Predictors of Subjective Olfactory Dysfunction and Sinonasal Quality-of-Life After Endoscopic Transsphenoidal Pituitary Surgery.

BACKGROUND: This is the largest study in North America investigating olfactory outcomes after pituitary surgery to date. OBJECTIVE: Characterize factors associated with subjective olfactory dysfunction (OD) and worsened sinonasal quality-of-life (QOL) after endoscopic TSA. METHODS: Patients undergoing primary TSA for secreting and non-secreting pituitary adenomas between 2017 and 2021 with pre- and post-operative SNOT-22 scores were included. Subjective OD was determined by the smell/taste dysfunction question on the SNOT-22 (smell-SNOT). RESULTS: 159 patients with pre- and post-operative SNOT-22 scores were included. Average total SNOT-22 scores worsened from pre-operative (16.91 ± 16.91) to POM1 (25.15 ± 20.83, P < .001), with no difference from pre-operative (16.40 ± 15.88) to POM6 (16.27 ± 17.92, P = .936) or pre-operative (13.63 ± 13.54) to POM12 (12.60 ± 16.45, P = .651). Average smell-SNOT scores worsened from pre-operative (0.40 ± 1.27) to POM1 (2.09 ± 2.01, P < .001), and pre-operative (0.46 ± 1.29) to POM6 (1.13 ± 2.45, P = .002), with no difference from pre-operative (0.40 ± 1.07) to POM12 (0.71 ± 1.32, P = .100). Female gender had a 0.9-point (95% CI 0.1 to 1.6) P = .021, increase in smell-SNOT at POM1, resolving by POM6 (0.1 [-0.9 to 1.1], P = .800) and POM12 (0.0 [-1.0 to 0.9], P = .942). Septoplasty with tunnel approach had a 1.1 [0.2 to 2.0] out of 5-point (P = .023) increase in smell-SNOT at POM1, resolving by POM6 (0.2 [-1.1 to 1.6], P = .764) and POM12 (0.4 [-0.9 to 1.6], P = .567). Female gender had a 9.5 (4.0 to 15.1)-point (P = .001) increase in SNOT-22 scores at POM1, resolving by POM6 (3.4 [-3.0 to 9.8], P = .292) and POM12 (6.4 [-5.4 to 18.2], P = .276). Intra-operative CSF leak had an 8.6 [2.1 to 15.1]-point (P = .009) increase in SNOT-22 scores at POM1, resolving by POM6 (5.4 [-1.7 to 12.5], P = .135), and POM12 (1.1 [-12.9 to 15.1], P = .873). CONCLUSION: Changes in subjective olfaction and sinonasal QOL after TSA may be associated with gender, operative approach, and intra-operative CSF leak, resolving 6-12 months post-operatively.

Pre-term labour: A study on evaluation of causes and outcome.

Background: Despite recent advances in medicine, the incidence of pre-term birth is increasing globally. Approximately 70% of neonatal deaths, 36% of infant deaths, and 25-50% of cases of neurological impairment in children can be attributed to pre-term births. Identification of risk factors in women, supervised obstetric care during pregnancy, female empowerment, and patient education are strategies to minimize the burden of preterm deliveries. Materials and Methods: A prospective cross-sectional study was conducted over a 1-year period among 658 women in the Department of Obstetrics and Gynecology, Pramukhswami Medical College, Anand, Gujarat. Detailed history, general, and obstetrical examinations were carried out. Maternal and foetal outcomes were noted. Statistical software STATA 14.2 was used for data analysis. Results: The incidence of pre-term birth in our study was 34.95%. The incidence of late pre-term, very term, and extremely pre-term was 28.42%, 4.71%, and 1.82%, respectively. Pre-mature rupture of the membrane was observed among 20.34% of patients with late pre-term labour. IUGR was identified in 9.52% and 15.94% of the very and late pre-term births, respectively. A statistically significant difference was found in the 1 minute and 5 minute Apgar scores between pre-term babies and term babies. Conclusion: Pre-maturity is a huge health and financial burden in rural and semi-urban central Gujarat. Pre-mature rupture of membranes, previous MTP, extreme physical activity, and maternal anaemia were the major risk factors linked with pre-term labour. Poor neonatal outcomes like LBW, IUGR, and a low Apgar score were significantly associated with the babies delivered pre-mature in our study.

Phenotype, outcomes and natural history of early-stage non-ischaemic cardiomyopathy.

AIMS: To characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM). METHODS AND RESULTS: We conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H-/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D-), or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalization or cardiovascular death. A subset of patients (n = 119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36-58], 94 [37%] women, median left ventricular ejection fraction [LVEF] 55% [52-59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p = 0.90), however fibrosis mass was lowest in early-NICM H-/D+, higher in early-NICM H+/D- and highest in early-NICM H+/D+ (p = 0.03). Over a median follow-up of 7.9 (5.5-10.0) years, 28 patients (11%) experienced MACE. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36-11.00, p < 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73-8.20, p < 0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73-15.18, p = 0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to dilated cardiomyopathy with LVEF <50% over a median of 16 (11-34) months. CONCLUSION: Early-NICM is not benign. Fibrosis develops early in the phenotypic course. In-depth characterization enhances risk stratification and might aid clinical management.

Conformational Manifold Sampled by Two Short Linear Motif Segments Probed by Circular Dichroism, Vibrational, and Nuclear Magnetic Resonance Spectroscopy.

Disordered protein segments called short linear motifs (SLiM) serve as recognition sites for a variety of biological processes and act as targeting signals, modification, and ligand binding sites. While SLiMs do not adopt one of the known regular secondary structures, the conformational distribution might still reflect the structural propensities of their amino acid residues and possible interactions between them. In the past, conformational analyses of short peptides provided compelling evidence for the notion that individual residues are less conformationally flexible than locally expected for a random coil. Here, we combined various spectroscopies (NMR, IR, vibrational, and UV circular dichroism) to determine the Ramachandran plots of two SLiM motifs, i.e., GRRDSG and GRRTSG. They are two representatives of RxxS motifs that are capable of being phosphorylated by protein kinase A, an enzyme that plays a fundamental role in a variety of biological processes. Our results reveal that the nearest and non-nearest interactions between residues cause redistributions between polyproline II and ß-strand basins while concomitantly stabilizing extended relative to turn-forming and helical structures. They also cause shifts in basin positions. With increasing temperature, ß-strand populations become more populated at the expense of polyproline II. While molecular dynamics simulations with Amber ff14SB and CHARMM 36m force fields indicate residue-residue interactions, they do not account for the observed structural changes.

Impact of a Vision Photoscreener in Very Young Children in an Inner-City Pediatric Clinic in Detroit.

Pediatric vision screening is important because approximately 80% of visual impairments, including amblyopia, can be prevented or cured, especially if caught early. This retrospective study aims to determine whether the implementation of a machine photoscreener improves vision outcomes in 1- to 4-year-old children in an urban clinic. Before the vision screener, 91 patients were seen (control group), while 205 were seen following its implementation (study group). The number of children screened increased by 27.4% after implementing the photoscreener (57.1% study, 29.7% control, P < .001). All patients who failed the screening, 14.6% in the study period, were referred to ophthalmology (n = 30); 40% (n = 12) were evaluated, and 9 were diagnosed with a true vision abnormality. Instrument vision screening allows children as young as 1 year to be screened and allows for early intervention for potential vision-threatening pathologies in a vulnerable urban population.

A qualitative exploration of allied health providers' perspectives on cultural humility in palliative and end-of-life care.

BACKGROUND: Cultural factors, including religious or cultural beliefs, shape patients' death and dying experiences, including palliative and end-of-life (EOL) care preferences. Allied health providers must understand their patients' cultural preferences to support them in palliative and EOL care effectively. Cultural humility is a practice which requires allied health providers to evaluate their own values, biases, and assumptions and be open to learning from others, which may enhance cross-cultural interactions by allowing providers to understand patients' perceptions of and preferences for their health, illness, and dying. However, there is limited knowledge of how allied health providers apply cultural humility in palliative and EOL care within a Canadian context. Thus, this study describes Canadian allied health providers' perspectives of cultural humility practice in palliative and EOL care settings, including how they understand the concept and practice of cultural humility, and navigate relationships with patients who are palliative or at EOL and from diverse cultural backgrounds. METHODS: In this qualitative interpretive description study, remote interviews were conducted with allied health providers who currently or recently practiced in a Canadian palliative or EOL care setting. Interviews were audio-recorded, transcribed, and analyzed using interpretive descriptive analysis techniques. RESULTS: Eleven allied health providers from the following disciplines participated: speech-language pathology, occupational therapy, physiotherapy, and dietetics. Three themes were identified: (1) Interpreting and understanding of cultural humility in palliative and EOL care (i.e., recognizing positionality, biases and preconceived notions and learning from patients); (2) Values, conflicts, and ethical uncertainties when practicing cultural humility at EOL between provider and patient and family, and within the team and constraints/biases within the system preventing culturally humble practices; (3) The 'how to' of cultural humility in palliative and EOL care (i.e., ethical decision-making in palliative and EOL care, complexities within the care team, and conflicts and challenges due to contextual/system-level factors). CONCLUSIONS: Allied health providers used various strategies to manage relationships with patients and practice cultural humility, including intra- and inter-personal strategies, and contextual/health systems enablers. Conflicts and challenges they encountered related to cultural humility practices may be addressed through relational or health system strategies, including professional development and decision-making support.

Methods and Protocols for Using Extracellular Vesicles as Delivery Vehicles in Neuronal Research.

Extracellular vesicles (EVs) transport nucleic acids, proteins, and lipid molecules for intercellular communication. The biomolecular cargo from EVs can modify the recipient cell genetically, physiologically, and pathologically. This innate ability of EVs can be harnessed to deliver the cargo of interest to a specific organ or a cell type. Importantly, due to their ability to cross the blood-brain barrier (BBB), the EVs can be used as delivery vehicles to transport therapeutic drugs and other macromolecules to inaccessible organs such as the brain. Therefore, the current chapter includes laboratory techniques and protocols focusing on the customization of EVs for neuronal research.

Indicators of life success from the perspective of individuals with traumatic brain injury: a scoping review.

PURPOSE: The purpose was to synthesize qualitative literature and identify indicators of life success (positive life outcomes and experiences) that can help in understanding resiliency in the context of traumatic brain injury (TBI). METHODS: This scoping review involved searching nine online databases for population (TBI) and context (qualitative literature). Searches retrieved 42 852 articles and, after two-stage screening, 76 articles met the inclusion criteria of reporting indicators of life success from the perspective of individuals with TBI. RESULTS: Most studies were conducted in North America, Australia, or Europe. Participants were people living with TBI (mild to severe), of all age ranges. Positive life experiences were organized within four domains: understanding of oneself and one's life, social relationships and interaction, doing (engagement in activities, sense of control and accomplishment), and hope for the future. CONCLUSIONS: The positive life experiences reflect both processes and outcomes (indicators of success) and highlight the need for a multidimensional approach when seeking to understand resiliency following TBI. The transactional framework of life experiences can be applied in future TBI resiliency research to understand how individuals negotiate adversity through experiences promoting understanding of oneself and the world, social relationships, engagement in activity and hope. Implications for rehabilitationRehabilitation services should consider how to afford opportunities for engagement in activity, social interaction, meaning making (i.e., coming to new understandings), and hope.With respect to engaging in activity and social relationships, having social interaction, being understood, being active and productive, having autonomy, and having accomplishments, reflect important experiences to enable within rehabilitation services.Rehabilitation professionals should consider how providing opportunities for their clients to have positive life experiences may contribute toward an adaptive and empowered mindset.

Treatment of Ekbom Syndrome With Clozapine and Electroconvulsive Therapy.

Delusion of parasitosis (DP), which is also known as Ekbom syndrome, is a delusional disorder characterised by a false, fixed belief of being infested by insects or mites, despite the lack of supporting medical evidence. This disorder presents most commonly with the "Matchbox sign." DP can present as a primary or secondary delusional disorder. It can be associated with various psychiatric conditions such as schizophrenia spectrum disorders, mood disorders, anxiety or substance abuse. Several organic conditions such as dementia, malignancies, vitamin deficiencies and cerebrovascular accidents can mimic symptoms of DP. Hereby, we present a case of schizophrenia in a young woman associated with DP in our inpatient care and the treatment outcome with the use of clozapine and electroconvulsive therapy (ECT) regimen.

Rehabilitation among individuals experiencing homelessness and traumatic brain injury: A scoping review.

Traumatic brain injury (TBI) is disproportionately prevalent among individuals experiencing homelessness. While rehabilitation is critical to facilitating recovery after TBI, there is currently limited information on the extent to which rehabilitation is provided to individuals experiencing homelessness and TBI. If unaddressed, this knowledge gap can perpetuate TBI-related challenges and contribute to a repetitive cycle of TBI and homelessness. This scoping review explored the extent to which rehabilitation, including the types of rehabilitation interventions, are available to, or used by, individuals experiencing homelessness and TBI. A systematic search of electronic databases (MEDLINE, Embase, Cochrane CENTRAL Register of Clinical Trials, CINAHL, APA PsycINFO, Applied Social Sciences Index and Abstracts, and Proquest Nursing and Allied Health) was conducted to identify peer-reviewed articles that met predetermined eligibility criteria. Gray literature and reference lists of eligible articles were also searched for relevant content. A descriptive numerical summary of extracted data was conducted, and qualitative analytic techniques were applied to analyze the data. Fifteen peer-reviewed articles and three gray literature reports were included, describing interventions for individuals experiencing homelessness and TBI (N = 4), rehabilitation for individuals experiencing homelessness without specific inclusion criteria for TBI (N = 11), and rehabilitation interventions that included individuals experiencing homelessness and TBI, without specific inclusion criteria for experiences of homelessness or TBI (N = 3). This review demonstrates that rehabilitation programs or interventions for this population already exist, and those that are focused on individuals experiencing homelessness are already serving individuals with TBI. Findings highlight opportunities to adapt existing rehabilitation for individuals who experience homelessness and TBI through screening for TBI, conducting cognitive and functional assessments, and tailoring interventions with multidisciplinary teams. Education and training for healthcare professionals working with individuals experiencing homelessness and TBI should be explored, including structured education and training, collaboration with a multidisciplinary team, and co-development of educational materials with service users. Research that considers the rehabilitation needs of diverse individuals experiencing homelessness and TBI is urgently needed.

Effectiveness of renal denervation in the treatment of hypertension: a literature review.

BACKGROUND: Catheter-based renal denervation has been studied as a potential therapeutic option to reduce high blood pressure (BP). Preclinical studies in some experimental models have demonstrated an antihypertensive effect of renal denervation but reports from clinical trials have been mixed METHODS: We performed a literature search using combinations of the key terms 'Cardiovascular diseases, Clinical trial, Pre-clinical trials, Resistant hypertension, Renal denervation, Ablation technique, Radiofrequency ablation, Ultrasound ablation, RADIANCE SOLO, SYMPLICITY HTN, SYPRAL HTN'. The databases searched were PubMed and OVID Medline. RESULTS: The initial SYMPLICITY HTN-1 AND HTN-2 clinical trials reported significant decreases in office BP but results from the more robustly designed SYMPLICITY HTN-3 trial, which included sham controls and ambulatory BP monitoring, showed no significant antihypertensive effect. Interest in the use of renal denervation in hypertension was once again sparked by favourable results from the SPYRAL HTN-OFF Med trial CONCLUSION: We provide a thorough, critical analysis of key preclinical and clinical studies investigating the efficacy of catheter-based renal denervation as a treatment for hypertension and highlight future areas for research to allow better translation into clinical practice.

A systematic review on integrated care for traumatic brain injury, mental health, and substance use.

Traumatic brain injuries (TBI) and mental health or substance use disorders (MHSU) are global public health concerns due to their prevalence and impact on individuals and societies. However, care for individuals with TBI and MHSU remains fragmented with a lack of appropriate services and supports across the continuum of healthcare. This systematic review provided an evidence-based foundation to inform opportunities to mobilize and adapt existing resources to integrate care for individuals with TBI and MHSU by comprehensively summarizing existing integrated activities and reported barriers and facilitators to care integration. MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Sociological Abstracts, and Dissertations & Theses Global were independently reviewed by two reviewers based on pre-determined eligibility criteria. Data on the integration activity, level and type of integration, reported barriers and facilitators, and the strategies aligning with the World Health Organization's (WHO) Framework on Integrated Person-Centred Care were extracted to form the basis for a narrative synthesis. Fifty-nine peer-reviewed articles were included, describing treatments (N = 49), programs (N = 4), or screening activities (N = 7). Studies discussing clinical integration at the micro- (N = 38) and meso- (N = 10) levels, service integration at the micro- (N = 6) and meso- (N = 5) levels, and functional integration at the meso-level (N = 1) were identified. A minority of articles reported on facilitators (e.g., cognitive accommodations in treatment plans; N = 7), barriers (e.g., lack of education on cognitive challenges associated with TBI; N = 2), or both (N = 6), related to integrating care. This review demonstrated that integrated TBI and MHSU care already exists across a range of levels and types. Given the finite and competing demands for healthcare resources, cognitive accommodations across treatment plans to facilitate integrated TBI and MHSU care should be considered. Multidisciplinary teams should also be explored to provide opportunities for education among health professionals so they can be familiar with TBI and MHSU. Trial registration: Prospero Registration: CRD42018108343.

Rehabilitation among individuals with traumatic brain injury who intersect with the criminal justice system: A scoping review.

Traumatic brain injury (TBI), a leading cause of morbidity and mortality globally, is highly prevalent among individuals who intersect with the criminal justice system (CJS). It is well-established that TBI negatively impacts individuals' interactions both within the CJS and upon release and is associated with serious disciplinary charges and higher recidivism rates. Although rehabilitation is fundamental to TBI recovery, it is not known to what extent rehabilitation is available to, or used by, individuals who intersect with the CJS. This scoping review explores the availability and extent of rehabilitation for individuals with TBI who intersect with the CJS, based on available literature. A systematic search of electronic databases (MEDLINE, Embase, Cochrane CENTRAL Register of Clinical Trials, CINAHL, APA PsycINFO, Applied Social Sciences Index and Abstracts, and Proquest Nursing and Allied Health), relevant organizations' websites, and reference lists of eligible articles identified 22 peer-reviewed articles and 2 gray literature reports that met predetermined eligibility criteria. Extracted data were synthesized through a descriptive numerical summary and qualitative content analysis. This review provides evidence that existing rehabilitation interventions are already serving individuals with TBI with a history of CJS involvement; however, they rarely consider or acknowledge TBI or CJS in their interventions. Findings also suggest opportunities to integrate rehabilitation for individuals with TBI who intersect with the CJS through TBI screening, education on TBI within CJS settings, and linkages to the community to facilitate continuity of care. This review also highlights significant gaps in knowledge regarding sex, gender, and other intersecting factors. Research to understand how these experiences impact the rehabilitation process throughout the CJS is urgently needed to enable timely and appropriate rehabilitation and continuity of care for diverse individuals with TBI who intersect with the CJS.

Iron Pathways and Iron Chelation Approaches in Viral, Microbial, and Fungal Infections.

Iron is an essential element required to support the health of organisms. This element is critical for regulating the activities of cellular enzymes including those involved in cellular metabolism and DNA replication. Mechanisms that underlie the tight control of iron levels are crucial in mediating the interaction between microorganisms and their host and hence, the spread of infection. Microorganisms including viruses, bacteria, and fungi have differing iron acquisition/utilization mechanisms to support their ability to acquire/use iron (e.g., from free iron and heme). These pathways of iron uptake are associated with promoting their growth and virulence and consequently, their pathogenicity. Thus, controlling microorganismal survival by limiting iron availability may prove feasible through the use of agents targeting their iron uptake pathways and/or use of iron chelators as a means to hinder development of infections. This review will serve to assimilate findings regarding iron and the pathogenicity of specific microorganisms, and furthermore, find whether treating infections mediated by such organisms via iron chelation approaches may have potential clinical benefit.

Metabolome-Informed Microbiome Analysis Refines Metadata Classifications and Reveals Unexpected Medication Transfer in Captive Cheetahs.

Even high-quality collection and reporting of study metadata in microbiome studies can lead to various forms of inadvertently missing or mischaracterized information that can alter the interpretation or outcome of the studies, especially with nonmodel organisms. Metabolomic profiling of fecal microbiome samples can provide empirical insight into unanticipated confounding factors that are not possible to obtain even from detailed care records. We illustrate this point using data from cheetahs from the San Diego Zoo Safari Park. The metabolomic characterization indicated that one cheetah had to be moved from the non-antibiotic-exposed group to the antibiotic-exposed group. The detection of the antibiotic in this second cheetah was likely due to grooming interactions with the cheetah that was administered antibiotics. Similarly, because transit time for stool is variable, fecal samples within the first few days of antibiotic prescription do not all contain detected antibiotics, and the microbiome is not yet affected. These insights significantly altered the way the samples were grouped for analysis (antibiotic versus no antibiotic) and the subsequent understanding of the effect of the antibiotics on the cheetah microbiome. Metabolomics also revealed information about numerous other medications and provided unexpected dietary insights that in turn improved our understanding of the molecular patterns on the impact on the community microbial structure. These results suggest that untargeted metabolomic data provide empirical evidence to correct records and aid in the monitoring of the health of nonmodel organisms in captivity, although we also expect that these methods may be appropriate for other social animals, such as cats.IMPORTANCE Metabolome-informed analyses can enhance omics studies by enabling the correct partitioning of samples by identifying hidden confounders inadvertently misrepresented or omitted from carefully curated metadata. We demonstrate here the utility of metabolomics in a study characterizing the microbiome associated with liver disease in cheetahs. Metabolome-informed reinterpretation of metagenome and metabolome profiles factored in an unexpected transfer of antibiotics, preventing misinterpretation of the data. Our work suggests that untargeted metabolomics can be used to verify, augment, and correct sample metadata to support improved grouping of sample data for microbiome analyses, here for nonmodel organisms in captivity. However, the techniques also suggest a path forward for correcting clinical information in microbiome studies more broadly to enable higher-precision analyses.

Association of socio-demographic, dietary and lifestyle factors with Premenstrual Syndrome (PMS) among undergraduate medical students of a tertiary care institute in Ahmedabad, Gujarat.

INTRODUCTION: The frequency, as well as the severity of the PMS (Pre-Menstrual Syndrome), varies from female to female based on various socio-demographic, dietary, and lifestyle factors. Nevertheless, the PMS is known to affect day-to-day functioning including interference with school/work productivity, relationships with friends, family, and colleagues. This is especially important for medical students where academic performance is much skillful and demanding. METHODOLOGY: The inclusion criteria for this cross-sectional survey were female medical students studying in one of the medical colleges of the city, having regular menstrual cycle (in the last three consecutive months) and willing to participate in the research. Students were assigned from each of the four professional years (First, Second, Third, and Final) through random sampling so that the desires sample size was achieved. The study used a pre-designed questionnaire, the "Premenstrual Symptoms Screening Tool (PSST)" (through Google form), that included 14 items assessing premenstrual symptoms of appetite, mood, sleep, anxiety and physical symptoms. It includes functional impairment items in five different domains as well. RESULTS: The common symptoms seen in the respondents were anger/irritability (Mild n = 76, 46.3%; Moderate to severe n = 68, 41.4%) followed by physical symptoms which included headaches, joint or muscle pain, breast tenderness, gain in weight and bloating. The commonest functional impairment was college/work efficiency or productivity (n = 79, 48.2%). Alcohol and tobacco consumption had a significant association with PMDD. The type of diet did not have significant statistical association with PMS or PMDD. CONCLUSION: The most common symptoms seen were anger/irritability as well as physical symptoms like headache, breast tenderness etc., Factors like sleep, diet, exercise, yoga, alcohol and smoking were assessed.

Bortezomib Effects on Human Microvascular Endothelium in vitro.

Cellular oxidative stress in the endothelium of blood vessels leads to several pathophysiological sequelae, including vascular damage and dysfunction, inflammation and atherosclerosis. Heme oxygenase-1 (HO-1) provides protection against oxidative stress-induced cell death and plays a crucial role in the regulation of cyclooxygenase-2 (COX-2) in endothelial cells. In the present study, we have investigated the effects of bortezomib, a clinically used proteasome inhibitor, on the regulation of HO-1 and COX-2 in cultured human microvascular endothelial cells (HMECs). Bortezomib treatment of HMECS induced dose- and time-dependent expression of HO-1 and COX-2 mRNA and protein, and triggered nuclear translocation of nuclear factor erythroid 2-related transcription factor (Nrf2). These findings suggest that HO-1/COX-2-mediated induction of antioxidant mechanisms via Nrf2 activation may contribute to the cytoprotective effects of bortezomib in microvascular endothelium.

Identification and Characterization of Novel Small RNAs in Rickettsia prowazekii.

Emerging evidence implicates a critically important role for bacterial small RNAs (sRNAs) as post-transcriptional regulators of physiology, metabolism, stress/adaptive responses, and virulence, but the roles of sRNAs in pathogenic Rickettsia species remain poorly understood. Here, we report on the identification of both novel and well-known bacterial sRNAs in Rickettsia prowazekii, known to cause epidemic typhus in humans. RNA sequencing of human microvascular endothelial cells (HMECs), the preferred targets during human rickettsioses, infected with R. prowazekii revealed the presence of 35 trans-acting and 23 cis-acting sRNAs, respectively. Of these, expression of two trans-acting (Rp_sR17 and Rp_sR60) and one cis-acting (Rp_sR47) novel sRNAs and four well-characterized bacterial sRNAs (RNaseP_bact_a, α-tmRNA, 4.5S RNA, 6S RNA) was further confirmed by Northern blot or RT-PCR analyses. The transcriptional start sites of five novel rickettsial sRNAs and 6S RNA were next determined using 5' RLM-RACE yielding evidence for their independent biogenesis in R. prowazekii. Finally, computational approaches were employed to determine the secondary structures and potential mRNA targets of novel sRNAs. Together, these results establish the presence and expression of sRNAs in R. prowazekii during host cell infection and suggest potential functional roles for these important post-transcriptional regulators in rickettsial biology and pathogenesis.