Convalescent Phase Research Articles

Alveolar macrophages and airway hyperresponsiveness associated with respiratory syncytial virus infection

Respiratory syncytial virus (RSV) is a ubiquitous pathogen of viral bronchiolitis and pneumonia in children younger than 2 years of age, which is closely associated with recurrent wheezing and airway hyperresponsiveness (AHR). Alveolar macrophages (AMs) located on the surface of the alveoli cavity are the important innate immune barrier in the respiratory tract. AMs are recognized as recruited airspace macrophages (RecAMs) and resident airspace macrophages (RAMs) based on their origins and roaming traits. AMs are polarized in the case of RSV infection, forming two macrophage phenotypes termed as M1-like and M2-like macrophages. Both M1 macrophages and M2 macrophages are involved in the modulation of inflammatory responses, among which M1 macrophages are capable of pro-inflammatory responses and M2 macrophages are capable of anti-proinflammatory responses and repair damaged tissues in the acute and convalescent phases of RSV infection. Polarized AMs affect disease progression through the alteration of immune cell surface phenotypes as well as participate in the regulation of T lymphocyte differentiation and the type of inflammatory response, which are closely associated with long-term AHR. In recent years, some progress have been made in the regulatory mechanism of AM polarization caused by RSV infection, which participates in acute respiratory inflammatory response and mediating AHR in infants. Here we summarized the role of RSV-infection-mediated AM polarization associated with AHR in infants.

Benign acute childhood myositis following human Influenza B virus infection - A case series.

Influenza virus primarily affects ciliated cells of respiratory epithelium. Humans do not have innate immunity for these viruses and are vulnerable to get attacked. Benign acute childhood myositis usually occurs at the early convalescent phase of a influenza viral illness when fever, cough, myalgia, nasal discharge are the initial presentation.

Retrospective detection of monkeypox virus in the testes of nonhuman primate survivors.

Close contact through sexual activity has been associated with the spread of monkeypox virus (MPXV) in the ongoing, global 2022 epidemic. However, it remains unclear whether MPXV replicates in the testes or is transmitted via semen to produce an active infection. We carried out a retrospective analysis of MPXV-infected crab-eating macaque archival tissue samples from acute and convalescent phases of infection of clade I or clade II MPXV using immunostaining and RNA in situ hybridization. We detected MPXV in interstitial cells and seminiferous tubules of testes as well as epididymal lumina, which are the sites of sperm production and maturation. We also detected inflammation and necrosis during the acute phase of the disease by histological analysis. Finally, we found that MPXV was cleared from most organs during convalescence, including healed skin lesions, but could be detected for up to 37 d post-exposure in the testes of convalescent macaques. Our findings highlight the potential for sexual transmission of MPXV in humans.

Clinical analysis of the epidemiology and changes in inflammatory indexes of Mycoplasma pneumonia in acute and recovery stage pediatric patients

As Mycoplasma pneumoniae pneumonia (MPP) is on the rise in children and adolescents, this work explored the clinical analysis of epidemiological and inflammatory changes in children with MPP during the acute and convalescent phases, and analyzed their relationship with clinical manifestations. One hundred and twenty MP patients (experimental group) and 100 healthy children (control group) were selected as the research objects. Enzyme-linked immunosorbent assay (ELISA) was used to detect the changes in tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and procalcitonin (PCT). The proportion of children aged 3-7 years was significantly higher than that of other age groups (0-1, 1-3, and 7-14 years old) (P<0.05). The serum levels of TNF-α, IL-6, IL-8, IL-10, and PCT in children with MP were significantly higher than those in the control group (P<0.05). Changes in pulmonary fibrosis and serum and pleural fluid TNF-α, IL-6, IL-8, IL-10, and PCT concentrations on chest X-ray and computed tomography (CT) in children with MP with pleural effusion significantly higher than that in children without pulmonary fibrosis (P<0.05). MPP was more common in children aged 3-7 years. In addition, the changes of inflammatory markers TNF-α, IL-6, IL-8, IL-10, and PCT in serum and pleural effusion of children with MP were of great value for the diagnosis, treatment, and prognosis of the disease.

A human monoclonal antibody to neutralize all four serotypes of dengue virus derived from patients at the convalescent phase of infection

Dengue virus (DENV) is a prevalent mosquito-transmitted human pathogen, causing about 100 million cases of acute dengue fever and 21,000 deaths annually worldwide. Therapeutic neutralizing antibodies against dengue virus might be effective to treat severe dengue fever. Here, we showed that human monoclonal antibody (HMAb) 9C7 bound to all four intact serotypes of DENV but not to the recombinant envelope protein, suggesting HMAb 9C7 recognized a conformational epitope of the envelope protein. Taken together our results suggested that HMAb 9C7 neutralized all four serotypes of DENV in vitro and, for DENV-1, indicated activity at the pre- and post-attachment steps in the viral life cycle. HMAb 9C7 potently protected suckling mice from lethal challenge with all four serotypes of DENV. FcγRII-mediated uptake of immune complexes and antibody-dependent enhancement at low doses of the antibody were abolished by two Leu-to-Ala (9C7-LALA) mutations or deletion of nine amino acids (9C7-9del) in HMAb 9C7 Fc. Therefore, HMAb 9C7 represented a promising prophylactic and therapeutic agent against all four serotypes of DENV.

Serum level of total histone 3, H3K4me3, and H3K27ac after non-emergent cardiac surgery suggests the persistence of smoldering inflammation at 3 months in an adult population

BackgroundDespite clinical relevance of immunological activation due to histone leakage into the serum following cardiac surgery, long-term data describing their longitudinal dynamic are lacking. Therefore, this study examines the serum levels of histone 3 (tH3) and its modifications (H3K4me3 and H3K27ac) alongside immune system activation during the acute and convalescence phases of cardiac surgery.MethodsBlood samples from fifty-nine individuals were collected before non-emergent cardiac surgery (tpre-op) and 24 h (t24hr), seven days (t7d), and three months (t3m) post-procedure to examine serum levels of tH3, H3K4me3, and H3K27ac. Serum heat shock protein-60 (HSP-60) was a surrogate of the cellular damage marker. Serum C-reactive protein (CRP) and interleukin 6 (IL-6) assessed smoldering inflammation. TNFα and IL-6 production by whole blood in response to lipopolysaccharide (LPS) evaluated immunological activation. Electronic medical records provided demographic, peri-operative, and clinical information. Paired longitudinal analyses were employed with data expressed as mean and standard deviation (X ± SD) or median and interquartile range (Me[IQ25; 75%].ResultsCompared to pre-operative levels (tH3Pre-op = 1.6[0.33;2.4]), post-operative serum tH3 significantly (p > 0.0001) increased after heart surgery (tH324hr = 2.2[0.3;28]), remained elevated at 7 days (tH37d = 2.4[0.37;5.3]), and at 3 months (tH33m = 2.0[0.31;2.9]). Serum H3K27ac was elevated at 24 h (H3K27ac24hr = 0.66 ± 0.51; p = 0.025) and seven days (H3K27ac7d = 0.94 ± 0.95; p = 0.032) as compared to baseline hours (H3K27acPre-op = 0.55 ± 0.54). Serum H3K4me3 was significantly diminished at three months (H3K4me3Pre-op = 0.94 ± 0.54 vs. H3K27ac3m = 0.59 ± 0.89; p = 0.008). tH3 correlated significantly with the duration of anesthesia (r2 = 0.38). In contrast, HSP-60 normalized seven days after surgery. Peri-operative intake of acetaminophen, but no acetylsalicylic acid (ASA), acid, ketorolac or steroids, resulted in the significant depression of serum H3K4me3 at 24 h (H3K4me3acetom- = 1.26[0.71; 3.21] vs H3K4me3acetom+ = 0.54[0.07;1.01]; W[50] = 2.26; p = 0.021). CRP, but not IL-6, remained elevated at 3 months compared to pre-surgical levels and correlated with tH324hrs (r2 = 0.43), tH37d (r2 = 0.71; p < 0.05), H3K4me37d (r2 = 0.53), and H3K27ac7d (r2 = 0.49). Production of TNFα by whole blood in response to LPS was associated with serum tH324hrs (r2 = 0.67). Diminished H3K4me324hrs, H3K27ac24hrs, and H3K27ac3m, accompanied the emergence of liver failure.ConclusionsWe demonstrated a prolonged elevation in serum histone 3 three months after cardiac surgery. Furthermore, histone 3 modifications had a discrete time evolution indicating differential immune activation.

Abstract P083: Progression Of Vascular Dysfunction In A Mouse Model Of Kawasaki Disease

Progression of vascular dysfunction in a mouse model of Kawasaki disease Alina Saiyid, Shubhnita Singh, Ariane Bruder-Nascimento, Thiago Bruder-Nascimento Kawasaki disease (KD) is an acute, self-limited vasculitis and the most common cause of acquired cardiovascular disease in young children. Although severe vascular inflammation is already well-established in KD, how the arteries functionally behave in acute and convalescent phases is poorly understood. Herein, we sought to investigate the vascular function using a mouse model of KD.KD was induced by the Candida albicans water-soluble fraction model (CAWS, 4mg/day for 5 days) in C57BL6/J male mice (5-6-week-old). Mice were divided into 3 groups: control (G0, PBS injections), 7-days post 1 CAWS injection (G7), and 28-days post 1 CAWS injection (G28). Heart and abdominal aorta (AA) were harvested for vasculitis characterization. Vascular function was studied in AA via wire myograph.G7 presented an increase in TNFα and IL1β gene expression in the heart and AA, but without clear vasculitis (analyzed by histology). However, G28 exhibited a severe immune cell infiltration in the aortic root, coronary arteries, and AA. In G7, AA displayed a drastic reduction in vascular response to norepinephrine [maximal response (Emax in mN): C: 5.4 ± 0.6 vs. G7: 2.0 ± 0.5*, *p&lt;0.05], such attenuation was abolished by pre-treating the AA with L-NAME (nitric oxide synthase inhibitor). In G28, a mild change was observed in maximal response; however, increased sensitivity was found (pD2: C: 6.0 ± 0.4 vs. G28: 6.8 ± 0.3*, *p&lt;0.05). After L-NAME pre-treatment, the difference persisted indicating a NO-dependent response. Furthermore, a severe endothelial dysfunction, characterized by impaired relaxation of acetylcholine, was observed in G28 [Emax (%): C: 85.7 ± 8.4 vs. G28: 54.8 ± 6.4*, *p&lt;0.05].In conclusion, the acute phase of KD is associated with impaired vascular contractility via an excess of NO, which could justify some children presenting shock in clinic. In the convalescent phase (G28), the arteries are injured and likely with an irreversible phenotype. Thus, an adequate and punctual treatment for KD is highly requested.

Reappraisal of VEGF in the Pathogenesis of Kawasaki Disease.

Vascular endothelial growth factor (VEGF) is an important factor in mediating the inflammation of Kawasaki disease (KD). The literature regarding the relationship between VEGF and KD is sparse. The purpose of this study was to investigate the correlation of VEGF and KD. In a prospective study of 42 Taiwanese KD patients (18.9 ± 12.2 months, M/F 22/20) treated with intravenous immunoglobulin (IVIG), a series of VEGF levels was measured from the acute to convalescent phases. KD patients were classified into two subgroups with (n =20) and without (n = 22) acute coronary artery lesions (CALs). Control samples were obtained from 30 febrile controls (19.1 ± 13.7 months, M/F 13/17). In KD patients, VEGF levels in the pre-IVIG acute phase were significantly higher than those in the subacute and convalescent phases (both p < 0.001). In KD patients with CALs, VEGF levels significantly increased immediately in the post-IVIG phase (p = 0.039), and then significantly decreased in the subacute phase (p = 0.002). KD patients with acute CALs had higher median VEGF levels than those without acute CALs from acute to convalescent phases. In the subacute phase, KD patients with acute CALs had significantly higher VEGF levels (p = 0.022) than those without acute CALs. Our data show that VEGF did not decrease after IVIG treatment, and increased significantly after IVIG treatment in KD patients with acute CALs in acute phase. VEGF might be related to the complications of CALs in KD patients.

Chikungunya Virus E2 Structural Protein B-Cell Epitopes Analysis.

The Togaviridae family comprises a large and diverse group of viruses responsible for recurrent outbreaks in humans. Within this family, the Chikungunya virus (CHIKV) is an important Alphavirus in terms of morbidity, mortality, and economic impact on humans in different regions of the world. The objective of this study was to perform an IgG epitope recognition of the CHIKV’s structural proteins E2 and E3 using linear synthetic peptides recognized by serum from patients in the convalescence phase of infection. The serum samples used were collected in the state of Sergipe, Brazil in 2016. Based on the results obtained using immunoinformatic predictions, synthetic B-cell peptides corresponding to the epitopes of structural proteins E2 and E3 of the CHIKV were analyzed by the indirect peptide ELISA technique. Protein E2 was the main target of the immune response, and three conserved peptides, corresponding to peptides P3 and P4 located at Domain A and P5 at the end of Domain B, were identified. The peptides P4 and P5 were the most reactive and specific among the 11 epitopes analyzed and showed potential for use in serological diagnostic trials and development and/or improvement of the Chikungunya virus diagnosis and vaccine design.

Spontaneous defervescence and its prediction in the acute phase of Kawasaki disease.

BackgroundIn Kawasaki disease (KD), fever occasionally resolves spontaneously before 10 days from the onset, right after diagnosing. However, there is not enough evidence of intravenous immunoglobulin (IVIG) treatment in this case. The aim of this study was to investigate the relationship between spontaneous defervescence and coronary artery aneurysm and to develop a scoring model for its prediction in acute KD.MethodsAll patients admitted for acute KD in Asan Medical Center were considered for inclusion. Acute management involved the administration of 2 g/kg of IVIG and 5 mg/kg/day of aspirin. The patient whose temperature was <37.5°C for more than 48 h from the diagnosis was discharged under the judgment of spontaneous defervescence, without IVIG administration.ResultsThe incidence of coronary artery aneurysm was 5.7% in 94 defervesced patients and 4.6% in the 1,277 patients treated with IVIG in the subacute phase (P = 0.593), and 2.5 and 2.2% in respective patient groups in the convalescent phase (P = 0.924). A scoring model which predicted spontaneous defervescence under the combination of C-reactive protein ≤10mg/dL and ≥2 conditions of no rash, neutrophil ≤65%, and/or alanine aminotransferase ≤80 IU/L, was developed and showed 80.7% sensitivity, 68.8% specificity, 15.8% positive predictive value, and a 97.8% negative predictive value.ConclusionThe incidence of coronary artery aneurysm in patients with the defervesced KD was not different from the IVIG treated patients. In the cases suitable for the predictive model, patients can wait for the spontaneous defervescence under intensive observation by medical professionals.

Yellow Fever Molecular Diagnosis Using Urine Specimens during Acute and Convalescent Phases of the Disease.

ABSTRACTPrior studies have demonstrated prolonged presence of yellow fever virus (YFV) RNA in saliva and urine as an alternative to serum. To investigate the presence of YFV RNA in urine, we used RT-PCR for YFV screening in 60 urine samples collected from a large cohort of naturally infected yellow fever (YF) patients during acute and convalescent phases of YF infection from recent YF outbreaks in Brazil (2017 to 2018). Fifteen urine samples from acute phase infection (up to 15 days post-symptom onset) and four urine samples from convalescent phase infection (up to 69 days post-symptom onset), were YFV PCR-positive. We genotyped YFV detected in seven urine samples (five collected during the acute phase and two collected during the YF convalescent phase). Genotyping indicated the presence of YFV South American I genotype in these samples. To our knowledge, this is the first report of wild-type YFV RNA detection in the urine this far out from symptom onset (up to 69 DPS), including YFV RNA detection during the convalescent phase of YF infection. The detection of YFV RNA in urine is an indicative of YFV infection; however, the results of RT-PCR using urine as sample should be interpreted with care, since a negative result does not exclude the possibility of YFV infection. With a possible prolonged period of detection beyond the viremic phase, the use of urine samples coupled with serological tests, epidemiologic inquiry, and clinical assessment could provide a longer diagnostic window for laboratory YF diagnosis.

Borrelia burgdorferi specific serum and cerebrospinal fluid antibodies in Lyme neuroborreliosis

We used definite Lyme neuroborreliosis (LNB) adult patient acute and convalescent phase serum (n = 63 and 61, respectively) and cerebrospinal fluid (CSF; acute n = 63, 3 weeks timepoint n = 41) samples to characterize Borrelia burgdorferi specific antibody responses in patient subgroups categorized by demographics, infection manifestation and phase, infecting B. burgdorferi genospecies, received antibiotic treatments, and treatment outcome. B. burgdorferi antibodies were analyzed using 4 different assays incorporating a large array of antigens. We observed that B. burgdorferi specific serum antibodies show a universal, antigen independent declining trend after antibiotic treatment of LNB at 1 year. Antibodies declined similarly among women and men over time, and the decline was independent of patient age. The antibody responses were independent of the predominant LNB manifestation, treatment received by the patient, infecting B. burgdorferi genospecies, or the subjective improvement experienced by the patients. Finally, the antibody specificities in CSF reflected the specificities observed in serum samples.

Assessment of Endothelial Dysfunction in Patients with Kawasaki Disease: A Meta-Analysis.

Kawasaki disease (KD) is a well-known systemic inflammatory vasculitis. Endothelial dysfunction is one of most easily overlooked non-coronary complications of KD. Several studies have assessed endothelial dysfunction using flow-mediated dilatation (FMD), nitroglycerin-mediated dilation (NMD), and biomarkers (E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cellular adhesion molecule-1 (VCAM-1)). However, the results were inconsistent and incomplete. We searched five databases for eligible studies until March 8, 2022. The summarized weighted mean difference (WMD) with 95% confidence intervals (CIs) were estimated for FMD, NMD, and four biomarkers level between KD and healthy children. A meta-analysis with subgroup analysis was conducted. 40 studies with a total of 2670 children (1665 KD patients and 1005 healthy children) were identified. During the acute phase, KD patients had lower FMD compared to the control group (WMD = -10.39, 95% CI: -13.80- -6.98). During the subacute phase, KD patients had lower FMD compared to the control group (WMD = -15.07, 95% CI: -17.61- -12.52). During the convalescence phase, KD patients had lower FMD and similar NMD compared to the control group (WMD = -4.95, 95% CI: -6.32- -3.58; WMD = -0.92, 95% CI: -2.39-0.55, respectively). During the convalescence phase, those KD patients without coronary artery lesion (CAL), with CAL, even with coronary artery aneurysm, had progressively lower FMD compared to healthy children (WMD = -3.82, 95% CI: -7.30- -0.34; WMD = -6.32, 95% CI: -7.60- -5.04; and WMD = -6.97, 95% CI: -7.99- -5.95, respectively). Compared to KD patients without CAL, those with CAL had lower FMD (WMD = -1.65, 95% CI: -2.92- -0.37). KD patients had higher levels of E-selectin, P-selectin, and ICAM-1 compared to healthy controls during different phases. KD patients had a higher level of VCAM-1 compared to healthy controls only during the acute phase (WMD = 61.62, 95% CI: 21.38-101.86). Endothelial dysfunction is present since the onset of KD and persists for years, confirmed by the measurement of FMD and biomarkers from different phases. An assumption is advanced that FMD impairment (the severity of endothelial dysfunction) may be positively correlated with CAL severity during the convalescence phase.

Mechanisms of Post-critical Illness Cardiovascular Disease.

Prolonged critical care stays commonly follow trauma, severe burn injury, sepsis, ARDS, and complications of major surgery. Although patients leave critical care following homeostatic recovery, significant additional diseases affect these patients during and beyond the convalescent phase. New cardiovascular and renal disease is commonly seen and roughly one third of all deaths in the year following discharge from critical care may come from this cluster of diseases. During prolonged critical care stays, the immunometabolic, inflammatory and neurohumoral response to severe illness in conjunction with resuscitative treatments primes the immune system and parenchymal tissues to develop a long-lived pro-inflammatory and immunosenescent state. This state is perpetuated by persistent Toll-like receptor signaling, free radical mediated isolevuglandin protein adduct formation and presentation by antigen presenting cells, abnormal circulating HDL and LDL isoforms, redox and metabolite mediated epigenetic reprogramming of the innate immune arm (trained immunity), and the development of immunosenescence through T-cell exhaustion/anergy through epigenetic modification of the T-cell genome. Under this state, tissue remodeling in the vascular, cardiac, and renal parenchymal beds occurs through the activation of pro-fibrotic cellular signaling pathways, causing vascular dysfunction and atherosclerosis, adverse cardiac remodeling and dysfunction, and proteinuria and accelerated chronic kidney disease.

The role of myocarditis in the acute phase of Kawasaki as a predictor of the future coronary aneurysm: a case–control study

BackgroundThis study aimed to evaluate the relationship between cardiac troponin I and T (cTnI, cTnT) and creatine kinase (CK)-MB during the acute phase of Kawasaki disease (KD) and the development of coronary artery involvement (CAI).ResultsNinety children diagnosed with KD and 38 attending ambulatory clinics as controls were enrolled in this study. Serum levels of cardiac enzymes were measured in all case and control groups. Serial echocardiograms were performed in KD patients during the acute, subacute and convalescence phases. Thirty-six percent of patients had CAI during the acute phase of KD; this rate was 21% and 18% in the echocardiography in the sub-acute and convalescent-phase, respectively. Elevated serum cTnI and cTnT levels were seen in 15.5% and 10% of KD patients, respectively, but not in the controls (P < 0.01). Patients with abnormal echocardiography had significantly higher levels of CK-MB but cTnI and cTnT. Cardiac troponins have high specificity, and CK-MB had a high sensitivity for predicting CAI in KD.ConclusionSubclinical myocarditis occurs during KD, and serum cardiac troponin levels are significantly elevated, but cardiac biomarkers cannot predict CAI in the future.

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

BACKGROUNDKawasaki 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. AIMTo estimate the levels of adipocytokines (adiponectin, leptin and resistin) during the convalescent phase of KD.METHODSTwenty 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.RESULTSMean 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). CONCLUSIONSerum 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.

Assessment of Diaphragm in Hemiplegic Patients after Stroke with Ultrasound and Its Correlation of Extremity Motor and Balance Function.

Background: A variety of functional disorders can be caused after stroke, among which impairment of respiratory function is a frequent and serious complication of stroke patients. The aim of this study was to examine diaphragmatic function after stroke by diaphragm ultrasonography and then to apply to explore its correlation with extremity motor function and balance function of the hemiplegia patients. Methods: This cross-sectional observational study recruited 48 hemiplegic patients after stroke and 20 matched healthy participants. The data of demographic and ultrasonographic assessment of all healthy subjects were recorded, and 45 patients successfully underwent baseline data assessment in the first 48 h following admission, including post-stroke duration, stroke type, hemiplegia side, pipeline feeding, pulmonary infection, ultrasonographic assessment for diaphragm, Fugl–Meyer Motor Function Assessment Scale (FMA Scale), and Berg Balance Scale assessment. Ultrasonographic assessment parameters included diaphragm mobility under quiet and deep breathing, diaphragm thickness at end-inspiratory and end-expiratory, and calculated thickening fraction of the diaphragm. The aim was to analyze the diaphragm function of hemiplegic patients after stroke and to explore its correlation with extremity motor function and balance function. Results: The incidence of diaphragmatic dysfunction under deep breath was 46.67% in 45 hemiplegia patients after stroke at the convalescent phase. The paralyzed hemidiaphragm had major impairments, and the mobility of the hemiplegic diaphragm was significantly reduced during deep breathing (p < 0.05). Moreover, the thickness fraction of hemiplegic side was extremely diminished when contrasted with the healthy control and non-hemiplegic side (p < 0.05). We respectively compared the diaphragm mobility under deep breath on the hemiplegic and non-hemiplegic side of patients with left and right hemiplegia and found there was no significant difference between the hemiplegic side of right and left hemiplegia (p > 0.05), but the non-hemiplegic side of right hemiplegia was significantly weaker than that of left hemiplegia patients (p < 0.05). The diaphragm mobility of stroke patients under quiet breath was positively correlated with age and FMA Scale score (R2 = 0.296, p < 0.05), and significant positive correlations were found between the diaphragm mobility under deep breath and Berg Balance Scale score (R2 = 0.11, p < 0.05), diaphragm thickness at end-inspiratory and FMA Scale score (R2 = 0.152, p < 0.05), and end-expiratory thickness and FMA Scale score (R2 = 0.204, p < 0.05). Conclusions: The mobility and thickness fraction of the hemiplegic diaphragm after stroke by diaphragm ultrasonography were significantly reduced during deep breathing. Diaphragm mobility on bilateral sides of the right hemiplegia patients were reduced during deep breathing. Moreover, the hemiplegic diaphragmatic function was positively correlated with extremity motor and balance function of the hemiplegia patients.

Rationale and Design for the Diabetes RElated to Acute Pancreatitis and Its Mechanisms Study: A Prospective Cohort Study From the Type 1 Diabetes in Acute Pancreatitis Consortium.

Acute pancreatitis (AP) is a disease characterized by an acute inflammatory phase followed by a convalescent phase. Diabetes mellitus (DM) was historically felt to be a transient phenomenon related to acute inflammation; however, it is increasingly recognized as an important late and chronic complication. There are several challenges that have prevented precisely determining the incidence rate of DM after AP and understanding the underlying mechanisms. The DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms) Study is a prospective cohort study designed to address these and other knowledge gaps to provide the evidence needed to screen for, prevent, and treat DM after AP. In the following article, we summarize literature regarding the epidemiology of DM after AP and provide the rationale and an overview of the DREAM study.

The expression of circulating hsa-miR-126-3p in dengue-infected Thai pediatric patients

ABSTRACT Circulating hsa-miRNA-126 (CmiR-126) has been reported to involve in the pathogenesis of many infectious diseases including dengue virus infection. However, no prior study has been conducted to describe more details in dengue-infected pediatric patients. This study aimed to describe CmiR-126-3p in dengue-infected pediatric patients during the febrile and convalescent phases. Additionally, the correlations between CmiR-126-3p and other relevant clinical laboratory factors were investigated. Sixty paired-serum specimens collected during febrile and convalescent phases were retrieved from patients with dengue fever (DF) (n = 30) and dengue hemorrhagic fever (DHF) (n = 30). Thirty paired-serum specimens collected from non-dengue acute febrile illness patients (AFI) were included as the control group. CmiR-126-3p was determined using reverse transcription quantitative real-time polymerase-chain reaction (RT-qPCR). Relative miRNA expression was calculated as 2−ΔCt using CmiR-16-5p for data normalization. CmiR-126-3p expression during febrile and convalescent phases in dengue-infected patients was significantly lower than AFI (p < 0.05). However, miRNA levels were not different (p > 0.05) compared between DF and DHF and between primary and secondary infection. CmiR-126-3p levels in DF in the convalescent were significantly higher than in the febrile phase (p = 0.025). No association between CmiR-126-3p and hematocrit, WBC level, platelet count, WBC differential count or dengue viral load was observed (p > 0.05). The data suggest that hsa-miR-126-3p involved in pathogenesis of dengue infection and may be a promising early and late biomarker for DENV infection. However, hsa-miR-126-3p alone cannot be used as a predictor for dengue severity.

Elevation of Myeloperoxidase Correlates with Disease Severity in Patients with Hantaan Virus Infection.

Hantaan orthohantavirus (HTNV) can cause hemorrhagic fever with renal syndrome (HFRS) characterized by acute kidney injury and hemorrhage. Neutrophils are the most abundant innate immune cell and the body's first line of defense against pathogens. Currently, an increasing number of studies have shown that neutrophils may be a mixed blessing in terms of viral infections. However, the role of neutrophils in HFRS patients with HTNV infection has not been fully declared. In this study, we analyzed plasma levels of both myeloperoxidase (MPO) and MPO-DNA in HFRS patients, together with the clinical parameters. Neutrophil-platelet aggregates (NPAs) during the acute and convalescent phases of HFRS were also assessed. The results showed that plasma MPO-DNA levels had no change in different disease phases or severities of HFRS patients. Whereas plasma MPO significantly increased in the acute phase and critical/severe groups of HFRS patients. Furthermore, plasma MPO was positively correlated with inflammatory clinical parameters, such as white blood cell counts, neutrophil counts, and renal injury-related parameters, such as blood urea nitrogen, blood uric acid, and serum creatinine, as well as negatively correlated with and platelet counts. In addition, NPAs increased both in acute and convalescent phase in HFRS patients compared with normal controls. These results suggested that elevated plasma MPO in HFRS patients correlated with disease severity, together with the increases of NPAs in HFRS patients, which may provide new insights into potential role of neutrophils in the pathogenesis of HFRS.