Effectiveness of Proximal Femur Nail in the Management of Unstable Per-Trochanteric Fractures: A Retrospective Cohort Study.

Background  Intertrochanteric (IT) fractures in the elderly demand surgical intervention for optimal recovery. While dynamic hip screw (DHS) is standard for stable fractures, its use in unstable cases is debated. Proximal femur nail (PFN) addresses unstable per-trochanteric fractures, boasting biomechanical advantages. Many studies favor PFN over DHS, despite concerns like screw migration. In resource-constrained developing nations, the choice of implant is pivotal. This research assesses proximal femur nailing outcomes for unstable fractures, providing insights for regional orthopedic protocols and contributing to tailored treatment guidelines in contexts with limited resources. Objective To assess the clinical and radiological outcomes in patients undergoing proximal femur nailing for unstable per-trochanteric fractures. Material and Methods This retrospective single-arm cohort study was conducted from January 2020 to July 2022. All the consecutive patients who underwent PFN for unstable per-trochanteric fractures were included in this study. Harris Hip Score (HHS) and ambulation status were recorded to evaluate functional outcomes. In contrast, the radiological outcome was assessed by calculating Radiographic Union Score for Hip (RUSH) scores at six weeks, three months, and six months post-operatively. Results  A total of 48 patients were included in this study with equal gender distribution and a mean age of 66 years. The functional outcome was recorded with 2.1% (1), 33.3% (16), and 50% (24) of patients achieving full weight bearing (FWB) without pain at six weeks, three months, and six months respectively while 14.6% (7) of the patients never achieved FWB. The radiological outcome was assessed by calculating RUSH score with 6.3% (3), 43.8% (21), and 50% (24) of the patients achieving complete union at the end of six weeks, three months, and six months respectively. One patient (2.1%) experienced malunion. Conclusion PFN remains an optimal treatment modality for the fixation of unstable per-trochanteric fractures yielding promising functional and radiological outcomes.

Clinico-pathological assessment of virulent Newcastle Disease Virus in ducks

Abstract Newcastle disease (ND) is an infectious, highly contagious and lethal disease of avian species. It is considered that ducks are natural reservoir or carrier for Newcastle disease virus (NDV) and are resistant against different strains of NDV. Current study was designed to evaluate the pathogenesis of Newcastle disease in domestic ducks through histopathology, immunohistochemistry (IHC) and serum biochemical changes. For this purpose, eighty ducks were reared for 42 days and divided in two groups A and B. Ducks in group A were challenged with (NDV) at rate of 0.1 ml of ELD50 (virus titer 107.32/100µl) on second week of age, whereas Group B was control negative. Splenomegaly, atrophy of thymus and necrotic lesion in kidney were observed on 9th day of post infection. Hepatic degeneration and mononuclear cell infiltration were noticed in proventriculus and intestine in challenged ducks. Viral antigen detected in lungs, intestine, proventriculus and lymphoid organs of infected ducks through IHC. Albumin and total protein values were significantly low in infected groups A as compared to control group B. ALT, AST, and ALP values were significantly high in infected group A. On 5th and 7th day of post infection oropharyngeal swabs were negative for NDV and cloacal swabs were positive for NDV through Reverse transcriptase polymerase chain reaction. It is concluded that ducks are susceptible to NDV and virulent strain of NDV caused disease in ducks.

Resumo A doença de Newcastle (DN) é uma doença infecciosa, altamente contagiosa e letal de espécies aviárias. Considera-se que os patos são reservatórios ou portadores naturais do vírus da doença de Newcastle (VDN) e são resistentes a diferentes cepas de VDN. O presente estudo foi desenvolvido para avaliar a patogênese da DN em patos domésticos por meio de histopatologia, imuno-histoquímica (IHQ) e alterações bioquímicas séricas. Para este propósito, 80 patos foram criados por 42 dias e divididos em dois grupos A e B. Os patos do grupo A foram submetidos ao VDN a uma taxa de 0,1 ml de ELD50 (título viral de 107,32 / 100 µl) na segunda semana de idade, enquanto o Grupo B foi controle negativo. Esplenomegalia, atrofia do timo e lesão necrótica no rim foram observadas no 9º dia pós-infecção. Degeneração hepática e infiltração de células mononucleares foram observadas no proventrículo e intestino em patos infectados. Antígeno viral foi detectado em pulmões, intestino, proventrículo e órgãos linfoides de patos infectados por IHQ. Os valores de albumina e proteína total foram significativamente baixos no grupo A infectado em comparação com o grupo B. Os valores de ALT, AST e ALP foram significativamente altos no grupo A. No 5º e no 7º dia após a infecção, os esfregaços orofaríngeos foram negativos para VDN, enquanto os esfregaços cloacais foram positivos para VDN por meio da reação em cadeia da polimerase via transcriptase reversa. Conclui-se que os patos são suscetíveis ao VDN e à cepa virulenta de VDN que causou doenças em patos.

Clinico-pathological assessment of virulent Newcastle Disease Virus in ducks / Avaliação clínico-patológica do Vírus da Doença de Newcastle em patos

Abstract Newcastle disease (ND) is an infectious, highly contagious and lethal disease of avian species. It is considered that ducks are natural reservoir or carrier for Newcastle disease virus (NDV) and are resistant against different strains of NDV. Current study was designed to evaluate the pathogenesis of Newcastle disease in domestic ducks through histopathology, immunohistochemistry (IHC) and serum biochemical changes. For this purpose, eighty ducks were reared for 42 days and divided in two groups A and B. Ducks in group A were challenged with (NDV) at rate of 0.1 ml of ELD50 (virus titer 107.32/100µl) on second week of age, whereas Group B was control negative. Splenomegaly, atrophy of thymus and necrotic lesion in kidney were observed on 9th day of post infection. Hepatic degeneration and mononuclear cell infiltration were noticed in proventriculus and intestine in challenged ducks. Viral antigen detected in lungs, intestine, proventriculus and lymphoid organs of infected ducks through IHC. Albumin and total protein values were significantly low in infected groups A as compared to control group B. ALT, AST, and ALP values were significantly high in infected group A. On 5th and 7th day of post infection oropharyngeal swabs were negative for NDV and cloacal swabs were positive for NDV through Reverse transcriptase polymerase chain reaction. It is concluded that ducks are susceptible to NDV and virulent strain of NDV caused disease in ducks.

Resumo A doença de Newcastle (DN) é uma doença infecciosa, altamente contagiosa e letal de espécies aviárias. Considera-se que os patos são reservatórios ou portadores naturais do vírus da doença de Newcastle (VDN) e são resistentes a diferentes cepas de VDN. O presente estudo foi desenvolvido para avaliar a patogênese da DN em patos domésticos por meio de histopatologia, imuno-histoquímica (IHQ) e alterações bioquímicas séricas. Para este propósito, 80 patos foram criados por 42 dias e divididos em dois grupos A e B. Os patos do grupo A foram submetidos ao VDN a uma taxa de 0,1 ml de ELD50 (título viral de 107,32 / 100 µl) na segunda semana de idade, enquanto o Grupo B foi controle negativo. Esplenomegalia, atrofia do timo e lesão necrótica no rim foram observadas no 9º dia pós-infecção. Degeneração hepática e infiltração de células mononucleares foram observadas no proventrículo e intestino em patos infectados. Antígeno viral foi detectado em pulmões, intestino, proventrículo e órgãos linfoides de patos infectados por IHQ. Os valores de albumina e proteína total foram significativamente baixos no grupo A infectado em comparação com o grupo B. Os valores de ALT, AST e ALP foram significativamente altos no grupo A. No 5º e no 7º dia após a infecção, os esfregaços orofaríngeos foram negativos para VDN, enquanto os esfregaços cloacais foram positivos para VDN por meio da reação em cadeia da polimerase via transcriptase reversa. Conclui-se que os patos são suscetíveis ao VDN e à cepa virulenta de VDN que causou doenças em patos.

Characterization of pH-induced conformational changes in recombinant DENV NS2B-NS3pro.

The increasing frequency of Dengue is a cause of severe epidemics and therefore demands strategies for effective prevention, diagnosis, and treatment. DENV-protease is being investigated as a potential therapeutic target. However, due to the flat and highly charged active site of the DENV-protease, designing orthosteric medicines is very difficult. In this study, we have done a thorough analysis of pH-dependent conformational changes in recombinantly expressed DENV protease using various spectroscopic techniques. Our spectroscopic study of DENV protease (NS2B-NS3pro) at different pH conditions gives important insights into the dynamicity of structural conformation. At physiological pH, the DENV-protease exists in a random-coiled state. Lowering the pH promotes the formation of alpha-helical and beta-sheet structures i.e. gain of secondary structure as shown by Far-UV CD. The light scattering and Thioflavin T (ThT)-binding assay proved the aggregation-prone tendency of DENV-protease at pH 4.0. Further, the confocal microscopy image intensity showed the amorphous aggregate formation of DENV protease at pH 4.0. Thus, the DENV protease acquires different conformations with changes in pH conditions. Together, these results have the potential to facilitate the design of a conformation destabilizer-based therapeutic strategy for dengue fever.

In-Depth Comparison of Genetic Variants Demonstrates a Close Relationship Between Invasive and Intraductal Components of Prostate Cancer.

Intraductal carcinoma (IDC) of the prostate is often associated with concurrent high-grade invasive prostate cancer (PCa) and poor clinical outcomes. In this context, IDC is thought to represent the retrograde spread of invasive prostatic adenocarcinoma into the acini and ducts. Prior studies have demonstrated a concordance of PTEN loss and genomic instability between the IDC and high-grade invasive components of PCa, but larger genomic association studies to solidify our understanding of the relationship between these 2 lesions are lacking. Here, we evaluate the genomic relationship between duct-confined (high-grade prostatic intraepithelial neoplasia and IDC) and invasive components of high-grade PCa using genetic variants generated by whole exome sequencing. High-grade prostatic intraepithelial neoplasia and IDC were laser-microdissected, and PCa and nonneoplastic tissue was manually dissected from 12 radical prostatectomies. A targeted next-generation sequencing panel was used to identify disease-relevant variants. Additionally, the degree of overlap between adjacent lesions was determined by comparing exome-wide variants detected using whole exome sequencing data. Our results demonstrate that IDC and invasive high-grade PCa components show common genetic variants and copy number alterations. Hierarchical clustering of genome-wide variants suggests that in these tumors, IDC is more closely related to the high-grade invasive components of the tumor compared with high-grade prostatic intraepithelial neoplasia. In conclusion, this study reinforces the concept that, in the context of high-grade PCa, IDC likely represents a late event associated with tumor progression.

Tuning the aggregation behavior of human insulin in the presence of luteolin: An in vitro and in silico approach.

Protein misfolding and related formation of amyloid fibrils are associated with several conformational diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), prion diseases, and Diabetes mellitus, Type 2 (DM-II). Several molecules including antibiotics, polyphenols, flavonoids, anthraquinones, and other small molecules are implicated to modulate amyloid assembly. The stabilization of the native forms of the polypeptides and prevention of their misfolding and aggregation are of clinical and biotechnological importance. Among the natural flavonoids, luteolin is of great importance because of its therapeutic role against neuroinflammation. Herein, we have explored the inhibitory effect of luteolin (LUT) on aggregation of a model protein, human insulin (HI). To understand the molecular mechanism of the inhibition of aggregation of HI by LUT, we employed molecular simulation, UV-Vis, fluorescence, and circular dichroism (CD) spectroscopies along with the dynamic light scattering (DLS). The analysis of the tuning of the HI aggregation process by luteolin revealed that interaction of HI with LUT resulted in the decrease in binding of the various fluorescent dyes, such as thioflavin T (ThT) and 8-anilinonaphthalene-1-sulfonic acid (ANS) to this protein. Retention of the native-like CD spectra and resistance to the aggregation in the presence of LUT has confirmed the aggregation inhibitory potential of LUT. The maximum inhibitory effect was found at the protein-to-drug ratio of 1:12, and no significant change was observed beyond this concentration.

Evaluating the inhibitory potential of natural compound luteolin on human lysozyme fibrillation.

Numerous pathophysiological conditions known as amyloidosis, have been connected to protein misfolding leading to aggregation of proteins. Inhibition of cytotoxic aggregates or disaggregation of the preformed fibrils is thus one of the important strategies in the prevention of such diseases. Growing interest and exploration of identification of small molecules mainly natural compounds can prevent or delay amyloid fibril formation. We examined the mechanism of interaction and inhibition of human lysozyme (HL) aggregates with luteolin (LT). Biophysical and computational approaches have been employed to study the effect of LT on HL amyloid aggregation. Transmission Electronic Microscopy, Thioflavin T fluorescence, UV-vis spectroscopy, and RLS demonstrates that LT inhibit HL fibril formation. ANS fluorescence and hemolytic assay was also employed to examine the effect of the LT on toxicity of HL aggregation. Docking and molecular dynamics results showed that LT interacted with HL via hydrophobic and hydrogen interactions, thus reducing fibrillation levels. These findings highlight the benefit of polyphenols as safe therapy for preventing amyloid related diseases.

In vitro and in vivo anthelmintic response of the seeds of Amomum subulatum roxb and Vitex negundo.

The current study was designed to check the anthelmintic activities of some local plants. Seeds of Amomum (A.) subulatum and Vitex (V.) negundo in different solvents were subjected to in vitro (adult motility assay; AMA and egg hatch assay; EHA) and in vivo (faecal egg count reduction test; FECRT) anthelmintic activity testing protocols using Haemonchus (H.) contortus as an experimental model. The results of AMA, EHA, and FECRT were statistically analysed through linear regression and Duncan multiple range test. In AMA test, at 50 mg mL-1 concentration, the percent mortality of H. contortus was higher in A. subulatum than V. negundo, whereas, in EHA test, A. subulatum was proven better ovicidal (LC50=14.2 µg mL-1) than V. negundo (LC50= 65.7405 µg mL-1). The FECRT also indicated the better efficacy of A. subulatum than V. negundo against natural infection of gastrointestinal (GI) parasites. The crude powder of plants used in this study showed 29.6% to 57.7% anthelmintic. The reduction rate was found higher for A. subulatum (3 g kg-1) as compared to V. negundo (7 g kg-1). Reagrding efficacy analysis of solvents used for plants extract, ethyl acetate and chloroform were found better in increasing ovicidal activity in adult worms (in vitro testing), whereas, the crude aqueous methanol was found better than the crude powders in in vivo testing. It will be beneficial to document the indigenous knowledge to standard scientific procedures for their validation. This study will help to motivate the farmers to make a better choice of cultivation of the indigenous plants because of their varying efficacies as an alternative preventive approach against the GI parasitic infections.

Mechanistic insight into inhibition of amyloid fibrillation of human serum albumin by Vildagliptin.

Protein aggregation leads to several human pathologies such as Alzheimer's disease (AD), type 2 diabetes (T2D), Parkinson's disease (PD), etc. Due to the overlap in the mechanisms of type 2 diabetes and brain disorders, common effective pharmacological interventions to treat both T2D and AD is under extensive research. Therefore, major aim of research is to repurpose already established treatment of diabetes to cure AD as well. This study evaluates mechanistic insight into anti-amyloidogenic potential of anti-diabetic drug Vildagliptin (VLD) on human serum albumin fibrillation (HSA) by using biophysical, calorimetric, imaging techniques along with hemolytic assay. Dynamic light scattering (DLS) and Rayleigh light scattering (RLS) results showed presence of few small-sized aggregates in the presence of VLD which are formed by deaccelerating the amyloidogenesis as shown by thioflavin T (ThT) fluorescence and Congo red (CR) binding assay. Further, Isothermal titration calorimetry (ITC), steady state fluorescence quenching, molecular docking results revealed that VLD form complex with amyloid facilitating state of HSA and consequently mask the hydrophobic residues involved in amyloidogenesis as evident from decrease in ANS fluorescence. Differential scanning calorimetry (DSC) results confirm that VLD stabilizes the amyloid facilitating state of HSA. In addition, SEM images demonstrated that VLD alleviates the hemolytic effect induced by fibrils of HSA. This study reports VLD as a potential inhibitor of amyloid fibrillation and provides promising results to repurpose VLD as a drug candidate for the cure of Alzheimer's diseases along with diabetes.

Mental health crisis in Somalia: a review and a way forward.

BACKGROUND: Somalia has been without an effective government since the collapse of the military regime in 1991. Years of conflict, disasters, and insecurity have all contributed to very low scores for most health indicators due to poor governance, protracted conflict, underdevelopment, economic decline, poverty, social and gender inequality, and environmental degradation. The three-decade long protracted conflict has led to widespread psychosocial trauma, social deprivation and substance abuse with devastating consequences on mental health. A WHO study showed Somalia has one of the highest rates of mental illness in the world. The main aim of this study is to assist policy makers in setting priorities for the design and delivery of interventions to promote mental health and psychosocial wellbeing in Somalia. METHODS: The study uses a systematic mapping technique (from January 1991 to May 2020) and data collected from public domain, to collect, collate, and present mental health data mainly from WHO's Global Health Observatory. Since there is no primary database for Somalia's public health research, the bibliographic databases used for mental health in this study included Medline, PubMed, CINAHL, PsycINFO, and Google Scholar. Data were extracted using techniques for web data mining for public health. RESULTS: Systematic mapping of mental health-related issues in Somalia showed that policy-related determinants and mental health services dominated (74.4%), followed by the disaster-related determinants and women's health consequences (39.3%). The ratio of the number of beds for mental health in general hospitals (per 100,000 population) in Somalia in 2017 is 0.5 compared to the Eastern Mediterranean region (EMR) at 6.4 and globally at 24. One of the biggest casualties of the civil war was loss of essential human resources in healthcare as most either fled the country or were part of the victims of the war. CONCLUSIONS: The vast scale of the mental health problems in Somalia and the priority setting guidelines for interventions to address the issues outlined in this paper, prompt a dire need that the Somali government and its national/international partners should prioritize and emphasize the need to invest in the prevention and the treatment of mental illness across the country.

Clinico-pathological assessment of virulent Newcastle Disease Virus in ducks.

Newcastle disease (ND) is an infectious, highly contagious and lethal disease of avian species. It is considered that ducks are natural reservoir or carrier for Newcastle disease virus (NDV) and are resistant against different strains of NDV. Current study was designed to evaluate the pathogenesis of Newcastle disease in domestic ducks through histopathology, immunohistochemistry (IHC) and serum biochemical changes. For this purpose, eighty ducks were reared for 42 days and divided in two groups A and B. Ducks in group A were challenged with (NDV) at rate of 0.1 ml of ELD50 (virus titer 107.32/100µl) on second week of age, whereas Group B was control negative. Splenomegaly, atrophy of thymus and necrotic lesion in kidney were observed on 9th day of post infection. Hepatic degeneration and mononuclear cell infiltration were noticed in proventriculus and intestine in challenged ducks. Viral antigen detected in lungs, intestine, proventriculus and lymphoid organs of infected ducks through IHC. Albumin and total protein values were significantly low in infected groups A as compared to control group B. ALT, AST, and ALP values were significantly high in infected group A. On 5th and 7th day of post infection oropharyngeal swabs were negative for NDV and cloacal swabs were positive for NDV through Reverse transcriptase polymerase chain reaction. It is concluded that ducks are susceptible to NDV and virulent strain of NDV caused disease in ducks.

Prevalence of Ruminant Paramphistomosis and Comparative Histopathology of the Infected Rumens in Narowal District, Punjab, Pakistan.

The present study reports the prevalence of Paramphistomum spp. in small and large ruminants and their association with the histopathology of the infected rumens. A total of 384 animals were screened for Paramphistomum spp. The animals found positive for Paramphistomum spp. were divided into three groups according to the worm load/5 cm2 (G1: 10 - 20 worms/5 cm2 = Low, G2: 20 - 40 worms/5 cm2 = Medium, and G3: >41 worms/5 cm2 = High). Tissue slides were prepared from samples of the rumen (1 cm2) taken from animals positive for ruminal fluke to determine the histological parameters, including epithelial length or thickness, length and width of the ruminal papilla, and thickness of tunica submucosa and mucularis externae. The overall prevalence of Paramphistomum spp. in the ruminant population of district Narowal was 56.25 % with a significant (P < 0.05) variation among different species of ruminants. The highest prevalence was in cattle, followed in order by buffalo, goat, and sheep. Epithelium thickness was significantly correlated with parasite load in large ruminants and the most significant (P < 0.05) decrease in epithelium thickness was in Group B (31.12 ± 1.82 µm) and Group C (31.07 ± 1.68 µm) and a same trend was recorded in small ruminants. Histopathological changes due to Paramphistomum spp. are reported for the first time, which explained the histomorphological and physiological changes in Paramphistomum-infected rumens which might be associated with lowered feed efficiency and productivity in ruminants.

Multifunctionality and intrinsic disorder of royal jelly proteome.

Royal Jelly (RJ) is a gelatinous white-yellowish fluid, possessing a sour taste and a slight phenolic smell that is secreted by the hypopharyngeal and mandibular salivary glands of the nurse honeybees, and is used in nutrition of larvae and adult queens. Similar to other substances associated with the activities of honeybees, RJ not only contains nutritive components, such as carbohydrates, proteins, peptides, lipids, vitamins, and mineral salts, but also represents a natural ingredient with cosmetic and health-promoting properties. RJ is characterized by remarkable multifunctionality, possessing numerous biological activities. Although this multifunctionality of RJ can be considered as a consequence of its complex nature, many proteins and peptides in RJ are polyfunctional entities themselves. In this article, we show that RJ proteins contain different levels of intrinsic disorder, have sites of post-translational modifications, can be found in multiple isoforms, and many of them possess disorder-based binding sites, suggesting that the conformational ensembles of the RJ proteins might undergo change as a result of their interaction with specific binding partners. All these observations suggest that the multifunctionality of proteins and peptides from RJ is determined by their structural heterogeneity and polymorphism, and serve as an illustration of the protein structure-function continuum concept.

Unravelling the inhibitory and cytoprotective potential of diuretics towards amyloid fibrillation.

Protein misfolding and deposition of aggregated proteins inside as well as outside of the cells have been associated with several neurotoxic and neurodegenerative disorders like Alzheimer's, Parkinson's and familial amyloid polyneuropathy etc. that could be controlled by anti-aggregation methodologies employing either inhibition or disaggregation of toxic aggregates. Also, the Alzheimer's disease develops in later life is somehow related to the high mid-life blood pressure. Therefore the present work targets the amyloid inhibiting potential of diuretics (a class of antihypertensive drugs) - Indapamide (INDP) and Hydrochlorothiazide (HCTZ) against human serum albumin (HSA) and human lysozyme (HL) fibrillogenesis. The effect of both INDP and HCTZ on the kinetics of amyloid formation of HSA and HL was illustrated and various biophysical techniques like Thioflavin T (ThT) and 8-Anilinonaphthalene-1-sulfonic acid (ANS) fluorescence measurement, Congo red measurements and circular dichroism (CD) measurements depicted the inhibitory action of both INDP and HCTZ in a dose dependent manner. Transmission Electronic Microscopy (TEM) confirmed the absence of fibrillar structures when HSA and HL were co-incubated with INDP and HCTZ. In addition, molecular docking results revealed that both the drugs interacts with HSA and HL through hydrophobic interactions as well as hydrogen bonding, and also showed non-hemolytic activity on human RBCs demonstrated by the Hemolytic assay. Thus, both INDP and HCTZ could be propitious as a therapeutic agent and aid in the cure of amyloid related diseases.

Microbial Colonization of Pneumatic Tourniquets in the Orthopedic Operating Room.

Background The rate of surgical site infections following orthopedic procedures is approximately 2% globally. Potential sources of contamination in the operating room include pneumatic tourniquets, blood pressure cuffs, and stethoscopes, among others. Our study aims to investigate microbial colonization on reusable pneumatic tourniquets stored and used in the orthopedic department of our institution and evaluate the efficacy of the cleaning protocols employed. Methods Over a course of two weeks, 26 samples were obtained. A total of 14 pneumatic tourniquets were sampled preoperatively on Monday morning following the weekly cleaning protocol of soaking the tourniquets in sodium hypochlorite for 30 minutes while 12 tourniquets were cultured immediately following the postoperative cleaning protocol of wiping the tourniquet clean with a cloth soaked in sodium hypochlorite. Samples were cultured on MacConkey and sheep blood agar and incubated at 37-degrees centigrade for a total of 48 hours. Organisms were identified and colony count was documented. The analysis was performed using the Fisher Exact test on SPSS v23 (IBM Corp., Armonk, NY, US). Results All 14 samples obtained after being soaked in sodium hypochlorite for 30 minutes cultured negative. However, four out of 12 (33%) samples obtained after simply wiping the pneumatic tourniquet with a cloth soaked in sodium hypochlorite cultured coagulase-negative Staphylococci. The difference between the two was significant (p=0.002). Conclusion Postoperative tourniquets, wiped with a cloth soaked in sodium hypochlorite and ready to be used on the next patient, were found to be contaminated with coagulase-negative Staphylococcus. This species is notorious for causing surgical site infections following implant-related surgeries potentially through direct inoculation and cross-infections intraoperatively and in storage. Efforts to identify the relationship with postoperative surgical site infections need to be made to suggest more aggressive cleaning protocols.

An interplay of structure and intrinsic disorder in the functionality of peptidylarginine deiminases, a family of key autoimmunity-related enzymes.

Citrullination is a post-translation modification of proteins, where the proteinaceous arginine residues are converted to non-coded citrulline residues. The immune tolerance to such citrullinated protein can be lost, leading to inflammatory and autoimmune diseases. Citrullination is a chemical reaction mediated by peptidylarginine deiminase enzymes (PADs), which are a family of calcium-dependent cysteine hydrolase enzymes that includes five isotypes: PAD1, PAD2, PAD3, PAD4, and PAD6. Each PAD has specific substrates and tissue distribution, where it modifies the arginine to produce a citrullinated protein with altered structure and function. All mammalian PADs have a sequence similarity of about 70-95%, whereas in humans, they are 50-55% homologous in their structure and amino acid sequences. Being calcium-dependent hydrolases, PADs are inactive under the physiological level of calcium, but could be activated due to distortions in calcium homeostasis, or when the cellular calcium levels are increased. In this article, we analyze some of the currently available data on the structural properties of human PADs, the mechanisms of their calcium-induced activation, and show that these proteins contain functionally important regions of intrinsic disorder. Citrullination represents an important trigger of multiple physiological and pathological processes, and as a result, PADs are recognized to play a number of important roles in autoimmune diseases, cancer, and neurodegeneration. Therefore, we also review the current state of the art in the development of PAD inhibitors with good potency and selectivity.

Elucidating the Inhibitory Potential of Designed Peptides Against Amyloid Fibrillation and Amyloid Associated Cytotoxicity.

Inhibition of fibrillation process and disaggregation of mature fibrils using small peptide are the promising remedial strategies to combat neurodegenerative diseases. However, designing peptide-based drugs to target ß-sheet-rich amyloid has been a major challenge. The current work describes, for the first time, the amyloid inhibitory potential of the two short peptides (selected on the basis of predisposition of their amino acid residues toward ß-sheet formation) using combination of biophysical, imaging methods, and docking approaches. Results showed that peptides employed different mechanisms to inhibit the amyloid fibrillation. Furthermore, they were also effective in blocking the amyloid fibrillation pathway. In contrary to the insulin fibrillar mesh, significantly less fibrillar species appeared in the presence of peptides, as confirmed by transmission electron microscopy. Circular dichroism analysis indicated that although peptides did not stabilize the native state of insulin, they inhibited amyloid aggregation by reducing the formation of ß-sheet rich structures. Hemolytic assay revealed the non-hemolytic nature of the species formed when insulin was co-incubated with the peptides. Therefore, despite the inherent potential to form ß-sheet structure, these peptides inhibited the amyloid formation and potentially can be used as therapeutics for the treatment of amyloid-related diseases.

Outcomes of internal hemipelvectomy for pelvic tumors: a developing country's prospective.

INTRODUCTION: Previously, external hemipelvectomy was the mainstay of treatment for pelvic tumors. However, with technological advancements, limb salvage procedures such as internal hemipelvectomy have emerged as a viable alternative. However, there is limited literature available on long-term outcomes and complications of internal hemipelvectomy, especially from developing countries. Therefore, the objective of this study was to share our experience of internal hemipelvectomy at a tertiary care center in a developing country. MATERIALS AND METHODS: A retrospective review was conducted in which all 24 patients undergoing internal hemipelvectomy from January 1, 2005 to December 31, 2015 at our institution were included. Medical record files were reviewed for intraoperative and early and late postoperative complications, and functional outcomes were assessed by contacting each patient on telephone. RESULTS: Ewing sarcoma was found to be the most common diagnosis, followed by osteosarcoma as the second most common. The mean follow-up period was 18.7±13.9 months. Intraoperatively there were 4 cases of iatrogenic neurovascular injury and 2 cases each of urinary tract injury and dural tear. Four patients developed early wound infections, 7 developed late wound infections, and 2 developed flap necrosis. Three patients developed recurrence, whereas 7 patients developed metastasis postoperatively. The mean survival was calculated to be 28 months and the mean Musculoskeletal Tumor Society score was 19.3±5.2. CONCLUSIONS: Outcomes and prevalence of complications shown in this study are comparable to those in the international literature, which suggests that hemipelvectomy is a viable option in developing countries also. However, more such studies are warranted to validate the findings and to identify the challenges and morbidities associated with hemipelvectomy in Asian and developing countries.

Sauromatum guttatum lectin: Spectral studies, lectin-carbohydrate interaction, molecular cloning and in silico analysis.

Non-immune carbohydrate binding proteins are broadly defined as lectins. Having been reported from all kingdoms of life, phytolectins are the most widely studied group of lectins. Sauromatum guttatum agglutinin (SGA) was isolated from the plant tubers and characterized for structural variations due to solvent perturbation using polarimetry, fluorescence and light scattering. For the ß-sheet rich SGA, a pH and temperature induced molten globule like intermediate was identified. In isothermal titration microcalorimetry, SGA demonstrated cooperative binding to a complex glycoprotein in enthalpically driven mechanism. Fine sugar specificity exploration identified core pentasaccharide as the most common and highest binding motif with complex N-glycans and fucosylated core N-glycans as additional motifs. Molecular cloning of SGA which has previously been demonstrated to have anti-cancer and anti-insect activities is being reported for the first time. Full length cDNA sequence was obtained with RACE-PCR based upon the conserved carbohydrate recognition site [QXDXNXVXY] present in all GNA-related lectins. Quaternary structure was proposed by homology modeling and an attempt was made to explain the structure-function relationship by in silico analysis.

Outpatient Percutaneous Release of Trigger Finger: A Cost Effective and Safe Procedure.

INTRODUCTION: Trigger finger is a common cause of pain and disability of the hand. Percutaneous release results in earlier functional recovery and patient satisfaction. This is a rapid and cost-effective method which saves a surgical procedure and results in better functional outcome. MATERIALS AND METHODS: This is a prospective observational study conducted on fifty-two fingers and thumbs in 52 patients treated from 1st July 2014 till 31st December 2014, in the Orthopaedic Section, Department of Surgery, Aga Khan University Hospital, Karachi, Pakistan. All the baseline characteristics of the patients, like demographics, symptoms, Quinell's criteria and functional outcome were recorded. The patients were treated at our hospital with trigger finger, managed with percutaneous release using an 18 gauge needle and followed up for a minimum period of three months. The follow-up information included range of motion scoring, patient satisfaction and overall outcome of the procedure in terms of patient acceptance. The data was analyzed to determine the functional outcome at three months. RESULTS: There was complete release of A1 pulleys in 52 out of 52 digits (100%) in the patients undergoing percutaneous release and significant patient satisfaction. No recurrence was observed. CONCLUSION: Percutaneous release of trigger finger with needle was not only associated with excellent functional outcome and recovery in terms of patient satisfaction and range of finger motion three months post-procedure but also was found to be cost effective.