Enabling conditions for an equitable and sustainable blue economy.

The future of the global ocean economy is currently envisioned as advancing towards a 'blue economy'-socially equitable, environmentally sustainable and economically viable ocean industries1,2. However, tensions exist within sustainable development approaches, arising from differing perspectives framed around natural capital or social equity. Here we show that there are stark differences in outlook on the capacity for establishing a blue economy, and on its potential outcomes, when social conditions and governance capacity-not just resource availability-are considered, and we highlight limits to establishing multiple overlapping industries. This is reflected by an analysis using a fuzzy logic model to integrate indicators from multiple disciplines and to evaluate their current capacity to contribute to establishing equitable, sustainable and viable ocean sectors consistent with a blue economy approach. We find that the key differences in the capacity of regions to achieve a blue economy are not due to available natural resources, but include factors such as national stability, corruption and infrastructure, which can be improved through targeted investments and cross-scale cooperation. Knowledge gaps can be addressed by integrating historical natural and social science information on the drivers and outcomes of resource use and management, thus identifying equitable pathways to establishing or transforming ocean sectors1,3,4. Our results suggest that policymakers must engage researchers and stakeholders to promote evidence-based, collaborative planning that ensures that sectors are chosen carefully, that local benefits are prioritized, and that the blue economy delivers on its social, environmental and economic goals.

Gastroesophageal reflux disease following laparoscopic vertical sleeve gastrectomy and laparoscopic roux-en-Y gastric bypass: meta-analysis and systematic review of 5-year data.

To compare 5-year gastroesophageal reflux outcomes following Laparoscopic Vertical Sleeve Gastrectomy (LVSG) and Laparoscopic Roux-en-Y gastric bypass (LRYGB) based on high quality randomized controlled trials (RCTs). We conducted a sub-analysis of our systematic review and meta-analysis of RCTs of primary LVSG and LRYGB procedures in adults for 5-year post-operative complications (PROSPERO CRD42018112054). Electronic databases were searched from January 2015 to July 2021 for publications meeting inclusion criteria. The Hartung-Knapp-Sidik-Jonkman random effects model was utilized to estimate weighted mean differences where meta-analysis was possible. Bias and certainty of evidence was assessed using the Cochrane Risk of Bias Tool 2 and GRADE. Four RCTs were included (LVSG n = 266, LRYGB n = 259). An increase in adverse GERD outcomes were observed at 5 years postoperatively in LVSG compared to LRYGB in all outcomes considered: Overall worsened GERD, including the development de novo GERD, occurred more commonly following LVSG compared to LRYGB (OR 5.34, 95% CI 1.67 to 17.05; p = 0.02; I2 = 0%; (Moderate level of certainty); Reoperations to treat severe GERD (OR 7.22, 95% CI 0.82 to 63.63; p = 0.06; I2 = 0%; High level of certainty) and non-surgical management for worsened GERD (OR 3.42, 95% CI 1.16 to 10.05; p = 0.04; I2 = 0%; Low level of certainty) was more common in LVSG patients. LVSG is associated with the development and worsening of GERD symptoms compared to LRYGB at 5 years postoperatively leading to either introduction/increased pharmacological requirement or further surgical treatment. Appropriate patient/surgical selection is critical to minimize these postoperative risks.

Effect of Vitamin D Deficiency on Periprosthetic Joint Infection and Complications After Primary Total Joint Arthroplasty.

BACKGROUND: Vitamin D deficiency is a global problem, and 13 to 75% of patients undergoing total joint arthroplasty (TJA) have vitamin D deficiency. Several studies have shown that low preoperative vitamin D levels may increase the risk of postoperative complications, including periprosthetic joint infection (PJI), in patients undergoing primary TJA. Most of the studies are underpowered. This study aimed to investigate the relationship between vitamin D deficiency and surgical and medical complications after primary TJA, with a specific focus on PJI. METHODS: Prospectively collected institutional multicenter arthroplasty databases were reviewed to identify patients who underwent primary total knee and hip arthroplasty. The study group was defined as patients whose vitamin D level is < 30 ng/dL and who received a single oral dose of 7.5 mg (300,000 IU) D3 within two weeks before index surgery (n = 488; mean age 63 years). Patients in the control group were those whose preoperative vitamin D levels were unknown and who did not receive vitamin D supplementation (n = 592, mean age 66). The groups were compared regarding 90-day medical and surgical complications, including PJI, mortality, and readmission rates. RESULTS: The total number of complications (8.6 and 4.3%; respectively; P = .005), superficial wound infection (2.5 and 0.2%, respectively; P < .001), and postoperative cellulitis (2.2 and 0% respectively; P < .001) were statistically significantly higher in the patient group who did not receive vitamin D supplementation. However, 90-day mortality (P = .524), PJI (P = .23), and readmission rate (P = .683) were similar between the groups. CONCLUSIONS: This study demonstrated that preoperative optimization of vitamin D levels may be beneficial in reducing postoperative complications, including superficial wound infection and postoperative cellulitis. Administering an oral 300,000 U single-dose vitamin D regimen to correct vitamin D deficiency can positively impact outcomes following primary TJA.

Increased Permeability of the Blood-Brain Barrier in a Diabetic Mouse Model (Leprdb/db Mice).

Type 2 Diabetes Mellitus (T2DM) is linked to multiple complications, including cognitive impairment, and the prevalence of memory-related neurodegenerative diseases is higher in T2DM patients. One possible theory is the alteration of the microvascular and macrovascular environment of the blood-brain barrier (BBB). In this study, we employed different approaches, including RT-PCR, functional pharmacokinetic studies using sodium fluorescein (NaFL), and confocal microscopy, to characterize the functional and molecular integrity of the BBB in a T2DM animal model, leptin receptor-deficient mutant mice (Leprdb/db mice). As a result, VCAM-1, ICAM-1, MMP-9, and S100b (BBB-related markers) dysregulation was observed in the Leprdb/db animal model compared to littermate wild-type mice. The brain concentration of sodium fluorescein (NaFL) increased significantly in Leprdb/db untreated mice compared to insulin-treated mice. Therefore, the permeability of NaFL was higher in Leprdb/db control mice than in all remaining groups. Identifying the factors that increase the BBB in Leprdb/db mice will provide a better understanding of the BBB microvasculature and present previously undescribed findings of T2DM-related brain illnesses, filling knowledge gaps in this emerging field of research.

A protein domain-based interactome network for C. elegans early embryogenesis.

Many protein-protein interactions are mediated through independently folding modular domains. Proteome-wide efforts to model protein-protein interaction or "interactome" networks have largely ignored this modular organization of proteins. We developed an experimental strategy to efficiently identify interaction domains and generated a domain-based interactome network for proteins involved in C. elegans early-embryonic cell divisions. Minimal interacting regions were identified for over 200 proteins, providing important information on their domain organization. Furthermore, our approach increased the sensitivity of the two-hybrid system, resulting in a more complete interactome network. This interactome modeling strategy revealed insights into C. elegans centrosome function and is applicable to other biological processes in this and other organisms.

Endophytic upper tract urothelial carcinoma in a solitary kidney treated by cryotherapy: an unorthodox case for successful management.

BACKGROUND: Nephroureterectomy remains the gold standard treatment for upper tract urothelial carcinoma (UTUC). Considering the high risk of developing renal function impairment after surgery, the rationale for nephron sparing approaches in treatment of UTUC has been raised. In this case, renal cryoablation was able to achieve successful oncologic control while preserving renal function during 5 years of follow up without intraoperative or post operative complications. CASE PRESENTATION: A 79 year old male presents after three months of macroscopic hematuria. Imaging revealed a 3.6 × 3.1 × 2.7 cm endophytic mass in the interpolar region of the left kidney and an atrophic right kidney. After weighing the lesion's location with the patient's of complex medical history, he was counselled to undergo a minimally invasive percutaneous cryoablation as treatment for his solitary renal mass. A diagnostic dilemma was encountered as imaging suggested a diagnosis of renal cell carcinoma. However, the pre-ablation biopsy established an alternative diagnosis, revealing UTUC. Percutaneous cryoablation became an unorthodox treatment modality for the endophytic component of his UTUC followed by retrograde ureteroscopic laser fulguration. The patient was followed in 3 months, 6 months, then annually with cross sectional imaging by MRI, cystoscopy, urine cytology and renal function testing. After five years of follow-up, the patient did not encountered recurrence of UTUC or deterioration in renal function, thereby maintaining a stable eGFR. CONCLUSION: Although evidence for nephron-sparing modalities for UTUC is mounting in recent literature, limited data still exists on cryotherapy as a line of treatment for urothelial carcinoma. We report successful management of a low-grade UTUC using cryoablation with the crucial aid of an initial renal biopsy and long-term follow-up. Our results provide insight into the role of cryoablation as a nephron-sparing approach for UTUC.

Cystatin C-derived estimated glomerular filtration rate in children with sickle cell anaemia.

BACKGROUND: Sickle cell disease is the most common inherited blood disorder in humans and constitutes a major public health burden. It is a multisystemic condition with long-term renal complications. Early detection of sickle cell nephropathy and initiation of appropriate interventions are associated with improved survival and quality of life. This study aimed to compare the cystatin C-derived estimated glomerular filtration rate (GFR) of the study groups and also, to correlate the clinical features of chronic kidney disease (CKD) with decreased GFR in children with sickle cell anaemia (SCA). METHODS: This hospital-based cross-sectional analytic study recruited 86 SCA subjects in steady-state and 86 age and sex-matched healthy HbAA controls aged 1-14 years who attended the Paediatric Haematology and Outpatient clinics of Federal Medical Centre Bida over six months. Data were collected using a semi-structured questionnaire, and participants' length/height, weight, and blood pressure were measured using standard procedures. Blood samples were drawn for serum cystatin C assay via the sandwich enzyme-linked immunosorbent assay (ELISA) technique. Filler's equation was used to calculate the glomerular filtration rate. RESULTS: There was a significant difference in the mean cystatin C-derived GFR between the two groups, i.e. 116 ± 30mL/min/1.73m2 vs. 106 ± 24mL/min/1.73m2 for the SCA and control groups, respectively (p = 0.017). The prevalence of supernormal GFR (i.e. GFR > 140mL/min/1.73m2) and decreased GFR (i.e. GFR < 90mL/min/1.73m2) was 19.8% and 22.1%, respectively, in children with SCA. There was no significant association between the age at diagnosis of SCA, blood transfusions, blood pressure, packed cell volume and presence of peripheral oedema with decreased GFR in the study subjects. CONCLUSIONS: Supernormal GFR is common in children with SCA and there is no significant association between clinical features of CKD with decreased GFR. Regular evaluation of renal function is, however, recommended in children with SCA for early detection and treatment of renal complications in order to halt the progression to end-stage kidney disease (ESKD).

Natural angiotensin converting enzyme inhibitors: A safeguard against hypertension, respiratory distress syndrome, and chronic kidney diseases.

Hypertension is a serious concern as it is one of the causes of kideny failure and pulmonary fibrosis. An important therapeutic strategy for treating chronic hypertension is to inhibit the angiotensin converting enzyme (ACE). ACE inhibition reduces kidney damage, pulmonary artery pressure, and high blood pressure. Due to their high efficacy and low risk of side effects, natural renin-angiotensin system inhibitors have drawn increasing attention over the past decades. Alkaloids, amino acids, anthocyanidins, flavonoids, glucosinolates, isoflavonoids, phenolic acids, polyphenolics, and triterpenoids are among the bioactive metabolites pocessing an impressive ACE inhibitory activity. Many herbs including Rosmarinus officinalis, Hibiscus sabdariffa, Curcuma longa, Rauwolfia serpentina, Emblica officinalis, Cynara scolymus, Punica granatum, Mucuna pruriens, Capsicum annuum, and Moringa olifera were found having ACE inhibitory activities comparable to captopril and enalpril. These enticing natural ACE inhibitors deserve to be a safeguard medicine against hypertension, respiratory distress syndrome, and chronic kidney diseases. More clinical trials are required before new natural compounds and herbs can be used to treat chronic hypertension and its ramifications, such as respiratory distress syndrome and kidney failure.

Hydrothermal impacts of water release on early life stages of white sturgeon in the Nechako river, B.C. Canada.

Water temperature plays a crucial role in the physiology of aquatic species, particularly in their survival and development. Thus, resource programs are commonly used to manage water quality conditions for endemic species. In a river system like the Nechako River system, central British Columbia, a water management program was established in the 1980s to alter water release in the summer months to prevent water temperatures from exceeding a 20 °C threshold downstream during the spawning season of Sockeye salmon (Oncorhynchus nerka). Such a management regime could have consequences for other resident species like the white sturgeon (Acipenser transmontanus). Here, we use a hydrothermal model and white sturgeon life stage-specific experimental thermal tolerance data to evaluate water releases and potential hydrothermal impacts based on the Nechako water management plan (1980-2019). Our analysis focused mainly on the warmest five-month period of the year (May to September), which includes the water release management period (July-August). Our results show that the thermal exposure risk, an index that measures temperature impact on species physiology of Nechako white sturgeon across all early life stages (embryo, yolk-sac larvae, larvae, and juvenile) has increased substantially, especially in the 2010s relative to the management program implementations' first decade (the 1980s). The embryonic life stage was the most impacted, with a continuous increase in potential adverse thermal exposure in all months examined in the study. We also recorded major impacts of increased thermal exposure on the critical habitats necessary for Nechako white sturgeon recovery. Our study highlights the importance of a holistic management program with consideration for all species of the Nechako River system and the merit of possibly reviewing the current management plan, particularly with the current concerns about climate change impacts on the Nechako River.

An integrated financial and environmental evaluation framework to optimize residential photovoltaic solar systems in Australia from recession uncertainties.

This study assesses the financial viability and environmental evaluation of Photovoltaic (PV) panels from the perspective of the recent economic recession due to the Russia-Ukraine war. The financial viability of PV installation is calculated based on the estimated price, solar rebates, feed-in tariff, energy supply cost, and other evaluation parameters available at the assessment time. This calculation implicitly assumes variable discount rates (4%, 7%, and 12%) to show how the future will unfold and its correlations with design parameters. Details of economic appraisal integrating current inflation, rebates, and incentives of solar systems have been analyzed for the first time in this study. Financial indicators reveal the advantages of installing a grid-connected solar system (SS) over a solar battery storage system (SSWB). Compared to other installation systems, the lowest payback (PB) and highest internal rate of return (IRR) are observed for a 7 kW grid-connected solar system. Relative uncertainties of solar installation systems represent the necessity of government subsidies (r = -0.602) for solar storage batteries. LCA signifies the energy-intensive process of manufacturing metallurgical-grade (MG) silicon is the primary cause of significant greenhouse gas (GHG) emissions and cumulative energy demand (CED) for PV panels. A potential amount of metal and fossil fuels is depleted for interconnective components of solar installation systems. Amorphous solar panels exhibit lower impacts than polycrystalline, but further upgradation in service life is required to become cost-effective and cope with current inflation.

Prospective of nanoscale metal organic frameworks [NMOFs] for cancer therapy.

Nano metal organic frameworks (NMOFs) belong to the group of nanoporous materials. Over the decades, the conducted researches explored the area for the potential applications of NMOFs in areas like biomedical, chemical engineering and materials science. Recently, NMOFs have been explored for their potential use in cancer diagnosis and therapeutics. The excellent physico-chemical features of NMOFs also make them a potential candiadate to facilitate drug design, delivery and storage against cancer cells. In this review, we have explored the characterstic features, synthesis methods, NMOFs based drug delivery, diagnosis and imaging in various cancer types. In addition to this, we have also pondered on the stability and toxicological concerns of NMOFs. Despite, a significant research has been done for the potential use of NMOFs in cancer diagonostic and therapeutics, more information regarding the stability, in-vivo clearance, toxicology, and pharmacokinetics is still needed to ehnace the use of NMOFs in cancer diagonostic and therapeutics.

Assessment of CD39 expression in regulatory T-cell subsets by disease severity in adult and juvenile COVID-19 cases.

COVID-19 is a disease characterized by acute respiratory failure and is a major health problem worldwide. Here, we aimed to investigate the role of CD39 expression in Treg cell subsets in COVID-19 immunopathogenesis and its relationship to disease severity. One hundred and ninety COVID-19 patients (juveniles, adults) and 43 volunteers as healthy controls were enrolled in our study. Flow cytometric analysis was performed using a 10-color monoclonal antibody panel from peripheral blood samples. In adult patients, CD39+ Tregs increased with disease severity. In contrast, CD39+ Tregs were decreased in juvenile patients in an age-dependent manner. Overall, our study reveals an interesting profile of CD39-expressing Tregs in adult and juvenile cases of COVID-19. Our results provide a better understanding of the possible role of Tregs in the mechanism of immune response in COVID-19 cases.

Projecting global mariculture production and adaptation pathways under climate change.

The sustainability of global seafood supply to meet increasing demand is facing several challenges, including increasing consumption levels due to a growing human population, fisheries resources over-exploitation and climate change. Whilst growth in seafood production from capture fisheries is limited, global mariculture production is expanding. However, climate change poses risks to the potential seafood production from mariculture. Here, we apply a global mariculture production model that accounts for changing ocean conditions, suitable marine area for farming, fishmeal and fish oil production, farmed species dietary demand, farmed fish price and global seafood demand to project mariculture production under two climate and socio-economic scenarios. We include 85 farmed marine fish and mollusc species, representing about 70% of all mariculture production in 2015. Results show positive global mariculture production changes by the mid and end of the 21st century relative to the 2000s under the SSP1-2.6 scenario with an increase of 17%±5 and 33%±6, respectively. However, under the SSP5-8.5 scenario, an increase of 8%±5 is projected, with production peaking by mid-century and declining by 16%±5 towards the end of the 21st century. More than 25% of mariculture-producing nations are projected to lose 40%-90% of their current mariculture production potential under SSP5-8.5 by mid-century. Projected impacts are mainly due to the direct ocean warming effects on farmed species and suitable marine areas, and the indirect impacts of changing availability of forage fishes supplies to produce aquafeed. Fishmeal replacement with alternative protein can lower climate impacts on a subset of finfish production. However, such adaptation measures do not apply to regions dominated by non-feed-based farming (i.e. molluscs) and regions losing substantial marine areas suitable for mariculture. Our study highlights the importance of strong mitigation efforts and the need for different climate adaptation options tailored to the diversity of mariculture systems, to support climate-resilient mariculture development.

Linagliptin ameliorates acetic acid-induced colitis via modulating AMPK/SIRT1/PGC-1α and JAK2/STAT3 signaling pathway in rats.

Ulcerative colitis is a chronic inflammatory disease, profoundly affecting the patient's quality of life and is associated with various complications. Linagliptin, a potent DPP- IV inhibitor, shows favorable anti-inflammatory effects in several animal model pathologies. To this end, the present study aimed to investigate the anti-inflammatory effect of linagliptin in a rat model of acetic acid-induced colitis. Moreover, the molecular mechanisms behind this effect were addressed. Accordingly, colitis was established by the administration of a 2 ml 6% acetic acid intrarectally and treatment with linagliptin (5 mg/kg) started 24 h after colitis induction and continued for 7 days. On one hand, the DPP-IV inhibitor alleviated the severity of colitis as evidenced by a decrease of disease activity index (DAI) scores, colon weight/length ratio, macroscopic damage, and histopathological deteriorations. Additionally, linagliptin diminished colon inflammation via attenuation of TNF-α, IL-6, and NF-κB p65 besides restoration of anti-inflammatory cytokine IL-10. On the other hand, linagliptin increased levels of p-AMPK, SIRT1, and PGC-1α while abolishing the increment in p-JAK2 and p-STAT3. In parallel linagliptin reduced mTOR levels and upregulated expression levels of SHP and MKP-1 which is postulated to mediate AMPK-driven JAK2/STAT3 inhibition. Based on these findings, linagliptin showed promising anti-inflammatory activity against acetic acid-induced colitis that is mainly attributed to the activation of the AMPK-SIRT1-PGC-1α pathway as well as suppression of the JAK2/STAT3 signaling pathway that might be partly mediated through AMPK activation.

Rebuilding fish biomass for the world's marine ecoregions under climate change.

Rebuilding overexploited marine populations is an important step to achieve the United Nations' Sustainable Development Goal 14-Life Below Water. Mitigating major human pressures is required to achieve rebuilding goals. Climate change is one such key pressure, impacting fish and invertebrate populations by changing their biomass and biogeography. Here, combining projection from a dynamic bioclimate envelope model with published estimates of status of exploited populations from a catch-based analysis, we analyze the effects of different global warming and fishing levels on biomass rebuilding for the exploited species in 226 marine ecoregions of the world. Fifty three percent (121) of the marine ecoregions have significant (at 5% level) relationship between biomass and global warming level. Without climate change and under a target fishing mortality rate relative to the level required for maximum sustainable yield of 0.75, we project biomass rebuilding of 1.7-2.7 times (interquartile range) of current (average 2014-2018) levels across marine ecoregions. When global warming level is at 1.5 and 2.6°C, respectively, such biomass rebuilding drops to 1.4-2.0 and 1.1-1.5 times of current levels, with 10% and 25% of the ecoregions showing no biomass rebuilding, respectively. Marine ecoregions where biomass rebuilding is largely impacted by climate change are in West Africa, the Indo-Pacific, the central and south Pacific, and the Eastern Tropical Pacific. Coastal communities in these ecoregions are highly dependent on fisheries for livelihoods and nutrition security. Lowering the targeted fishing level and keeping global warming below 1.5°C are projected to enable more climate-sensitive ecoregions to rebuild biomass. However, our findings also underscore the need to resolve trade-offs between climate-resilient biomass rebuilding and the high near-term demand for seafood to support the well-being of coastal communities across the tropics.

Global analyses of the effect of different cellular contexts on microRNA targeting.

MicroRNA (miRNA) regulation clearly impacts animal development, but the extent to which development-with its resulting diversity of cellular contexts-impacts miRNA regulation is unclear. Here, we compared cohorts of genes repressed by the same miRNAs in different cell lines and tissues and found that target repertoires were largely unaffected, with secondary effects explaining most of the differential responses detected. Outliers resulting from differential direct targeting were often attributable to alternative 3' UTR isoform usage that modulated the presence of miRNA sites. More inclusive examination of alternative 3' UTR isoforms revealed that they influence ∼10% of predicted targets when comparing any two cell types. Indeed, considering alternative 3' UTR isoform usage improved prediction of targeting efficacy significantly beyond the improvements observed when considering constitutive isoform usage. Thus, although miRNA targeting is remarkably consistent in different cell types, considering the 3' UTR landscape helps predict targeting efficacy and explain differential regulation that is observed.

Recycling waste vehicle tyres into crumb rubber and the transition to renewable energy sources: A comprehensive life cycle assessment.

This study conducts a comprehensive life cycle assessment (LCA) on converting waste vehicle tyres into recycled crumb rubber (CR) granules as an alternative polymer for enhancing asphalt properties. The LCA study has been performed on acquired industrial primary data by incorporating CR at different proportions of binder in one ton (1-ton) of asphalt mix following the wet method. The uncertainty analysis of design variables identified a relatively strong positive relation of emissions with the equipment energy consumption (r = 0.98). Monte Carlo simulations evaluate the potential renewable sources (solar, hydro, and wind) in sequence over fossil fuels for the possible transition in the Australian grid by 2030 and 2050, as per the Paris Agreement. 71.91% reduction of CO2 emissions is achievable by recycling vehicle tyres into crumb rubber compared to landfill and incineration. Recycling by-products of CR production, such as steel and textile, significantly mitigates negative impacts. A decrease of 2.23% emissions was associated to the use of crumb rubber as a binder modifier in the asphalt mixture via the midpoint assessment. In endpoint LCA, a higher association of resource (US$) saving costs was observed than for other protective zones, i.e., human health and ecosystem damage. Recycling 466,000 tonnes of disposable waste tyres contributes to 16.1 million US$ worth of resource savings. An equitable industry-based LCA and uncertainty analysis of design parameters can assist in prioritizing suitable options to improve efficiency and future emission strategies on a global scale.

Evaluation of Bi-Lateral Co-Infections and Antibiotic Resistance Rates among COVID-19 Patients in Lahore, Pakistan.

Background and Objective: Bacterial infections are among the major complications of many viral respiratory tract illnesses, such as influenza and coronavirus disease-2019 (COVID-19). These bacterial co-infections are associated with an increase in morbidity and mortality rates. The current observational study was conducted at a tertiary care hospital in Lahore, Pakistan among COVID-19 patients with the status of oxygen dependency to see the prevalence of bacterial co-infections and their antibiotic susceptibility patterns. Materials and Methods: A total of 1251 clinical samples were collected from already diagnosed COVID-19 patients and tested for bacterial identification (cultures) and susceptibility testing (disk diffusion and minimum inhibitory concentration) using gold standard diagnostic methods. Results: From the total collected samples, 234 were found positive for different bacterial isolates. The most common isolated bacteria were Escherichia coli (E. coli) (n = 62) and Acinetobacter baumannii (A. baumannii) (n = 47). The E. coli isolates have shown the highest resistance to amoxicillin and ampicillin, while in the case of A. baumannii, the highest resistance was noted against tetracycline. The prevalence of methicillin resistant Staphylococcus aureus (MRSA) was 14.9%, carbapenem resistant Enterobacteriaceae (CRE) was 4.5%, and vancomycin resistant Enterococcus (VRE) was 3.96%. Conclusions: The results of the current study conclude that empiric antimicrobial treatment in critically ill COVID-19 patients may be considered if properly managed within institutional or national level antibiotic stewardship programs, because it may play a protective role in the case of bacterial co-infections, especially when a patient has other AMR risk factors, such as hospital admission within the previous six months.

Contribution of germline PALB2 variants to an unselected and prospectively registered pancreatic cancer patient cohort in Pakistan.

BACKGROUND: Partner and localizer of BRCA2 (PALB2) is a pancreatic cancer (PC) susceptibility gene reported in Caucasians. However, limited data are available among Asians. We investigated the contribution of PALB2 germline variants to Pakistani PC patients. METHODS: 150 unselected and prospectively enrolled PC patients were comprehensively screened for PALB2 variants, using denaturing high-performance liquid chromatography and DNA sequencing. Novel variants were investigated for their pathogenic effect using in-silico tools. Potentially functional variants were screened in 200 controls. RESULTS: Twenty-two different PALB2 variants were identified. A missense variant (p.Arg37His) was identified in a 48-years-old male patient with a family history of breast cancer. Another missense variant (p.Trp898Arg) was identified in a 48-years-old male patient with a family history of esophageal cancer. A novel 3' downstream variant (c.∗480A>G) was detected in a 34-years-old female patient with family history of lung cancer. Another novel 3' downstream variant (c.∗417A>C) was identified in a 41-years-old male patient. All these variants were absent in 200 controls. p.Arg37His and p.Trp898Arg were predicted as likely pathogenic. c.∗417A>C and c.∗480A>G were classified as variants of uncertain significance. CONCLUSION: This is the first study that suggests a minimal contribution of PALB2 variants to PC risk in Pakistani population.

FUNCTION ROLE OFIL-6-174 GENE POLYMORPHISMS IN ASSOCIATION WITH IL-6 LEVELS IN TYPE 2 DIABETES MELLITUS.

OBJECTIVE: The aim: To distinguish the function role of IL-6 protein levels as well as IL-6 (-174) gene polymorphism in diabetes mellitus patients. PATIENTS AND METHODS: Materials and methods: in present case-control study160 (cases 86, control 74) volunteers were enrolled in this study 2.5 ml were added to EDTA tube for molecular investigation IL6 (-174), and other 2.5 ml use for measurement of fasted glucose by spectrophotometry and insulin levels as well as IL-6 level by ELISA. RESULTS: Results: Regarding IL-6-174 (rs1800795), results revealed significant difference at genotype CC (p- value 0.05 with odds ratio 3.49) and allele frequency C (p-value 0.02 with odds 2.17), also at protein level the IL-6 showed significant difference between IL-6 levels and T2DM especial in insulin resistance (IR) group (p-value 0.03) compared with control one (Cont). CONCLUSION: Conclusions: There is potent relation between IL-6 levels with T2DM and IR groups. There is potent relationship between CC variation of IL-6 (-174) and risk of each T2DM and IR condition.