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Rapidly advancing biotechnological research and easy access to biological information have created challenges for preventing their intentional misuse. Because of the dedicated efforts of science and policy leaders in Pakistan, the country is on the road to becoming a regional role model in ensuring biosafety and capacity for biosecurity. Although Pakistan has made remarkable efforts promoting a culture of biosafety and biosecurity, several constraints persist related to sustainable development and the expansion of the biosecurity capacity in Pakistan. Studies suggest there is little understanding of dual-use research of concern among the majority of life scientists in Pakistan. Further, Pakistan has yet to fully develop and implement approaches for risk assessment, frameworks for oversight and regulation, or tools and procedures for monitoring and reporting situations in which misuse of biological materials might occur. More data are needed to answer questions about key biosecurity hazards specific to the country or region and the procedures that may be required for periodic risk assessments. Integrating biosecurity into the existing infrastructure with limited resources is key challenge in implementation. More coordination is required among various stakeholders to develop an effective biosecurity framework. This article focuses on Pakistan's strides toward biosecurity preparedness in terms of protecting pathogens, toxins, or biological technologies with dual-use risks to prevent their malevolent use. We propose a multidimensional biosecurity management model at the national level to strengthen the biosecurity enterprise in Pakistan.

Protection of crop plants from phytopathogens through endophytic bacteria is a newly emerged area of biocontrol. In this study, endophytic bacteria were isolated from the rhizosphere of Cannabis sativa. Based on initial antimicrobial screening, three (03) bacteria Serratia marcescens MOSEL-w2, Enterobacter cloacae MOSEL-w7, and Paenibacillus MOSEL-w13 were selected. Antimicrobial assays of these selected bacteria against Phytophthora parasitica revealed that E. cloacae MOSEL-w7 and Paenibacillus sp. MOSEL-w13 possessed strong activity against P. parasitica. All these bacterial extracts showed strong inhibition against P. parasitica at different concentrations (4–400 µg mL−1). P. parasitica hyphae treated with ethyl acetate extract of E. cloacae MOSEL-w7 resulted in severe growth abnormalities compared to control. The extracts were further evaluated for in vivo detached-leaf assay against P. parasitica on the wild type tobacco. Application of 1% ethyl acetate bacterial extract of S. marcescens MOSEL-w2, E. cloacae MOSEL-w7, and Paenibacillus sp. MOSEL-w13 reduced P. parasitica induced lesion sizes and lesion frequencies by 60–80%. HPLC based fractions of each extract also showed bioactivity against P. parasitica. A total of 24 compounds were found in the S. marcescens MOSEL-w2, 15 compounds in E. cloacae MOSEL-w7 and 20 compounds found in Paenibacillus sp. MOSEL-w13. LC–MS/MS analyses showed different bioactive compounds in the bacterial extracts such as Cotinine (alkylpyrrolidine), l-tryptophan, l-lysine, l-Dopa, and l-ornithine. These results suggest that S. marcescens MOSEL-w2, E. cloacae MOSEL-w7, and Paenibacillus MOSEL-w13 are a source of bioactive metabolites and could be used in combination with other biocontrol agents, with other modes of action for controlling diseases caused by Phytophthora in crops. They could be a clue for the broad-spectrum biopesticides for agriculturally significant crops.

Silybum marianum L. commonly known as milk thistle is a medicinally potent plant with a multitude of pharmacological applications. The present investigations demonstrated the effects of Zinc Oxide ...

Yellow rust is caused by Pst ( Puccinia striiformis tritici ), the most devastating wheat disease with continuous challenge of emerging virulences breaking vertical resistance worldwide resulting in epidemics. Vertical resistance genes incorporation is a sustainable, economical and environment-friendly approach to control rust diseases. Wheat landraces (WLR) acquired vertical resistance through long time exposure of host-pathogen survival competition in a specific area having unique agronomic traits, genetic base and resistance against biotic and abiotic agents can be an exploitable commodity for future food production. Fifty Pakistani WLRs already with known vertical resistance were screened against 7 potential Pakistani Pst races at seedling stage under glasshouse conditions to postulate resistance genes. Resistance magnitude was compared among the landraces. Six genes Yr1, Yr8, Yr9, Yr43, Yr44, and YrTr1 were successfully postulated either singly or in combination along with unidentified genes in 45 landraces. Pakistani Pst races are avirulent to Yr5, Yr10 , Yr15 , Yr24 , Yr32, YrSp and YrTye . Most frequently postulated genes are Yr44 found in 22 genotypes, YrTr1 in 21, Yr9 in 19, Yr43 in 18, Yr8 and Yr1 in 14 wheat landraces. Multiple Yr gene pyramiding was observed in (B-74, B-281, B-530) with the presence of Yr8, Yr9, Yr43, Yr44, and YrTr1 and single gene were postulated from 12 genotypes. WLRs (B-03, B-158, B-160, B-171) reaction was immune showing presence of novel Yr genes. The study provides information regarding yellow rust resistance genes originated independently against localized Pst races with desirable agronomic traits since long and can be an option for food security in changing environmental challenges.

PURPOSE: All people with oculocutaneous albinism (OCA) have reduced vision. This study aimed to assess the benefits of low vision aids for people with OCA. METHODS: Seventy-seven consecutive people with OCA age 4 years and above examined in a low vision clinic were included in the study. Uncorrected and best-corrected visual acuity (VA), VA with low vision devices, types of low vision aids, and refractive errors data were analyzed. RESULTS: Of the 77 people with OCA, 57% were in the age group between 4 and 15 years and 43% in the age group of 16 years and above. At the time of presentation, the percentages of visually impaired, severe visually impaired, and blind (using WHO low vision criteria) were 52%, 22%, and 25%. Among them, 39% has near VA of 1 M or better. Difference in the means of the spherical equivalent refractive error in the right eyes and left eyes was −0.494 diopters (−01.686, 0.699; 95% confidence interval). VA improved significantly after adequate refractive correction by more than one log MAR lines in 38.6% (P < 0.01). With low vision devices, in 85.7% (n = 66) participants, VA was enhanced to normal level (6/18 or better) in the better eye while 7.8% still remained in the blind category. Telescopes were prescribed to 61% people for the enhancement of distance VA and hand hold magnifiers were prescribed to 22% people to meet their needs. CONCLUSION: Low vision aids can be successfully used in visual rehabilitation of people with OCA to meet their needs.

The present study involved the bio-fabrication of silver nanoparticles (AgNPs) by using the Euphorbia helioscopia L. leaves aqueous extract to improve the production of secondary metabolites in industrially important sunflower (Helianthus annuus L.) plants. Phyto-fabrication of AgNPs was confirmed by using spectrophotometry, SEM imaging and X-ray diffraction analysis. The morphological and optical characterization manifested that the AgNPs are crystalline and exist in the size range of 30–100 nm. Various concentrations (10, 20, 40, 60, 80 and 100 mg/L) of AgNPs were applied in combinations on sunflower seeds and crop plants. The effects of biosynthesized AgNPs were evaluated for agro-morphological parameters (plant height, flowering initiation and seed weight), biochemical metabolites (chlorophyll, proline, soluble sugar, amino acid and protein contents) and enzymatic activities (superoxide dismutase and ascorbate peroxidase) in sunflower and 60 mg/L concentration of AgNPs on sunflower seeds and foliar sprays on plants in combination were found to be effective to elicit biochemical modifications to improve secondary metabolites. It was also observed experimentally that 60 mg/L concentration of AgNPs improved the biochemical, fatty acid and enzymatic attributes of sunflower plants, which in turn improved the plant agro-morphological parameters. Near-infrared spectroscopic analysis results confirmed the improvement in the seed quality, oil contents and fatty acid composition (palmitic acid, oleic acid and linoleic acid) after the applications of AgNPs. The findings of the present investigation confirm the exogenous applications of bio-fabricated AgNPs in combinations on seeds and plants to improve the plant yield, seed quality and secondary metabolite contents of the sunflower plants.

In this work, series of pH-responsive hydrogels (FMA1–FMA9) were synthesized, characterized, and evaluated as potential carrier for oral delivery of an antiviral drug, acyclovir (ACV). Different proportions of β-cyclodextrin (β-CD), chitosan (CS), methacrylic acid (MAA) and N′ N′-methylenebis-acrylamide (MBA) were used to fabricate hydrogels via free radical polymerization technique. Fourier transform infrared spectroscopy confirmed fabrication of new polymeric network, with successful incorporation of ACV. Scanning electron microscopy (SEM) indicated presence of slightly porous structure. Thermal analysis indicated enhanced thermal stability of polymeric network. Swelling studies were carried out at 37 °C in simulated gastric and intestinal fluids. The drug release data was found best fit to zero-order kinetics. The preliminary investigation of developed hydrogels showed a pH-dependent swelling behavior and drug release pattern. Acute oral toxicity study indicated no significant changes in behavioral, clinical, or histopathological parameters of Wistar rats. Pharmacokinetic study indicated that developed hydrogels caused a significant increase in oral bioavailability of ACV in rabbit plasma as compared to oral suspension when both were administered at a single oral dose of 20 mg kg−1 bodyweight. Hence, developed hydrogel formulation could be used as potential candidate for controlled drug delivery of an antiviral drug acyclovir.

Radiomic features based classifiers and neural networks have shown promising results in tumor classification. The classification performance can be further improved greatly by exploring and incorporating the discriminative features towards cancer into mathematical models. In this research work, we have developed two radiomics driven likelihood models in Computed Tomography(CT) images to classify lung, colon, head and neck cancer. Initially, two diagnostic radiomic signatures were derived by extracting 105 3-D features from 200 lung nodules and by selecting the features with higher average scores from several supervised as well as unsupervised feature ranking algorithms. The signatures obtained from both the ranking approaches were integrated into two mathematical likelihood functions for tumor classification. Validation of the likelihood functions was performed on 265 public data sets of lung, colon, head and neck cancer with high classification rate. The achieved results show robustness of the models and suggest that diagnostic mathematical functions using general tumor phenotype can be successfully developed for cancer diagnosis.

A prospective survey of neurotrauma admitted to neurosurgical units in three low and middle income countries (LMIC) indicated a frequent lack of organised prehospital care. On site care was usually provided by a member of the public. The accident victim was rarely accompanied within an equipped ambulance by trained personnel. Intensive care management and intracranial pressure monitoring was rare. There appeared to be limited rehabilitation in all regions.

Background: Posterior capsular opacification (PCO) is the most frequent complication of cataract surgery. The objective of this study was to determine the frequency of acute rise of intraocular pressure (IOP) following Neodymium-Yttrium Aluminum Garnet (Nd:Yag) laser posterior capsulotomy. Materials & Methods: This cross-sectional study was conducted in the Department of Ophthalmology, HMC, Peshawar, Pakistan, from July-December 2016. Sample size was 325 selected by consecutive sampling technique. Inclusion criteria were all patients having significant PCO after uneventful cataract surgery with intra ocular lens implant. Demographic variables were sex, age groups and age in years. Research variable was presence of acute rise of IOP following Yag laser capsulotomy. Pre-laser assessment included slit lamp examination and recording of IOP with Goldmann applanation tonometer by a single ophthalmologist. IOP was measured 3 hours after Nd: Yag laser capsulotomy. Rise in IOP was labeled when IOP was ≥5 mmhg from baseline. Mean ±SD was used to express quantitative variables like age. Categorical variables were analyzed as frequency and percentage. Goodness-of-fit was applied to compare the frequency of acute rise in IOP between sample and population. SPSS-20 was used for data entry and its analysis. Results: Out of 325 patients, 170(52.3%) were men and 155(47.7%) were women. The mean age of the sample was 44.92 ±23.843 years. A total of 107(32.9%) patients were 20-39 years old whereas 218(67.1%) were 40-70 years. IOP was raised in 61 (18.8%) patients while in 264(81.2%) patients it was not raised. The frequency of acute rise in IOP after Yag laser capsulotomy was significantly different in sample compared to population. Conclusion: Men were more than women, especially of old age. The frequency of acute rise in IOP after Yag laser capsulotomy was significantly different in sample compared to population.

Highlights • An estimated 27 million traumatic brain injuries (TBIs) occur worldwide every year. • In certain cases, neurosurgical intervention for TBI is necessary and life-saving. • The timing and quality of surgery for TBI has long been known to dramatically affect outcome. • There is a paucity of data on outcomes following neurosurgery globally. • GNOS will compare outcomes following emergency surgery for TBI worldwide., Introduction Traumatic brain injury (TBI) accounts for a significant amount of death and disability worldwide and the majority of this burden affects individuals in low-and-middle income countries. Despite this, considerable geographical differences have been reported in the care of TBI patients. On this background, we aim to provide a comprehensive international picture of the epidemiological characteristics, management and outcomes of patients undergoing emergency surgery for traumatic brain injury (TBI) worldwide. Methods and analysis The Global Neurotrauma Outcomes Study (GNOS) is a multi-centre, international, prospective observational cohort study. Any unit performing emergency surgery for TBI worldwide will be eligible to participate. All TBI patients who receive emergency surgery in any given consecutive 30-day period beginning between 1st of November 2018 and 31st of December 2019 in a given participating unit will be included. Data will be collected via a secure online platform in anonymised form. The primary outcome measures for the study will be 14-day mortality (or survival to hospital discharge, whichever comes first). Final day of data collection for the primary outcome measure is February 13th. Secondary outcome measures include return to theatre and surgical site infection. Ethics and dissemination This project will not affect clinical practice and has been classified as clinical audit following research ethics review. Access to source data will be made available to collaborators through national or international anonymised datasets on request and after review of the scientific validity of the proposed analysis by the central study team.

Background Traumatic brain injury (TBI) and stroke have devastating consequences and are major global public health issues. For patients that require a cerebral decompression after suffering a TBI or stroke, a decompressive craniectomy (DC) is the most commonly performed operation. However, retrospective non-randomized studies suggest that a decompressive craniotomy (DCO; also known as hinge or floating craniotomy), where a bone flap is replaced but not rigidly fixed, has comparable outcomes to DC. The primary aim of this project was to understand the current extent of usage of DC and DCO for TBI and stroke worldwide. Method A questionnaire was designed and disseminated globally via emailing lists and social media to practicing neurosurgeons between June and November 2019. Results We received 208 responses from 60 countries [40 low- and middle-income countries (LMICs)]. DC is used more frequently than DCO, however, about one-quarter of respondents are using a DCO in more than 25% of their patients. The three top indications for a DCO were an acute subdural hematoma (ASDH) and a GCS of 9-12, ASDH with contusions and a GCS of 3-8, and ASDH with contusions and a GCS of 9-12. There were 8 DCO techniques used with the majority (60/125) loosely tying sutures to the bone flap. The majority (82%) stated that they were interested in collaborating on a randomized trial of DCO vs. DC. Conclusion Our results show that DCO is a procedure carried out for TBI and stroke, especially in LMICs, and most commonly for an ASDH. The majority of the respondents were interested in collaborating on a is a future randomized trial.

Background Statins or 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors are one of the most commonly prescribed medications in cardiac patients. Just like any other class of drugs, they have the potential to cause liver injury over time even with judicious use. This drug-induced liver injury (DILI) can be either direct (hepatocellular) or idiosyncratic. As with multiple other hepatic pathologies, DILI may be asymptomatic or clinically silent. Therefore, it is prudent to carry out liver function tests (LFTs) from time to time. LFTs are an inexpensive, noninvasive, and quick first-line investigation to monitor liver status. However, the pattern of liver injury with statin use is not specific and a correlation over time may not be apparent. Aims To evaluate derangement in LFTs over time with respect to statin use and determine if a correlation exists. Methods This was a retrospective observational cohort. All data were collected from the online database of the National Institute of Cardiovascular Diseases (NICVD), Karachi. Patients admitted to the NICVD from July 1, 2018, to December 31, 2018, were eligible for inclusion in the study. Only patients already taking a statin (in any dose) were considered for inclusion. LFTs were recorded from the database at inclusion, post-induction at six and 12 months. Extensive workup was done and great care taken to rule out other diseases that may have affected the LFTs. Results Two hundred and four patients were eventually inducted into the study after a meticulous exclusion process. The male to female ratio was 4:1. The mean duration of statin use before induction into the study was 19.92±14.34 months. Patients were predominantly using only one of two statins, i.e., rosuvastatin 20mg/day or atorvastatin 40 mg/day. Elevations of LFTs were seen with both drugs throughout the study period. These elevations were almost always

Ischemic stroke is categorized by either permanent or transient blood flow obstruction, impeding the distribution of oxygen and essential nutrients to the brain. In this study, we examined the neuroprotective effects of compound A3, a synthetic polyphenolic drug product, against ischemic brain injury by employing an animal model of permanent middle cerebral artery occlusion (p-MCAO). Ischemic stroke induced significant elevation in the levels of reactive oxygen species and, ultimately, provoked inflammatory cascade. Here, we demonstrated that A3 upregulated the endogenous antioxidant enzymes, such as glutathione s-transferase (GST), glutathione (GSH), and reversed the ischemic-stroke-induced nitric oxide (NO) and lipid peroxidation (LPO) elevation in the peri-infarct cortical and striatal tissue, through the activation of endogenous antioxidant nuclear factor E2-related factor or nuclear factor erythroid 2 (Nrf2). In addition, A3 attenuated neuroinflammatory markers such as ionized calcium-binding adapter molecule-1 (Iba-1), cyclooxygenase-2 (COX-2), tumor necrotic factor-&alpha, (TNF-&alpha, ), toll-like receptors (TLR4), and nuclear factor-&kappa, B (NF-&kappa, B) by down-regulating p-JNK as evidenced by immunohistochemical results. Moreover, treatment with A3 reduced the infarction area and neurobehavioral deficits. We employed ATRA to antagonize Nrf2, which abrogated the neuroprotective effects of A3 to further assess the possible involvement of the Nrf2 pathway, as demonstrated by increased infarction and hyperexpression of inflammatory markers. Together, our findings suggested that A3 could activate Nrf2, which in turn regulates the downstream antioxidants, eventually mitigating MCAO-induced neuroinflammation and neurodegeneration.

Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti-inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2-mercaptobenzimidazole amino acid conjugates (4a-4o) and screened them for analgesic, anti-inflammatory and gastro-protective effects. The synthesized 2-mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1 H NMR and 13 C NMR spectroscopic techniques. The 2-mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti-inflammatory and gastroprotective activities, particularly with compound 4j and 4k. Most of the compounds exhibited remarkable anti-ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX-2 (PDB ID: 3LN1) and H+ /K+ -ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2-mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.

This study focuses on the production of cellulase from a thermophilic bacterium Brevibacillus sp. MT5 and prospects of utilizing the enzyme preparation for the saccharification of sugarcane bagasse (SB). The data revealed that cellulase produced at 70 °C expressed an IFPU (international filter paper unit) of 1.776 when assayed at 60 °C and showed good activity towards SB. Consequently, the conditions affecting saccharification of SB were studied by employing a Plackett–Burman design and reducing sugars were determined by dinitrosalicylic acid method and glucose oxidase kit. The analysis of the design highlighted that the factors affecting the hydrolysis process varies in terms of their significance with respect to the duration of the reaction, however, agitation remained a consistent significant factor throughout the process. Gravimetric analysis displayed a reduction of 49.7 and 22.6% in cellulose content after saccharification of SB from an industry and SB from a fruit juice vendor, respectively. The effect of enzyme action on SB was further visualized by scanning electron microscopy and Fourier transform infra-red spectroscopy that showed increased porosity and a diminished peak for cellulose, indicating degradation of the substrate by the enzyme preparation.

Biotechnological strategies are needed to produce larger quantities of biomass and phytochemicals. In this study, callus cultures of Fagonia indica were elicited with different concentrations of chemically and biologically synthesized silver nanoparticles (chem- and bioAgNPs) to compare their effects on biomass, total phenolic content (TPC), total flavonoid content (TFC) and antioxidant activity of the extracts from callus. The results revealed that bioAgNPs being more biocompatible produced the highest biomass initially on day 10 (FW = 4.2152 ± 0.13 g; DW = 0.18527 ± 0.01 g) and day 20 (FW = 7.6558 ± 0.10 g; DW = 0.3489 ± 0.01 g) when supplemented in media as 62.5 µg/mL and 250 µg/mL, respectively. Initially, the highest TPC (319.32 ± 8.28 µg GAE/g of DW) was recorded on day 20 in chemAgNPs (31.25 µg/mL) induced callus as compared to TPC = 302.85 ± 3.002 µg GAE/g of DW in bioAgNPs-induced callus. Compared to the highest values of TFC (108.15 ± 2.10 µg QE/g of DW) produced in 15.6 µg/mL chemAgNPs-induced callus on day 20, TFC produced in bioAgNPs (62.5 µg/mL) was 168.61 ± 3.17 µg GAE/g of DW on day 10. Similarly, chemAgNPs-induced callus (62.5 µg/mL) showed the highest free radical scavenging activity (FRSA) i.e. 87.18% on day 20 while bioAgNPs (125 µg/mL) showed 81.69% FRSA on day 20 compared to highest among control callus (63.98% on day 40). The highest total antioxidant capacity of chemAgNPs-(125 µg/mL) induced callus was 330.42 ± 13.65 µg AAE/g of DW on day 20 compared to bioAgNPs-(62.5 µg/mL) induced callus (312.96 ± 1.73 µg AAE/g of DW) on day 10. Conclusively, bioAgNPs are potent elicitors of callus cultures of F. indica. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12298-020-00851-w) contains supplementary material, which is available to authorized users.

Trauma/stroke centres optimise acute 24/7/365 surgical/critical care in high-income countries (HICs). Concepts from low-income and middle-income countries (LMICs) offer additional cost-effective healthcare strategies for limited-resource settings when combined with the trauma/stroke centre concept. Mass casualty centres (MCCs) integrate resources for both routine and emergency care—from prevention to acute care to rehabilitation. Integration of the various healthcare systems—governmental, non-governmental and military—is key to avoid both duplication and gaps. With input from LMIC and HIC personnel of various backgrounds—trauma and subspecialty surgery, nursing, information technology and telemedicine, and healthcare administration—creative solutions to the challenges of expanding care (both daily and disaster) are developed. MCCs are evolving initially in Chile and Pakistan. Technologies for cost-effective healthcare in LMICs include smartphone apps (enhance prehospital care) to electronic data collection and analysis (quality improvement) to telemedicine and drones/robots (support of remote regions and resource optimisation during both daily care and disasters) to resilient, mobile medical/surgical facilities (eg, battery-operated CT scanners). The co-ordination of personnel (within LMICs, and between LMICs and HICs) and the integration of cost-effective advanced technology are features of MCCs. Providing quality, cost-effective care 24/7/365 to the 5 billion who lack it presently makes MCCs an appealing means to achieve the healthcare-related United Nations Sustainable Development Goals for 2030.

Majority of the BRCA1 and BRCA2 mutations are associated with the risk of sporadic and familial breast cancer. Since these genes are significant in DNA repair mechanisms, we focused homology-directed DNA repair (HDDR) and BRCA complex.We selected BRCA1 variant (rs80356932, 4491C/T) and BRCA2 variant (rs80359182, 319T/C) from the interaction region of BRCA complex and studied in 100 breast cancer patients and 100 controls using tetra-ARMS-PCR.Here we show that BRCA1 and BRCA2 variants are significantly associated with high breast cancer risk (BRCA1 rs80356932; Genotype T/T OR 8.66, 95% CI 3.16-23.71, p 0.0001; Allele-T, OR 2.48, 95% CI 1.62-3.81, p 0.0001 and BRCA2 rs80359182; Genotype C/C OR 4.32, 95% CI 1.95-9.53, p = 0.0001; Allele-C, OR 2.19, 95% CI 1.43-3.34, p = 0.0002). Additionally, bioinformatics analysis showed that BRCA2-tryptophan arginine substitutions result in altered interaction of BRCA1/PALB2/BRCA2/protein complex and impaired HDDR pathway. We also observed that breast cancer risk was significantly increased in over-weighted and obese women.Our results indicate that high risk of breast cancer is significantly associated with BRCA1 and BRCA2 variants, and mutations may alter the protein interactions of BRCA complex that results in tumor genesis.

Ajuga bracteosa a highly demanding pharmaceutical plant, is getting endangered in several regions of the world due to ruthless and destructive harvesting. Research efforts need to be done for its sustainable production and utilization. In this study, effects of Thidiazuron (TDZ) in comparison to conventional cytokinins were tested in vitro on shoot morphogenesis, antioxidant system and biosynthesis of volatile organic compounds in A. bracteosa. Thidiazuron alone acted as the best growth regulator for direct shoot morphogenesis in explants by promoting highest induction of shoots (88%) in stem explants cultivated on MS (Murashige and Skoog) medium supplemented with 1.2 ppm (TDZ). At lower doses (0.5 ppm), TDZ resulted in highest multiplication (18 shoots) and elongation (5.8 cm) of shoots. Further, shoot cultures raised in vitro at TDZ (1.2 ppm) displayed higher activities of superoxide dismutase (SOD: 4.2 U/mg protein), peroxidase (POD: 2.8 U/mg protein) and ascorbate peroxidase (APx: 1.8 U/mg protein), respectively. Maximum total phenolic content (TPC; 4.5 mg GAE/g DW) and total flavonoid content (TFC; 3.5 mg QE/g DW), respectively were detected in shoot cultures grown over MS medium combined with 1.2 ppm TDZ plus 2.0 ppm benzylaminopurine (BA). Analysis through gas chromatography-mass spectrometry (GC–MS) showed, biosynthesis of 34 volatile compounds in the in vitro raised shoots. Wherein, TDZ (1.2 ppm) resulted in production of substantial amounts of bioactive monoterpene hydrocarbons including α-pinene (5.3%), camphene (4.45%), limonene (3.4%), 1,8–cineole (14.3%), α-thujone (9.4%) and oxygenated monoterpenes such as camphor (12.2%), borneol (11.4%) and nerol (9.2%). Thus, besides providing an ex-situ conservation strategy for a high valued medicinal herb, this study has the potential for commercial production of important bioactive volatile compounds.

Manipulation in the light regimes combined with the effects of plant growth regulators (PGRs) and elicitors through plant cell culture technology is a promising strategy for enhancing the yield of medicinally important secondary metabolites. In this study, the effects of interplay between PGRs, elicitors and light regimes on cell cultures of F. indica have been investigated. The results showed that callus cultures resulted in maximum biomass formation (13.2 g/L) when incubated on solid MS (Murashige and Skoog) medium containing 1.0 mg/L BA under continuous light for 4 weeks. Among the other PGRs, compared with the auxins such as 2,4-D, and IBA, TDZ resulted in higher biomass accumulation (12.1 g/L). Elicitors (Me-J and PAA) resulted in a lower growth response, when compared with cytokinins and a higher response than auxins under all the light regimes on solid MS media. However, in liquid media, no significant increase in biomass was observed in response to the combined effects of PGRs and photoperiod regimes. Further, the highest phenolic content (TPC = 6.8 mg) and flavonoid content (TFC = 5.2 mg) were detected in the dark-grown cell cultures raised in vitro at 0.5 mg/L Me-J. The highest antioxidant activity (88%) was recorded in the dark-grown cell cultures harvested from LOG phase of the growth cycle supplemented with 0.5 mg/L Me-J. Furthermore, BA resulted in considerable flavonoids production (TFC = 4.7 mg) in the cell cultures grown under continuous light. However, overall dark treatment and elicitation with Me-J resulted in the optimal metabolic response in terms of secondary metabolites accumulation in cell suspension cultures of F. indica.

Lung nodule segmentation in CT images and its subsequent volume analysis can help determine the malignancy status of a lung nodule. While several efficient segmentation schemes have been proposed, only a few studies evaluated the segmentation's performance for large nodules. In this research, we contribute a semi-automatic system which is capable of performing robust 3-D segmentations on both small and large nodules with good accuracy. The target CT volume is de-noised with an anisotropic diffusion filter and a region of interest is selected around the target nodule on a reference slice. The proposed model performs nodule segmentation by incorporating a mean intensity based threshold in Geodesic Active Contour model in level sets. We also devise an adaptive technique using image intensity histogram to estimate the desired mean intensity of the nodule. The proposed system is validated on both lung nodules and phantoms collected from publicly available diverse databases. Quantitative and visual comparative analysis of the proposed work with the Chan-Vese algorithm and statistic active contour model of 3D Slicer platform is also presented. The resulting mean spatial overlap between segmented nodules and reference nodules is 0.855, the mean volume bias is 0.10 ± 0.2 ml and the algorithm repeatability is 0.060 ml. The achieved results suggest that the proposed method can be used for volume estimations of small as well as large-sized nodules.

Quality of Total Hip Arthroplasty (THA) is decided by the range of motion (ROM), a patient can achieve after the transplant. The ROM plays an important role to perform different daily life activities. The post-operation achievement of ROM is dependent on pre-operation plans. Surgeons plan and perform operations based on their previous experiences because of the unavailability of authentic quantitative criteria due to various limitations. This study attempts to support pre-operation planning to calculate post-operation ROM achieved by the patient in THA, alongside, the risk evaluation with respect to flexion which is the most critical ROM of hip joint.

Fagonia indica is an important medicinal plant highly traded for its multitude of potentials against breast cancer. The natural availability of this high-valued herb is not fulfilling the ever-increasing demand. Alternative options should be adopted to balance the supply with demand. Adventitious root culture provides a preferred platform to produce commercially important secondary metabolites. In the present report, adventitious roots (AR) were induced from callus explants in F. indica for the first time. Higher adventitious root induction frequency (88%) and biomass accumulation (6.9 DW g/L) were observed when callus explants were treated with 0.5 mg/L Methyl Jasmonate (Me-J) for 2 h and subsequently incubated on solid Murashige and Skoog (MS) media containing 1.0 mg/L Naphthalene acetic acid (NAA). Variations in growth of roots in suspension cultures were analyzed to estimate the impact of elicitors on adventitious rooting in F. indica. In response to 1.0 mg/L NAA, a lag phase of 6 days, logarithmic (log) phase of 15 days and stationary phase of 6 days were observed in the growth curve of AR in suspension culture. Maximum biomass (9.5 g DW g/L) was recorded on the 27th day in log phase of culture. Analysis of AR samples derived from different growth stages showed that at 0.5 mg/L Me-J, maximum Total Phenolic Content (TPC; 6.0 mg GAE/g of DW) and Total Flavonoid Content (TFC; 5.0 mg QE/g of DW) were produced, respectively in the lag phase compared to other growth lines. Quantification of vital plant secondary metabolites through High-Performance Liquid Chromatography (HPLC) revealed a higher amount of Gallic acid (148.0 ± 4.8 μg/mg of DW) detected in Control (CTR) samples raised in vitro at 1.0 mg/L NAA. This was followed by Rutin (122.3 ± 3.8 μg/mg of DW) in LOG phase and Myricetin (32.3 ± 0.7 μg/mg of DW) in LAG phase during growth of AR suspension cultures. In response to 0.5 mg/L Me-J, more Apigenin (25.3 ± 0.6 μg/mg of DW), Caffeic acid (25.3 ± 0.6 μg/mg of DW) and Catechin (9.4 ± 0.07 μg/mg DW) were accumulated in the LOG phase in comparison to other growth stages. Thus, a feasible protocol was developed for induction and proliferation of adventitious roots with sustainable metabolite profiles through elicitation.

Dieulafoy’s lesion is an abnormally large and tortuous submucosal artery that protrudes through a small mucosal defect resulting in gastrointestinal bleeding. We present a case of a 53-year-old man with a history of HIV and alcohol abuse who presented to the emergency room with hematemesis and melena. Upper endoscopy revealed an actively bleeding dieulafoy lesion, but due to uncontrolled bleeding, embolization of the left artery was necessitated. The incidence of dieulafoy lesions is about 0.3% to 6.7% within the stomach. The etiology remains uncertain but has been linked to alcoholism and antiplatelet drugs. We are emphasizing the importance of considering uncommon causes of upper gastrointestinal bleeding in patients with portal hypertension.

Alzheimer's disease (AD), is the most common type of dementia primarily affecting the later years of life. Its prevalence is likely to increase in any aging population and will be a major burden on healthcare system by the mid of the century. Despite scientific and technological breakthroughs in the last 50 years, that have expanded our understanding of the disease on a system, cellular and molecular level, therapies that could stop or slow the progression of the disease are still unavailable. The Food and Drug Administration (FDA), has approved acetylcholinesterase (AChE) inhibitors (donepezil, galantamine, tacrine and rivastigmine) and glutamate receptor antagonist (memantine) for the treatment of AD. In this review we summarize the studies reporting phytocompounds and extracts from medicinal plants that show AChE inhibitory activities and could be of potential benefit in AD. Future research directions are suggested and recommendations made to expand the use of medicinal plants and their formulations to prevent, mitigate and treat AD.

Ajuga bracteosa is a medicinally important plant globally used in the folk medicine against many serious ailments. In the present study, effects of two significant elicitors, methyl jasmonate (Me-J) and phenyl acetic acid (PAA) were studied on growth parameters, secondary metabolites production, and antioxidant potential in adventitious root suspension cultures of A. bracteosa. The results showed a substantial increase in biomass accumulation, exhibiting longer log phases of cultures growth in response to elicitor treatments, in comparison to control. Maximum dry biomass formation (8.88 DW g/L) was recorded on 32nd day in log phase of culture when 0.6 mg/L Me-J was applied; however, PAA at 1.2 mg/L produced maximum biomass (8.24 DW g/L) on day 40 of culture. Furthermore, we observed the elicitors-induced enhancement in phenolic content (total phenolic content), flavonoid content (total flavonoid content) and antioxidant activity (free radical scavenging activity) in root suspension cultures of A. bracteosa. Application of 0.6 mg/L and 1.2 mg/L of Me-J, root cultures accumulated higher TPC levels (3.6 mg GAE/g DW) and (3.7 mg GAE/g DW) in the log phase and stationary phase, respectively, while 2.5 mg/L Me-J produced lower levels (1.4 mg GAE/g DW) in stationary phase of growth stages. Moreover, TFC and FRSA values were found in correspondence to TPC values in the respective growth phases at the similar elicitor treatment. Thus, a feasible protocol for establishment of adventitious roots in A. bracteosa was developed and enhancement in biomass and metabolite content in adventitious root was promoted through elicitation.

It has been well-documented recently that 5 billion people globally lack surgical care. Also well-documented is the need to improve mass casualty disaster response. Many of the United Nations (UN) Sustainable Development Goals (SDGs) for 2030—healthcare and economic milestones—require significant improvement in global surgical care, particularly in low-income and middle-income countries. Trauma/stroke centres evolved in high-income countries with evidence that 24/7/365 surgical and critical care markedly improved morbidity and mortality for trauma and stroke and for cardiovascular events, difficult childbirth, acute abdomen. Duplication of emergency services, especially civilian and military, often results in suboptimal, expensive care. By combining all healthcare resources within the ongoing healthcare system, more efficient care for both individual emergencies and mass casualty situations can be achieved. We describe progress in establishing mass casualty centres in Chile and Pakistan. In both locations, planning among the stakeholders (primarily civilian and military) indicates the feasibility of such integrated surgical and emergency care. We also review other programmes and initiatives to provide integrated mass casualty disaster response. Integrated mass casualty centres are a feasible means to improve both day-to-day surgical care and mass casualty disaster response. The humanitarian aspect of mass casualty disasters facilitates integration among stakeholders—from local healthcare systems to military resources to international healthcare organisations. The benefits of mass casualty centres—both healthcare and economic—can facilitate achieving the 2030 UN SDGs.

Background Relative telomere length (RTL), the biological chronometer, varies considerably among individuals under the influence of multiple risk factors such as socioeconomic status (SES). It is anticipated that during fetal life, telomeres undergo reprogramming. The purpose of this study is to find the association between SES and telomere length of mother-newborn and genetic remodeling that occurs during fetal life. Results The mean telomere/single gene copy (T/S) ratio and RTL (base pairs) among 250 mother-newborn dyads were higher in cord blood of newborns (1.18 ± 0.23) (6765 ± 1350 bp) (95% confidence level) compared to maternal blood (1.13 ± 0.18) (6432 ± 1350 bp) of all SES of the Pakistani population. A positive association (r = 0.396, p

Objective The goal of the study was to see if anti-ganglioside antibodies have a role in the diagnosis of Guillain-Barre syndrome (GBS). Study design Between May 2016 to October 2017, we conducted a prospective pilot study of 15 patients with a clinical diagnosis of GBS with equivocal cerebrospinal fluid (CSF) analysis and/or nerve conduction studies (NCS) . Materials and methods All adult patients (age >18 years) whose clinical diagnosis was GBS but diagnostic tests (either NCS or CSF analysis or both) were not suggestive of GBS were included in the study and were tested for anti-gangliosides antibodies. Data was entered in SPSS, version 21.0 (IBM, Armonk, New York) and analyzed. Results Of the 15 patients fulfilling the inclusion criteria, 60% had a normal CSF analysis while 40% had normal NCS. The percentages of different GBS variants observed in sampled patients were acute inflammatory demyelinating polyradiculopathy (AIDP) 40%, acute motor axonal neuropathy (AMAN) 40%, acute motor and sensory axonal neuropathy (AMSAN) 13.3%, and Miller Fisher syndrome 6.7%. However, the anti-ganglioside antibodies were negative in all patients. Conclusion Anti-gangliosides antibodies cannot be used as an alternative diagnostic investigation in GBS patients as our study failed to show positive results in different GBS variants.

Background The early detection of elevated intracranial pressure (ICP) can not only prevent mortality but also aid in more aggressive management. Brain computed tomography (CT) is a mainstay modality in detecting elevated ICP, but the feasibility of using brain CTs to detect elevated ICP in critically ill patients is limited, especially for patients who require high levels of inotropic support. The optic nerve sheath is a direct extension of the brain meninges. Therefore, the elevation of ICP is directly transmitted to the sheath. Measuring the optic nerve sheath diameter (ONSD) through ultrasound (US) is a bedside, noninvasive means to detect elevated ICP. The goal of this study was to assess the correlation of ONSD with elevated ICP as measured via US in an intensive care unit (ICU). Methods We conducted a six-month prospective, single-center, observational study of mass effect stroke patients aged 18 to 65 years who had a traumatic brain injury (TBI) and were admitted to the ICU. Patients with chronic hydrocephalus, extensive local orbit trauma, a pre-existing ocular disease affecting the optic nerve and/or orbital cavity, hyperthyroidism with exophthalmos, and facial trauma affecting the orbits and/or eyeballs were excluded. We measured the ONSD at the entry of optic nerve into the globe using two-dimensional (2D) US. Results One hundred patients were included in the study. Forty-nine patients had diffuse cerebral edema detected on CT scan correlating with increased ONSD notable via bedside US. The mean ONSD related to CT-detectable elevated ICP was 0.61 cm. The sensitivity for the ONSD cut-off value of ≥5.8 mm was 94% (95% confidence interval [CI], 84.05% to 98.79%), and the specificity was 96.08% (95% CI, 86.7% to 99.52%).The positive predictive value was 92.08% (95% CI, 86.28% to 98.96%), and the negative predictive value was 94.23% (95% CI, 84.47% to 98.00%). Conclusion The greatest accuracy in ONSD was found with a cut-off of >0.58 cm in patients with positive CT brain findings. Therefore, US can be used as an initial screening test when physicians suspect a patient has elevated ICP.

Objective The goal of the study was to determine the percentage of hyperchloremia in patients who died in medical intensive care unit (ICU) and thus emphasizing the need of avoiding chloride-rich solutions due to their deleterious effects. Study design We conducted a retrospective study of data from 206 patients who expired in medical ICU in one year from January 2017 to December 2017 in the department of critical care medicine at Shifa International Hospital, Islamabad. Material and methods The study included 206 patients: 93 (43.1%) men and 123 (56.9%) women, over the age of 18 years who expired in medical ICU in one year from January 2017 to December 2017. Patients included for the study were all those who expired with any diagnosis but those who remained admitted in ICU for at least 72 hours and received intravenous fluids. The serum chloride levels of the patients at the time of admission and at 72 hours of stay in ICU were collected. The patients who were having serum chloride levels of 107 milliequivalent per deciliter (meq/dl) or more were labeled as having hyperchloremia. The data were analyzed using IBM SPSS Statistics for Windows, Version 23.0 (IBM Crop., Armonk, NY, USA). The mean and standard deviations were calculated for continuous variables while frequency and percentages were calculated for qualitative variables. Results Among 206 patients who expired in our ICU, 109 (50.5%) patients had hyperchloremia at 72 hours of admission in ICU while 107 (49.5%) patients did not had hyperchloremia. Hyperchloremia was more frequent in patients with sepsis or septic shock. Conclusion Higher percentage (50.5%) of hyperchloremia at 72 hours of admission among patients (who expired in our medical ICU) indicates excessive use of chloride-rich intravenous fluids. This finding may have significant impact on mortality along with other contributing factors that lead to death of the patients. Keeping in view the findings of the study, chloride-rich solutions should be used carefully to counter the effects of hyperchloremia in patients requiring large volume fluid resuscitation in ICU. Fluids with lower content of chloride such as lactated ringer may be equally good in large volume fluid resuscitation with advantage of avoiding hyperchloremia.

Fagonia indica is a widely known medicinal plant. The extracts of Fagonia species contain secondary metabolites such as flavonoids, phenolic compounds, and terpenoids. Silver nanoparticles are known for antibacterial properties. In this study, AgNPs were synthesized using the callus extract of F. indica as a reducing agent. Characterization through different techniques suggests that the AgNPs absorbed light and gave SPR peaks at 414 nm while in case of ciprofloxacin supplemented callus mediated AgNPs the peak were recorded at 419 nm. Furthermore, FTIR analysis revealed the role of amides, acyl group, nitro group of callus extract of F. indica, and some functional groups of the ciprofloxacin in the reduction process as well as the capping and stabilization of AgNPs. Similarly, X-Ray Diffraction analysis indicate the structure of AgNPs as face-centered cubic crystalline particles. The antibacterial activity of AgNPs and ciprofloxacin and callus extract as control against resistant bacteria such as Escherichia coli, Citrobacter amalonaticus, Shigella sonnei, and Salmonella typhi was studied. The combination of AgNPs and antibiotic showed better antibacterial activity as compared to AgNPs alone and ciprofloxacin alone. Maximum inhibition zone of E. coli, C. amalonaticus, S. sonnei, and S. typhi in response to AgNPs and ciprofloxacin was 38.5 mm, 35.5 mm, 33 mm, and 35.5 mm, respectively. It can, therefore, be suggested that the AgNPs along with Ciprofloxacin might have worked in interaction and resulted in better antibacterial activity against all the tested pathogens.

Objective The objective of this study is to find a correlation between internal jugular vein (IJV) and common carotid artery (CCA) diameter ratio and central venous pressure (CVP) measurement and find a cut-off value for the IJV/CCA ratio to predict low CVP i.e. < 10 cm H20, for estimating the volume status in critically ill patients. Methods This prospective cross-sectional study was conducted at the critical care department of Shifa International Hospital, Islamabad, from July to December 2017. A sample of 49 patients ≥ 18 years with intrathoracic central venous catheters (CVCs) who underwent bedside sonographic assessments of IJV and CCA diameter were included in this study using convenient sampling. The IJV/CCA diameter ratio was calculated and correlated with CVP and the predictive value of the IJV/CCA diameter ratio to predict CVP < 10 cm H2O was explored by calculating the area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, and positive and negative predictive values. Results A total of 49 patients, 30 males (61.2%) and 19 females (38.8%) with a mean age of 56.00±16.11 years were included in the study. The mean CVP was 8.98±2.37cm H2O in ventilated (51%) and 10.7± 6.01 cm H2O in non-ventilated (49%) patients. The mean IJV/CCA diameter ratio was 1.60±0.55 at expiration and 1.41±0.56 at inspiration. There was a significant correlation between the IJV/CCA diameter ratio and CVP at expiration (r=0.401, p=0.004). The correlation between IJV/CCA and CVP was significant in non-ventilated patients at expiration (r=0.439, p=0.032). The area under the ROC curve for the IJV/CCA diameter ratio for predicting CVP < 10 cm H2O was 0.684 (p=0.028). The predictive value of the IJV/CCA diameter ratio for CVP < 10 cm H20 at the cutoff value of < 2 was insignificant. A new cut-off < 1.75 was taken for the IJV/CCA diameter ratio from the coordinates of the ROC curve. The sensitivity, specificity, PPV, and NPV of an IJV/CCA diameter ratio of < 1.75 for predicting a CVP < 10 cm H20 were 84.62%, 52.17%, 66.67%, and 75.00%, respectively. Conclusion The assessment of volume status by the IJV/CCA diameter ratio with a sonographic device may be a useful noninvasive alternative for a central venous catheterization with a cut-off < 1.75.

Piper species are aromatic plants used as spices in the kitchen, but their secondary metabolites have also shown biological effects on human health. These plants are rich in essential oils, which can be found in their fruits, seeds, leaves, branches, roots and stems. Some Piper species have simple chemical profiles, while others, such as Piper nigrum, Piper betle, and Piper auritum, contain very diverse suites of secondary metabolites. In traditional medicine, Piper species have been used worldwide to treat several diseases such as urological problems, skin, liver and stomach ailments, for wound healing, and as antipyretic and anti-inflammatory agents. In addition, Piper species could be used as natural antioxidants and antimicrobial agents in food preservation. The phytochemicals and essential oils of Piper species have shown strong antioxidant activity, in comparison with synthetic antioxidants, and demonstrated antibacterial and antifungal activities against human pathogens. Moreover, Piper species possess therapeutic and preventive potential against several chronic disorders. Among the functional properties of Piper plants/extracts/active components the antiproliferative, anti-inflammatory, and neuropharmacological activities of the extracts and extract-derived bioactive constituents are thought to be key effects for the protection against chronic conditions, based on preclinical in vitro and in vivo studies, besides clinical studies. Habitats and cultivation of Piper species are also covered in this review. In this current work, available literature of chemical constituents of the essential oils Piper plants, their use in traditional medicine, their applications as a food preservative, their antiparasitic activities and other important biological activities are reviewed.

Background A challenging task in the intensive care unit is weaning intubated patients from mechanical ventilation. The most commonly used weaning parameter, the rapid shallow breathing index (RSBI), gives thorough guidance on extubation timing with spontaneous breathing trials. Diaphragm plays vital role in tidal volume generation. The main objective of the study was to compare ultrasound-based diaphragmatic excursion (DE) with RSBI as weaning predictors. Methods We conducted an observational prospective cohort study on patients on mechanical ventilation. During a spontaneous breathing trial (SBT) we simultaneously evaluated right hemidiaphragm excursion by using M-mode ultrasonography as well as the RSBI. To be included, patients must have been on mechanical ventilation for longer than 48 hours, have no excessive tracheobronchial secretions, and their underlying critical illness (for which they were intubated) must be resolved. Patients younger than 14 years, patients with neuromuscular disorder, patients with pneumothorax, and patients with cervical spine injury were excluded from the study. We analyzed the data to determine the significance of DE and RSBI. Results A total of 90 patients were included in our study; 54 (60%) were men, and 36 (40%) were women. The average age of all the participants was 55 ± 16 years (range, 19 to 83 years). Sixty-two patients (68.9%) were successfully weaned. The mean DE was 1.44 ± 0.26 cm, and the mean RSBI was 56.88 ± 8.30 in all patients. Successful weaning patients had a mean DE of 1.51 ± 0.26 cm and a mean RSBI of 54.05 ± 7.00. The greater the DE value, the greater the weaning success rate, and the lesser the RSBI value, the greater the weaning success rate. The area under the receiver operator curve for DE and RSBI was 0.795 and 0.815, respectively (p < 0.0001). Conclusion RSBI is an optimized clinical predictor in classifying weaning outcomes for intubated patients, but DE is also helpful in extubation assurance and reintubation prevention.

Objective The goal of this study was to determine the efficacy of early tracheostomy (i.e., ≤ 10 days of intubation) compared with a late tracheostomy (> 10 days of intubation) with regards to timing, frequency of ventilator-associated pneumonia (VAP), mortality rate, and hospital stay in patients who received decompressive craniectomy. Study design We conducted a retrospective study of data from 168 patients who underwent decompression in the department of critical care medicine at Shifa International Hospital, Islamabad, Pakistan, from January 2017 to December 2017. Materials and methods The study included men and women over the age of 18 years who had undergone tracheostomy following decompressive craniectomy in the intensive care unit as a result of stroke, traumatic brain injury, or acute severe injury. Data were analyzed using IBM SPSS Statistics for Windows, Version 23.0 (IBM Corp., Armonk, NY, US). We also applied the Chi-square test, and p ≤ 0.05 was considered significant. Results Of 168 patient records reviewed, tracheostomy was performed in 48 patients (21 men, 27 women). In the 48 tracheostomy patients, 15 (31%) were early tracheostomies and 33 (69%) were late tracheostomies. The mean age of patients was 44 ± 11 years. Twenty-eight patients (58.3%) were in the younger age group (age 18 to 45 years) and 20 patients (41.7%) were in the older age group (age > 45 years). Patients who received an early tracheostomy spent significantly less time on a ventilator (≤ 12 days) than those patients receiving a late tracheostomy (> 12 days, p = 0.004). The early tracheostomy group also had a lower incidence rate of VAP than patients with a late tracheostomy (𝑥2 = 7.855, p = 0.005). Patients who received an early tracheostomy had lower mortality rates than those who received late tracheostomies (𝑥2 = 6.158, p = 0.013). Finally, the length of hospital stay was ≤ 15 days for patients who received early tracheostomies; most patients who received a late tracheostomy had a hospital stay of > 15 days (𝑥2 =11.965, p = 0.001). Conclusions Performing a tracheostomy within 10 days of intubation following decompressive craniectomy significantly reduced ventilator time, mortality, the incidence of VAP, and length of hospital stay. Given the potential benefits of early tracheostomy in critical care patients following decompressive craniectomy, physicians should consider early tracheostomy in appropriate cases.

Funder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272, Funder: Great Ormond Street Hospital for Children; doi: http://dx.doi.org/10.13039/501100003784, Hinge craniotomy (HC) is a technique that allows for a degree of decompression whilst retaining the bone flap in situ, in a ‘floating’ or ‘hinged’ fashion. This provides expansion potential for ensuing cerebral oedema whilst obviating the need for cranioplasty in the future. The exact indications, technique and outcomes of this procedure have yet to be determined, but it is likely that HC provides an alternative technique to decompressive craniectomy (DC) in certain contexts. The primary objective was to collate and describe the current evidence base for HC, including perioperative parameters, functional outcomes and complications. The secondary objective was to identify current nomenclature, operative technique and operative decision-making. A scoping review was performed in accordance with the PRISMA-ScR Checklist. Fifteen studies totalling 283 patients (mean age 45.1 and M:F 199:46) were included. There were 12 different terms for HC. The survival rate of the cohort was 74.6% (n = 211). Nine patients (3.2%) required subsequent formal DC. Six studies compared HC to DC following traumatic brain injury (TBI) and stroke, finding at least equivalent control of intracranial pressure (ICP). These studies also reported reduced rates of complications, including infection, in HC compared to DC. We have described the current evidence base of HC. There is no evidence of substantially worse outcomes compared to DC, although no randomised trials were identified. Eventually, a randomised trial will be useful to determine if HC should be offered as first-line treatment when indicated.

Background: Two randomised trials assessing the effectiveness of decompressive craniectomy (DC) following traumatic brain injury (TBI) were published in recent years: DECRA in 2011 and RESCUEicp in 2016. As the results have generated debate amongst clinicians and researchers working in the field of TBI worldwide, it was felt necessary to provide general guidance on the use of DC following TBI and identify areas of ongoing uncertainty via a consensus-based approach. Methods: The International Consensus Meeting on the Role of Decompressive Craniectomy in the Management of Traumatic Brain Injury took place in Cambridge, UK, on the 28th and 29th September 2017. The meeting was jointly organised by the World Federation of Neurosurgical Societies (WFNS), AO/Global Neuro and the NIHR Global Health Research Group on Neurotrauma. Discussions and voting were organised around six pre-specified themes: (1) primary DC for mass lesions, (2) secondary DC for intracranial hypertension, (3) peri-operative care, (4) surgical technique, (5) cranial reconstruction and (6) DC in low- and middle-income countries. Results: The invited participants discussed existing published evidence and proposed consensus statements. Statements required an agreement threshold of more than 70% by blinded voting for approval. Conclusions: In this manuscript, we present the final consensus-based recommendations. We have also identified areas of uncertainty, where further research is required, including the role of primary DC, the role of hinge craniotomy and the optimal timing and material for skull reconstruction. publishedVersion

Antimicrobial resistance is mushrooming as a silent pandemic. It is considered among the most common priority areas identified by both national and international agencies. The global development of multidrug-resistant strains now threatens public health care improvement by introducing antibiotics against infectious agents. These strains are the product of both continuous evolution and unchecked antimicrobial usage (AMU). The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of nosocomial infections throughout the world. Most of them are now multidrug-resistant, which pose significant challenges in clinical practice. Understanding these bacteria’s resistance mechanisms is crucial for developing novel antimicrobial agents or other alternative tools to fight against these pathogens. A mechanistic understanding of resistance in these pathogens would also help predict underlying or even unknown mechanisms of resistance of other emerging multidrug-resistant pathogens. Research and development to find better antibacterial drugs and research on tools like CRISPER-Cas9, vaccines, and nanoparticles for treatment of infections that can be further explored in the clinical practice health sector have recognized these alternatives as essential and highly effective tools to mitigate antimicrobial resistance. This review summarizes the known antimicrobial resistance mechanisms of ESKAPE pathogens and strategies for overcoming this resistance with an extensive overview of efforts made in this research area.

Fagonia indica, a very important anticancer plant, has been less explored for its in vitro potential. This is the first report on thidiazuron (TDZ)-mediated callogenesis and elicitation of commercially important phenolic compounds. Among the five different plant growth regulators tested, TDZ induced comparatively higher fresh biomass, 51.0 g/100 mL and 40.50 g/100 mL for stem and leaf explants, respectively, after 6 weeks of culture time. Maximum total phenolic content (202.8 μg gallic acid equivalent [GAE]/mL for stem-derived callus and 161.3 μg GAE/mL for leaf-derived callus) and total flavonoid content (191.03 μg quercetin equivalent [QE]/mL for stem-derived callus and 164.83 μg QE/mL for leaf-derived callus) were observed in the optimized callus cultures. The high-performance liquid chromatography (HPLC) data indicated higher amounts of commercially important anticancer secondary metabolites such as gallic acid (125.10 ± 5.01 μg/mL), myricetin (32.5 ± 2.05 μg/mL), caffeic acid (12.5 ± 0.52 μg/mL), catechin (9.4 ± 1.2 μg/mL), and apigenin (3.8 ± 0.45 μg/mL). Owing to the greater phenolic content, a better 2-2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity (69.45 % for stem explant and 63.68 % for leaf explant) was observed in optimized calluses. The unusually higher biomass and the enhanced amount of phenolic compounds as a result of lower amounts of TDZ highlight the importance of this multipotent hormone as elicitor in callus cultures of F. indica.

Oxidative stress-mediated neuroinflammatory events are the hallmark of neurodegenerative diseases. The current study aimed to synthesize a series of novel succinamide derivatives and to further investigate the neuroprotective potential of these compounds against scopolamine-induced neuronal injury by in silico, morphological, and biochemical approaches. The characterization of all the succinamide derivatives was carried out spectroscopically via proton NMR (1H-NMR), FTIR and elemental analysis. Further in vivo experiments showed that scopolamine induced neuronal injury, characterized by downregulated glutathione (GSH), glutathione S-transferase (GST), catalase, and upregulated lipid peroxidation (LPO). Moreover, scopolamine increased the expression of inflammatory mediators such as cyclooxygenase2 (COX2), nuclear factor kappa B (NF-kB), tumor necrosis factor (TNF-&alpha, ), further associated with cognitive impairment. On the other hand, treatment with succinamide derivatives ameliorated the biochemical and immunohistochemical alterations induced by scopolamine, further supported by the results obtained from molecular docking and binding affinities.

The rising burden of cancer worldwide calls for an alternative treatment solution. Herbal medicine provides a very feasible alternative to western medicine against cancer. This article reviews the selected plant species with active phytochemicals, the animal models used for these studies, and their regulatory aspects. This study is based on a meticulous literature review conducted through the search of relevant keywords in databases, Web of Science, Scopus, PubMed, and Google Scholar. Twenty plants were selected based on defined selection criteria for their potent anticancer compounds. The detailed analysis of the research studies revealed that plants play an indispensable role in fighting different cancers such as breast, stomach, oral, colon, lung, hepatic, cervical, and blood cancer cell lines. The in vitro studies showed cancer cell inhibition through DNA damage and activation of apoptosis-inducing enzymes by the secondary metabolites in the plant extracts. Studies that reported in vivo activities of these plants showed remarkable results in the inhibition of cancer in animal models. Further studies should be performed on exploring more plants, their active compounds, and the mechanism of anticancer actions for use as standard herbal medicine.

Microbial contamination is the major cause of economic losses in commercial and scientific plant tissue culture laboratories. For successful micropropagation, it is important to control contamination during in vitro cultures. The present study was designed to isolate, identify and eradicate endophytic contaminants from in vitro cultures of medicinally important plant Fagonia indica. A total of eight distinct bacterial isolates from in vitro grown plantlets of F. indica were selected based on analysis of colony morphology. The endophytic bacterial contaminants identified at the species level through 16S rRNA sequence analysis were Enterobacter xiangfangensis, Bacillus vallismortis, Bacillus tequilensis, Terribacillus halophilus, Pantoea dispersa, Serratia marcescens subsp. Sakuensis, Staphylococcus epidermidis and Bacillus atrophaeus. It was observed that almost 60% of seedlings were contaminated with Bacillus sp. and out of those, Bacillus tequelensis contributed to most infections (70% out of the Bacillus infections). The other most frequently occurring bacteria were Bacillus vallismortis, Terribacillus halophilus and Serratia marcescens subsp. sakuensis. Furthermore, the addition of antimicrobials to the media either completely inhibited or drastically decreased the growth of endophytic bacteria as compared to the control in which 92% of the plantlets were contaminated with these endophytes. Nine different antibiotics (rifampicin, teicoplanin, gentamicin, vancomycin, ciprofloxacin, tobramycin, tetracycline, doxycycline and ampicillin) were tested for their activity against the identified endophytes. Antibiotics such as ciprofloxacin and tobramycin showed a good response and inhibited the growth of all the bacterial isolates at low doses compared to the other antibiotics. Tobramycin was the most effective as it inhibited the growth of five of the bacterial isolates at a dosage as low as 4 mg/L. In case of tetracycline (16 mg/L) and doxycycline (64 mg/L), the contamination frequency in plantlets was 25.6 and 45%, respectively. It is, therefore, important to search for more endophytes, causing adverse effects during in vitro cultures and should devise a feasible anti-microbial strategy for controlling such contamination.

Background Acute encephalitis syndrome (AES) is endemic to certain parts of India, with limited treatment options. In our initial exploratory comparative observational study of 151 patients with AES, there was significantly reduced mortality with adjunctive homeopathy compared to institutional management protocol (IMP). The present randomized placebo-controlled trial brings more statistical rigor to this research program. Methods This study was conducted at a pediatric unit from 2013 to 2015. Children aged > 6 months and ≤ 18 years and receiving IMP were randomized to receive adjunctive homeopathy (n = 325) or placebo as control (n = 323). The primary effectiveness analysis was based on Glasgow Outcome Scale (GOS). Morbidity was assessed using the Liverpool Outcome Score for Assessing Children at Follow-up. Analysis was by intention to treat. Results A total of 612 children were analyzed (Homeopathy [H] = 304; Control [C] = 308). The primary outcome, GOS, differed significantly between H and C groups. There was 14.8% death/neuro-vegetative state in the H group compared to 29.8% in the C group. Relative risk was 0.49 (95% confidence interval [CI]: 0.36 to 0.68), with absolute risk reduction of 15.0% (95% CI: 8.6 to 21.6%). Number needed to treat to prevent one additional death/neuro-vegetative state was 6.6 (95% CI: 4.6 to 11.6). Proportional-odds analysis also revealed a greater effect in the H group: odds ratio, 0.40 (95% CI: 0.27 to 0.60). The most frequently used medicines were Belladonna (n = 116), Stramonium (n = 33), Arsenicum album (n = 25), Sulfur (n = 18), Opium (n = 17), and Nux vomica (n = 10). Conclusion Adjunctive homeopathic medicines may improve clinical outcomes associated with AES. Further randomized and controlled studies, using double-blinded trial design, are recommended to discover if the current findings may be corroborated.

Research was conducted to identify a series of neuropsychological tests to assess the ability to drive. Driving performance of young and old UK drivers was modeled through multiple linear regression and univariate logistic regression tools. The UFOV3 test (i.e. the third subtest of the UFOV test) had comparatively high discriminating ability in separating poor-drivers from not-poor-drivers, with 92.86% of the drivers correctly classified; the UFOV3 test resulted in a Sensitivity of 62.5%. Age and a composite cognitive measure were also found to be sound discriminators of poor-drivers and not-poor-drivers with 91.07% and 89.28% of the drivers correctly classified respectively; both age and the composite cognitive measure resulted in a Sensitivity of 50%. It was found that the commonly recommended Clock Drawing Test and the Trail Making-B test were insignificant predictors of driving ability. Results suggest that for a score greater than 220 on the UFOV3 test, the driver may be further evaluated by a driving specialist to ascertain questionable driving behavior. Also, drivers above the age of 77 were more susceptible to exhibiting unusual driving behavior; if such drivers have UFOV3 scores greater than 220 it would be more appropriate to evaluate driving behavior through a driving specialist.

Esta revisión describe la base de evidencia que ha ayudado a definir el papel de la craniectomía descompresiva (CD) en la manejo de pacientes con traumatismo craneoencefálico (TBI). Hallazgos recientes La publicación de dos ensayos aleatorizados (DECRA y RESCUEicp) ha fortalecido la base de pruebas. Los El ensayo DECRA mostró que la CD bifrontal neuroprotectora para la hipertensión intracraneal moderada no es útil, mientras que la El ensayo RESCUEicp encontró que la CD de último nivel para la hipertensión intracraneal severa y refractaria puede reducir significativamente la mortalidad tasa, pero se asocia con una tasa más alta de discapacidad. Estos hallazgos han reabierto el debate sobre (1) las indicaciones de la CD en varios subtipos de LCT, (2) técnicas alternativas (por ejemplo, craneotomía con bisagra), (3) tiempo y material óptimos para la reconstrucción craneal, y (4) el papel de la toma de decisiones compartida en la atención de TBI. Además, el papel de la CD primaria al evacuar un subdural agudo El hematoma se encuentra actualmente en evaluación en el contexto del ensayo aleatorizado RESCUE-ASDH. Esta revisión proporciona una descripción general de la base de evidencia actual, analiza sus limitaciones y presenta una perspectiva sobre el papel de la CD, ya que existe un creciente reconocimiento de que la atención también debe centrarse en los ingresos bajos y medios países debido a su carga de LCT mucho mayor. This review describes the evidence base that has helped define the role of decompressive craniectomy (DC) in the management of patients with traumatic brain injury (TBI). Recent Findings The publication of two randomized trials (DECRA and RESCUEicp) has strengthened the evidence base. The DECRA trial showed that neuroprotective bifrontal DC for moderate intracranial hypertension is not helpful, whereas the RESCUEicp trial found that last-tier DC for severe and refractory intracranial hypertension can significantly reduce the mortality rate but is associated with a higher rate of disability. These findings have reopened the debate about (1) the indications for DC in various TBI subtypes, (2) alternative techniques (e.g., hinge craniotomy), (3) optimal time and material for cranial reconstruction, and (4) the role of shared decision-making in TBI care. Additionally, the role of primary DC when evacuating an acute subdural hematoma is currently undergoing evaluation in the context of the RESCUE-ASDH randomized trial. This review provides an overview of the current evidence base, discusses its limitations, and presents a global perspective on the role of DC, as there is growing recognition that attention should also focus on low- and middle-income countries due to their much greater TBI burden.

Exposure to Pb among automobile technicians in selected towns of Khyber Pakhtunkhwa Province, Pakistan, was studied using a questionnaire, biological sampling (blood, hair, nails), and analysis of Pb biomonitoring data across various subgroups of occupation, age, and years of exposure. The study population included exposed automobile technicians (n = 50) and a control group (n = 50). The automobile technicians were further stratified into 4 groups: mechanics, auto-body technicians, electricians, and painters. Mean Pb levels in biological samples of the automobile technicians were significantly higher than in the control group (P 50 μg dL−1, but only 14% of the control group exceeded this level. Considering that Pb blood levels of 50 μg dL−1 exceed maximum concentrations recommended by leading public health organizations, appropriate measures should be taken to protect the welfare of the exposed automobile technicians and their families.