Cryptococcus neoformans presenting as a large pulmonary cavitary lesion in an immunocompetent female.

Pulmonary cryptococcus is a rare but fatal fungal infection historically associated with Human Immunodeficiency Virus (HIV) and immunosuppression, yet increasingly also being recognized in immunocompetent patients as a result of antiretroviral therapy and improved HIV control reducing HIV-associated cryptococcus in advanced countries. Appropriate management may be delayed if left unrecognized. We present the case of an immunocompetent middle-aged female with nonspecific respiratory symptoms who was found to have a large cavitary lung mass resulting in external compression of the pulmonary vein, ultimately leading to a diagnosis of pulmonary Cryptococcus neoformans. By presenting this case, we hope to elucidate the challenges in diagnosing and managing this fatal disease in timely fashion.

Prevalence and correlates of Schistosoma haematobium infections among school going-children aged 5 to 17 years in Kawama, Ndola, Zambia.

Introduction: schistosomiasis is a neglected tropical disease and remains a disease of public health concern. Despite its relative importance, paucity of information on schistosomiasis in urban settings such as Ndola remains. Here, we present findings on the prevalence and factors associated with Schistosoma haematobium (S. haematobium) infections among School-going children in the Kawama in Ndola district in Zambia, an urban area in the Copperbelt Province, Zambia. Methods: we employed a cross-sectional study design among 354 school going-children between 5 and 17 years of age between November 2020 and February 2021. A Multivariate forward step-wise logistic regression model was used to determine the associations of risk factors. Adjusted odds ratios and 95% confidence intervals are reported. Results: of the 354 school-going children included in the analysis, 13.3% had S. haematobium infection. Children who swam in the stream/dam were more likely to have S. haematobium infection as compared to those who did not (aOR 6.531, 95% CI: 2.90-14.69). Conclusion: S. haematobium infection is endemic among school-going children in an urban setup of the Kawama area of Ndola City, Zambia. There is a need for targeted interventions to mitigate infections among this population.

Hematologic Malignancy Episodes Exceed Target Price in Oncology Care Model.

The current study evaluated whether total cost of care (TCOC) and target price were aligned in Oncology Care Model (OCM) hematologic malignancy episodes and identified factors associated with episodes exceeding target price. Hematologic malignancy episodes from OCM performance period 1-4 reconciliation reports were identified from a large academic medical center. Of the 516 hematologic malignancies episodes included in the analysis, 283 (54.8%) exceeded the target price. Episode characteristics found to be statistically significantly associated with exceeding target price were Medicare Part B drug use and Part D drug use, novel therapy use, home health agency, and >730 days from last chemotherapy. The mean TCOC was $85 374 (± $26 342) for the episodes that exceeded target price while the mean target price was $56 106 (±$16 309). The results found a substantial misalignment between the TCOC and target price for hematologic malignancy episodes, adding to the existing evidence on the lack of adequate adjustment to the OCM target price.

Therapeutic potential of endoplasmic reticulum stress inhibitors in the treatment of diabetic peripheral neuropathy.

Endoplasmic stress response, the unfolded protein response (UPR), is a homeostatic signaling pathway comprising transmembrane sensors that get activated upon alterations in ER luminal environment. Studies suggest a relation between activated UPR pathways and several disease states such as Parkinson, Alzheimer, inflammatory bowel disease, tumor growth, and metabolic syndrome. Diabetic peripheral neuropathy (DPN), a common microvascular complication of diabetes-related chronic hyperglycemia, causes chronic pain, loss of sensation, foot ulcers, amputations, allodynia, hyperalgesia, paresthesia, and spontaneous pain. Factors like disrupted calcium signaling, dyslipidemia, hyperglycemia, inflammation, insulin signaling, and oxidative stress disturb the UPR sensor levels manifesting as DPN. We discuss new effective therapeutic alternatives for DPN that can be developed by targeting UPR pathways like synthetic ER stress inhibitors like 4-PhenylButyric acid (4-PBA), Sephin 1, Salubrinal and natural ER stress inhibitors like Tauroursodeoxycholic acid (TUDCA), Cordycepin, Proanthocyanidins, Crocin, Purple Rice extract and cyanidin and Caffeic Acid Phenethyl Ester (CAPE).

Pontine Infarct Resulting in Millard-Gubler Syndrome: A Case Report.

Millard-Gubler syndrome is a crossed brainstem syndrome involving the facial nerve, abducens nerve, and the pyramidal tracts, typically resulting in ipsilateral facial weakness and contralateral hemiparesis. Here we report the case of a 76-year-old female with no pertinent past medical history who presented to the emergency department with acute left-sided facial droop and right upper extremity sensory loss. A pontine infarction was identified on imaging and she was managed medically with complete recovery. Pontine infarction can result in Millard-Gubler syndrome and present with facial weakness and subtle contralateral limb symptoms.

Crosstalk between Sirtuins and Nrf2: SIRT1 activators as emerging treatment for diabetic neuropathy.

About 50% of the diabetic patients worldwide suffer from Diabetic peripheral neuropathy (DPN) which is characterized by chronic pain and loss of sensation, frequent foot ulcerations, and risk for amputation. Numerous factors like hyperglycemia, oxidative stress (OS), impaired glucose signaling, inflammatory responses, neuronal cell death are known to be the various mechanisms underlying DACD and DPN. Development of tolerance, insufficient and inadequate relief and potential toxicity of classical antinociceptives still remains a challenge in the clinical setting. Therefore, there is an emerging need for novel treatments which are both without any potential side effects as well as which focus more on the pathophysiological mechanisms underlying the disease. Also, sirtuins are known to deacetylate Nrf2 and contribute to its action of reducing ROS by generation of anti-oxidant enzymes. Therefore, targeting sirtuins could be a favourable therapeutic strategy to treat diabetic neuropathy by reducing ROS and thereby alleviating OS in DPN. In the present review, we outline the potential use of SIRT1 activators as therapeutic alternatives in treating DPN. We have tried to highlight how sirtuins are interlinked with Nrf2 and NF-κB and put forth how SIRT activators could serve as potential therapy for DPN.

Recent advancements in biomarker research in schizophrenia: mapping the road from bench to bedside.

Schizophrenia (SZ) is a severe progressive neurodegenerative as well as disruptive behavior disorder affecting innumerable people throughout the world. The discovery of potential biomarkers in the clinical scenario would lead to the development of effective methods of diagnosis and would provide an understanding of the prognosis of the disease. Moreover, breakthrough inventions for the treatment and prevention of this mysterious disease could evolve as a result of a thorough understanding of the clinical biomarkers. In this review, we have discussed about specific biomarkers of SZ an emphasis has been laid to delineate (1) diagnostic biomarkers like neuroimmune biomarkers, metabolic biomarkers, oligodendrocyte biomarkers and biomarkers of negative and cognitive symptoms, (2) therapeutic biomarkers like various neurotransmitter systems and (3) prognostic biomarkers. All the biomarkers were evaluated in drug-naïve (at least for 4 weeks) patients in order to achieve a clear comparison between schizophrenic patients and healthy controls. Also, an attempt has been made to elucidate the potential genes which serve as predictors and tools for the determination of biomarkers and would ultimately help in the prevention and treatment of this deadly illness.

Pasteurella Endocarditis in a Patient with Rheumatic Mitral Valve Disease.

BACKGROUND As a common member of the oral bacterial flora of cats and dogs, Pasteurella multocida can cause skin and soft tissue infection in humans after bites, licks, or scratches from animals. Uncommonly, infection due to Pasteurella can cause sepsis in humans. Even more rare is the development of infectious endocarditis from a Pasteurella infection. CASE REPORT A 76-year-old woman presented with malaise and symptoms of fluid overload. Blood cultures were positive for Pasteurella multocida, and an echocardiogram was significant for mitral valve vegetation and severe biatrial enlargement. A diagnosis of Pasteurella endocarditis was made. Surgical intervention was recommended, but owing to the risk involved, the patient elected for conservative management involving long-term treatment with intravenous antibiotics. CONCLUSIONS While exceedingly rare, Pasteurella multocida can cause infectious endocarditis in patients with predisposing factors. This patient had a known history of rheumatic heart disease, which is believed to have caused the significant findings on imaging. To the best of our knowledge, our case is the only one to depict Pasteurella endocarditis in a patient with rheumatic heart disease and severe biatrial enlargement. It is the authors' belief that the rheumatic heart disease and remodeling of the heart increased her susceptibility to severe infection from Pasteurella. The purpose of this case is to describe the pathogenicity of an otherwise low-attack bacterial infection in an elderly patient with underlying structural acquired heart damage.

Computational Modeling of Fluidized Beds with a Focus on Pharmaceutical Applications: A Review.

The fluidized bed is an essential and standard equipment in the field of process development. It has a wide application in various areas and has been extensively studied. This review paper aims to discuss computational modeling of a fluidized bed with a focus on pharmaceutical applications. Eulerian, Lagrangian, and combined Eulerian-Lagrangian models have been studied for fluid bed applications with the rise of modeling capabilities. Such models assist in optimizing the process parameters and expedite the process development cycle. This paper discusses the background of modeling and then summarizes research papers relevant to pharmaceutical unit operations.

Role of NRF2 and Sirtuin activators in COVID-19.

COVID-19 is a pandemic requiring immediate solution for treatment because of its complex pathophysiology. Exploration of novel targets and thus treatment will be life savers which is the need of the hour. 2 host factors- TMPRSS2 and ACE2 are responsible for the way the virus will enter and replicate in the host. Also NRF2 is an important protein responsible for its anti-inflammatory role by multiple mechanisms of action like inhibition of NF-kB, suppression of pro-inflammatory genes, etc. NRF2 is deacetylated by Sirtuins and therefore both have a direct association. Absence of SIRT indicates inhibition of NRF2 expression and thus no anti-oxidative and anti-inflammatory protection for the cell. Therefore, we propose that NRF2 activators and/or SIRT activators can be evaluated to check their efficacy in ameliorating the symptoms of COVID-19.

Evaluation of smartphone sound level meter applications as a reliable tool for noise monitoring.

Noise is a constant and ongoing health hazard across many workplaces and industries worldwide. The effective management of noise-related health effects is primarily dependent on accurate measurements of sound levels. The accuracy and feasibility of smartphone sound level meter applications (apps) for noise monitoring in occupational and environmental scenarios was tested. Ten iOS and Android smartphones were used to conduct sound level measurements with five apps for each respective platform. Five different sound signals were utilized to represent the spectra present in an occupational environment, at four different reference sound levels (60, 70, 80, and 90 dBA) for a total of 1,000 tests. A calibrated Larson Davis LxT sound level meter was used as a reference. Results suggest that across all four measured sound levels the difference in smartphone app performance on the two platform is fairly nuanced. However, at the 90dBA sound level Android apps consistently underreport sound levels. This study concludes that some apps have the possibility to be appropriate for use only as screening tools and cannot be used for accurate determination of sound levels.

Sequencing and analysis of the whole genome of Indian Gujarati male.

The article presents the analysis of whole genome sequence of a Gujarati Indian individual (IHGP01) that was sequenced at 23.05× coverage with a total of 74.93 Gb of sequence data generated using Illumina HiSeq 2000 platform. Variant analysis revealed over 3.9 million single nucleotide variants (SNVs) and about 393,000 small insertions and deletions (InDels) including novel variants. The known variants were analyzed for their health and disease relevance and pharmacogenomic profile. Mitochondrial and Y-chromosome haplogroup analysis clearly indicated arrival on the continent not more than 20,000-25,000 years ago, following the route out of Africa to central Europe, then into Asian continent and subsequent migration to West part of the Indian subcontinent. The current research has added 141,000 novel genetic variations to the human DNA database. Functional analysis and validation of these novel variations and revelation of their role in health and disease will add a newer dimension to understand people of this subcontinent.

Crosstalk between endoplasmic reticulum stress and oxidative stress in schizophrenia: The dawn of new therapeutic approaches.

Disruption of oxidant/anti-oxidant ratio as well as endoplasmic reticulum (ER) stress are thought to be involved in the pathophysiology of schizophrenia. These stresses can lead to impairments in brain functions progressively leading to neuronal inflammation followed by neuronal cell death. Moreover, the cellular stresses are interlinked leading us to the conclusion that protein misfolding, oxidative stress and apoptosis are intricately intertwined events requiring further research into their mechanistic and physiological pathways. These pathways can be targeted by using different therapeutic interventions like anti-oxidants, sigma-1 receptor agonists and gene therapy to treat the neurodegenerative course of schizophrenia. We have also put empahsis on use of synthetic and natural ER stress inhibitors like 4-phenylbutyrate or salubrinal for the treatment of this disorder. This would provide an opportunity to create new therapeutic benchmarks in the field of neuropsychiatric disorders like schizophrenia, dissociative identity disorder and obsessive compulsive disorder.

Outcomes of concomitant renal reconstruction during open paravisceral aortic aneurysm repair.

OBJECTIVE: The objective of this study was to review the outcomes of renal artery revascularizations during open aortic aneurysm repair. METHODS: Open abdominal aneurysm repairs performed from 2010 to 2015 at a single institution were reviewed, including type IV thoracoabdominal, suprarenal, and juxtarenal aneurysms. Direct renal reconstruction techniques included eversion endarterectomy, bypass, and vessel reimplantation based on the patient's anatomy. Renal loss was defined by artery occlusion. RESULTS: The study included 125 patients; of these, 57 patients (46%) had 76 renal reconstructions (38 single, 19 bilateral) performed. Interventions included endarterectomy (n = 21), transaortic stenting (n = 2), reimplantation with (n = 25) or without (n = 17) endarterectomy, bypass (n = 4), and ligation (n = 7). Mean aneurysm size was 6.4 cm, with 23% (n = 29) urgent/emergent operations and 20% (n = 25) having had a prior open or endovascular repair. Overall complication rate was 50%, with significant increase among the group requiring renal intervention, primarily accounted for by a 33% early or late dialysis requirement compared with 16% in patients with no renal revascularization (P = .01). Overall 30-day mortality was 9%, with no difference between groups. Urgent/emergent operation (P < .001) was associated with increased 30-day mortality (24% vs 4% elective procedures), but prior open or endovascular repair (P = .4) was not. Mean follow-up was 26 months, with directed imaging out to a mean of 18 months. Renal intervention (P = .01) and urgent/emergent status (P = .04) were predictive of dialysis requirement; however, among those undergoing intervention, renal loss was not associated with an increase in dialysis requirement (P = .2). Of the directed intervention techniques, renal reimplantation with or without endarterectomy was associated with increased risk of dialysis requirement (P = .005) and renal loss (P = .04) relative to endarterectomy alone. Mean creatinine concentration on late follow-up was 1.4 mg/dL (from 1.3 mg/dL preoperatively) and was not statistically significantly different between those undergoing renal intervention (1.5 mg/dL) and those who did not (1.4 mg/dL). CONCLUSIONS: Renal artery reconstruction at the time of open repair of paravisceral aneurysms is associated with an increased complication rate, primarily driven by occlusion of reimplanted vessels and increased dialysis requirement. As reported by others, nonelective presentation is the greatest determinant of early death or adverse outcomes.

Retrospective Evaluation of a Teleretinal Screening Program in Detecting Multiple Nondiabetic Eye Diseases.

BACKGROUND: Diabetic teleretinal screening programs have been utilized successfully across the world to detect diabetic retinopathy (DR) and are well validated. Less information, however, exists on the ability of teleretinal imaging to detect nondiabetic ocular pathology. INTRODUCTION: This study performed a retrospective evaluation to assess the ability of a community-based diabetic teleretinal screening program to detect common ocular disease other than DR. MATERIALS AND METHODS: A retrospective chart review of 1,774 patients who underwent diabetic teleretinal screening was performed. Eye clinic notes from the Veterans Health Administration's electronic medical record, Computerized Patient Record System, were searched for each of the patients screened through teleretinal imaging. When a face-to-face examination note was present, the physical findings were compared to those obtained through teleretinal imaging. Sensitivity, specificity, and positive and negative predictive values were calculated for suspicious nerve, cataract, and age-related macular degeneration. RESULTS: A total of 903 patients underwent a clinical examination. The positive predictive value was highest for cataract (100%), suspicious nerve (93%), and macular degeneration (90%). The negative predictive value and the percent agreement between teleretinal imaging and a clinical examination were over 90% for each disease category. DISCUSSION: A teleretinal imaging protocol may be used to screen for other common ocular diseases. CONCLUSION: It may be feasible to use diabetic teleretinal photographs to screen patients for other potential eye diseases. Additional elements of the eye workup may be added to enhance accuracy of disease detection. Further study is necessary to confirm this initial retrospective review.

Concomitant Parallel Endografting and Fenestrated Experience in a Regional Aortic Center.

BACKGROUND: Off-label parallel endografting (PE) has been increasingly criticized in favor of on-label custom fenestrated endografts. There remain limited direct comparisons, however, between concurrent patient populations treated by similarly experienced operators. Hence, we seek to evaluate the relative efficacy of the two techniques in treating complex aortic pathology. METHODS: All patients treated by PE or with Cook Zenith Fenestrated (Zfen) devices from January 2010 to June 2015 were reviewed, excluding those treated for rupture. Patients were all evaluated for open repair as well as for fenestrated devices since its availability at our center in July 2013. Patients predating fenestrated access or not meeting anatomic indications for use criteria and preferring endovascular therapy were treated with PE. RESULTS: A total of 93 patients were treated during the period reviewed, 54 (58.1%) by PE and 39 (41.9%) with Zfen. The two procedures required similar length of surgery (234 min PE vs. 239 min Zfen), blood loss (634 cc vs. 409 cc), and length of stay (median 6 days). PE, however, was associated with less fluoroscopy time (52.8 vs. 64.6 min) and contrast volume (103.5 cc PE vs. 133 cc Zfen). At mean 202 days follow-up, Zfen has required three reinterventions (two type III endoleaks and one superior mesenteric artery stenosis causing mesenteric ischemia) and there have been zero branch vessels lost. At mean 427 days follow-up, PE patients experienced three stent occlusions (one repaired endovascularly) and required eight additional interventions (two type I endoleaks, two type II endoleaks with sac growth, two type III endoleaks, one graft infection, and one aneurysm rupture). Reintervention rates for PE and Zfen were 17.6% and 7.7%, respectively, with branch patency rates of 98% and 100%. CONCLUSIONS: PE and fenestrated repair offer similarly high branch patency and technical success. PE performed for juxtarenal aneurysms has similar reintervention rate to fenestrated repair. The two techniques have similar length of stay, operative time, and blood loss, but fenestrated repair is associated with greater fluoroscopy time and contrast usage.

Factors Affecting Inducible Expression of Outer Membrane Protein A (OmpA) of Shigella dysenteriae Type-1 in Lactococcus lactis Using Nisin Inducible Controlled Expression (NICE).

Potential use of Lactococcus lactis (L. lactis) as a heterologous protein expression host as well as for delivery of multiple therapeutic proteins has been investigated extensively using Nisin Inducible Controlled Expression (NICE) system. Optimum inducible expression of heterologous protein by NICE system in L. lactis depends on multiple factors. To study the unexplored role of factors affecting heterologous protein expression in L. lactis using NICE, the present study outlines the optimization of various key parameters such as inducer concentration, host's proteases and precipitating agent using Outer membrane protein A (OmpA). For efficient expression and secretion of OmpA, pSEC:OmpA vector was successfully constructed. To circumvent the troubles encountered during detection of expressed OmpA, the precipitating agent was switched from TCA to methanol. Nevertheless, detection was achieved accompanied by degraded protein products. Speculating the accountability of observed degradation at higher inducer concentration, different nisin concentrations were evaluated. Lower nisin concentrations were found desirable for optimum expression of OmpA. Consistently observed degradation was eliminated by incorporation of protease inhibitor cocktail which inhibits intracellular proteases and expression in VEL1153 (NZ9000 ΔhtrA) strain which inhibits extracellular protease leading to optimum expression of OmpA. Versatility and complexity of NICE system in L. lactis requires fine-tuning of target protein specific parameters for optimum expression.