Haemorrhage control beyond Advanced Trauma Life Support (ATLS) protocol in life threatening maxillofacial trauma - experience from a level â trauma centre.

Maxillofacial injuries are usually not life-threatening and do not get priority over other associated injuries. However, some maxillofacial injuries with active oral or nasal bleeding need immediate management due to threatened airway and blood loss. In the case of major active vascular bleeding, measures such as local pressure, anterior nasal packing, posterior nasal packing, and balloon tamponade are ineffective. In these cases, angiography and transcatheter arterial embolisation (TAE) are used to treat life-threatening haemorrhage caused by maxillofacial trauma. We analysed the medical records of 39 patients with severe maxillofacial trauma and life-threatening haemorrhage that was a result of intractable oral or nasal bleeding. These patients were considered for TAE from January 2010 to December 2019. A total of 1668 patients was admitted, out of which 39 (2.3%) had severe maxillofacial injuries with life-threatening oral or nasal bleeding and underwent TAE. Out of a total of 39 patients, 38 were male and one female. Ages ranged from 16 to 65 years. Road traffic injury was the most common cause of injury (79.5%), Lefort I and II were the most common facial fractures, and traumatic brain injury was the most common associated injury. Embolisation and bleeding control were done successfully in all 39 patients with no procedure-related complications. A total of 17 deaths during the study period were due to severe traumatic brain injuries or haemorrhagic shock.

The impact of cervical cytobrush sampling on cervico-vaginal immune parameters and microbiota relevant to HIV susceptibility.

The immunology and microbiota of the female genital tract (FGT) are key determinants of HIV susceptibility. Cervical cytobrush sampling is a relatively non-invasive method permitting the longitudinal assessment of endocervical immune cells, but effects on FGT immunology are unknown. Blood, cervico-vaginal secretions and cervical cytobrushes were collected from sexually transmitted infection (STI)-free women at baseline and after either 6 hours or 48 hours. Endocervical immune cell subsets were assessed by flow cytometry, and pro-inflammatory cytokines by multiplex ELISA. The density of Lactobacillus species and key bacterial vaginosis-associated bacterial taxa were determined by qPCR. Paired changes were assessed before and after cytobrush sampling. After 6 hours there were significant increases in CD4 + T cell, antigen presenting cell (APC) and neutrophil numbers; APC elevations persisted at 48 hours, while neutrophil and CD4 + T cell numbers returned to baseline. In addition, pro-inflammatory cytokine levels were increased at 6 hours and returned to baseline by 48 hours. No significant changes were observed in the absolute abundance of Lactobacillus species or BV-associated bacteria at either time point. Overall, cytobrush sampling altered genital immune parameters at 6 hours, but only APC number increases persisted at 48 hours. This should be considered in longitudinal analyses of FGT immunology.

Toxicocladosporium aquimarinum sp. nov. and Toxicocladosporium qatarense sp. nov., isolated from marine waters of the Arabian Gulf surrounding Qatar.

The Arabian Gulf surrounding Qatar is distinct from other marine ecosystems due to its high salinity (35-75 PSU) and extreme water temperature fluctuations (11-40 °C). Furthermore, in the last decade, Qatar has been witnessing an industrial boom as well as extensive infrastructure construction activities. Marine micro-organisms, including fungi, remain largely unexplored in the Arabian Gulf. During a 3 year study, we investigated the diversity of marine fungi in coastal waters around Qatar. As a result, two new Toxicocladosporium species were isolated from the Qatari marine environment. Molecular and phylogenetic analyses of rRNA gene sequences of five loci, namely the internal transcribed spacer 1 and 2 regions and the D1/D2 domains of the large subunit rRNA, actin, RNA polymerase second largest subunit and beta-tubulin genes, were used to confirm the identity of the novel species for which we propose the names Toxicocladosporium aquimarinum sp. nov. and Toxicocladosporium qatarense sp. nov.

Practical consensus recommendations regarding the management of sentinel lymph node issues in early breast cancer.

Axillary lymph node involvement is a very important poor prognostic factor in the clinical staging and management of breast cancer patients. Traditionally, axillary lymph node dissection (ALND) has been used for determining the status of the axillary lymph nodes. More recently the sentinel lymph node biopsy (SLNB) procedure has gained wider acceptance as the standard of care, having the advantage of being less invasivewhile providing good accuracy. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations in regards with the use of the two different procedures and other issues in patients with early breast cancer for the benefit of community oncologists.

EPS production by Propionibacterium freudenreichii facilitates its immobilization for propionic acid production.

AIMS: Immobilization of microbial cells is a useful strategy for developing high cell density bioreactors with improved stability and productivity for production of different chemicals. Functionalization of the immobilization matrix or biofilm forming property of some strains has been utilized for achieving cell attachment. The aim of the present study was to investigate the production of exopolysaccharide (EPS) by Propionibacterium freudenreichii C.I.P 59.32 and utilize this feature for immobilization of the cells on porous glass beads for production of propionic acid. METHODS AND RESULTS: Propionibacterium freudenreichii was shown to produce both capsular and excreted EPS during batch cultivations using glucose as carbon source. Different electron microscopy techniques confirmed the secretion of EPS and formation of cellular aggregates. The excreted EPS was mainly composed of mannose and glucose in a 5·3 : 1 g g-1 ratio. Immobilization of the cells on untreated and polyethyleneimine (PEI)-treated Poraver beads in a bioreactor was evaluated. Higher productivity and yield of propionic acid (0·566 g l-1  h-1 and 0·314 g g-1 , respectively) was achieved using cells immobilized to untreated beads and EPS production reached 617·5 mg l-1 after 48 h. CONCLUSION: These results suggest an important role of EPS-producing strains for improving cell immobilization and propionic acid production. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the EPS-producing microbe to be easily immobilized on a solid matrix and to be used in a bioprocess. Such a system could be optimized for achieving high cell density in fermentations without the need for functionalization of the matrix.

Distinct Effects of the Cervicovaginal Microbiota and Herpes Simplex Type 2 Infection on Female Genital Tract Immunology.

Background: Genital inflammation is a key determinant of human immunodeficiency virus (HIV) transmission, and may increase HIV-susceptible target cells and alter epithelial integrity. Several genital conditions that increase HIV risk are more prevalent in African, Caribbean, and other black (ACB) women, including bacterial vaginosis and herpes simplex virus type-2 (HSV-2) infection. Therefore, we assessed the impact of the genital microbiota on mucosal immunology in ACB women and microbiome-HSV-2 interactions. Methods: Cervicovaginal secretions and endocervical cells were collected by cytobrush and Instead Softcup, respectively. T cells and dendritic cells were assessed by flow cytometry, cytokines by multiplex enzyme-linked immunosorbent assay (ELISA), and the microbiota by 16S ribosomal ribonucleic acid gene sequencing. Results: The cervicovaginal microbiota of 51 participants were composed of community state types (CSTs) showing diversity (20/51; 39%) or predominated by Lactobacillus iners (22/51; 42%), L. crispatus (7/51; 14%), or L. gasseri (2/51; 4%). High-diversity CSTs and specific bacterial phyla (Gardnerella vaginalis and Prevotella bivia) were strongly associated with cervicovaginal inflammatory cytokines, but not with altered endocervical immune cells. However, cervical CD4+ T-cell number was associated with HSV-2 infection and a distinct cytokine profile. Conclusions: This suggests that the genital microbiota and HSV-2 infection may influence HIV susceptibility through independent biological mechanisms.

Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota.

Cervical human papillomavirus (HPV) infection may increase HIV risk. Since other genital infections enhance HIV susceptibility by inducing inflammation, we assessed the impact of HPV infection and clearance on genital immunology and the cervico-vaginal microbiome. Genital samples were collected from 65 women for HPV testing, immune studies and microbiota assessment; repeat HPV testing was performed after 6 months. All participants were HIV-uninfected and free of bacterial STIs. Cytobrush-derived T cell and dendritic cell subsets were assessed by multiparameter flow cytometry. Undiluted cervico-vaginal secretions were used to determine cytokine levels by multiplex ELISA, and to assess bacterial community composition and structure by 16S rRNA gene sequence analysis. Neither HPV infection nor clearance were associated with broad differences in cervical T cell subsets or cytokines, although HPV clearance was associated with increased Langerhans cells and HPV infection with elevated IP-10 and MIG. Individuals with HPV more frequently had a high diversity cervico-vaginal microbiome (community state type IV) and were less likely to have an L. gasseri predominant microbiome. In summary, HPV infection and/or subsequent clearance was not associated with inflammation or altered cervical T cell subsets, but associations with increased Langerhans cells and the composition of the vaginal microbiome warrant further exploration.

T4 lysozyme fused with cellulose-binding module for antimicrobial cellulosic wound dressing materials.

AIMS: Bacterial infection is a major challenge in wound care. Antimicrobial wound dressings are of great value for treating wound infections. Endolysins are evolving as a new class of antimicrobials with multiple applications. This study describes the production and evaluation of T4 lysozyme (T4Lyz), product of gene e of the T4 bacteriophage, fused with Cellulose Binding Module (CBM) for facile immobilization to cellulosic wound dressing. METHODS AND RESULTS: Genes encoding T4Lyz-CBM and T4Lyz were cloned and expressed in Escherichia coli and the enzymes were purified by cation exchange chromatography. While the CBM tag did not alter the optimum pH and stability features of T4Lyz, the lytic activity of the fusion protein was lowered. The bactericidal activity of T4Lyz-CBM, determined by viable count plating assay after 1 h incubation with Micrococcus lysodeikticus was 97·5% with 10 µg ml(-1) , and 99·96% and 95% for E. coli and Pseudomonas mendocina, respectively, with 200 µg ml(-1) enzyme. T4Lyz-CBM was immobilized to wound dressing gauze with a capacity of 5·5 µg mg(-1) matrix, whereas the unmodified T4Lyz did not exhibit any binding. The immobilized protein retained its bactericidal activity against Gram-positive and Gram-negative bacteria. Both free and immobilized T4Lyz-CBM, after heat denaturation, retained their bactericidal activities against Gram-negative bacteria only. The immobilized enzyme exhibited higher stability than the free enzyme when stored in dry form or in the presence of polyol stabilizers. CONCLUSION: Tagging T4Lyz with CBM provides a facile, irreversible binding to cellulosic wound dressing while retaining its activity. This approach may be suitable even for other antimicrobial enzymes and -peptides. SIGNIFICANCE AND IMPACT OF THE STUDY: The spread of antibiotic resistance requires innovative strategies for discovery and development of effective antimicrobial alternatives. This report presents a novel strategy for producing antimicrobial wound dressing materials.

Identification of preferential CD4+ T-cell targets for HIV infection in the cervix.

A better understanding of the cellular targets of HIV infection in the female genital tract may inform HIV prevention efforts. Proposed correlates of cellular susceptibility include the HIV co-receptor CCR5, peripheral homing integrins, and immune activation. We used a CCR5-tropic pseudovirus to quantify HIV entry into unstimulated endocervical CD4(+) T cells collected by cytobrush. Virus entry was threefold higher into cervix-derived CD4(+) T cells than blood, but was strongly correlated between these two compartments. Cervix-derived CD4(+) T cells expressing CD69, α(4)ß(7), or α(4)ß(1) were preferential HIV targets; this enhanced susceptibility was strongly correlated with increased CCR5 expression in α(4)ß(7)(+) and CD69(+) CD4(+) T cells, and to a lesser extent in α(4)ß(1)(+) CD4(+) T cells. Direct binding of gp140 to integrins was not observed, integrin inhibitors had no effect on virus entry, and pseudotypes with an env that preferentially binds α(4)ß(7) still demonstrated enhanced entry into α(4)ß(1)(+) cells. In summary, a rapid and sensitive HIV entry assay demonstrated enhanced susceptibility of activated endocervical CD4(+) T cells, and those expressing α(4)ß(7) or α(4)ß(1). This may relate to increased CCR5 expression by these cell subsets, but did not appear to be due to direct interaction of α(4)ß(7) or α(4)ß(1) with HIV envelope.

Purification and dose-dependent toxicity study of abrin in swiss albino male mice.

Abrin, a phytotoxin obtained from the seeds of the Abrus precatorius plant, is highly toxic with an estimated human fatal dose of 0.1­1 µg/kg. In this study, abrin was purified and characterized through SDS PAGE and mass spectrometry analysis; further study on toxicity was carried out to investigate the alteration in biochemical, and hematological variables through histopathological observations in mice. The intraperitoneal LD50 value of purified abrin for mice was found to be 0.91µg/kg of body weight. Mice were exposed to 0.4 and 1.0 LD50 abrin doses intraperitoneally and observed on days 1, 3, and 7. Plasma GOT and GPT levels increased significantly at both doses. At 1.0 LD50 dose, alkaline phosphatase, bilirubin, urea, uric acid, and creatinine levels increased, whereas albumin, total protein, glucose and cholesterol levels decreased significantly. Abrin intoxication also altered the hemoglobin, WBC, and RBC counts significantly at 1.0 LD50 dose. Liver GSH levels decreased while lipid peroxidation increased significantly in a dose­dependent manner. Biochemical changes were supported by the histological investigation, which also showed the degenerative changes in organs. In conclusion, abrin intoxication caused toxic effects and severe damages on studied organs mediated through alteration in biochemical and hematological variables, lipid peroxidation, and degeneration.

Retrospective analysis of spinal trauma in patients with ankylosing spondylitis: a descriptive study in Indian population.

OBJECTIVE: This study aims to understand the demographics, mode of trauma, hospital stay, complications, neurological improvement, mortality and expenditure incurred by Indian patients with spinal trauma and ankylosing spondylitis (AS). METHODS: Retrospective analysis of the patient data admitted to a tertiary referral hospital from 2008 to 2013 with the diagnosis of AS and spinal trauma was carried out. The variables studied were demographics, mode of trauma, neurological status, neurological improvement, involved vertebral level, duration of hospital stay, comorbid factors, expenditure and complications during the stay. RESULTS: Forty-six patients with diagnosis of AS with spine trauma were admitted over the last 5 years with a total of 52 fractures. All were male patients; 58.6% had injury because of trivial trauma and 78.2% patients presented with neurological injury. C5 C6, C6 C7, C7 D1 and D12 were the most common injured level. Fractures through intervertebral disc were most common in cervical spine. Of the patients, 52.7% had shown neurological improvement of at least grade 1(AIS). Mean expenditure of patient admitted with spinal cord injury (SCI) with AS is 7957 USD (United States dollar), which is around five times the per capita income in India (as per year 2013). CONCLUSION: Males with AS are much more prone to spinal fractures than females and its incidence may be higher than previously reported. Domestic falls are the most common mechanism of spinal trauma in this population. High velocity injuries are associated with complete SCI. The study reinforces the need for development of subsidized spinal care services for SCI management.

Do we have an ideal classification system for thoracolumbar and subaxial cervical spine injuries: what is the expert's perspective?

STUDY DESIGN: Online questionnaire survey. OBJECTIVE: To obtain the opinion of experts on whether the currently available classification systems for thoracolumbar and subaxial cervical spine injuries meet their expectations with regard to the desired objectives of a good classification system and practical implementability. METHODS: An online survey was conducted during August-September 2013 using a specially designed questionnaire. Members of Spine Trauma Study Group of International Spinal Cord Society and other spinal injury experts were approached, and responses were analyzed. RESULTS: Forty-two spine experts responded. Majority (87.50%, n=35) were involved with education and research. For subaxial cervical spine injuries, Allen Ferguson classification was more commonly used (37.50%, n=15) and thought to be practically implementable in day-to-day practice (30.77%). For thoracolumbar injuries, while Thoracolumbar Injury Classification and Severity Score (TLICS) was more commonly used (47.50%, n=19), the response of experts for practical implementability in day-to-day practice was more evenly distributed among TLICS, AO (Association for Osteosynthesis) and Dennis classifications (30.77, 23.08 and 25.64%, respectively). Experts felt that the classification systems did not serve all the desired objectives. The reliability for residents was especially a concern. CONCLUSION: We may still be far from an ideal classification system. Many experts continue to prefer or would consider shifting back to traditional and simpler systems. There is a need for developing classification systems that would be better implementable practically in day-to-day clinical practice, better guide treatment, be more reliable, incorporate other modifiers influencing treatment and be more comprehensive in that order of priority.

Oncolytic viruses in head and neck cancer: a new ray of hope in the management protocol.

This paper intends to highlight the different types of oncolytic viruses (OVs), mechanism of tumor specificity, its safety, and various obstacles in the design of treatment and combination therapy utilizing oncotherapy. Search was conducted using the internet-based search engines and scholarly bibliographic databases with key words such as OVs, head and neck cancer, viruses, oral squamous cell carcinoma, and gene therapy. Revolutionary technologies in the field of cancer treatment have gone through a series changes leading to the development of innovative therapeutic strategies. Oncolytic virotherapy is one such therapeutic approach that has awaited phase III clinical trial validation. OVs are self-replicating, tumor selective and lyse cancer cells following viral infection. By modifying the viral genome, it is possible to direct their toxicity toward cancer cells. Viruses that are used for treatment of head and neck cancer are either naturally occurring or genetically modified. OVs are tumor selective and potential anticancer agents. Virotherapy may become the standard of care and part of combination therapy in the management of head and neck cancer in the future.

Novel magnetism of Ir5+(5d4) Ions in the double perovskite Sr2YIrO6.

We synthesize and study single crystals of a new double-perovskite Sr2YIrO6. Despite two strongly unfavorable conditions for magnetic order, namely, pentavalent Ir5+(5d4) ions which are anticipated to have Jeff=0 singlet ground states in the strong spin-orbit coupling (SOC) limit and geometric frustration in a face-centered cubic structure formed by the Ir5+ ions, we observe this iridate to undergo a novel magnetic transition at temperatures below 1.3 K. We provide compelling experimental and theoretical evidence that the origin of magnetism is in an unusual interplay between strong noncubic crystal fields, local exchange interactions, and "intermediate-strength" SOC. Sr2YIrO6 provides a rare example of the failed dominance of SOC in the iridates.

Acute drop in blood monocyte count differentiates NEC from other causes of feeding intolerance.

OBJECTIVE: Necrotizing enterocolitis (NEC) is characterized by macrophage infiltration into affected tissues. Because intestinal macrophages are derived from recruitment and in situ differentiation of blood monocytes in the gut mucosa, we hypothesized that increased recruitment of monocytes to the intestine during NEC reduces the blood monocyte concentration and that this fall in blood monocytes can be a useful biomarker for NEC. STUDY DESIGN: We reviewed medical records of very-low-birth-weight (VLBW) infants treated for NEC and compared them with a matched control group comprised of infants with feeding intolerance but no signs of NEC. Clinical characteristics and absolute monocyte counts (AMCs) were recorded. Diagnostic accuracy of AMC values was tested using receiver-operator characteristics (ROC). RESULT: We compared 69 cases and 257 controls (median 27 weeks, range 26 to 29 in both the groups). In stage II NEC, AMCs decreased from median 1.7 × 10(9) l(-1) (interquartile range (IQR) 0.98 to 2.4) to 0.8 (IQR 0.62 to 2.1); P < 0.05. In stage III NEC, monocyte counts decreased from median 2.1 × 10(9) l(-1) (IQR 0.1.5 to 3.2) to 0.8 (IQR 0.6 to 1.9); P < 0.05. There was no change in AMCs in control infants. ROC of AMC values showed a diagnostic accuracy (area under the curve) of 0.76. In a given infant with feeding intolerance, a drop in AMCs of > 20% indicated NEC with sensitivity of 0.70 (95% confidence interval (CI) 0.57 to 0.81) and specificity of 0.71 (95% CI 0.64 to 0.77). CONCLUSION: We have identified a fall in blood monocyte concentration as a novel biomarker for NEC in VLBW infants.

ZnO nanoparticles induced exopolysaccharide production by B. subtilis strain JCT1 for arid soil applications.

ZnO nanoparticle induced exopolysaccharide (EPS) production from Bacillus subtilis strain JCT1 (NCBI GenBank Accession No. JN194187) is a novel approach for arid soil applications. In the series of investigations, environmentally benign protocol was followed for the synthesis of ZnO nanoparticles using extracellular enzymes obtained from Aspergillus fumigatus TFR8. Putative characterization techniques were employed for confirmation of size, shape, surface structure, crystalline nature and elemental proportion of ZnO nanoparticles. Results established an average size of ZnO nanoparticles to be 2.9 nm at least at one dimension and oblate spherical in structure. The qualitative composition of the nanoparticles exhibited 97.5% Zn element atom percentage. Biosynthesized ZnO nanoparticles enhanced exopolysaccharide production by 596.1% as compared to control and further EPS amelioration led to enhanced soil aggregation (up to 82%), moisture retention (10.7-14.2%) and soil organic carbon. Soil aggregation stability was further confirmed by Fourier transform infra-red spectroscopy. A possible ZnO nanoparticle mediated biological mechanism for enhancing exopolysaccharide production has been discussed.

Immune correlates of HIV exposure without infection in foreskins of men from Rakai, Uganda.

Human immunodeficiency virus (HIV) susceptibility is heterogenous, with some HIV-exposed but seronegative (HESN) individuals remaining uninfected despite repeated exposure. Previous studies in the cervix have shown that reduced HIV susceptibility may be mediated by immune alterations in the genital mucosa. However, immune correlates of HIV exposure without infection have not been investigated in the foreskin. We collected sub-preputial swabs and foreskin tissue from HESN (n=20) and unexposed control (n=57) men undergoing elective circumcision. Blinded investigators assayed swabs for HIV-neutralizing IgA, innate antimicrobial peptides, and cytokine levels. Functional T-cell subsets from foreskin tissue were assessed by flow cytometry. HESN foreskins had elevated α-defensins (3,027 vs. 1,795 pg ml(-1), P=0.011) and HIV-neutralizing IgA (50.0 vs. 13.5% of men, P=0.019). Foreskin tissue from HESN men contained a higher density of CD3 T cells (151.9 vs. 69.9 cells mm(-2), P=0.018), but a lower proportion of these was Th17 cells (6.12 vs. 8.04% of CD4 T cells, P=0.007), and fewer produced tumor necrosis factor α (TNFα) (34.3 vs. 41.8% of CD4 T cells, P=0.037; 36.9 vs. 45.7% of CD8 T cells, P=0.004). A decrease in the relative abundance of susceptible CD4 T cells and local TNFα production, in combination with HIV-neutralizing IgA and α-defensins, may represent a protective immune milieu at a site of HIV exposure.

Prevalence of ß-thalassemia and other haemoglobinopathies in six cities in India: a multicentre study.

The population of India is extremely diverse comprising of more than 3,000 ethnic groups who still follow endogamy. Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. The data on the prevalence of ß-thalassemias and other haemoglobinopathies in different caste/ethnic groups of India is scarce. Therefore the present multicentre study was undertaken in six cities of six states of India (Maharashtra, Gujarat, West Bengal, Assam, Karnataka and Punjab) to determine the prevalence of haemoglobinopathies in different caste/ethnic groups using uniform methodology. Fifty-six thousand seven hundred eighty individuals (college students and pregnant women) from different caste/ethnic groups were screened. RBC indices were measured on an automated haematology counter while the percentage of HbA(2), HbF and other abnormal Hb variants were estimated by HPLC on the Variant Hemoglobin Testing System. The overall prevalence of ß-thalassemia trait was 2.78 % and varied from 1.48 to 3.64 % in different states, while the prevalence of ß-thalassemia trait in 59 ethnic groups varied from 0 to 9.3 %. HbE trait was mainly seen in Dibrugarh in Assam (23.9 %) and Kolkata in West Bengal (3.92 %). In six ethnic groups from Assam, the prevalence of HbE trait varied from 41.1 to 66.7 %. Few subjects with δß-thalassemia, HPFH, HbS trait, HbD trait, HbE homozygous and HbE ß-thalassemia as well as HbS homozygous and HbS-ß-thalassemia (<1 %) were also identified. This is the first large multicentre study covering cities from different regions of the country for screening for ß-thalassemia carriers and other haemoglobinopathies where uniform protocols and methodology was followed and quality control ensured by the co-ordinating centre. This study also shows that establishment of centres for screening for ß-thalassemia and other haemoglobinopathies is possible in medical colleges. Creating awareness, screening and counselling can be done at these centres. This experience will help to formulate a national thalassemia control programme in India.

A role for mucosal IL-22 production and Th22 cells in HIV-associated mucosal immunopathogenesis.

Interleukin-22 (IL-22) is a cytokine with epithelial reparative and regenerative properties that is produced by Th22 cells and by other immune cell subsets. Therefore, we explored the hypothesis that disruption of the gut barrier during HIV infection involves dysregulation of these cells in the gastrointestinal mucosa. Sigmoid IL-22-producing T cell and Th22 cells were dramatically depleted during chronic HIV infection, epithelial integrity was compromised, and microbial translocation was increased. These alterations were reversed after long-term antiretroviral therapy. While all mucosal IL-22-producing T-cell subsets were also depleted very early during HIV infection, at these early stages IL-22 production by non-T-cell populations (including NKp44+ cells) was increased and gut epithelial integrity was maintained. Circulating Th22 cells expressed a higher level of the HIV co-receptor/binding molecules CCR5 and α4ß7 than CD4+ T-cell subsets in HIV-uninfected participants, but this was not the case after HIV infection. Finally, recombinant IL-22 was protective against HIV and tumor necrosis factor-α-induced gut epithelial damage in a validated in vitro gut epithelial system. We conclude that reduced IL-22 production and Th22 depletion in the gut mucosa are important factors in HIV mucosal immunopathogenesis.

Mucosal correlates of isolated HIV semen shedding during effective antiretroviral therapy.

Effective antiretroviral therapy (ART) suppresses the blood HIV RNA viral load (VL) below the level of detection. However, some individuals intermittently shed HIV RNA in semen despite suppression of viremia, a phenomenon termed "isolated HIV semen shedding (IHS)". In a previously reported clinical study, we collected blood and semen samples from HIV-infected men for 6 months after ART initiation, and documented IHS at ≥1 visit in almost half of the participants, independent of ART regimen or semen drug levels. We now report the mucosal immune associations of IHS in these men. Blood and semen plasma cytokine levels were assayed by multiplex enzyme-linked immunosorbent assay, T-cell populations were evaluated by flow cytometry in freshly isolated blood and semen mononuclear cells, and semen cytomegalovirus (CMV) DNA levels were measured by PCR. Although IHS was not associated with altered blood or semen cytokine levels, the phenomenon was associated with a transient, dramatic increase in CD4+ and CD8+ T-cell activation that was restricted to the semen compartment. All participants were CMV infected, and although semen CMV reactivation was common despite ART, this was not associated with T-cell activation or IHS. Further elucidation of the causes of compartmentalized mucosal T-cell activation and IHS may have important public health implications.