A Comparative Study between Staplers and Suture (Silk 2-0) for Skin Closure in Cesarean Sections at Gandaki Medical College Teaching Hospital

Background: Skin closure in the abdominal surgeries is an important factor that affects the prognosis of wound in terms of hospital stay as well as overall outcome of the surgery. Objectives: Cesarean section being the commonly performed operation, choice of suture material has the unexceptional role on it. This study has been performed with an objective to look for the merits and demerits of the skin closure by suture (Silk 2-0) and stapler. Methods: Prospective comparative study conducted among the patients admitted in a Maternity Ward of Gandaki Medical College Teaching Hospital for elective and emergency cesarean section. The comparison has been made in terms of time taken during the skin closure, presence or absence of soakage and wound dehiscence, day of suture removal and pain during the suture removal. Results: The average time taken for skin closure for suture group was found to be 5.46 min (±0.97) and the same for stapler group was found to be 1.22 min (±0.15) respectively. Similarly, the mean day of stitch removal in suture and staples were found to be 6.94 (±1.75) and 7.95 (±1.89) respectively. Surgical site infection (SSI) i.e. soakage was present in eight percent of those in suture group and 20% in stapler group. Wound dehiscence was present in two percent among the suture group and five percent among the stapler group. The severity of pain is more in stapler group than that of suture group during its removal. Conclusions: Our study concluded suture being superior to staplers for skin closure during cesarean section. Though time taken for the closure is less in the stapler group, other factors like wound complications, duration of hospital stay, pain during its removal favored for the suture to be used. J-GMC-N | Volume 11 | Issue 01 | January-June 2018, Page: 1-

Pest risk assessment of African Leucinodes species for the European Union

Following a request from the European Commission, the EFSA Panel on Plant Health performed a quantitative risk assessment for the EU of African Leucinodes species (Lepidoptera: Crambidae), which are fruit and shoot borers, especially of eggplant type fruit. The assessment focused on (i) potential pathways for entry, (ii) distribution of infested imports within EU, (iii) climatic conditions favouring establishment, (iv) spread and (v) impact. Options for risk reduction are discussed, but their effectiveness was not quantified. Leucinodes spp. are widely distributed across sub-Saharan Africa but are little studied and they could be much more widespread in Africa than reported. Much African literature erroneously reports them as Leucinodes orbonalis which is restricted to Asia. The import of eggplant type fruit from sub-Saharan Africa consists of special fruit types and caters mostly to niche markets in the EU. The main pathway for entry is fruit of Solanum aethiopicum and exotic varieties of eggplant (S. melongena). CLIMEX modelling was used with two possible thresholds of ecoclimatic index (EI) to assess establishment potential. Climates favouring establishment occur mostly in southern Europe, where, based on human population, 14% of the imported produce is distributed across NUTS2 regions where EI ≥ 30; or where 23% of the produce is distributed where EI ≥ 15. Over the next 5 years, an annual median estimate of ~ 8600 fruits, originating from Africa, and infested with African Leucinodes spp. are expected to enter EU NUTS2 regions where EI ≥ 15 (90% CR ~ 570–52,700); this drops to ~ 5200 (90% CR ~ 350–32,100) in NUTS2 regions where EI ≥ 30. Escape of adult moths occurs mostly from consumer waste; considering uncertainties in pathway transfer, such as adult emergence, mate finding and survival of progeny, the annual median probability of a mated female establishing a founder population in NUTS regions where EI ≥ 15 was estimated to be 0.0078 (90% CR 0.00023–0.12125). This equates to a median estimate of one founder population ~ every 128 years (90% CR approximately one every 8–4280 years). Using an EI ≥ 30, the median number of founder populations establishing in the EU annually is 0.0048 (90% CR 0.0001–0.0739), equating to a median estimate of one founder population approximately every 210 years (90% CR approximately one every 14–7020 years). Under climate change for the period 2040–2059, the percent of infested produce going to suitable areas would be increased to 33% for EI ≥ 15 and to 21% for EI ≥ 30. Accordingly, the waiting time until the next founder population would be reduced to median estimates of 89 years for EI ≥ 15 (90% CR ~ 6–2980 years) and 139 years for EI ≥ 30 (90% CR 9–4655 years). If a founder population were to establish, it is estimated to spread at a rate of 0.65–7.0 km per year after a lag phase of 5–92 years. Leucinodes spp. are estimated to reduce eggplant yield by a median value of 4.5% (90% CR 0.67%–13%) if growers take no specific action, or 0.54% (90% CR between 0.13% and 1.9%) if they do take targeted action, matching previous estimates made during a risk assessment of L. orbonalis from Asia

Mutation Detection with Next-Generation Resequencing through a Mediator Genome

The affordability of next generation sequencing (NGS) is transforming the field of mutation analysis in bacteria. The genetic basis for phenotype alteration can be identified directly by sequencing the entire genome of the mutant and comparing it to the wild-type (WT) genome, thus identifying acquired mutations. A major limitation for this approach is the need for an a-priori sequenced reference genome for the WT organism, as the short reads of most current NGS approaches usually prohibit de-novo genome assembly. To overcome this limitation we propose a general framework that utilizes the genome of relative organisms as mediators for comparing WT and mutant bacteria. Under this framework, both mutant and WT genomes are sequenced with NGS, and the short sequencing reads are mapped to the mediator genome. Variations between the mutant and the mediator that recur in the WT are ignored, thus pinpointing the differences between the mutant and the WT. To validate this approach we sequenced the genome of Bdellovibrio bacteriovorus 109J, an obligatory bacterial predator, and its prey-independent mutant, and compared both to the mediator species Bdellovibrio bacteriovorus HD100. Although the mutant and the mediator sequences differed in more than 28,000 nucleotide positions, our approach enabled pinpointing the single causative mutation. Experimental validation in 53 additional mutants further established the implicated gene. Our approach extends the applicability of NGS-based mutant analyses beyond the domain of available reference genomes

Peptide and nucleic acid-directed self-assembly of cationic nanovehicles through giant unilamellar vesicle modification: targetable nanocomplexes for in vivo nucleic acid delivery

One of the greatest challenges for the development of genetic therapies is the efficient targeted delivery of therapeutic nucleic acids. Towards this goal, we have introduced a new engineering initiative in self-assembly of biologically safe and stable nanovesicle complexes (∼90-140 nm) derived from giant unilamellar vesicle (GUV) precursors and comprising plasmid DNA or siRNA and targeting peptide ligands. The biological performance of the engineered nanovesicle complexes were studied both in vitro and in vivo and compared with cationic liposome-based lipopolyplexes. Compared with cationic lipopolyplexes, nanovesicle complexes did not show advantages in transfection and cell uptake. However, nanovesicle complexes neither displayed significant cytotoxicity nor activated the complement system, which are advantageous for intravenous injection and tumour therapy. On intravenous administration into a neuroblastoma xenograft mouse model, nanovesicle complexes were found to distribute throughout the tumour interstitium, thus providing an alternative safer approach for future development of tumour-specific therapeutic nucleic acid interventions. On oropharyngeal instillation, nanovesicle complexes displayed better transfection efficiency than cationic lipopolyplexes. The technological advantages of nanovesicle complexes, originating from GUVs, over traditional cationic liposome-based lipopolyplexes are discussed. STATEMENT OF SIGNIFICANCE: The efficient targeted delivery of nucleic acids in vivo provides some of the greatest challenges to the development of genetic therapies. Giant unilamellar lipid vesicles (GUVs) have been used mainly as cell and tissue mimics and are instrumental in studying lipid bilayers and interactions. Here, the GUVs have been modified into smaller nanovesicles. We have then developed novel nanovesicle complexes comprising self-assembling mixtures of the nanovesicles, plasmid DNA or siRNA, and targeting peptide ligands. Their biophysical properties were studied and their transfection efficiency was investigated. They transfected cells efficiently without any associated cytotoxicity and with targeting specificity, and in vivo they resulted in very high and tumour-specific uptake and in addition, efficiently transfected the lung. The peptide-targeted nanovesicle complexes allow for the specific targeted enhancement of nucleic acid delivery with improved biosafety over liposomal formulations and represent a promising tool to improve our arsenal of safe, non-viral vectors to deliver therapeutic cargos in a variety of disorders

Recurrence of Type 1 Diabetes After Simultaneous Pancreas-Kidney Transplantation, Despite Immunosuppression, Is Associated With Autoantibodies and Pathogenic Autoreactive CD4 T-Cells

ObjectiveTo investigate if recurrent autoimmunity explained hyperglycemia and C-peptide loss in three immunosuppressed simultaneous pancreas-kidney (SPK) transplant recipients.Research design and methodsWe monitored autoantibodies and autoreactive T-cells (using tetramers) and performed biopsy. The function of autoreactive T-cells was studied with in vitro and in vivo assays.ResultsAutoantibodies were present pretransplant and persisted on follow-up in one patient. They appeared years after transplantation but before the development of hyperglycemia in the remaining patients. Pancreas transplant biopsies were taken within approximately 1 year from hyperglycemia recurrence and revealed beta-cell loss and insulitis. We studied autoreactive T-cells from the time of biopsy and repeatedly demonstrated their presence on further follow-up, together with autoantibodies. Treatment with T-cell-directed therapies (thymoglobulin and daclizumab, all patients), alone or with the addition of B-cell-directed therapy (rituximab, two patients), nonspecifically depleted T-cells and was associated with C-peptide secretion for >1 year. Autoreactive T-cells with the same autoantigen specificity and conserved T-cell receptor later reappeared with further C-peptide loss over the next 2 years. Purified autoreactive CD4 T-cells from two patients were cotransplanted with HLA-mismatched human islets into immunodeficient mice. Grafts showed beta-cell loss in mice receiving autoreactive T-cells but not control T-cells.ConclusionsWe demonstrate the cardinal features of recurrent autoimmunity in three such patients, including the reappearance of CD4 T-cells capable of mediating beta-cell destruction. Markers of autoimmunity can help diagnose this underappreciated cause of graft loss. Immune monitoring during therapy showed that autoimmunity was not resolved by the immunosuppressive agents used

Etiology of hospital mortality in children living in low- and middle-income countries:a systematic review and meta-analysis

In 2019, 80% of the 7.4 million global child deaths occurred in low- and middle-income countries (LMICs). Global and regional estimates of cause of hospital death and admission in LMIC children are needed to guide global and local priority setting and resource allocation but are currently lacking. The study objective was to estimate global and regional prevalence for common causes of pediatric hospital mortality and admission in LMICs. We performed a systematic review and meta-analysis to identify LMIC observational studies published January 1, 2005-February 26, 2021. Eligible studies included: a general pediatric admission population, a cause of admission or death, and total admissions. We excluded studies with data before 2,000 or without a full text. Two authors independently screened and extracted data. We performed methodological assessment using domains adapted from the Quality in Prognosis Studies tool. Data were pooled using random-effects models where possible. We reported prevalence as a proportion of cause of death or admission per 1,000 admissions with 95% confidence intervals (95% CI). Our search identified 29,637 texts. After duplicate removal and screening, we analyzed 253 studies representing 21.8 million pediatric hospitalizations in 59 LMICs. All-cause pediatric hospital mortality was 4.1% [95% CI 3.4%–4.7%]. The most common causes of mortality (deaths/1,000 admissions) were infectious [12 (95% CI 9–14)]; respiratory [9 (95% CI 5–13)]; and gastrointestinal [9 (95% CI 6–11)]. Common causes of admission (cases/1,000 admissions) were respiratory [255 (95% CI 231–280)]; infectious [214 (95% CI 193–234)]; and gastrointestinal [166 (95% CI 143–190)]. We observed regional variation in estimates. Pediatric hospital mortality remains high in LMICs. Global child health efforts must include measures to reduce hospital mortality including basic emergency and critical care services tailored to the local disease burden. Resources are urgently needed to promote equity in child health research, support researchers, and collect high-quality data in LMICs to further guide priority setting and resource allocation

The Lipopolysaccharide from Capnocytophaga canimorsus Reveals an Unexpected Role of the Core-Oligosaccharide in MD-2 Binding

Capnocytophaga canimorsus is a usual member of dog's mouths flora that causes rare but dramatic human infections after dog bites. We determined the structure of C. canimorsus lipid A. The main features are that it is penta-acylated and composed of a “hybrid backbone” lacking the 4′ phosphate and having a 1 phosphoethanolamine (P-Etn) at 2-amino-2-deoxy-d-glucose (GlcN). C. canimorsus LPS was 100 fold less endotoxic than Escherichia coli LPS. Surprisingly, C. canimorsus lipid A was 20,000 fold less endotoxic than the C. canimorsus lipid A-core. This represents the first example in which the core-oligosaccharide dramatically increases endotoxicity of a low endotoxic lipid A. The binding to human myeloid differentiation factor 2 (MD-2) was dramatically increased upon presence of the LPS core on the lipid A, explaining the difference in endotoxicity. Interaction of MD-2, cluster of differentiation antigen 14 (CD14) or LPS-binding protein (LBP) with the negative charge in the 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) of the core might be needed to form the MD-2 – lipid A complex in case the 4′ phosphate is not present