Dengue virus-specific suppressor T cells: current perspectives

Dengue virus was the first microorganism that was shown to induce generation of antigen-specific suppressor T (TS) cells in mice. The cascade of the three generations of TS cells (TS1, TS2, TS3) and their secretary products, the suppressor factors (SF1, SF2), was delineated. The TS pathway was proposed to be protective through inhibition of the production of enhancing antibody, which may enhance the severity of dengue disease. The currently second most favoured mechanism of severe dengue disease is the 'cytokine tsunami'. During the last decade, suppressor/regulatory T cells have been studied in greater detail using modern techniques in various diseases, including viral infections. This brief review discusses the role of dengue-specific suppressor T cells in protection and/or induction of severe dengue disease in view of our current understanding of suppressor/regulatory T cells

Leveraging high-resolution 7-tesla MRI to derive quantitative metrics for the trigeminal nerve and subnuclei of limbic structures in trigeminal neuralgia

Background: Trigeminal Neuralgia (TN) is a chronic neurological disease that is strongly associated with neurovascular compression (NVC) of the trigeminal nerve near its root entry zone. The trigeminal nerve at the site of NVC has been extensively studied but limbic structures that are potentially involved in TN have not been adequately characterized. Specifically, the hippocampus is a stress-sensitive region which may be structurally impacted by chronic TN pain. As the center of the emotion-related network, the amygdala is closely related to stress regulation and may be associated with TN pain as well. The thalamus, which is involved in the trigeminal sensory pathway and nociception, may play a role in pain processing of TN. The objective of this study was to assess structural alterations in the trigeminal nerve and subregions of the hippocampus, amygdala, and thalamus in TN patients using ultra-high field MRI and examine quantitative differences in these structures compared with healthy controls. Methods: Thirteen TN patients and 13 matched controls were scanned at 7-Tesla MRI with high resolution, T1- weighted imaging. Nerve cross sectional area (CSA) was measured and an automated algorithm was used to segment hippocampal, amygdaloid, and thalamic subregions. Nerve CSA and limbic structure subnuclei volumes were compared between TN patients and controls. Results: CSA of the posterior cisternal nerve on the symptomatic side was smaller in patients (3.75mm2) compared with side-matched controls (5.77mm2, p = 0.006). In TN patients, basal subnucleus amygdala volume (0.347mm3) was reduced on the symptomatic side compared with controls (0.401mm3, p = 0.025) and the paralaminar subnucleus volume (0.04mm3) was also reduced on the symptomatic side compared with controls (0.05mm3, p = 0.009). The central lateral thalamic subnucleus was larger in TN patients on both the symptomatic side (0.033mm3) and asymptomatic side (0.035mm3), compared with the corresponding sides in controls (0.025mm3 on both sides, p = 0.048 and p = 0.003 respectively). The inferior and lateral pulvinar thalamic subnuclei were both reduced in TN patients on the symptomatic side (0.2mm3 and 0.17mm3 respectively) compared to controls (0.23mm3, p = 0.04 and 0.18 mm3, p = 0.04 respectively). No significant findings were found in the hippocampal subfields analyzed. Conclusions: These findings, generated through a highly sensitive 7 T MRI protocol, provide compelling support for the theory that TN neurobiology is a complex amalgamation of local structural changes within the trigeminal nerve and structural alterations in subnuclei of limbic structures directly and indirectly involved in nociception and pain processing

Bioavailability of Orally Administered rhGM-CSF: A Single-Dose, Randomized, Open-Label, Two-Period Crossover Trial

BACKGROUND: Recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is usually administered by injection, and its oral administration in a clinical setting has been not yet reported. Here we demonstrate the bioavailability of orally administered rhGM-CSF in healthy volunteers. The rhGM-CSF was expressed in Bombyx mori expression system (BmrhGM-CSF). METHODS AND FINDINGS: Using a single-dose, randomized, open-label, two-period crossover clinical trial design, 19 healthy volunteers were orally administered with BmrhGM-CSF (8 microg/kg) and subcutaneously injected with rhGM-CSF (3.75 microg/kg) respectively. Serum samples were drawn at 0.0h, 0.5h ,0.75h,1.0h,1.5h,2.0h ,3.0h,4.0h,5.0h,6.0h,8.0h,10.0h and 12.0h after administrations. The hGM-CSF serum concentrations were determined by ELISA. The AUC was calculated using the trapezoid method. The relative bioavailability of BmrhGM-CSF was determined according to the AUC ratio of both orally administered and subcutaneously injected rhGM-CSF. Three volunteers were randomly selected from 15 orally administrated subjects with ELISA detectable values. Their serum samples at the 0.0h, 1.0h, 2.0h, 3.0h and 4.0h after the administrations were analyzed by Q-Trap MS/MS TOF. The different peaks were revealed by the spectrogram profile comparison of the 1.0h, 2.0h, 3.0h and 4.0h samples with that of the 0.0h sample, and further analyzed using both Enhanced Product Ion (EPI) scanning and Peptide Mass Fingerprinting Analysis. The rhGM-CSF was detected in the serum samples from 15 of 19 volunteers administrated with BmrhGM-CSF. Its bioavailability was observed at an average of 1.0%, with the highest of 3.1%. The rhGM-CSF peptide sequences in the serum samples were detected by MS analysis, and their sizes ranging from 2,039 to 7,336 Da. CONCLUSIONS: The results demonstrated that the oral administered BmrhGM-CSF was absorbed into the blood. This study provides an approach for an oral administration of rhGM-CSF protein in clinical settings. TRIAL REGISTRATION: www.chictr.orgChiCTR-TRC-00000107

Mammalian microRNA: an important modulator of host-pathogen interactions in human viral infections

MicroRNAs (miRNAs), which are small non-coding RNAs expressed by almost all metazoans, have key roles in the regulation of cell differentiation, organism development and gene expression. Thousands of miRNAs regulating approximately 60æ% of the total human genome have been identified. They regulate genetic expression either by direct cleavage or by translational repression of the target mRNAs recognized through partial complementary base pairing. The active and functional unit of miRNA is its complex with Argonaute proteins known as the microRNA-induced silencing complex (miRISC). De-regulated miRNA expression in the human cell may contribute to a diverse group of disorders including cancer, cardiovascular dysfunctions, liver damage, immunological dysfunction, metabolic syndromes and pathogenic infections. Current day studies have revealed that miRNAs are indeed a pivotal component of host-pathogen interactions and host immune responses toward microorganisms. miRNA is emerging as a tool for genetic study, therapeutic development and diagnosis for human pathogenic infections caused by viruses, bacteria, parasites and fungi. Many pathogens can exploit the host miRNA system for their own benefit such as surviving inside the host cell, replication, pathogenesis and bypassing some host immune barriers, while some express pathogen-encoded miRNA inside the host contributing to their replication, survival and/or latency. In this review, we discuss the role and significance of miRNA in relation to some pathogenic viruses

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

ASSOCIATION OF HEAVY METALS COMPOSITION OF PARTICULATE MATTER WITH ENVIRONMENTAL TOBACCO SMOKE AND COOKING FUELS IN INDOOR AIR OF DELHI

ABSTRACT The present study was carried out in the industrial locations of Delhi with the primary objective to find out the association of heavy metals composition of suspended particulate matter (SPM) with environmental tobacco smoke (ETS) and cooking fuels in indoor air of Delhi, India. Indoor SPM level was measured by the handy air sampler and the concentration of heavy metals were determined in indoor SPM using atomic absorption spectrometer. The mean level of indoor SPM was 1080.0±482.4 g/m 3 . The Concentration of indoor SPM was greater in the houses where ETS exposure was recorded in the family, and where families were using biomass fuels for cooking. The heavy metals such as Cr, Co, Pb, Ni, Zn, Cu, Mo, Cd, were identified in indoor SPM. The mean level of Co and Pb was significantly higher in the houses where ETS exposure was noticed when compared to the houses without ETS exposure. Other heavy metals like Cr, Ni, Zn, Cu and Cd were also associated with ETS exposure in the houses. The mean level of Co, Ni, ZN, Pb, Cu, Mo and Cd were higher in the houses where families were using biomass fuels (coal, wood, cow dung cakes and kerosene) for cooking as compared to families using liquefied petroleum gas (LPG). This study revealed that ETS and biomass cooking fuels increased the concentration of SPM with heavy metals in the indoor environment. The high concentration of indoor SPM and heavy metals may be harmful for human health and may caused different types of diseases in the family members

Interdictory contribution of Vitamin D to prevent corona virus infections

The impact of vitamin D on the musculoskeletal system is well known. The diverse role of vitamin D is well supported by the functionality of vitamin D receptors and vitamin D activating enzymes (hydroxylase) present in tissues and cells. Hypovitaminosis D causes rickets, osteomalacia, hyperparathyroidism, and an increased risk of bone fracture. Vitamin D has immune-stimulatory effects on both the innate and adaptive immune systems. Vitamin D induces antimicrobial peptide cathelicidin and defensin that can inhibit viral replication of pro-inflammatory cytokines that regulate inflammatory encasement. Moreover, several studies on vitamin D have shown its interdictory role in the immune and respiratory systems. This global crisis, the COVID-19 pandemic condition has increased the risk of acute respiratory tract infection by immune dysregulation along with cytokine storm, which further progress into acute respiratory distress syndrome. Vitamin D has immunomodulatory and anti-inflammatory properties which are effective against respiratory viral infections. Vitamin D supplementation has shown a compatible effect on viral infection. This review article discusses the role of vitamin D in reducing the risk of respiratory infections including the severity of COVID-19 infections. This review focuses on the therapeutic role of vitamin D to improve clinical outcome during COVID-19 infection and suggest its possible role in the prevention and treatment of respiratory infections

Femoral stem displacement as a complication of reduction of a dislocated total hip arthroplasty

Acute displacement at cement-prosthesis interface of a polished femoral component of hip arthroplasty occurring as a consequence of attempted closed manipulation is rare. This complication can be avoided by placing cement over the shoulder of the prosthesis and using fluoroscopic control during closed manipulation if there is a dislocation

Aggregative Escherichia coli, Salmonella, and Shigella are associated with increasing duration of diarrhea

In order to relate etiology of diarrhea to the duration of the episode, a cohort of 452 children upto 36 months of age was visited once weekly at their households for 18 consecutive months to record diarrheal morbidity. Fecal specimens were obtained in 453 diarrheal episodes occurring in 354 children during this period. The common putative agents as single isolations associated with diarrhea were EA-AggEC (17·2%), ETEC (14·1%), EPEC (6·0%) and rotavirus (4·0%). The pathogens with higher median duration of diarrhea were Shigella (13·5; mean ±SD 13·7±2·7), Salmonella (8·8: 15·3±4·5) and EA=AggEC (12·0: 15·1 ±1·8). Of 55 episodes with duration of >14 days, the main pathogens isolated were EA-AggEC (32·7%), ETEC (9·0), Salmonella, G. lambia (5·5% each) and Shigella (3·5%). These data provide a preliminary evidence to suggest that EA-AggEC may well be the main long sought microbial agent responsible for diarrhea of long duration. © 1989 Dr. K C Chaudhuri Foundation