Potassium ion channel Kir2.1 negatively regulates protective responses to Mycobacterium bovis BCG.

Tuberculosis caused by the pathogen Mycobacterium tuberculosis leads to increased mortality and morbidity worldwide. The prevalence of highly drug resistant strains has reinforced the need for greater understanding of host-pathogen interactions at the cellular and molecular levels. Our previous work demonstrated critical roles of calcium ion channels in regulating protective responses to mycobacteria. In this report we deciphered the roles of inwardly rectifying K+ ion channel Kir2.1 in epithelial cells. Data showed that infection of epithelial cells (and macrophages) increases the surface expression of Kir2.1. This increased expression of Kir2.1 results in higher intracellular mycobacterial survival, since either inhibiting or knocking down Kir2.1 results in mounting of a higher oxidative burst leading to a significant attenuation of mycobacterial survival. Further, inhibiting Kir2.1 also led to increased expression of T cell costimulatory molecules accompanied with increased activation of MAP Kinases and transcription factors NF-κB and pCREB. Furthermore, inhibiting Kir2.1 induced increased autophagy and apoptosis that could also contribute to decreased bacterial survival. Interestingly, an increased association of heat shock protein-70 with Kir2.1 was observed. The above results showed that mycobacteria modulate the expression and function of Kir2.1 in epithelial cells to its advantage.

Evaluating the Impact of Annual Resident Retreats on Radiology Resident Wellbeing.

RATIONALE AND OBJECTIVES: To investigate the effect of resident-run wellness retreats on measures of stress, resilience, and cohesion amongst radiology residents. MATERIALS AND METHODS: All diagnostic and interventional radiology residents in a single academic medical center were invited to participate in a wellness-focused off-campus retreat. Three retreats were held on an annual basis from 2018 to 2022 and included physical exercises, nutritional wellness, and team-building activities. Participants were surveyed pre- and post- retreat attendance focusing on the following domains: Perceived Stress Scale, higher scores indicating higher levels of perceived stress; Brief Resilience Scale, higher scores indicating greater resilience; Cohesion Scale, higher scores indicating greater cohesion. Paired t-tests and linear regression models were used to compare mean Perceived Stress, Brief Resilience, and Cohesion Scales pre- and post-retreat across covariates. RESULTS: Of 78 total retreat attendances, 75 residents (96%) completed pre- and/or post-surveys. Study population was 51% female and 49% male, with mean age 29 ± 2.8 years. Comparing post- with pre-surveys, retreat attendance was associated with a significant reduction in mean Perceived Stress (12.7 vs 16.3; 95% CI 2.1-5.3) and significant increase in Brief Resilience (3.9 vs 3.7; 95% CI 0.05-0.34) and Cohesion (33 vs 27; 95% CI 4.3-6.7). First year residents experienced the greatest increase in Cohesion compared to fourth year residents (p < 0.001). Pre-retreat cohesion was significantly lower in 2022 than in 2018-2019 (26.6 vs 28.7 vs 28.6; p = 0.04), with stress and resilience not significantly different by year. CONCLUSION: An annual resident retreat decreased stress, while increasing resilience and cohesion within a radiology residency, supporting retreats as a potentially viable intervention to promote physician well-being.

Effect of Prostate Artery Embolization on Erectile Function - A Single Center Experience of 167 Patients.

BACKGROUND: Prostate artery embolization (PAE) is an emerging therapy for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). AIM: This retrospective study was conducted to assess the effect of prostate artery embolization (PAE) on erectile function in a cohort of patients with LUTS attributable to BPH at 3-months after the procedure. METHODS: A retrospective review was performed on 167 patients who underwent PAE. Data collected included Sexual Health Inventory in Men (SHIM) scores at 3, 6, and 12 months post-PAE, in conjunction with the International Prostate Symptom Scores (IPSS), Quality of Life (QoL) scores, and prostate volumes. Primary outcome was erectile function as assessed by SHIM scores at 3 months after PAE. An analysis was performed to identify patients with a ±5-point SHIM change to group them according to this minimum clinically significant difference in erectile function. Adverse events were recorded using the Clavien-Dindo (CD) classification. OUTCOMES: At 3 months following PAE, median IPSS decreased by 16.0 [IQR, 9.0-22.0] points, median QOL decreased by 4.0 [IQR, 2.0-5.0] points, and median prostate volume decreased by 33 g [IQR, 14-55]. RESULTS: Median SHIM score was 17.0 [IQR, 12.0-22.0] at baseline, 18.0 [IQR, 14.0-23.0] at 3 months [P = .031], 19.0 [IQR, 14.5-21.5] at 6 months [P = .106] and 20 [IQR, 16.0-24.0] at 12 months [P = .010] following PAE. In patients with no erectile dysfunction (ED) at baseline, 21% (n = 9) reported some degree of decline in erectile function post-PAE. However, 38% (n = 40) of patients who presented with mild-to-moderate ED reported improvement in their erectile function 3 months following PAE. Overall, the changes in baseline SHIM score were relatively small; 82% (n = 137) of patients did not have more than 5 points of change in their SHIM scores at 3 months following PAE. CLINICAL IMPLICATIONS: Our findings suggest PAE has no adverse impact on erectile function for most patients. STRENGTHS & LIMITATIONS: The study was performed at a single center with 1 operator's experience, and is retrospective with no control group. CONCLUSION: Findings suggest that prostate artery embolization has no adverse effect on erectile function in the majority of patients with LUTS attributable to BPH at 3 months after the procedure. Bhatia S, Acharya V, Jalaeian H, et al., Effect of Prostate Artery Embolization on Erectile Function - A Single Center Experience of 167 Patients. J Sex Med 2022;19:594-602.

Variants in regulatory elements of PDE4D associate with major mental illness in the Finnish population.

We have previously reported a replicable association between variants at the PDE4D gene and familial schizophrenia in a Finnish cohort. In order to identify the potential functional mutations underlying these previous findings, we sequenced 1.5 Mb of the PDE4D genomic locus in 20 families (consisting of 96 individuals and 79 independent chromosomes), followed by two stages of genotyping across 6668 individuals from multiple Finnish cohorts for major mental illnesses. We identified 4570 SNPs across the PDE4D gene, with 380 associated to schizophrenia (p ≤ 0.05). Importantly, two of these variants, rs35278 and rs165940, are located at transcription factor-binding sites, and displayed replicable association in the two-stage enlargement of the familial schizophrenia cohort (combined statistics for rs35278 p = 0.0012; OR = 1.18, 95% CI: 1.06-1.32; and rs165940 p = 0.0016; OR = 1.27, 95% CI: 1.13-1.41). Further analysis using additional cohorts and endophenotypes revealed that rs165940 principally associates within the psychosis (p = 0.025, OR = 1.18, 95% CI: 1.07-1.30) and cognitive domains of major mental illnesses (g-score p = 0.044, ß = -0.033). Specifically, the cognitive domains represented verbal learning and memory (p = 0.0091, ß = -0.044) and verbal working memory (p = 0.0062, ß = -0.036). Moreover, expression data from the GTEx database demonstrated that rs165940 significantly correlates with the mRNA expression levels of PDE4D in the cerebellum (p-value = 0.04; m-value = 0.9), demonstrating a potential functional consequence for this variant. Thus, rs165940 represents the most likely functional variant for major mental illness at the PDE4D locus in the Finnish population, increasing risk broadly to psychotic disorders.

Prostate Artery Embolization in Patients with Prostate Volumes of 80 mL or More: A Single-Institution Retrospective Experience of 93 Patients.

PURPOSE: To evaluate the safety and efficacy of prostate artery embolization (PAE) for the treatment of benign prostatic hyperplasia for prostates ≥ 80 mL. PATIENTS AND METHODS: A retrospective review was conducted of 93 patients with prostate volumes (PVs) ≥ 80 mL treated with PAE from April 2014 through October 2017. Mean patient age was 68.5 years (range 52-88) and mean age-adjusted Charlson comorbidity index was 3.2 (range 1-8). Exclusion criteria included history of biopsy-proven prostate cancer or catheter dependency. Clinical and urodynamic outcomes were reviewed at 1, 3, 6, and 12 months. Adverse events were graded according to the Clavien-Dindo classification. RESULTS: Mean PV decreased significantly from 141.7 mL to 98.1 mL at 3 months (P < .01) and 82.2 mL at 12 months (P < .01). Significant improvements were seen in 3- and 12-month mean International Prostate Symptom Scores (IPSS) (22.3 vs 7.1 and 7.3, respectively; P < .01 for both), quality of life (QOL) (4.4 vs 1.2 and 1.3; P < .01 for both), and postvoid residual volume (196.7mL vs 92.1 and 61.2 mL; P < .01 and P < .01, respectively). Significant improvement was also seen in 3-month mean maximum urinary flow: 7.7 mL/s vs 12.8 mL/s (P < .01). One grade II complication of stroke occurred; all other complications were self-limited and grade I. CONCLUSIONS: PAE achieved a clinically and statistically significant improvement in symptom burden and secondary outcome measures in patients with PVs ≥ 80 mL. PAE may be an alternate treatment for patients for whom conventional surgical options are limited or associated with significant morbidity.

Gender differences in obsessive-compulsive disorder: Findings from a multicentric study from India.

Obsessive-compulsive disorder (OCD) is phenotypically heterogeneous. Gender is an important factor mediating this heterogeneity. We examined gender differences in a large sample (n = 945) of OCD patients under a multi-centric study in India. Cross-sectional assessments were done on consecutive adult (>18 years) treatment-seeking patients with a DSM-5 diagnosis of OCD. Subjects were assessed on Structured Clinical Interview for DSM-5-Research Version for comorbid psychiatric illnesses, Yale Brown Obsessive Compulsive Scale for OCD phenomenology and symptom severity, Brown Assessment of Beliefs Scale for insight, Beck's Depression Inventory for severity of depressive symptoms, and the Obsessive Beliefs Questionnaire. On multivariate backward Wald logistic regression analysis, males (59.7%) had more years of education, had a higher rate of checking compulsions and comorbid substance use disorders. Women were more likely to be married, more commonly reported precipitating factors, had a higher rate of hoarding compulsions and comorbid agoraphobia. Findings from this large study validate gender as an important mediator of phenotypic heterogeneity in OCD. The mechanistic basis for these differences might involve complex interactions between biological, cultural and environmental factors.

Rare gene deletions in genetic generalized and Rolandic epilepsies.

Genetic Generalized Epilepsy (GGE) and benign epilepsy with centro-temporal spikes or Rolandic Epilepsy (RE) are common forms of genetic epilepsies. Rare copy number variants have been recognized as important risk factors in brain disorders. We performed a systematic survey of rare deletions affecting protein-coding genes derived from exome data of patients with common forms of genetic epilepsies. We analysed exomes from 390 European patients (196 GGE and 194 RE) and 572 population controls to identify low-frequency genic deletions. We found that 75 (32 GGE and 43 RE) patients out of 390, i.e. ~19%, carried rare genic deletions. In particular, large deletions (>400 kb) represent a higher burden in both GGE and RE syndromes as compared to controls. The detected low-frequency deletions (1) share genes with brain-expressed exons that are under negative selection, (2) overlap with known autism and epilepsy-associated candidate genes, (3) are enriched for CNV intolerant genes recorded by the Exome Aggregation Consortium (ExAC) and (4) coincide with likely disruptive de novo mutations from the NPdenovo database. Employing several knowledge databases, we discuss the most prominent epilepsy candidate genes and their protein-protein networks for GGE and RE.

Efficacy of Prostatic Artery Embolization for Catheter-Dependent Patients with Large Prostate Sizes and High Comorbidity Scores.

PURPOSE: To evaluate efficacy and safety of prostate artery embolization (PAE) in urinary catheter-dependent patients with large prostate volumes and high comorbidity scores. MATERIALS AND METHODS: A retrospective single-center review was conducted of 30 patients with urinary retention at time of PAE from November 2014 through February 2017. Mean (range) age was 73.1 years (48-94 y), age-adjusted Charlson comorbidity index was 4.5 (0-10), duration of urinary retention was 63.4 days (2-224 d), International Prostate Symptom Score quality-of-life (IPSS-QOL) was 5.3 (3-6), and prostate volume was 167.3 cm3 (55-557 cm3). These parameters were collected at 3, 6, and 12 months after PAE. Trials of voiding were performed approximately 2 weeks after PAE and, if failed, every 2 weeks thereafter. Adverse events were graded using the Clavien-Dindo classification. RESULTS: At a mean (range) of 18.2 days (1-72 d), 26 (86.7%) patients were no longer reliant on catheters. Follow-up was obtained in all patients eligible at 3 and 6 months and 17 of 20 (85.0%) patients eligible at 1 year. Mean (range) IPSS-QOL improved significantly to 1.2 (0-5), 0.7 (0-4), and 0.6 (0-4) at 3, 6, and 12 months (all P < .001). Mean (range) prostate volume decreased significantly to 115.9 cm3 (27-248 cm3) at 3 months (P < .001). Two patients experienced grade II urosepsis complications, which were successfully treated with intravenous antibiotics. All other complications were self-limited grade I complications. CONCLUSIONS: PAE represents a safe and effective option for management of patients with urinary retention, especially patients with large prostates who are not ideal surgical candidates.

Erectile Dysfunction: An Underestimated Presentation in Patients with Diabetes Mellitus.

INTRODUCTION: Erectile dysfunction (ED) is a common complication of diabetes mellitus. ED, like other sexual disorders, is often under-reported and under-diagnosed, as talking about sex is considered a taboo in our society. METHODOLOGY: All the male patients with diabetes mellitus (with or without active complaints of ED) attending Medicine or Psychiatry OPD of the institute during the study period were enrolled in the study. They were investigated for their body-mass index (BMI), blood sugar and lipid profile; and were assessed on HAM-D, General Health Questionnaire-30, IIEF, sex myth checklist and QOL Instrument for Indian Diabetes Patients (QOLID). RESULT AND DISCUSSION: In the present study, a total of 138 diabetic patients were assessed, and those with severe ED were found to have poor glycemic control, worse lipid profile, higher body mass index, later age of onset, and longer duration of untreated diabetes as compared to non-ED patients. ED patients also scored higher on depression rating scale, had poorer general health and quality of life (QOL). Early attention to ED in diabetic patients can improve general health and QOL of the sufferers. CONCLUSION: DM patients with poor glycemic control and advanced age have a higher propensity of developing severe ED, which further deteriorates the already compromised health & QOL.

The NDE1 genomic locus can affect treatment of psychiatric illness through gene expression changes related to microRNA-484.

Genetic studies of familial schizophrenia in Finland have observed significant associations with a group of biologically related genes, DISC1, NDE1, NDEL1, PDE4B and PDE4D, the 'DISC1 network'. Here, we use gene expression and psychoactive medication use data to study their biological consequences and potential treatment implications. Gene expression levels were determined in 64 individuals from 18 families, while prescription medication information has been collected over a 10-year period for 931 affected individuals. We demonstrate that the NDE1 SNP rs2242549 associates with significant changes in gene expression for 2908 probes (2542 genes), of which 794 probes (719 genes) were replicable. A significant number of the genes altered were predicted targets of microRNA-484 (p = 3.0 × 10-8), located on a non-coding exon of NDE1 Variants within the NDE1 locus also displayed significant genotype by gender interaction to early cessation of psychoactive medications metabolized by CYP2C19. Furthermore, we demonstrate that miR-484 can affect the expression of CYP2C19 in a cell culture system. Thus, variation at the NDE1 locus may alter risk of mental illness, in part through modification of miR-484, and such modification alters treatment response to specific psychoactive medications, leading to the potential for use of this locus in targeting treatment.

Prostate Artery Embolization via Transradial or Transulnar versus Transfemoral Arterial Access: Technical Results.

PURPOSE: To compare safety and feasibility of prostate artery embolization (PAE) via transradial/transulnar access (TR/UA) and transfemoral access (TFA). MATERIALS AND METHODS: A retrospective analysis was conducted for 3 cohorts: the first 32 consecutive PAE procedures performed via TFA (initial TFA, January 2014 to August 2015), the following 32 procedures performed via TFA (advanced TFA, August 2015 to February 2016), and the first 32 procedures performed via TR/UA (February 2016 to July 2016). Indications included lower urinary tract symptoms (n = 68), urinary retention (n = 24), and preoperative embolization before prostatectomy (n = 4). A single operator performed all procedures at a single institution. RESULTS: Technical success was achieved in 29/32 (90.6%) initial TFA procedures, 31/32 (96.9%) advanced TFA procedures, and 30/32 (93.8%) TR/UA procedures. Mean procedure time was 110.0 minutes in TR/UA group, 155.1 min in initial TFA group, and 131.3 minutes in advanced TFA group (P < .01 and P = .03 relative to TR/UA); mean fluoroscopy time was 38.8 minutes in TR/UA group, 56.5 minutes in initial TFA group, and 48.0 minutes in advanced TFA group (P < .01 and P = .02 relative to TR/UA). Access site-related and overall adverse events did not vary significantly among study cohorts (P > .15 and P > .05, respectively). CONCLUSIONS: TR/UA represents a safe and feasible approach to PAE with a comparable safety profile to TFA. Reduced procedure and fluoroscopy times might be attributable to the learning curve or method of arterial access.

Role of Coil Embolization during Prostatic Artery Embolization: Incidence, Indications, and Safety Profile☆.

PURPOSE: To determine if coil embolization is a safe adjunctive measure to prevent nontarget embolization during prostatic artery embolization (PAE). MATERIALS AND METHODS: A retrospective analysis of patients who underwent PAE with coil embolization (cPAE) or without coil embolization (nPAE) between January 2014 and June 2016 was conducted. Adverse events, identified in accordance with SIR guidelines, and procedural variables were compared between the 2 cohorts. RESULTS: Of 122 patients, 32 (26.2%) underwent coil embolization in 39 arteries, with coils placed to prevent nontarget embolization (n = 36), treat prostatic artery extravasation (n = 2), and occlude an intraprostatic arteriovenous fistula (n = 1). Compared with nPAE, cPAE had a nonsignificant increase in dose area product (64,516 µGy·m2 vs 52,100 µGy·m2, P = .053) but significantly longer procedure (160.1 min vs 137.1 min, P = .022) and fluoroscopy (62.9 min vs 46.1 min, P = .023) times. One major complication (urosepsis) occurred in each group (cPAE, 1/32 [3.1%]; nPAE, 1/80 [1.3%]). Both cases resolved after 2 weeks of intravenous antibiotics. A minor ischemic complication (1/32 [3.1%]) occurred in a patient with coil embolization, which manifested as white discoloration of the glans penis and resolved with topical therapy. There were no statistically significant differences in major and minor complications between cohorts at 1-month and 3-month follow-up visits. CONCLUSIONS: Although coil embolization leads to increases in procedure and fluoroscopy times, it is a safe adjunctive technique to occlude communications between the prostatic artery and pelvic vasculature to potentially prevent nontarget embolization.

Efficacy and Safety of Levosulpiride Versus Haloperidol Injection in Patients With Acute Psychosis: A Randomized Double-Blind Study.

BACKGROUND: Injectable antipsychotics are frequently required for controlling agitation and aggression in acute psychosis. No study has examined the use of injectable levosulpiride for this indication. OBJECTIVE: To compare the efficacy and safety of injectable levosulpiride and haloperidol in patients with acute psychosis. METHODS: This was a randomized, double-blind, parallel-group study in which 60 drug-naive patients having acute psychosis were randomly assigned to receive either intramuscular haloperidol (10-20 mg/d) or levosulpiride (25-50 mg/d) for 5 days. All patients were rated on Brief Psychiatric Rating Scale (BPRS), Overt Agitation Severity Scale (OASS), Overt Aggression Scale-Modified (OAS-M) scores, Simpson Angus Scale (SAS), and Barnes Akathisia Rating Scale (BARS). RESULTS: Repeated-measures ANOVA for BPRS scores showed significant effect of time (P < 0.001) and a trend toward greater reduction in scores in haloperidol group as shown by group × time interaction (P = 0.076). Repeated-measures ANOVA for OASS showed significant effect of time (P < 0.001) but no group × time interaction. Repeated-measures ANOVA for OAS-M scores showed significant effect of time (P < 0.001) and greater reduction in scores in haloperidol group as shown by group × time interaction (P = 0.032). Lorazepam requirement was much lower in haloperidol group as compared with those receiving levosulpiride (P = 0.022). Higher rates of akathisia and extrapyramidal symptoms were noted in the haloperidol group. CONCLUSIONS: Haloperidol was more effective than levosulpiride injection for psychotic symptoms, aggression, and severity of agitation in acute psychosis, but extrapyramidal adverse effects were less frequent with levosulpiride as compared with those receiving haloperidol.

Indian psychiatric society multicentric study: Correlates of prescription patterns of psychotropics in India.

BACKGROUND: There is a lack of information on the clinical and sociodemographic correlates of prescription of psychotropics by psychiatrists. AIM AND OBJECTIVE: This study aimed to evaluate the relationship of prescription patterns with various clinical and sociodemographic variables. METHODOLOGY: Data of prescription patterns, psychiatric diagnosis, sociodemographic variables, and comorbid physical illnesses were collected for 4480 patients, across 11 centers. RESULTS: Females are more often prescribed escitalopram, sertraline, amitriptyline, amisulpride, nonlithium mood stabilizers, and benzodiazepines, whereas males are more often prescribed fluoxetine, olanzapine, two antipsychotics concurrently, typical antipsychotics, valproate, lithium, and more than one benzodiazepine. Elderly (>65 years) participants are more often prescribed sertraline when compared to adolescents. In addition, elderly more often receive quetiapine and less often are prescribed benzodiazepines. Those with comorbid neurological disorders are commonly prescribed antipsychotics, amitriptyline, and more than one antidepressant and are less commonly prescribed lithium, combination of two mood stabilizers, and benzodiazepines. Those with cardiac ailments are more commonly prescribed sertraline, quetiapine, and lithium and less frequently prescribed amitriptyline, fluoxetine, olanzapine, risperidone, and typical antipsychotics. Those with diabetes mellitus more often received escitalopram and quetiapine. Presence of more than one psychiatric diagnosis was associated with the use of more number of medications. Further, diagnosis of affective disorders was associated with the use of a higher number of medications. CONCLUSION: Findings of the present study suggest that sociodemographic variables and physical and psychiatric comorbidity influence the prescription patterns of psychotropics.

Phenomenology and beliefs of patients with Dhat syndrome: A nationwide multicentric study.

AIM: To assess the phenomenology and associated beliefs in patients with Dhat syndrome. METHODS: A total of 780 male patients aged more than 16 years were recruited from 15 centers spread across the country and were assessed on Dhat Syndrome Questionnaire. RESULTS: The most commonly reported reasons for passage of Dhat were excessive masturbation (55.1%), sexual dreams (47.3%), excessive sexual desire (42.8%) and consumption of high energy foods (36.7%). The most common situation in which participants experienced passage of Dhat were as 'night falls' (60.1%) and 'while passing stools' (59.5%). The most common consequence due to passage of Dhat was weakness in sexual ability (75.6%). In terms of psychological and somatic symptoms, the common symptoms included bodily weakness (78.2%); feeling tired or having low energy (75.9%); feeling down, depressed, or hopeless (67.9%); and little interest or pleasure in doing things (63.7%). In terms of treatment expectations, about half of the patients (49.1%) expected that energizing medications like vitamins/tonics/tablets were required and more than one-third (38.2%) expected that there was a need for taking energizing injections. CONCLUSION: Present study shows that Dhat syndrome is a distinct clinical entity seen all over India, with its characteristic features.