71 infected HFMD patients remains unclear. The ideal sampling time of paired serum samples for serological diagnosis of EV-A71 infection is not well defined. METHODS: HFMD inpatients admitted to Henan Children's Hospital between February 15, 2017 and February 15, 2018 were enrolled. Serial serum samples collected during hospitalisation and up to 1.5 years after discharge were tested for NAb against EV-A71. Random intercept modelling with B-spline was conducted to characterize the kinetics of the EV-A71 NAb response over time after illness onset. FINDINGS: A total of 524 serum samples from 264 EV-A71 RNA positive HFMD inpatients were collected. NAb titres of EV-A71 infected patients were estimated to increase from 40 (95% CI: 9-180) at the day of onset to the peak of 2417 (95% CI: 1859-3143) at day 13, then remained above 1240 until 26 months. For serological diagnosis of EV-A71 infection, if at least a 4-fold rise in titre was used as the criteria, the acute phase serum should be collected at 0-4 days, the corresponding convalescent serum should be collected 14.9 days (95% CI: 9.1-23.8) after illness onset. INTERPRETATION: EV-A71 infection induced a strong and persistent humoral immune response in HFMD patients. The findings provide a scientific support for determining the collection time of paired serum samples for serological diagnosis of EV-A71 infected HFMD patients. FUNDING: National Science Fund for Distinguished Young Scholars.

A longitudinal follow-up of COVID-19 patients in the convalescent phase showed recovery in radiological results, the dynamics of lymphocytes, and a decrease in the level of IgG antibody: a single-centre, observational study.

BACKGROUND: Given the high prevalence of coronavirus disease 2019 (COVID-19) globally, and the increased number of patients being discharged, it is necessary to understand the health consequences of COVID-19 to formulate and manage public policy concerning convalescent patients. METHODS: A longitudinal follow-up investigation of 25 patients from a tertiary hospital in Henan provincial was conducted 8 weeks after discharge. Of these patients, 15 attended a second follow-up appointment 8 weeks after that. A throat swab reverse transcription-polymerase chain reaction (RT-PCR) analysis for SARS-CoV-2 and chest computerized tomography (CT) scans were implemented at the first follow-up appointment, and a total of 40 blood samples (25 from the first and 15 from the second follow-up appointment) were collected. Patients' levels of Immunoglobulin G (IgG) antibody against S-Receptor binding domain (S-RBD) and Nucleocapsid Protein (NP) of SARS-CoV-2 and the subpopulation of lymphocytes were evaluated using an enzyme-linked immunoassay (ELISA) test and flow cytometry, respectively. RESULTS: At the first follow-up appointment, 10 of the 25 patients (40.0%) showed complete radiological resolution. Of these patients, 80.0% were classified as moderate, and 80.0% were younger (those whose age was ≤ the median age of all the patients). The predominant patterns of abnormalities included an irregular line (12/25, 48.0%), ground-glass opacity (GGO) (44.0%), and multiple GGOs (28.0%). At the first follow-up appointment, 40.0% (10/25) of patients still had lymphopenia. Of the 15 patients who were followed-up with twice, the ratio of lymphopenia was 80% (12/15), 60.0% (9/15), and 46.7% (7/15) at 0, 8, and 16 weeks after discharge, respectively. This was mainly due to a decrease in the cluster of differentiation (CD) 4+ T lymphocyte, which was observed in 60% (9/15), 60% (9/15), and 46.7% (7/15) of total patients at 0, 8, and 16 weeks after discharge, respectively. All of the patients were S-RBD and NP IgG antibody positive at the first follow-up appointment. 40.0% (6/15) and 66.7% (10/15) of patients showed a decrease over 50.0% in the level of NP and S-RBD IgG antibodies, respectively, at the second follow-up appointment. The NP and S-RBD IgG antibodies' levels declined to 44.6% (P=0.044) and 28.1% (P=0.18), respectively. 0 and 26.7% (4/15) of patients turned from NP and S-RBD IgG antibody positive to negative, respectively. CONCLUSIONS: About half of the patients still showed at least 1 abnormality in chest CT scans 8 weeks after discharge and lymphopenia 16 weeks after discharge. The level of the IgG antibody had declined by the follow-up appointment. Notably, the S-RBD IgG antibody declined more dramatically than that of NP. These results may have implications in the making of policies related to disease prevention, the long-term management of discharged patients, and vaccines' development.

Transitional and Long-Term Care System in Japan and Current Challenges for Stroke Patient Rehabilitation.

In Japan, the national medical insurance system and long-term care insurance (LTCI) system cover rehabilitation therapy for patients with acute, convalescent, and chronic stroke. Medical insurance covers early and multidisciplinary rehabilitation therapy during acute phase hospitalizations. Patients requiring assistance in their activities of daily living (ADL) after hospitalization are transferred to kaifukuki (convalescent) rehabilitation wards (KRW), which the medical insurance system has also covered. In these wards, patients can receive intensive and multidisciplinary rehabilitation therapy to improve their ADL and transition to a smooth home discharge. After discharge from these hospitals, elderly patients with stroke can receive outpatient (day-care) rehabilitation and home-based rehabilitation using the LTCI system. The Japanese government has proposed building a community-based integrated care system by 2025 to provide comprehensive medical services, long-term care, preventive care, housing, and livelihood support for patients. This policy aims to promote smooth coordination between medical insurance services and LTCI providers. Accordingly, the medical insurance system allows hospitals to receive additional fees by providing patient information to rehabilitation service providers in the LTCI system. A comprehensive database on acute, convalescent, and chronic phase stroke patients and seamless cooperation between the medical care system and LTCI system is expected to be established in the future. There are only 2,613 board-certified physiatrists in Japan, and many medical schools lack a department for rehabilitation medicine; establishing such a department at each school is encouraged to teach students efficient medical care procedures, to conduct research, and to facilitate the training of personnel in comprehensive stroke rehabilitation.

Quantifying Absolute Neutralization Titers against SARS-CoV-2 by a Standardized Virus Neutralization Assay Allows for Cross-Cohort Comparisons of COVID-19 Sera.

The global coronavirus disease 2019 (COVID-19) pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent-phase plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous biosafety level 3 (BSL3) conditions, which limits high-throughput screening of patient and vaccine sera. Myriad BSL2-compatible surrogate virus neutralization assays (VNAs) have been developed to overcome this barrier. Yet, there is marked variability between VNAs and how their results are presented, making intergroup comparisons difficult. To address these limitations, we developed a standardized VNA using CoV2-S pseudotyped particles (CoV2pp) based on vesicular stomatitis virus bearing the Renilla luciferase gene in place of its G glycoprotein (VSVΔG); this assay can be robustly produced at scale and generate accurate neutralizing titers within 18 h postinfection. Our standardized CoV2pp VNA showed a strong positive correlation with CoV2-S enzyme-linked immunosorbent assay (ELISA) results and live-virus neutralizations in confirmed convalescent-patient sera. Three independent groups subsequently validated our standardized CoV2pp VNA (n > 120). Our data (i) show that absolute 50% inhibitory concentration (absIC50), absIC80, and absIC90 values can be legitimately compared across diverse cohorts, (ii) highlight the substantial but consistent variability in neutralization potency across these cohorts, and (iii) support the use of the absIC80 as a more meaningful metric for assessing the neutralization potency of a vaccine or convalescent-phase sera. Lastly, we used our CoV2pp in a screen to identify ultrapermissive 293T clones that stably express ACE2 or ACE2 plus TMPRSS2. When these are used in combination with our CoV2pp, we can produce CoV2pp sufficient for 150,000 standardized VNAs/week.IMPORTANCE Vaccines and antibody-based therapeutics like convalescent-phase plasma therapy are premised upon inducing or transferring neutralizing antibodies that inhibit SARS-CoV-2 entry into cells. Virus neutralization assays (VNAs) for measuring neutralizing antibody titers (NATs) are an essential part of determining vaccine or therapeutic efficacy. However, such efficacy testing is limited by the inherent dangers of working with the live virus, which requires specialized high-level biocontainment facilities. We therefore developed a standardized replication-defective pseudotyped particle system that mimics the entry of live SARS-CoV-2. This tool allows for the safe and efficient measurement of NATs, determination of other forms of entry inhibition, and thorough investigation of virus entry mechanisms. Four independent labs across the globe validated our standardized VNA using diverse cohorts. We argue that a standardized and scalable assay is necessary for meaningful comparisons of the myriad of vaccines and antibody-based therapeutics becoming available. Our data provide generalizable metrics for assessing their efficacy.

Efficacy of Getong Tongluo Capsule () for Convalescent-Phase of Ischemic Stroke and Primary Hypertension: A Multicenter, Randomized, Double-Blind, Controlled Trial.

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION: GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

Relationship Between Physical Function and Health Utility in Patients Undergoing Surgical Treatment for Malignant Pleural Mesothelioma.

PURPOSE: Health utility, which is a measure of patient-reported outcome (PRO), has recently been used in health-related quality of life for patients with various cancers. However, the relationship between health utility and the physical function and of patients undergoing pleurectomy/decortication (P/D) as surgical treatment for malignant pleural mesothelioma (MPM) has not been reported in the perioperative and convalescent phases. This study aimed to evaluate the perioperative and postoperative health utility of patients undergoing P/D for MPM at one year postoperatively and to examine the relationship with physical function. METHODS: We included patients underwent P/D. Grip strength, knee extension strength, 6-minute walk distance (6MWD), forced vital capacity (FVC), and forced expiratory volume in one second (FEV1) were measured to assess physical function, and the Short-Form Six-Dimension (SF-6D) was completed to assess health utility. These assessments were performed preoperatively, postoperatively, and one year postoperatively. Statistical analysis was performed using one-way analysis of variance for comparison of pre and postoperative and one year mean values. RESULTS: There were 24 subjects (23 males, 65.5±8.3 year). SF-6D, 6MWD, FVC, and FEV1 values one year operatively improved significantly compared with postoperative. Additionally, SF-6D was correlated with 6MWD. CONCLUSION: Health utility were also correlated with exercise capacity.

Rationale and design of the theRapeutic effects of peroneal nerve functionAl electrical stimuLation for Lower extremitY in patients with convalescent poststroke hemiplegia (RALLY) study: study protocol for a randomised controlled study.

INTRODUCTION: Increasing evidence supports the utilisation of functional electrical stimulation (FES) to improve gait following stroke; however, few studies have focused exclusively on its use in the convalescent phase. In addition, its efficacy in patients with a non-Western life style has not been evaluated. METHODS AND ANALYSIS: This is a randomised, controlled, open-label multicentre study, comparing rehabilitation with and without FES. The purpose of our study is to test the hypothesis that the FES system improves walking ability in Japanese patients with hemiplegia during the convalescent phase. Two hundred patients aged 20-85 years who had an initial stroke ≤6 months prior to the enrolment, are in a convalescent phase (after the end of acute phase treatment, within 6 months after the onset of stroke) with functional ambulation classification 3 or 4 and have a hemiplegic gait disorder (drop foot) due to stroke have been recruited from 21 institutions in Japan. The patients are randomised in 1:1 fashion to usual gait rehabilitation or rehabilitation using FES (Walkaide). The trial duration is 8 weeks, and the primary outcome measured will be the change in maximum distance from baseline to the end of the trial, as measured with the 6 min walk test (6-MWT). The 6-MWT is performed barefoot, and the two treatment groups are compared using the analysis of covariance. ETHICS AND DISSEMINATION: This study is conducted in accordance with the principles of the Declaration of Helsinki and the Ethical Guidelines for Medical and Health Research Involving Human Subjects and is approved by the ethics committee of all participating institutions. The published results will be disseminated to all the participants by the study physicians. TRIAL REGISTRATION NUMBER: The University Hospital Medical Information Network-Clinical Studies Registry (UMIN000020604).

Decreased uric acid levels in the acute phase of Plasmodium vivax malaria

Abstract INTRODUCTION Uric acid is one of the compounds associated with the inflammatory process in malaria. It acts as an indicator of cellular damage by activating the immune response and inflammatory process. METHODS: We measured serum concentrations of uric acid in 60 symptomatic patients before and after treatment for malarial infections caused by Plasmodium vivax. RESULTS: Lower serum concentrations of uric acid were found during the acute phase of P. vivax malaria compared to those in its convalescent phase (p < 0.0001). CONCLUSIONS: Patients in the acute phase of malaria had lower uric acid levels than those in its convalescent phase.

Comparative analysis of salivary zinc level in recurrent herpes labialis.

BACKGROUND: Recurrent Herpes Labialis (RHL) is one of most common infective vesiculoulcerative lesions. According to some studies administration of topical and/or systemic zinc compositions has been effective in treatment and prevention. This article aims to comparison of zinc level in healthy subjects and RHL patients in acute and convalescent phases. MATERIALS AND METHODS: This was a retrospective case - control study, carried on 80 individuals (40 normal and 40 RHL patients) mean age=34.5 and 34.4, respectively. Saliva samples were taken in patients in acute phase once and after healing of lesions in convalescent phase (averagely 21 days later) and in normal individuals. Salivary zinc level concentration was measured by flame atomic absorption spectrophotometer by dry digestion method. The results were statistically analyzed with SPSS software by t-test (α=0.05). RESULTS: Results showed that salivary zinc level in case group in acute and convalescent phases were 160.8 (ngr)/(ml)and 205.7 (ngr)/(ml) respectivly and significant differences between them were existed (P <0.05). Also significant differences were existed between zinc concentration in healthy subjects and patient groups (in both phases) (P=.001 and .002 for acute and convalescent phases respectively). CONCLUSION: According to the results, zinc level is significantly lower in acute phase than in convalescent phase and significantly lower in both phases compared to healthy individuals,so determination of serum zinc level and prescribing zinc complement in low serum status has both treatmental and preventive effects in RHL patients.