Search

Objective: To compare the surgical outcomes in terms of recovery and complications of laparoscopic versus open appendectomy in patients presenting to tertiary care hospitals in Rawalpindi. Study Design: Prospective comparative study. Place and Duration of Study: The study was conducted at the Department of Surgery at Combined Military Hospital (CMH) Rawalpindi, Pakistan from 1st July 2022 to 31st December 2022. Methods: Seventy patients with clinically and radiologically confirmed acute appendicitis were segregated by lottery method into two equal groups of 35 each. Patients undergoing open appendectomy (OA) were placed in Group A, those planned for laparoscopic appendectomy (LA) were placed in Group B. Pre and postoperative outcomes, including Alvarado score, operating time, postoperative pain, and hospital stay documented and compared between the groups. Results: A mean age of 28.40 ± 6.73 years in the open appendectomy group and 29.06 ± 9.84 years in the laparoscopic appendectomy group was noted (P=0.745). The mean Alvarado score was 7.29 ± 0.95 in Group A and 6.86 ± 1.16 in Group B (P=0.098). A statistically significant difference was noted in the mean operation time of 67.29 ± 9.67 minutes for open appendectomy versus 38.77 ± 8.67 minutes for laparoscopic appendectomy (P < 0.05). The mean hospital stay was shorter for laparoscopic appendectomy, with 1.51 ± 0.61 days compared to 2.00 ± 0.54 days for open appendectomy (P

Spider venoms are a complex concoction of enzymes, polyamines, inorganic salts, and disulfide-rich peptides (DRPs). Although DRPs are widely distributed and abundant, their bevolutionary origin has remained elusive. This knowledge gap stems from the extensive molecular divergence of DRPs and a lack of sequence and structural data from diverse lineages. By evaluating DRPs under a comprehensive phylogenetic, structural and evolutionary framework, we have not only identified 78 novel spider toxin superfamilies but also provided the first evidence for their common origin. We trace the origin of these toxin superfamilies to a primordial knot – which we name ‘Adi Shakti’, after the creator of the Universe according to Hindu mythology – 375 MYA in the common ancestor of Araneomorphae and Mygalomorphae. As the lineages under evaluation constitute nearly 60% of extant spiders, our findings provide fascinating insights into the early evolution and diversification of the spider venom arsenal. Reliance on a single molecular toxin scaffold by nearly all spiders is in complete contrast to most other venomous animals that have recruited into their venoms diverse toxins with independent origins. By comparatively evaluating the molecular evolutionary histories of araneomorph and mygalomorph spider venom toxins, we highlight their contrasting evolutionary diversification rates. Our results also suggest that venom deployment (e.g. prey capture or self-defense) influences evolutionary diversification of DRP toxin superfamilies.

Among the medically most important snakes in the world, the species belonging to the genus Daboia have been attributed to the highest number of human envenomings, deaths and disabilities. Given their significant clinical relevance, the venoms of Russell’s vipers (D. russelii and D. siamensis) have been the primary focus of research. In contrast, the composition, activity, ecology and evolution of venom of its congener, the Palestine viper (D. palaestinae), have remained largely understudied. Therefore, to unravel the factors responsible for the enhanced medical relevance of D. russelii in comparison to D. palaestinae, we comparatively evaluated their venom proteomes, biochemical activities, and mortality and morbidity inflicting potentials. Furthermore, the synthesis and regulation of venom in snakes have also remained underinvestigated, and the relative contribution of each venom gland remains unclear. We address this knowledge gap by sequencing the tissue transcriptomes of both venom glands of D. palaestinae, and comparatively evaluating their contribution to the secreted venom concoction. Our findings highlight the disparity in the venom composition, function and toxicities of the two Daboia species. We also show that toxin production is not partitioned between the two venom glands of D. palaestinae.

ABSTRACT OBJECTIVE: To assess the usefulness of class tests by comparing their results with annual University examination results of preclinical medical students. STUDY DESIGN: A cross sectional analytical study METHODOLOGY: All (82) preclinical students of 2nd year MBBS passing the First Professional Part-II in first attempt were included in the study. Average of class test results of each student during the 2nd year was entered as percentage and compared with percentage total marks of same students in their 1st professional Part-II examination conducted by the University. Data maintained by Physiology Department was entered and analysed by SPSS 21. Descriptive statistics in the form of numbers and percentages were used and further analyzed using Pearson Correlation and Paired T Test of Significance. The p value of < 0.05 was considered to be significant. RESULTS: Out of total 82 students 65(79.3%) were females and 17(20.7%) males. All students were within the age group of 17-20 years, mean age being 18.7 years. Mean test score was 70.55 (Range=57-84, Median=71.19). Percentage marks in annual exam had a mean of 70.70 (Range=61-80, Median=71). Class test average in percentage was directly assessed against the percentage marks obtained in annual exam for each student. The average performance in class tests was significantly related to the marks in the final exam (p=0.01). Performance difference was noted amongst different genders in the class tests (Mean 65.27 for Males Vs 71.93 for Females) but not in the annual exam (Mean 69.75 for Males Vs 70.95 for Females) CONCLUSION: In preclinical years in a medical college regular class test results may be good predictors of the academic performance in professional examination. Male students show a tendency to improve their performance in the annual examination as compared to female students.

Sea stars are an abundant group of marine invertebrates that display remarkably robust regenerative capabilities throughout all life stages. Numerous proteins and peptides have been identified in a proteome study on the coelomic fluid (biofluid) of the common sea star Asterias rubens, which appear to be involved with the wound-healing response in the organism. However, the three-dimensional structure and function of several of these injury-responsive peptides, including the peptide KASH2, are yet to be investigated. Here, we show that the KASH2 peptide adopts a disulfide-directed β-hairpin fold (DDH). The DDH motif appears to be evolutionarily related to the inhibitor cystine knot motif, which is one of the most widespread disulfide-rich peptide folds. The DDH motif was originally thought to be restricted to arachnids, but our study suggests that as a result of convergent evolution it could also have originated in sea stars. Although the widely conserved DDH fold has potential cross-phyla wound-healing capacity, we have shown that KASH2 does not enhance the proliferation of human fibroblasts, a simple method for wound-healing re-epithelialisation screening. Therefore, additional research is necessary to determine the role of KASH2 in the sea stars., (© 2024 The Author(s). FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The escalating global health challenge posed by infections prompts the exploration of innovative solutions utilizing MXene-based nanostructures. Societally, the need for effective antimicrobial strategies is crucial for public health, while scientifically, MXenes present promising properties for therapeutic applications, necessitating scalable production and comprehensive characterization techniques. Here we review the versatile physicochemical properties of MXene materials for combatting microbial threats and their various synthesis methods, including etching and top-down or bottom-up techniques. Crucial characterization techniques such as XRD, Raman spectroscopy, SEM/TEM, FTIR, XPS, and BET analysis provide insightful structural and functional attributes. The review highlights MXenes' diverse antimicrobial mechanisms, spanning membrane disruption and oxidative stress induction, demonstrating efficacy against bacterial, viral, and fungal infections. Despite translational hurdles, MXene-based nanostructures offer broad-spectrum antimicrobial potential, with applications in drug delivery and diagnostics, presenting a promising path for advancing infection control in global healthcare., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Catalyst-controlled C-H functionalization using donor/acceptor carbenes has been shown to be an efficient process capable of high levels of site control and stereocontrol. This study demonstrated that the scope of the donor/acceptor carbene C-H functionalization can be extended to systems where the acceptor group is a phosphonate. When using the optimized dirhodium catalyst, Rh 2 ( S-di -(4-Br)TPPTTL) 4 , ((aryl)(diazo)methyl)phosphonates undergo highly enantioselective (84-99% ee) and site-selective (>30:1 r.r.) benzylic C-H functionalization. The phosphonate group is much more sterically demanding than the previously studied carboxylate ester group, leading to much higher selectivity for a primary site versus more sterically crowded positions. The effectiveness of this methodology has been demonstrated by the late-stage primary C-H functionalization of estrone, adapalene, ( S )-naproxen, clofibrate, and gemfibrozil derivatives., Competing Interests: The authors declare the following competing financial interest(s): H.M.L.D. is a named inventor on a patent entitled, Dirhodium Catalyst Compositions and Synthetic Processes Related Thereto (US 8,974,428, issued March 10, 2015). The other authors have no competing financial interests., (© 2023 The Authors. Published by American Chemical Society.)

Hole-transport materials (HTMs) based on triarylamine derivatives play important roles in organic electronics applications including organic light-emitting diodes and perovskite solar cells. For some applications, triarylamine derivatives bearing appropriate binding groups have been used to functionalize surfaces, while others have been incorporated as side chains into polymers to manipulate the processibility of HTMs for device applications. However, only a few approaches have been used to incorporate a single surface-binding group or polymerizable group into triarylamine materials. Here, we report that Rh-carbenoid chemistry can be used to insert carboxylic esters and norbornene functional groups into sp 2 C-H bonds of a simple triarylamine and a 4,4'-bis(diarylamino)biphenyl, respectively. The norbenene-functionalized monomer was polymerized by ring-opening metathesis; the electrochemical, optical, and charge-transport properties of these materials were similar to those of related materials synthesized by conventional means. This method potentially offers straightforward access to a diverse range of HTMs with different functional groups.

Background: Several reports of unheeded complications secondary to the current mass international rollout of SARS-COV-2 vaccines, one of which is myocarditis occurring with the FDA fully approved vaccine, Pfizer, and others., Main Body of the Abstract: Certain miRNAs (non-coding RNA sequences) are involved in the pathogenesis in viral myocarditis, and those miRNAs are interestingly upregulated in severe COVID-19. We hypothesize that the use of mRNA-based vaccines may be triggering the release of host miRNAs or that trigger the occurrence of myocarditis. This is based on the finding of altered host miRNA expression promoting virus-induced myocarditis., Short Conclusion: In conclusion, miRNAs are likely implicated in myocarditis associated with mRNA vaccines. Our hypothesis suggests the use of miRNA as a biomarker for the diagnosis of mRNA vaccine-induced myocarditis. Additionally, the interplay between viral miRNA and the host immune system could alter inflammatory profiles, hence suggesting the use of therapeutic inhibition to prevent such complications., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2022.)

Background: Several vaccines have been fast-tracked in an attempt to decrease the morbidity and mortality of COVID-19. However, post-exposure prophylaxis has been overlooked in battling COVID-19., Main Text: Inhaled nitric oxide is a potential tool in post-exposure prophylaxis of COVID-19. It decreases cytosolic calcium levels, which impairs the action of Furin. SARS-CoV-2 uses Furin to replicate in the respiratory tract., Short Conclusion: Inhaled nitric oxide could decrease the viral load in the upper respiratory tract, abort clinically symptomatic infection, and prevent subsequent complications. Nitric oxide might be a tool for post-exposure chemoprophylaxis in at-risk groups, especially medical personnel., (© 2021. The Author(s).)

We report a novel glycan array architecture that binds the mannose-specific glycan binding protein, concanavalin A (ConA), with sub-femtomolar avidity. A new radical photopolymerization developed specifically for this application combines the grafted-from thiol-(meth)acrylate polymerization with thiol-ene chemistry to graft glycans to the growing polymer brushes. The propagation of the brushes was studied by carrying out this grafted-to/grafted-from radical photopolymerization (GTGFRP) at >400 different conditions using hypersurface photolithography, a printing strategy that substantially accelerates reaction discovery and optimization on surfaces. The effect of brush height and the grafting density of mannosides on the binding of ConA to the brushes was studied systematically, and we found that multivalent and cooperative binding account for the unprecedented sensitivity of the GTGFRP brushes. This study further demonstrates the ease with which new chemistry can be tailored for an application as a result of the advantages of hypersurface photolithography., (© 2021 Wiley-VCH GmbH.)

Synthetic carbohydrate receptors (SCRs) that selectively recognize cell-surface glycans could be used for detection, drug delivery, or as therapeutics. Here we report the synthesis of seven new C 2h symmetric tetrapodal SCRs. The structures of these SCRs possess a conserved biaryl core, and they vary in the four heterocyclic binding groups that are linked to the biaryl core via secondary amines. Supramolecular association between these SCRs and five biologically relevant C 1 -O-octyloxy glycans, α/β-glucoside (α/β-Glc), α/β-mannoside (α/β-Man), and β-galactoside (β-Gal), was studied by mass spectrometry, 1 H NMR titrations, and molecular modeling. These studies revealed that selectivity can be achieved in these tetrapodal SCRs by varying the heterocyclic binding group. We found that SCR017 (3-pyrrole), SCR021 (3-pyridine), and SCR022 (2-phenol) bind only to β-Glc. SCR019 (3-indole) binds only to β-Man. SCR020 (2-pyridine) binds β-Man and α-Man with a preference to the latter. SCR018 (2-indole) binds α-Man and β-Gal with a preference to the former. The glycan guests bound within their SCR hosts in one of three supramolecular geometries: center-parallel, center-perpendicular, and off-center. Many host-guest combinations formed higher stoichiometry complexes, 2:1 glycan⋅SCR or 1:2 glycan⋅SCR, where the former are driven by positive allosteric cooperativity induced by glycan-glycan contacts., (© 2020 Wiley-VCH GmbH.)

Interactions between cell surface glycans and glycan binding proteins (GBPs) have a central role in the immune response, pathogen-host recognition, cell-cell communication, and a myriad other biological processes. Because of the weak association between GBPs and glycans in solution, multivalent and cooperative interactions in the dense glycocalyx have an outsized role in directing binding affinity and selectivity. However, a major challenge in glycobiology is that few experimental approaches exist for examining and understanding quantitatively how glycan density affects avidity with GBPs, and there is a need for new tools that can fabricate glycan arrays with the ability to vary their density controllably and systematically in each feature. Here, we use thiol-ene reactions to fabricate glycan arrays using a recently developed photochemical printer that leverages a digital micromirror device and microfluidics to create multiplexed patterns of immobilized mannosides, where the density of mannosides in each feature was varied by dilution with an inert spacer allyl alcohol. The association between these immobilized glycans and FITC-labeled concanavalin A (ConA) - a tetrameric GBP that binds to mannosides multivalently - was measured by fluorescence microscopy. We observed that the fluorescence decreased nonlinearly with increasing spacer concentration in the features, and we present a model that relates the average mannoside-mannoside spacing to the abrupt drop-off in ConA binding. Applying these recent advances in microscale photolithography to the challenge of mimicking the architecture of the glycocalyx could lead to a rapid understanding of how information is trafficked on the cell surface.

Spatially encoded glycan microarrays promise to rapidly accelerate our understanding of glycan binding in myriad biological processes, which could lead to new therapeutics and previously unknown drug targets. Here, we bring together a digital micromirror device, microfluidic introduction of inks, and advanced surface photochemistry to produce multiplexed glycan microarrays with reduced feature diameters, an increased number of features per array, and precise control of glycan density at each feature. The versatility of this platform was validated by printing two distinct glycan microarrays where, in the first, different glycans were immobilized to create a multiplexed array and, in another, the density of a single glycan was varied systematically to explore the effect of surface presentation on lectin-glycan binding. For lectin binding studies on these miniaturized microarrays, a microfluidic incubation chip was developed that channels multiple different protein solutions over the array. Using the multiplexed array, binding between eight lectin solutions and five different glycosides was determined, such that a single array can interrogate the binding between 40 lectin-glycan combinations. The incubation chip was then used on the array with varied glycan density to study the effects of glycan density on lectin binding. These results show that this novel printer could rapidly advance our understanding of critical unresolved questions in glycobiology, while simultaneously increasing the throughput and reducing the cost of these experiments.

Zika virus (ZIKV), a mosquito-borne flavivirus, is a global health concern because of its association with severe neurological disorders. Currently, there are no antiviral therapies that have been specifically approved to treat ZIKV, and there is an urgent need to develop effective anti-ZIKV agents. Here, we report anti-ZIKV activity of 16 synthetic carbohydrate receptors (SCRs) that inhibit ZIKV infection in Vero and HeLa cells. Using a ZIKV reporter virus particle-based infection assay, our data demonstrates these SCRs are highly potent with IC 50 s as low as 0.16 μM and negligible toxicity at several-fold higher concentrations. Time-of-addition studies showed that these SCRs inhibit the early stages of the virus infection, which is consistent with the proposed mode of action, where the SCRs likely inhibit binding between the virus and cell-surface glycans, thereby preventing viral entry into the cells and, as such, this study demonstrates a potential new strategy against ZIKV.

Synthetic carbohydrate receptors could serve as agents for disease detection, drug delivery, or even therapeutics, however, they are rarely used for these applications because they bind weakly and with a preference towards the all-equatorial glucosides that are not prevalent on the cell surface. Herein the binding of 8 receptors with 5 distinct octyloxy pyranosides, which was measured by mass spectrometry and by 1 H NMR titrations in CD 2 Cl 2 at 298 K, is reported, providing binding affinities that vary from ≈10 1 -10 4  m -1 . Although the receptors are promiscuous, 1 shows selectivity for β-Man at a ratio of 103:1 β-Man:β-Gal, receptors 2-4 and 6 have preference for α-Man, 5 is selective for β-Gal, and 10 prefers α-Glc (Man=mannose; Gal=galactose, Glc=glucose). A variety of 1D and 2D NMR, and computational techniques were used to determine the thermodynamic binding parameters (ΔH o and ΔS o ) and the structure of the host-guest complex, revealing that dimeric receptor 10 binds β-Man with increased enthalpy, but a larger entropic penalty than 1. The first-principles modelling suggests that 10⋅β-Man forms an inclusion-type complex where the glycan engages both monomeric subunits of 10 through H-bonding and C-H⋅⋅⋅π interactions. Like natural glycan-binding proteins, these receptors bind pyranosides by accessing multivalent and cooperative interactions, and these studies suggest a new approach towards biomimetic synthetic carbohydrate receptors, where conformational flexibility and promiscuity are incorporated into design., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Laparoscopic common bile duct exploration (LCBDE) has been proven to be a safe, efficient, and cost-effective option for the management of common bile duct (CBD) stones. There are two guiding methods during LCBDE: fluoroscopic or choledochoscopic. Most surgeons prefer the use of flexible choledochoscopy at LCBDE, but it is a fragile, delicate, and expensive instrument. The aim of this work was to report our experience in fluoroscopically guided LCBDE., Patients and Methods: A retrospective review of all patients who underwent LCBDE in the Mansoura Gastroenterology surgical center between March 2007 and September 2014 was performed. Patients with gallstones and concomitant CBD stones were included. After the initial assessment, all patients fulfilling the criteria of enrollment underwent magnetic resonance cholangiopancreatography, and only patients with magnetic resonance cholangiopancreatography or endoscopic retrograde cholangiopancreatography evidence of CBD stones were included. Choledochoscopy was not used in any patient, and we depended on fluoroscopic guidance for CBD stone retrieval in all LCBDE., Results: A total of 290 patients were assessed for LCBDE: 76 patients were excluded; 11 patients were not completed laparoscopically due to negative intraoperative cholangiography (n=7) and conversion to laparotomy (n=4); the remaining 203 patients were analyzed. LCBDE failed in 16 of the 203 (7.9%) cases, with a success rate of 92.1%. The median operative time was 79 minutes, and the median hospital stay was 2.4 days. Complications were bile leakage (n=4), mild pancreatitis (n=2), wound infection (n=2), port hernia (n=1), and internal hemorrhage (n=1)., Conclusions: Compared with published studies using choledochoscopy at LCBDE, we found comparable results in terms of the success/failure rate, the morbidity and mortality, the operative time, and the length of hospital stay. LCBDE under fluoroscopic guidance may be as safe and efficient as with choledochoscopic guidance.