Brugia malayi Antigen (BmA) inhibits HIV-1 trans-infection but neither BmA nor ES-62 alter HIV-1 infectivity of DC induced CD4+ Th-cells

One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co-infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA) and excretory-secretory product 62 (ES-62) from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-α. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th) cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs

Genomic Islands as a Marker to Differentiate between Clinical and Environmental Burkholderia pseudomallei

Burkholderia pseudomallei, as a saprophytic bacterium that can cause a severe sepsis disease named melioidosis, has preserved several extra genes in its genome for survival. The sequenced genome of the organism showed high diversity contributed mainly from genomic islands (GIs). Comparative genome hybridization (CGH) of 3 clinical and 2 environmental isolates, using whole genome microarrays based on B. pseudomallei K96243 genes, revealed a difference in the presence of genomic islands between clinical and environmental isolates. The largest GI, GI8, of B. pseudomallei was observed as a 2 sub-GI named GIs8.1 and 8.2 with distinguishable %GC content and unequal presence in the genome. GIs8.1, 8.2 and 15 were found to be more common in clinical isolates. A new GI, GI16c, was detected on chromosome 2. Presences of GIs8.1, 8.2, 15 and 16c were evaluated in 70 environmental and 64 clinical isolates using PCR assays. A combination of GIs8.1 and 16c (positivity of either GI) was detected in 70% of clinical isolates and 11.4% of environmental isolates (P<0.001). Using BALB/c mice model, no significant difference of time to mortality was observed between K96243 isolate and three isolates without GIs under evaluation (P>0.05). Some virulence genes located in the absent GIs and the difference of GIs seems to contribute less to bacterial virulence. The PCR detection of 2 GIs could be used as a cost effective and rapid tool to detect potentially virulent isolates that were contaminated in soil

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

Background The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Modeling study of mesospheric planetary waves: genesis and characteristics

The Numerical Spectral Model (NSM) extends from the ground into the thermosphere and incorporates Hines' Doppler Spread Parameterization for small-scale gravity waves (GWs). In the present version of the model we account for a tropospheric heat source in the zonal mean (m = 0), which reproduces qualitatively the observed zonal jets near the tropopause and the accompanying reversal in the latitudinal temperature variations. In the study presented here, we discuss the planetary waves (PWs) that are solely generated internally, i.e. without the explicit excitation sources related to tropospheric convection or topography. Our analysis shows that PWs are not produced when the zonally averaged heat source into the atmosphere is artificially suppressed, and that the PWs are generally weaker when the tropospheric source is not applied. Instabilities associated with the zonal mean temperature, pressure and wind fields, which still need to be explored, are exciting PWs that have amplitudes in the mesosphere comparable to those observed. Three classes of PWs are generated in the NSM. (1) Rossby type PWs, which slowly propagate westward relative to the mean zonal flow, are carried by the winds so that they appear (from the ground) to propagate, respectively, eastward and westward in the winter and summer hemispheres below 80 km. Depending on the zonal wave number and magnitudes of the zonal winds, and under the influence of the equatorial oscillations, these PWs typically have periods between 2 and 20 days. Their horizontal wind amplitudes can exceed 40 m/s in the lower mesosphere. (2) Rossby-gravity waves, which propagate westward at low latitudes and have periods around 2 days for zonal wave numbers m = 2 to 4. (3) Eastward propagating equatorial Kelvin waves, which are generated in the upper mesosphere with periods between 1 and 3 days depending on m. A survey of the PWs reveals that the largest wind amplitudes tend to occur below 80 km in the winter hemisphere; but above that altitude the amplitudes are larger in the summer hemisphere where the winds can approach 50 m/s. This pattern in the seasonal variations also appears in the baroclinity of the zonal mean (m = 0). The non-migrating tides in the mesosphere are significantly larger for the model with the tropospheric heat source, in which PWs are apparently generated by the instabilities that arise around the tropopause

Mesospheric non-migrating tides generated with planetary waves: I. Characteristics

In light of the measurements from the TIMED spacecraft and coordinated ground-based observations, we discuss results from a modeling study with our Numerical Spectral Model (NSM), which specifically deals with the non-migrating tides generated in the mesosphere. The NSM extends from the ground to the thermosphere, incorporates Hines' Doppler Spread Parameterization for small-scale gravity waves (GWs), and it describes the major dynamical features of the atmosphere including the wave driven equatorial oscillations (QBO and SAO), and the seasonal variations of tides and planetary waves (PWs). Accounting solely for the excitation Sources of the solar migrating tides, the NSM generates through nonlinear interactions also non-migrating tides in the mesosphere that are comparable in magnitude to those observed. (The important non-migrating tides generated explicitly by processes like tropospheric latent heat release and convection are not included.) Large non-migrating tides ire produced in the diurnal and semi-diurnal oscillations for the zonal mean (wave number m = 0) and in the semidiurnal oscillation for m = 1. In general, significant eastward and westward propagating tides are generated for all the zonal wave numbers m = 1-4. To identify the cause, the NSM is run without the solar heating for the zonal mean (m = 0), and the amplitudes of the resulting non-migrating tides are then negligibly small. In this case, the PWs generated by instabilities are artificially suppressed. This leads to the conclusion that the non-migrating tides are produced through nonlinear interactions between PWs and migrating tides, as had been previously proposed. In the accompanying paper, we present results from numerical experiments, which demonstrate that GW filtering contributes significantly to produce the nonlinear coupling that is involved. Published by Elsevier Ltd

Planetary-scale inertio gravity waves in the Mesosphere

In the polar region of the upper mesosphere, horizontal wind oscillations have been observed with periods around 10 hours. Waves with such periods are generated in our Numerical Spectral Model (NSM), and they are identified as planetary-scale inertio gravity waves (IGW). These waves have periods between 9 and 11 hours and appear above 70 km in the zonal mean (m = 0), as well as in m = 1 to 4 propagating eastward and westward. They grow in magnitude to altitudes near 100 km and have vertical wavelengths of about 25 km. The m = 1 westward IGWs have the largest amplitudes, up to 30 m/s at the poles. The IGWs occur intermittently but reveal systematic seasonal variations. Their amplitudes generally are largest in late winter and spring. Numerical experiments show that the waves also appear without tidal excitation. Like the planetary waves in the model, the IGWs are produced by instabilities that arise in the mean zonal circulation