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Corynebacterium pseudotuberculosis is a facultative intracellular pathogen and the causative agent of several infectious and contagious chronic diseases, including caseous lymphadenitis, ulcerative lymphangitis, mastitis, and edematous skin disease, in a broad spectrum of hosts. In addition, Corynebacterium pseudotuberculosis infections pose a rising worldwide economic problem in ruminants. The complete genome sequences of 15 C. pseudotuberculosis strains isolated from different hosts and countries were comparatively analyzed using a pan-genomic strategy. Phylogenomic, pan-genomic, core genomic, and singleton analyses revealed close relationships among pathogenic corynebacteria, the clonal-like behavior of C. pseudotuberculosis and slow increases in the sizes of pan-genomes. According to extrapolations based on the pan-genomes, core genomes and singletons, the C. pseudotuberculosis biovar ovis shows a more clonal-like behavior than the C. pseudotuberculosis biovar equi. Most of the variable genes of the biovar ovis strains were acquired in a block through horizontal gene transfer and are highly conserved, whereas the biovar equi strains contain great variability, both intra- and inter-biovar, in the 16 detected pathogenicity islands (PAIs). With respect to the gene content of the PAIs, the most interesting finding is the high similarity of the pilus genes in the biovar ovis strains compared with the great variability of these genes in the biovar equi strains. Concluding, the polymerization of complete pilus structures in biovar ovis could be responsible for a remarkable ability of these strains to spread throughout host tissues and penetrate cells to live intracellularly, in contrast with the biovar equi, which rarely attacks visceral organs. Intracellularly, the biovar ovis strains are expected to have less contact with other organisms than the biovar equi strains, thereby explaining the significant clonal-like behavior of the biovar ovis strains.

Diphtheria is an acute and highly infectious disease, previously regarded as endemic in nature but vaccine-preventable, is caused by Corynebacterium diphtheriae (Cd). In this work, we used an in silico approach along the 13 complete genome sequences of C. diphtheriae followed by a computational assessment of structural information of the binding sites to characterize the “pocketome druggability.” To this end, we first computed the “modelome” (3D structures of a complete genome) of a randomly selected reference strain Cd NCTC13129; that had 13,763 open reading frames (ORFs) and resulted in 1,253 (∼9%) structure models. The amino acid sequences of these modeled structures were compared with the remaining 12 genomes and consequently, 438 conserved protein sequences were obtained. The RCSB-PDB database was consulted to check the template structures for these conserved proteins and as a result, 401 adequate 3D models were obtained. We subsequently predicted the protein pockets for the obtained set of models and kept only the conserved pockets that had highly druggable (HD) values (137 across all strains). Later, an off-target host homology analyses was performed considering the human proteome using NCBI database. Furthermore, the gene essentiality analysis was carried out that gave a final set of 10-conserved targets possessing highly druggable protein pockets. To check the target identification robustness of the pipeline used in this work, we crosschecked the final target list with another in-house target identification approach for C. diphtheriae thereby obtaining three common targets, these were; hisE-phosphoribosyl-ATP pyrophosphatase, glpX-fructose 1,6-bisphosphatase II, and rpsH-30S ribosomal protein S8. Our predicted results suggest that the in silico approach used could potentially aid in experimental polypharmacological target determination in C. diphtheriae and other pathogens, thereby, might complement the existing and new drug-discovery pipelines.

Since the first successful attempt at sequencing the Corynebacterium pseudotuberculosis genome, large amounts of genomic, transcriptomic and proteomic data have been generated. C. pseudotuberculosis is an interesting bacterium due to its great zoonotic potential and because it causes considerable economic losses worldwide. Furthermore, different strains of C. pseudotuberculosis are capable of causing various diseases in different hosts. Currently, we seek information about the phylogenetic relationships between different strains of C. pseudotuberculosis isolates from different hosts across the world and to employ these data to develop tools to diagnose and eradicate the diseases these strains cause. In this review, we present the latest findings on C. pseudotuberculosis that have been obtained with the most advanced techniques for sequencing and genomic organization. We also discuss the development of in silico tools for processing these data to prompt a better understanding of this pathogen.

Background: Adherence to self-administered biologic therapies is important to induce remission and prevent adverse clinical outcomes in Inflammatory bowel disease (IBD). This study aimed to use administrative claims data and machine learning methods to predict nonadherence in an academic medical center test population., Methods: A model-training dataset of beneficiaries with IBD and the first unique dispense of a self-administered biologic between June 30, 2016 and June 30, 2019 was extracted from the Commercial Claims and Encounters and Medicare Supplemental Administrative Claims Database. Known correlates of medication nonadherence were identified in the dataset. Nonadherence to biologic therapies was defined as a proportion of days covered ratio <80% at 1 year. A similar dataset was obtained from a tertiary academic medical center's electronic medical record data for use in model testing. A total of 48 machine learning models were trained and assessed utilizing the area under the receiver operating characteristic curve as the primary measure of predictive validity., Results: The training dataset included 6998 beneficiaries ( n  = 2680 nonadherent, 38.3%) while the testing dataset included 285 patients ( n  = 134 nonadherent, 47.0%). When applied to test data, the highest performing models had an area under the receiver operating characteristic curve of 0.55, indicating poor predictive performance. The majority of models trained had low sensitivity and high specificity., Conclusions: Administrative claims-trained models were unable to predict biologic medication nonadherence in patients with IBD. Future research may benefit from datasets with enriched demographic and clinical data in training predictive models., Competing Interests: The authors have no relevant competing or financial interests to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Guarding against an anti-science camouflage within infodemics is paramount for sustaining the global vaccination drive. Vaccine hesitancy remains a growing concern and a significant threat to public health, especially in developing countries. Infodemics, conspiracy beliefs and religious fatalism primarily fuel vaccine hesitancy. In addition, anti-vaccine disinformation, lack of understanding, and erroneous religious beliefs also trigger vaccine hesitancy. Global behavioral strategies such as wearing face masks and long-term preventive measures (i.e., COVID-19 vaccination) have effectively limited the virus's spread. Despite the alarming rate of global deaths (i.e., over 99% being unvaccinated), a large proportion of the global population remains reluctant to vaccinate. New evidence validates the usefulness of technology-driven communication strategies (i.e., digital interventions) to address the complex socio-psychological influence of the pandemic. Hence, the present research explored the digital information processing model to assess the interface between informational support (through digital interventions) and antecedents of vaccine hesitancy. This research involved two separate studies: a focus group to operationalize the construct of infodemics, which remained ambiguous in previous literature (Study 1), followed by a cross-sectional survey (Study 2) to examine the conceptual model. Data were collected from 1906 respondents through a standard questionnaire administered online. The focus group's findings revealed a multi-dimensional nature of infodemics that was also validated in Study 2. The cross-sectional survey results substantiated infodemics, religious fatalism and conspiracy beliefs as significant predictors of vaccine hesitancy. Similarly, conspiracy beliefs negatively influence an individual's psychological well-being. Furthermore, information support (through digital intervention) affected infodemics and religious fatalism, whereas it inversely influenced the strength of their relationships with vaccine hesitancy. Information support (through digital intervention) also moderated the relationship between conspiracy beliefs and psychological well-being., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

The relationship between managing patient expectations and postoperative functional outcomes has been studied widely in other areas of orthopedics, but there is a paucity of information in the foot and ankle literature. The primary objective of the study was to identify the most common patient "expectations" from hallux valgus surgery and establish over what time period postsurgery they would meet those goals. A prospective study of 45 consecutive patients was performed at a single center. This included adult patients (>18 years old) that underwent a scarf osteotomy for primary hallux valgus correction. Patients were followed up for 6 months and completed pre- and postoperative Manchester-Oxford Foot Questionnaire and Visual Analogue Scale scores. A separate "expectations" questionnaire was designed and completed assessing the patient's preoperative rehabilitation expectations compared to the actual time taken to achieve those goals. These included 5 domains: pain improvement, return to walking unaided, return to normal foot sensation, return to normal footwear, and return to driving. The postoperative functional scores demonstrated statistically significant improvement postsurgery (p < .001). It also highlighted the overall time frame over which the above expectations were met. On average, patients achieved satisfactory pain improvements 1.4 weeks earlier than expected (p < .001) along with trends toward an earlier return to driving function of patient expectation (p < .05). Patients can thus be reliably informed that their pain symptoms are likely to settle within one month of surgery. This should allow patients to prepare for their rehabilitation more informed, thus facilitating earlier weightbearing and return to function., (Copyright © 2022. Published by Elsevier Inc.)

Renewed COVID-19 outbreaks, stemming from the highly infectious Delta and Omicron variants, prompted rising fears of a 'pandemic among the unvaccinated'. To address this prevalent vaccination crisis, media framing communication strategies can amplify the scientific evidence on COVID-19 vaccines to reach diverse geographic and socio-economic communities. The critical role of media framing strategies to engage and encourage large populations regarding vaccine acceptance has been rarely studied, despite growing evidence on vaccine hesitancy. The present study used a multi-method approach (i.e., content analysis and quasi-experiments) that unpacked the framing practices employed by the mainstream media in Pakistan. The findings of the content analysis revealed that the media extensively used uncertainty, conflict, consequences, and action rather than new evidence and reassurance frames in its COVID-19 related campaigns. In a series of quasi-experiments involving 720 participants, we manipulated these six frames of COVID-19 related news coverage (i.e., uncertainty, conflict, consequences, action, new evidence, and reassurance) to investigate the underlying mechanism that influences vaccine acceptance. The findings established that the message-consistent effects of media frames manifesting fear (e.g., consequence and uncertainty) and action cues made receivers more supportive of vaccination. The present study findings theoretically address the calls for a more inclusive "community-health reporting model", besides offering new evidence on the media framing strategies to deliver more targeted, meaningful, and effective campaigns to raise public acceptance for COVID-19 vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction Diabetes mellitus (DM) is a significant and common risk factor for the development of peripheral vascular disease (PVD). Peripheral vascular disease is the atherosclerotic narrowing of peripheral arteries and has a high prevalence among patients with diabetes. Material and methods A cross-sectional study was conducted in the Department of Medicine of Ayub Teaching Hospital, Abbottabad. A total of 271 diagnosed diabetic patients aged 40 years or above were included in the study. Ankle-brachial pressure index (ABPI) was measured using a hand-held Doppler device and sphygmomanometer. An ABPI < 0.9 was taken to be abnormal. The risk factors were noted through history taking, physical examination, and appropriate investigations.  Results Our study sample included 271 patients. A hundred and forty-five (53.5%) of them were males, and 126 (46.5%) were females. Fifty-three (19.9%) out of 271 patients had peripheral vascular disease. The prevalence of peripheral vascular disease was stratified among smoking (p=0.00), hypertension (p=0.00), obesity (p=0.004), and hypercholesterolemia (p=0.005) to determine if there was any association between these and peripheral vascular disease. A p-value less than 0.05 was taken to be significant. Conclusion This study showed a significant association between PVD and smoking, hypertension, hypercholesterolemia, and obesity., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Majid Khan et al.)

We present a novel minimally invasive percutaneous approach for the surgical treatment of tricuspid valve infective endocarditis. In this case, the patient presented with a malfunctioning implantable cardiac device, right ventricle implantable cardiac device lead infection, and infective endocarditis of the tricuspid valve.   The infective endocarditis vegetations were removed via a percutaneous approach using the AngioVac suction device. The device was modified by the surgeon, who sutured 2 threads to the head of the device in order to allow adjustments to be made to the angle of suction by applying tension on the suture. Real-time visualization of the procedure was achieved via transesophageal echocardiography.   This approach, utilizing the AngioVac device, is a feasible and effective treatment strategy for endocarditis vegetation removal in selected patients who would otherwise be unsuitable candidates for open heart surgery., (© The Author 2020. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Since its first description over 30 years ago arthroscopic stabilisation has evolved. With improvements in knowledge, surgical techniques and materials technology, arthroscopic bankart repair has become the most widely used method for treating patients with symptomatic anterior shoulder instability. These procedures are typically performed in a younger, high demand patient population after a primary dislocation or to treat recurrent instability. A thorough clinical evaluation is required in the clinic setting not only to fully understand the injury pattern but also consider patient expectations prior to embarking on surgery. Diagnostic imaging will aid the clinician in determining the soft tissue pathology as well as assessing bone loss, which facilitates surgical decision-making. Selected patients may benefit from adjunctive procedures such as a remplissage for an "engaging" Hill-sachs lesion. This review will focus on the indications, pre-operative considerations, surgical techniques and outcomes of arthroscopic stabilisation., (© 2019 Delhi Orthopedic Association. All rights reserved.)

We report a rare case of IgG4-associated mediastinal fibrosis with complete superior vena cava (SVC) obstruction successfully managed by thrombolysis and stenting in a 33-year-old male. The patient presented with a mediastinal mass lesion with clinical findings of SVC obstruction. Surgical biopsy of the mediastinal mass lesion with histology and immunohistochemistry staining established the diagnosis of IgG4 associated mediastinal fibrosis. The patient was treated with a systemic steroid and rituximab, but despite treatment, SVC obstruction and thromboses persisted, surgical intervention was declined by the thoracic surgeon due to extensive mediastinal fibrosis and an expected poor outcome. Percutaneous SVC angioplasty, intravascular thrombolysis with tissue plasminogen activator and afterward stent placement was done by the interventional radiology service. This intervention is rare and possibly was lifesaving as it restored complete patency of the SVC. Our case is probably the first with IgG4 mediastinitis and SVC complete obstruction relieved by intravascular thrombolysis and SVC stent placement. It demonstrates that SVC stenting can relieve SVC obstruction in patients with a high risk of surgery either due to medical comorbidities or an expected high surgical risk like bleeding in the mediastinal fibrosis, which in our case of SVC obstruction was due to a nonoperable mediastinal tumor. SIMILAR CASES PUBLISHED: None to our knowledge.

Background: Pulmonary hypertension (PH) is an idiopathic or secondary disorder associated with many systemic illnesses. Long-term survival in PH depends on the severity and functional class. Several new drugs are now available to treat PH, but their impact on clinical outcome and survival are not well established., Objectives: Evaluate severity parameters and the impact of current recommended therapy on survival in PH., Design: Cross-sectional., Settings: Tertiary care center., Patients and Methods: The study included adult patients who had undergone right heart catheterization since 2012 and were diagnosed with pulmonary hypertension. Survival was recorded after 6 years, at the end of the study. Nine severity variables for PH were assessed including right ventricular size by echocardiogram and pulmonary artery diameter (PA diameter) and the ratio of pulmonary artery diameter to ascending aorta diameter (PA/Ao ratio) by CT., Main Outcome Measures: Evaluation of severity parameters., Sample Size: 30 patients., Results: Twenty-five patients were positive for 8/9 severity parameters. Eight of 30 (26.6%) patients died. In nonsurvivors, right ventricular size was increased by 25% ( P=.427), pulmonary vascular resistance increased by 29.4% in nonsurvivors ( P=.302), the 6-minute walk distance decreased by 21% ( P=.875), median brain natriuretic peptide increased by 96% ( P=.890), median GGT and alkaline phosphatase were 3 times higher in nonsurvivors ( P=.893 and P=.047, respectively) and PA/Ao was nonsignificantly decreased in nonsurvivors ( P=.373), Survival was decreased by a median of 2.3 years in nonsurvivors., Conclusion: Our study identified a subgroup of PH patients with NYHA functional class III and above with worsening severity indicators who were labeled as a high-risk group. These patients showed continuous deterioration in their clinical status despite escalation of therapy with current guidelines. We recommend these high-risk group patients be referred for early lung transplantation., Limitations: Low sample size and only a single center. Needs confirmation with a larger multicenter trial., Conflict of Interest: None.

In this video tutorial, we emphasize the main pitfalls in adequate sizing and expansion of the Perceval valve during a concomitant mitral valve replacement with a bioprosthetic. Following mitral valve replacement with a tissue-stented bioprosthesis, a transverse aortotomy was performed at 3 cm above the level of the aortic annulus. Three guiding sutures were then placed 120° apart in each valve sinus, 2-3 mm below the leaflet hinge point. The commissural struts of the mitral prosthesis can be seen in the aortic annulus. This positioning minimizes any potential protrusion in the left ventricular outflow tract.  Next, sizing of the Perceval was performed. The small transparent sizer fit nicely; however, a clear gap at the annulus could be appreciated with the small white sizer. The medium transparent sizer was then utilized, and it fit nicely; however, the medium white sizer was not able to pass through the aortic annulus. Given the gap present with the small sizer, we opted for a medium-size prosthesis. A medium Perceval prosthesis was parachuted into the aortic annulus with the help of the guiding sutures and the valve was deployed. Next, balloon expansion of the stent was performed. Given the potential concern of under-expansion of the stent, we opted for a longer dilatation at 4 atm for 1 min rather than the usual 30 sec. The aortotomy was then closed., (© The Author 2016. Published by MMCTS on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Disorders of the long head of the biceps tendon (LHB) are a well-recognised cause of shoulder pain despite the function of the long head of the biceps remaining poorly understood. There has been a dramatic rise in the number of biceps tenodesis procedures being performed in the last decade. This may partly be attributed to concerns regarding residual cosmetic deformity and pain after biceps tenotomy though there is little evidence to suggest that functional outcomes of tenodesis are superior to biceps tenotomy. Current literature focuses on LHB disorders with concomitant rotator cuff tears. The aim of this review is to discuss the anatomy of the LHB, the pathogenesis of tendinopathy of the LHB, indications of biceps tenodesis and tenotomy and compare the current literature on the functional outcomes of these procedures for LHB disorders in the absence of rotator cuff tears.

Background: Snakehead fish ( Channa striatus) is a fresh water fish indigenous to many Asia countries and believed to have medical value. Studies showed that it contains all the essential amino acids and fatty acids able to accelerate wound healing and it has antinociceptive effect. However, little human study has been done to assess the effectiveness of Channa striatus in wound healing. A prospective RCT has been conducted on the effect of Channa striatus spray versus placebo on clean wound to assess its pain control effect and cosmetic outcome., Methodology: One hundred and two patients (102) underwent clean elective surgery; postoperatively they were randomized into two group. One group received Channa striatus extract spray (n=51) another group received placebo (n=51) on daily basis for 2 weeks. They were followed up on 2 nd , 4 th , and 6 th weeks. Pain control effect was assessed based on Visual Analog Pain Score (VAPS) and cosmetic outcome based on Visual Analog Cosmetic Scale (VACS), Wound Evaluation Scale (WES), and Vancouver Scar Scale (VSS)., Result: The patient treated with Channa striatus spray displayed a better outcome in terms of pain control compared to placebo. During analysis using repeated measure ANOVA, there was significant difference of patient's pain score based on VAPS between Channa striatus spray and placebo (F-stat (df) = 4.80 (2), p-value = 0.010). For cosmetic outcome it showed a better result in Channa striatus spray group for all the 3-scoring system, VACS, (F-stat (df) = 2.68 (2) , p-value <0.001), WES (F-stat (df) = 3.09 (2), p-value = 0.048), and VSS (F-stat (df) = 1.72 (2) , p-value = 0.011)., Conclusion: Our study suggest that application of Channa striatus extract spray on clean wound has shown a significant better pain score result and cosmetic outcome on week 2, week 4, and week 6 comparatively with placebo.

Gastrointestinal (GI) complications including graft-versus-host disease (GVHD) are a major cause of morbidity and mortality in allogenic stem transplant recipients. Although several studies have previously looked into the acute GI complications, fewer smaller studies have reported late complications. In this large study we focus on the late (100 days post-transplant) GI complications in allogenic stem transplant recipients. In this single-center, retrospective study of all adult allogenic stem cell transplant recipients who had their transplant at Duke University over a 6-year period, 479 patients underwent allogenic stem cell transplant, of whom 392 recipients survived for at least 100 days post-transplant. Late GI symptoms were noted in 71 patients, prompting endoscopic evaluation. The primary endpoint of our study was the diagnosis of GI-GVHD based on endoscopic findings, whereas overall survival and nonrelapse mortality were the secondary endpoints. Of the 71 patients who underwent endoscopy, 45 (63%) had GI-GVHD. Of these 45 patients, 39 (87%) had late acute GVHD, 1 (2%) had chronic GVHD, and 5 patients (11%) had overlap disease. Of the patients who did not have GVHD, the symptoms were mostly related to infectious and inflammatory causes. Less common causes included drug toxicity, food intolerance, disease relapse, and motility issues. In a multivariate analysis the factors most indicative of GI-GVHD were histologic findings of apoptosis on the tissue specimen (odds ratio, 2.35; 95% confidence interval, 1.18 to 4.70; P = .015) and clinical findings of diarrhea (odds ratio, 5.43; 95% confidence interval, 1.25 to 23.54; P = .024). The median survival time from the first endoscopy was 8.5 months. The incidence of nonrelapse mortality at 6 months was 31% in patients with GI-GVHD and 19% in patients without GI-GVHD (P = .42). All patients with GI-GVHD were on steroid therapy, and 31% of them received total parenteral nutrition. In our population close to one-fifth of allogenic transplant recipients experienced late GI complications, warranting endoscopic evaluation. Most of these patients were found to have GI-GVHD that had a high incidence of nonrelapse mortality at 6 months and close to one-third of these patients needed total parenteral nutrition., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Traumatic brain injury (TBI) elicits intense sympathetic nervous system (SNS) activation with profuse catecholamine secretion. The resultant hyperadrenergic state is linked to immunomodulation both within the brain and systemically. Dysregulated inflammation post-TBI exacerbates secondary brain injury and contributes to unfavorable patient outcomes including death. The aim of this study was to characterize the early dynamic profile of circulating inflammatory cytokines/chemokines in patients admitted for moderate-to-severe TBI, to examine interrelationships between these mediators and catecholamines, as well as clinical indices of injury severity and neurological outcome., Methods: Blood was sampled from 166 isolated TBI patients (aged 45 ± 20.3 years; 74.7 % male) on admission, 6-, 12-, and 24-h post-injury and from healthy controls (N = 21). Plasma cytokine [interleukin (IL)-1β, -2, -4, -5, -10, -12p70, -13, tumor necrosis factor (TNF)-α, interferon (IFN)-γ] and chemokine [IL-8, eotaxin, eotaxin-3, IFN-γ-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, -4, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1β, thymus activation regulated chemokine (TARC)] concentrations were analyzed using high-sensitivity electrochemiluminescence multiplex immunoassays. Plasma catecholamines [epinephrine (Epi), norepinephrine (NE)] were measured by immunoassay. Neurological outcome at 6 months was assessed using the extended Glasgow outcome scale (GOSE) dichotomized as good (>4) or poor (≤4) outcomes., Results: Patients showed altered levels of IL-10 and all chemokines assayed relative to controls. Significant differences in a number of markers were evident between moderate and severe TBI cohorts. Elevated IL-8, IL-10, and TNF-α, as well as alterations in 8 of 9 chemokines, were associated with poor outcome at 6 months. Notably, a positive association was found between Epi and IL-1β, IL-10, Eotaxin, IL-8, and MCP-1. NE was positively associated with IL-1β, IL-10, TNF-α, eotaxin, IL-8, IP-10, and MCP-1., Conclusions: Our results provide further evidence that exaggerated SNS activation acutely after isolated TBI in humans may contribute to harmful peripheral inflammatory cytokine/chemokine dysregulation. These findings are consistent with a potentially beneficial role for therapies aimed at modulating the inflammatory response and hyperadrenergic state acutely post-injury.

Background: Adverse events (AEs), such as intracranial hemorrhage, thromboembolic event, and progressive aortic insufficiency, create substantial morbidity and mortality during continuous flow left ventricular assist device support yet their relation to blood pressure control is underexplored., Methods and Results: A multicenter retrospective review of patients supported for at least 30 days and ≤18 months by a continuous flow left ventricular assist device from June 2006 to December 2013 was conducted. All outpatient Doppler blood pressure (DOPBP) recordings were averaged up to the time of intracranial hemorrhage, thromboembolic event, or progressive aortic insufficiency. DOPBP was analyzed as a categorical variable grouped as high (>90 mm Hg; n=40), intermediate (80-90 mm Hg; n=52), and controlled (<80 mm Hg; n=31). Cumulative survival free from an AE was calculated using Kaplan-Meier curves and Cox hazard ratios were derived. Patients in the high DOPBP group had worse baseline renal function, lower angiotensin-converting enzyme inhibitor or angiotensin receptor blocker usage during continuous flow left ventricular assist device support, and a more prevalent history of hypertension. Twelve (30%) patients in the high DOPBP group had an AE, in comparison with 7 (13%) patients in the intermediate DOPBP group and only 1 (3%) in the controlled DOPBP group. The likelihood of an AE increased in patients with a high DOPBP (adjusted hazard ratios [95% confidence interval], 16.4 [1.8-147.3]; P=0.012 versus controlled and 2.6 [0.93-7.4]; P=0.068 versus intermediate). Overall, a similar association was noted for the risk of intracranial hemorrhage (P=0.015) and progressive aortic insufficiency (P=0.078) but not for thromboembolic event (P=0.638). Patients with an AE had a higher DOPBP (90±10 mm Hg) in comparison with those without an AE (85±10 mm Hg; P=0.05)., Conclusions: In a population at risk, higher DOPBP during continuous flow left ventricular assist device support was significantly associated with a composite of AEs., (© 2015 American Heart Association, Inc.)

Continuous-flow left ventricular assist device (CF-LVAD) insertion is a life-saving procedure that is being increasingly used in patients with advanced heart failure. However, patients with CF-LVADs are at an increased risk of gastrointestinal bleeding (GIB). Bleeding can occur anywhere in the GI tract with lesions being more prevalent in the upper GI tract than in the lower GI tract. The pathophysiology of GIB in patients with CF-LVADs is unique and likely involves three synergistic mechanisms-coagulopathy, acquired von Willebrand disease and continuous non-pulsatile blood flow. Management strategies vary depending on the presentation and site of bleeding. Prevention strategies to prevent GIB in these patients include low pump speed, close hemodynamic monitoring and a low threshold for endoscopy. We aim to review in detail the pathophysiology, management, complications and preventive strategies in patients with CF-LVAD who present with GIB.

Background: The bacterium Corynebacterium pseudotuberculosis (Cp) causes caseous lymphadenitis (CLA), mastitis, ulcerative lymphangitis, and oedema in a number of hosts, comprising ruminants, thereby intimidating economic and dairy industries worldwide. So far there is no effective drug or vaccine available against Cp. Previously, a pan-genomic analysis was performed for both biovar equi and biovar ovis and a Pathogenicity Islands (PAIS) analysis within the strains highlighted a large set of proteins that could be relevant therapeutic targets for controlling the onset of CLA. In the present work, a structural druggability analysis pipeline was accomplished along 15 previously sequenced Cp strains from both biovar equi and biovar ovis., Methods and Results: We computed the whole modelome of a reference strain Cp1002 (NCBI Accession: NC&#95;017300.1) and then the homology models of proteins, of 14 different Cp strains, with high identity (≥ 85%) to the reference strain were also done. Druggability score of all proteins pockets was calculated and only those targets that have a highly druggable (HD) pocket in all strains were kept, a set of 58 proteins. Finally, this information was merged with the previous PAIS analysis giving two possible highly relevant targets to conduct drug discovery projects. Also, off-targeting information against host organisms, including Homo sapiens and a further analysis for protein essentiality provided a final set of 31 druggable, essential and non-host homologous targets, tabulated in table S4, additional file 1. Out of 31 globally druggable targets, 9 targets have already been reported in other pathogenic microorganisms, 3 of them (3-isopropylmalate dehydratase small subunit, 50S ribosomal protein L30, Chromosomal replication initiator protein DnaA) in C. pseudotuberculosis., Conclusion: Overall we provide valuable information of possible targets against C. pseudotuberculosis where some of these targets have already been reported in other microorganisms for drug discovery projects, also discarding targets that might be physiologically relevant but are not amenable for drug binding. We propose that the constructed in silico dataset might serve as a guidance for the scientific community to have a better understanding while selecting putative therapeutic protein candidates as druggable ones as effective measures against C. pseudotuberculosis.

Background/aim: The severity of disease outcome in dyspepsia has been attributed to Helicobacter pylori virulence genes. The aim of this study was to determine the distribution of H. pylori virulence genes (cagA, babA2, and dupA) and to determine whether or not there arises a significant correlation with clinical dyspepsia outcomes., Materials and Methods: H. pylori genotypes cagA, babA2, and dupA were identified by polymerase chain reactions from gastric biopsy samples in 105 H. pylori-positive patients., Results: The positive rates for cagA, babA2, and dupA genes in H. pylori dyspeptic patients were 69.5%, 41.0%, and 22.9%, respectivel cagA was more prevalent in Indians (39.7%), babA2 was more prevalent in Malays (39.5%), and dupA detection occurred more frequently in both Indians and Malays and at the same rate (37.5%). The Chinese inhabitants had the lowest prevalence of the three genes. Nonulcer disease patients had a significantly higher distribution of cagA (76.7%), babA2 (74.4%), and dupA (75.0%). There was no apparent association between these virulence genes and the clinical outcomes., Conclusion: The lower prevalence of these genes and variations among different ethnicities implies that the strains are geographically and ethnically dependent. None of the virulence genes were knowingly beneficial in predicting the clinical outcome of H. pylori infection in our subjects.

Background: Restoring normal fecal flora through intestinal microbiota transplantation (IMT) was successful in curing recurrent Clostridium difficile infection (CDI). However, only a few cases have been reported of IMT being utilized for the treatment of severe or fulminant CDI., Aim: Is IMT a simple and effective treatment for severe and recurrent CDI?, Methods: In this retrospective study, we report 14 patients with severe CDI refractory to conventional medical therapy, who underwent IMT. Fresh donor stool specimen was manually homogenized with warm tap water, filtered through gauze and then instilled through nasogastric tube (NGT). The primary outcome was clinical cure, defined as less than 3 loose bowel movements a day on day 7 after IMT and no need for further CDI therapy. The secondary outcomes were recurrence of CDI within 100 days of IMT and 30-day mortality after IMT. Descriptive statistics were done., Results: Fourteen patients with severe and refractory CDI received IMT. Mean age was 73.4 ± 11.9 years (range 52-92). IMT was given via NGT in 13 of the 14 patients. Eleven patients (79 %) achieved cure after IMT. No recurrence was seen in the patients who responded to IMT and were alive within the 100 day follow-up period. IMT was well tolerated. The 30-day all-cause mortality was 29 %, all 4 patients died as a result of their underlying cancer. No patients died as a result of CDI or IMT., Conclusions: IMT performed at the bedside via NGT is effective and safe for the treatment of severe and refractory CDI, and prevents recurrence.

A 62-year-old man was found to have bradycardia, hypothermia and respiratory failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation. Thyroid-stimulating hormone was found to be 168 μIU/mL (nl. 0.3-5 μIU/mL) and free thyroxine (FT4) was <0.2 ng/dL (nl. 0.8-1.8 ng/dL). He received intravenous fluids, vasopressor therapy and stress dose steroids; he was intubated and admitted to the intensive care unit. He received 500 μg of intravenous levothyroxine in the first 18 h of therapy, and 150 µg intravenous daily thereafter. Haemodynamic improvement, along with complete recovery of mental status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4 was 0.96 ng/dL. The patient was maintained on levothyroxine 175 (g POorally daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25-756 ( mcg). The only two cases of amiodarone-induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone-induced myxoedema coma with a history significant for subclinical thyroid disease.

A 67-year-old motorcyslist was admitted to hospital following a high-speed road traffic collision and found to have a left midshaft clavicle fracture and multiple ipsilateral rib fractures. He was treated conservatively and went on to have non-union of the clavicle. The non-union was managed non-operatively. The patient then re-attended the hospital with an acute ischaemic left hand 3 years after the original injury date. An arterial duplex scan confirmed a embolus to the brachial artery. A brachial embolectomy was urgently performed. A computed tomography scan showed non-union of the clavicle fracture and an inflammatory mass compressing the left subclavian artery, which was the focus of the embolic event. The clavicle non-union was managed operatively with lateral half claviculectomy. Immediately after clavicle excision, the vascular team performed reconstruction of the brachial artery. At follow-up,there was normal shoulder and hand function at outpatient clinic. A duplex scan confirmed good triphasic waveforms throughout the arteries of the left upper limb.

Background: Helicobacter pylori (H. pylori) is one of the most important causes of dyspepsia and gastric cancer and diagnosis can be made by invasive or non-invasive methods. The Atlas Helicobacter pylori antigen test is a new rapid non-invasive method which is simple to conduct. The aim of this study was to determine its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy., Materials and Methods: This prospective study was conducted between July 2012 and December 2013. Stool samples of 59 dyspeptic patients who underwent upper endoscopy were evaluated for H. pylori stool antigen., Results: From the 59 patients who participated in this study, there were 36 (61%) males and 23 (39%) females. H. pylori was diagnosed in 24 (40.7%) gastric biopsies, 22 (91.7 %) of these being positive for the Atlas H. pylori antigen test. The sensitivity, specificity, PPV, NPV and accuracy were 91.7%, 100%, 100%, 94.6% and 96.6% respectively., Conclusions: The Atlas H. pylori antigen test is a new non-invasive method which is simple to perform and avails reliable results in a few minutes. Thus it can be the best option for the diagnosis of H. pylori infection due to its high sensitivity and specificity.

Background: Hyponatremia has significant prognostic implications in patients with heart, failure. However, little data are available regarding its significance in patients presenting with myocardial infarction. In addition, it is not known if correction of hyponatremia impacts outcomes in these patients. The aim of this study was to evaluate the prognostic value of hyponatremia in patients with myocardial infarction and the effect of its correction on all-cause mortality., Methods: Patients with the discharge diagnosis of myocardial infarction at our institution between 2000 and 2010 with serum sodium levels measured within 24 h of admission were included in this retrospective analysis. Multivariate analysis was used to determine the predictors of all-cause mortality. Cox proportional hazard model was applied to determine the adjusted survival., Results: A total of 11,562 patients (67.15 ± 14.6 years, males 56.3 %) were included in the analysis. There were a total of 1,535 (13.3 %) deaths within mean follow-up duration of 5.5 ± 3.3 years. There were 425 (27.9 %) deaths in patients with corrected hyponatremia and 155 (55.3 %) deaths in persistent hyponatremia patients. Multivariate analysis indicated that corrected hyponatremia and persistent hyponatremia were independent predictors of all cause mortality (p < 0.0001). When analyzing short-term (30 days) and long-term mortality, corrected hyponatremia group did not have associated long term mortality. Various methods to correct hyponatremia were also analyzed and use of vaptans was associated with decrease in mortality in patients with hyponatremia from 115 to 125 (HR 0.45; 95 % CI 0.26-0.78, p = 0.005)., Conclusion: Our analysis showed that corrected and persistent hyponatremia in patients presenting with myocardial infarction is a predictor of all-cause mortality, major adverse cardiac events and heart failure related 30 day rehospitalization. In certain cases, correction of hyponatremia may actually improve survival of the patients.

Vasculopathy in patients with neurofibromatosis-1 are rare but serious and have potentially life-threatening complications. It mostly involves the thoracic, abdominal and intracranial vessels. In this case study we describe the first reported case of spontaneous intestinal haematoma in a young male patient. The first episode occurred at the age of 30, following which 2 years later the second episode was noted at the same anatomical site, which was spontaneous without any inciting event.

We present a case of a 43-year-old woman with a history of Parkinson's disease and chronic neuropathic pain secondary to trauma. She was implanted with a spinal cord simulator to relieve her persistent intractable pain. After the implantation of the device the patient not only was relieved of her neuropathic pain but also found significant improvement in her Parkinson symptoms., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

When dealing with nano targeted drug delivery process the significant area of virtual reality application can be visualizing real time process and simulating it at nano-scale, since the effectiveness of a drug primarily depends on the affected cell and targeted doze. This paper proposes virtual reality (VR) as a tool to analyze and simulate nanoparticles (NPs) manipulation, in this paper amorphous NPs are analyzed and simulated in virtual environment. Haptic guides virtualizing the atomic force microscope (AFM) is applied in the virtual environment which allows the operators to sense and touch the NPs when evaluating its structure, drug release time, and behavioral study. Cisplatin was loaded as a modal drug to the self-assembled amorphous copolymer P(3HV-co-4HB)-b-mPEG NPs, where the efficiency and bioavailability of Cisplatin was further investigated. The prepared NPs when simulated in virtual environment proved to show good biocompatibility. Results showed that amorphous polymeric NPs could be efficient vehicles for the constant and targeted delivery of toxic anticancer drugs.

Objectives of this study were (1) to evaluate preoperative predictors of systolic and diastolic heart failure in patients undergoing liver transplantation (LT) and (2) to describe the prognostic implications of systolic and diastolic heart failure in these patients. The onset of heart failure after orthotopic LT remains poorly understood. Data were obtained for all LT recipients between January 2000 and December 2010. The primary outcome was post-LT heart failure: systolic (ejection fraction ≤ 50%), diastolic, or mixed heart failure. Patients underwent echocardiographic evaluation before and after LT. Pretransplant variables were evaluated as predictors of heart failure with Cox proportional hazards model. 970 LT recipients were followed for 5.3 ± 3.4 years. Ninety-eight patients (10.1%) developed heart failure in the posttransplant period. There were 67 systolic (6.9%), 24 diastolic (2.5%), and 7 mixed systolic/diastolic (0.7%) heart failures. Etiology was ischemic in 18 (18.4%), tachycardia-induced in 8 (8.2%), valvular in 7 (7.1%), alcohol-related in 4 (4.1%), hypertensive heart disease in 3 (3.1%), and nonischemic in majority of patients (59.2%). Pretransplant grade 3 diastolic dysfunction, diabetes, hypertension, mean arterial pressure ≤ 65 mm Hg, mean pulmonary artery pressure ≥ 30 mm Hg, mean pulmonary capillary wedge pressure ≥ 15 mm Hg, hemodialysis, brain natriuretic peptide level and QT interval > 450 ms were found to be predictive for the development of new-onset systolic heart failure. However beta-blocker use before LT and tacrolimus after LT were associated with reduced development of new-onset systolic heart failure. In conclusion, pretransplant risk factors, hemodynamic variables, and echocardiographic variables are important predictors of post-LT heart failure. In patients undergoing LT, postoperative onset of systolic or diastolic heart failure was found to be an independent predictor of mortality., (Copyright © 2013 American Association for the Study of Liver Diseases.)

Tropical spastic paraparesis (TSP) or human T-cell leukemia virus-type 1 (HTLV-I)-associated myelopathy is caused by human T-lymphotropic virus type 1. It is a slow, progressive spastic paraparesis with significant morbidity and causing profound repercussions on quality of life. No therapies have been found to persistently improve the outcome in these patients. We present a patient with HTLV-1-associated myelopathy/TSP (HAM/TSP) who was treated with Combivir (lamivudine-zidovudine, GlaxoSmithKline, London, UK). She was walker-dependent for several years but, soon after treatment with lamivudine-zidovudine, was able to walk using only a cane. The role of lamivudine-zidovudine should be investigated further in this patient population., (Published by Elsevier Ltd.)

Heparin-induced thrombocytopenia (HIT), a prothrombotic complication of heparin therapy, can lead to serious thromboembolic events and cause significant morbidity and mortality. We aim to study the prevalence of HIT in the transplant population at our institute. This is a retrospective, single-center study which looked into the transplant database over a 25-year period. In patients with clinical suspicion of HIT, the 4T score was used, and laboratory tests such as ELISA HIT antibody and functional serotonin release assay, along with clinical manifestation of thromboembolic events were reviewed. Medical records of 2800 patients who underwent transplantation from January 1985 to December 2010 were reviewed. HIT antibody assay was performed in 262 patients from this group in which HIT was suspected. Of these, only 48 patients were HIT antibody positive along with moderate to high 4T score. The mean 4T score was 6.75 ± 1.4. Thrombotic complications were seen in 11 patients, with the highest in cardiac transplant recipients. Direct thrombin inhibitor (DTI) therapy was used in only eight patients who had thrombotic event. No other complications or mortality was reported in any of the HIT antibody-positive transplant patients. To our knowledge, this is the first study of its kind that has shown very low incidence of HIT in the transplant population except for in cardiac transplant recipients., (© 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.)

We report a case of 53year old female with history of acute myelogenous leukemia, for which she underwent allogeneic peripheral blood stem cell transplant; her course was complicated by chronic graft versus host disease. Seven years later she presents with squamous cell carcinoma of the skin which metastasize to her heart. Here, in this case we tend to highlight the aggressive nature of the squamous cell carcinoma in an immunocompromised individual., (Copyright © 2013 King Faisal Specialist Centre & Research Hospital. Published by Elsevier B.V. All rights reserved.)

A Caucasian woman in her 60s with a history of rheumatoid arthritis presented to our institution complaining of skin ulceration. Her initial course was complicated by superinfection and sepsis until a diagnosis of cryofibrinogenaemia was finally established. Cryofibrinogenaemia remains as an under-recognised entity in part, because it can mimic other causes of skin ulcerations. In addition, its diagnosis can be challenging because of the particular handling techniques required of lab specimens. This case exemplifies some of the diagnostic and treatment challenges encountered while managing the patient with cryofibrinogenaemia.