Rabies vaccine and neuraxial anaesthesia

This case report of neuraxial anaesthesia for emergency orthopaedic surgery serves to highlight the dilemma faced by anaesthetists when surgical intervention becomes necessary in a patient on anti-rabies vaccine. The two issues of importance are the possible reduction in the efficacy of vaccination by an immunosuppressive effect of anaesthesia and surgery, and the possible need to avoid local anaesthetics for the provision of postoperative analgesia to assist in the early detection of any neurological deficit.Keywords: rabies; vaccine; anaesthesia; neuraxial bloc

Hypercoagulability progresses to hypocoagulability during evolution of acetaminophen-induced acute liver injury in pigs

Increases in prothrombin time (PT) and international normalised ratio (INR) characterise acute liver injury (ALI) and failure (ALF), yet a wide heterogeneity in clotting abnormalities exists. This study defines evolution of coagulopathy in 10 pigs with acetaminophen (APAP)-induced ALI compared to 3 Controls. APAP administration began at 0 h and continued to ‘ALF’, defined as INR >3. In APAP pigs, INR was 1.05 ± 0.02 at 0 h, 2.15 ± 0.43 at 16 h and > 3 at 18 ± 1 h. At 12 h thromboelastography (TEG) demonstrated increased clot formation rate, associated with portal vein platelet aggregates and reductions in protein C, protein S, antithrombin and A Disintegrin and Metalloprotease with Thrombospondin type 1 repeats–13 (ADAMTS-13) to 60%, 24%, 47% and 32% normal respectively. At 18 ± 1 h, INR > 3 was associated with: hypocoagulable TEG profile with heparin-like effect; falls in thrombin generation, Factor V and Factor VIII to 52%, 19% and 17% normal respectively; further decline in anticoagulants; thrombocytopenia; neutrophilia and endotoxemia. Multivariate analysis, found that ADAMTS-13 was an independent predictor of a hypercoagulable TEG profile and platelet count, endotoxin, Protein C and fibrinogen were independent predictors of a hypocoagulable TEG profile. INR remained normal in Controls. Dynamic changes in coagulation occur with progression of ALI: a pro-thrombotic state progresses to hypocoagulability

Perspectives on voluntary assisted partner notification among providers, people with HIV and the general population in Indonesia: a formative qualitative study.

BACKGROUND: Voluntary assisted partner notification (aPN) services are effective in increasing access to and uptake of HIV testing among partners of people with HIV. Following recommendations by the World Health Organization in 2016, Indonesia evaluated various approaches to aPN. We present the lessons learned from formative operational research undertaken to understand provider and patient perspectives on aPN from three demonstration sites in cities with a high HIV burden. METHODS: We conducted a formative qualitative study in three cities: Jakarta, Semarang, and Denpasar between September and October 2019. We conducted six focus group discussions (FGDs) (n = 44 participants) among health-care providers, people living with HIV and the general population. We explored participant preferences and concerns about how aPN should be delivered, including the methods of and messaging for contacting partners. All FGDs were conducted in the Indonesian language. Qualitative data were analysed using thematic analysis. RESULTS: aPN was acceptable across different participant populations, although with caveats. Some differences were observed between the general population, providers and people living with HIV. People living with HIV were mainly concerned with confidentiality of the procedure and preferred the use of telecommunication and messages that avoid explicit mention of HIV exposure. Providers preferred similar approaches but for different reasons, being concerned mainly with self-efficacy and security. There was consensus regarding dual referral models. The use of phone calls and short messages were preferred as these are perceived to minimize negative reactions and stigma, protect client confidentiality and are suitable in the current legal situation. The general population was mainly concerned with effectiveness and prefer direct provider-led approaches, such as preferring in-person meeting with explicit notification of potential HIV exposure. CONCLUSIONS: We found consensus among stakeholders on acceptance of aPN, especially dual referral methods. Development and implementation of aPN protocols should also consider clients' individual situations and concerns regarding safeguarding of confidentiality, and offer a range of options to accommodate all stakeholders involved

Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa

Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa.In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12-99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO).After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2-6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2-3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02).One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure

Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas

<p>Abstract</p> <p>Background</p> <p>Loss of heterozygosity of chromosome 10q26 has been shown to be associated with the aggressiveness of astrocytic tumors (or astrocytomas), but the responsible gene(s) residing in this region has not been fully identified. The <it>BCCIP </it>gene is located at chromosome 10q26. It encodes a BRCA2 and CDKN1A (p21) interacting protein. Previous studies have shown that down-regulation of BCCIP impairs recombinational DNA repair, G1/S cell cycle checkpoint, p53 trans-activation activity, cytokinesis, and chromosome stability, suggesting a potential role of <it>BCCIP </it>in cancer etiology. In this study, we investigated whether <it>BCCIP </it>is altered in astrocytomas.</p> <p>Methods</p> <p>Genomic DNA from 45 cases of grade IV astrocytic tumor (glioblastoma) tissues and 12 cases of normal tissues were analyzed by quantitative PCR. The BCCIP protein expression in 96 cases of grade II–IV astrocytic tumors was detected by immunohistochemistry (IHC). IHC staining of glial fibrillary acid protein (GFAP), a marker for astrocytic cells, was used to identify cells of the astrocytic lineage.</p> <p>Results</p> <p>We found that BCCIP protein is expressed in normal cells with positive staining of GFAP. However, BCCIP protein expression was not detectable in ~45% of all astrocytic tumors, and in > 60% in the grade IV glioblastoma. About 45% glioblastoma have significant (p < 0.01) reduction of <it>BCCIP </it>gene copy number when compared to normal DNA. Furthermore, the frequency of lacking BCCIP expression is associated with the aggressiveness of astrocytic tumors.</p> <p>Conclusion</p> <p>Our data implicate a role of BCCIP in astrocytic tumorigenesis, and lack of <it>BCCIP </it>may be used as a marker for astrocytomas.</p

Essential Roles of BCCIP in Mouse Embryonic Development and Structural Stability of Chromosomes

BCCIP is a BRCA2- and CDKN1A(p21)-interacting protein that has been implicated in the maintenance of genomic integrity. To understand the in vivo functions of BCCIP, we generated a conditional BCCIP knockdown transgenic mouse model using Cre-LoxP mediated RNA interference. The BCCIP knockdown embryos displayed impaired cellular proliferation and apoptosis at day E7.5. Consistent with these results, the in vitro proliferation of blastocysts and mouse embryonic fibroblasts (MEFs) of BCCIP knockdown mice were impaired considerably. The BCCIP deficient mouse embryos die before E11.5 day. Deletion of the p53 gene could not rescue the embryonic lethality due to BCCIP deficiency, but partially rescues the growth delay of mouse embryonic fibroblasts in vitro. To further understand the cause of development and proliferation defects in BCCIP-deficient mice, MEFs were subjected to chromosome stability analysis. The BCCIP-deficient MEFs displayed significant spontaneous chromosome structural alterations associated with replication stress, including a 3.5-fold induction of chromatid breaks. Remarkably, the BCCIP-deficient MEFs had a ∼20-fold increase in sister chromatid union (SCU), yet the induction of sister chromatid exchanges (SCE) was modestly at 1.5 fold. SCU is a unique type of chromatid aberration that may give rise to chromatin bridges between daughter nuclei in anaphase. In addition, the BCCIP-deficient MEFs have reduced repair of irradiation-induced DNA damage and reductions of Rad51 protein and nuclear foci. Our data suggest a unique function of BCCIP, not only in repair of DNA damage, but also in resolving stalled replication forks and prevention of replication stress. In addition, BCCIP deficiency causes excessive spontaneous chromatin bridges via the formation of SCU, which can subsequently impair chromosome segregations in mitosis and cell division

The journey to antiretroviral therapy in Karnataka, India: who was lost on the road?

One important operational challenge facing antiretroviral treatment (ART) programmes in low- and middle-income countries is the loss to follow-up between diagnosis of human immunodeficiency virus (HIV) and initiation of ART. This is a major obstacle to achieving universal access to ART. This study from Karnataka, India, tried to measure such losses by determining the number of HIV-positive individuals diagnosed, the number of them reaching ART centres, the number initiated on ART and the reasons for non-initiation of ART