A clinical and pathological study of genito-urinary tuberculosis

A brief note has been given of the earlier work on genito-urinary tuberculosis and its diagnosis by specialised methods.The etiology and pathology of the disease has been discussed at some length. It is maintained that only by an accurate knowledge of the genesis of tuberculosis can we hope to be successful in our treatment.The clinical manifestations described are based on personal observations made over a period of twenty-six years. Recent methods of diagnosis are mentioned.A brief outline is given of treatment particularly in regard to the giving of tuberculin, and a plea is put forward for its more extensive use in the disease. The relationship of surgery to genito-urinary tuberculosis is discussed

The application of attenuated total reflection infrared spectroscopy to investigate the liquid phase hydrogenation of benzaldehyde over an alumina-supported palladium catalyst

The hydrogenation of benzaldehyde in cyclohexane over a 5 wt% Pd/Al2O3 catalyst at 313 K is firstly investigated at ambient pressure in a stirred batch reactor. The formation of benzyl alcohol is a facile process and a small mass imbalance is indirectly attributed to the formation of benzene as a by-product. No hydrogenolysis reaction to form toluene is observed. Secondly, examination of this reaction system by attenuated total reflection infrared (ATR-IR) spectroscopy enables the chemistry at the liquid/solid interface to be probed. Specifically, the ν(C=O) modes of solvated and adsorbed benzaldehyde are evident at 1712 and 1691 cm−1 respectively, providing information on how the reagent is partitioning within the reaction medium. Spectral acquisition on initiation of hydrogenation then enables the benzaldehyde → benzyl alcohol transition to be tracked. The additional presence of a broad CO stretching band of chemisorbed carbon monoxide (1852–1929 cm−1) is attributed to the hydrogen-assisted decarbonylation pathway that forms the benzene by-product

Formylated Peptide Receptor-1 (FPR1) mediated gut inflammation as a therapeutic target in Inflammatory Bowel Disease

Background: Formylated peptide receptor (FPR)-1 is a G-coupled receptor that senses foreign bacterial and host-derived mitochondrial formylated peptides (FPs), leading to innate immune system activation. Aim: We sought to investigate the role of FPR1-mediated inflammation and its potential as a therapeutic target in inflammatory bowel disease (IBD). Methods: We characterized FPR1 gene and protein expression in 8 human IBD (~1000 patients) datasets with analysis on disease subtype, mucosal inflammation, and drug response. We performed in vivo dextran-sulfate sodium (DSS) colitis in C57/BL6 FPR1 knockout mice. In ex vivo studies, we studied the role of mitochondrial FPs and pharmacological blockade of FPR1 using cyclosporin H in human peripheral blood neutrophils. Finally, we assess mitochondrial FPs as a potential mechanistic biomarker in the blood and stools of patients with IBD. Results: Detailed in silico analysis in human intestinal biopsies showed that FPR1 is highly expressed in IBD (n = 207 IBD vs 67 non-IBD controls, P &lt; .001), and highly correlated with gut inflammation in ulcerative colitis (UC) and Crohn’s disease (CD) (both P &lt; .001). FPR1 receptor is predominantly expressed in leukocytes, and we showed significantly higher FPR1+ve neutrophils in inflamed gut tissue section in IBD (17 CD and 24 UC; both P &lt; .001). Further analysis in 6 independent IBD (data available under Gene Expression Omnibus accession numbers GSE59071, GSE206285, GSE73661, GSE16879, GSE92415, and GSE235970) showed an association with active gut inflammation and treatment resistance to infliximab, ustekinumab, and vedolizumab. FPR1 gene deletion is protective in murine DSS colitis with lower gut neutrophil inflammation. In the human ex vivo neutrophil system, mitochondrial FP, nicotinamide adenine dinucleotide dehydrogenase subunit-6 (ND6) is a potent activator of neutrophils resulting in higher CD62L shedding, CD63 expression, reactive oxygen species production, and chemotactic capacity; these effects are inhibited by cyclosporin H. We screened for mitochondrial ND6 in IBD (n = 54) using ELISA and detected ND6 in stools with median values of 2.2 gg/mL (interquartile range [IQR] 0.0–4.99; range 0–53.3) but not in blood. Stool ND6 levels, however, were not significantly correlated with paired stool calprotectin, C-reactive protein, and clinical IBD activity. Conclusions: Our data suggest that FPR1-mediated neutrophilic inflammation is a tractable target in IBD; however, further work is required to clarify the clinical utility of mitochondrial FPs as a potential mechanistic marker for future stratification.</p

Sharing a household with children and risk of COVID-19: a study of over 300 000 adults living in healthcare worker households in Scotland

Objective: Children are relatively protected from COVID-19, due to a range of potential mechanisms. We investigated if contact with children also affords adults a degree of protection from COVID-19. Design: Cohort study based on linked administrative data. Setting: Scotland. Study population: All National Health Service Scotland healthcare workers and their household contacts as of March 2020. Main exposure: Number of young children (0–11 years) living in the participant’s household. Main outcomes: COVID-19 requiring hospitalisation, and any COVID-19 (any positive test for SARS-CoV-2) in adults aged ≥18 years between 1 March and 12 October 2020. Results: 241 266, 41 198, 23 783 and 3850 adults shared a household with 0, 1, 2 and 3 or more young children, respectively. Over the study period, the risk of COVID-19 requiring hospitalisation was reduced progressively with increasing numbers of household children—fully adjusted HR (aHR) 0.93 per child (95% CI 0.79 to 1.10). The risk of any COVID-19 was similarly reduced, with the association being statistically significant (aHR per child 0.93; 95% CI 0.88 to 0.98). After schools reopened to all children in August 2020, no association was seen between exposure to young children and risk of any COVID-19 (aHR per child 1.03; 95% CI 0.92 to 1.14). Conclusion: Between March and October 2020, living with young children was associated with an attenuated risk of any COVID-19 and COVID-19 requiring hospitalisation among adults living in healthcare worker households. There was no evidence that living with young children increased adults’ risk of COVID-19, including during the period after schools reopened

Evaluating the Impact of Intravitreal Aflibercept on Diabetic Retinopathy Progression in the VIVID-DME and VISTA-DME Studies

Purpose To evaluate the impact of intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Tarrytown, NY) versus laser on progression of diabetic retinopathy (DR) severity in Intravitreal Aflibercept Injection in Vision Impairment due to DME (VIVID-DME) and Study of Intravitreal Aflibercept Injection in Patients with Diabetic Macular Edema (VISTA-DME). Design Secondary and exploratory analyses of 2 phase 3, randomized, controlled studies. Participants All patients with a baseline Diabetic Retinopathy Severity Scale (DRSS) score based on fundus photograph (full analysis), patients who progressed to proliferative DR (PDR) (safety analysis) in VIVID-DME (n = 403) and VISTA-DME (n = 459), or both. Methods We randomized patients with diabetic macular edema (DME) to intravitreal aflibercept 2 mg every 4 weeks (2q4), intravitreal aflibercept 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation at baseline and sham injections at every visit. Main Outcome Measures Proportions of patients with 2-step or more and 3-step or more improvements from baseline in DRSS score, who progressed to PDR, and who underwent panretinal photocoagulation (PRP). Results Among patients with an assessable baseline DRSS score, most showed moderately severe or severe nonproliferative DR. The proportions of patients treated with 2q4, 2q8, and laser with a 2-step or more improvement in DRSS score at week 100 were 29.3%, 32.6%, and 8.2%, respectively, in VIVID-DME and 37.0%, 37.1%, and 15.6%, respectively, in VISTA-DME; the proportions with a 3-step or more improvement in DRSS score were 7.3%, 2.3%, and 0%, respectively, and 22.7%, 19.9%, and 5.2%, respectively. Fewer patients in the 2q4 and 2q8 groups versus the laser group progressed to PDR at week 100 in VISTA-DME (1.5% and 2.2% vs. 5.3%) and VIVID-DME (3.2% and 2.0% vs. 12.3%). The proportions of patients who underwent PRP were 2.9%, 0.7%, and 4.5%, respectively, in VIVID-DME and 1.9%, 0.7%, and 5.2%, respectively, in VISTA-DME. The most frequent serious ocular adverse event at week 100 was cataract (pooled intravitreal aflibercept, 1.7% of patients; laser, 3.5% of patients). Conclusions These analyses demonstrate the benefit of intravitreal aflibercept over laser with respect to DR progression, suggesting a benefit on DME, and on underlying DR

Performance of Cardiovascular Disease Risk Scores in People Diagnosed With Type 2 Diabetes:External Validation Using Data From the National Scottish Diabetes Register

Objective: To evaluate the performance of five cardiovascular disease (CVD) risk scores developed in diabetes populations and compare their performance to QRISK2. Research Design and Methods: A cohort of people diagnosed with type 2 diabetes between 2004 and 2016 was identified from the Scottish national diabetes register. CVD events were identified using linked hospital and death records. Five-year risk of CVD was estimated using each of QRISK2, ADVANCE (Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation), Cardiovascular Health Study (CHS), New Zealand Diabetes Cohort Study (NZ DCS), Fremantle Diabetes Study, and Swedish National Diabetes Register (NDR) risk scores. Discrimination and calibration were assessed using the Harrell C statistic and calibration plots, respectively. Results: The external validation cohort consisted of 181,399 people with type 2 diabetes and no history of CVD. There were 14,081 incident CVD events within 5 years of follow-up. The 5-year observed risk of CVD was 9.7% (95% CI 9.6, 9.9). C statistics varied between 0.66 and 0.67 for all risk scores. QRISK2 overestimated risk, classifying 87% to be at high risk for developing CVD within 5 years; ADVANCE underestimated risk, and the Swedish NDR risk score calibrated well to observed risk. Conclusions: None of the risk scores performed well among people with newly diagnosed type 2 diabetes. Using these risk scores to predict 5-year CVD risk in this population may not be appropriate

Religious Identification, Switching, and Apostasy Among Protestants and Catholics in Northern Ireland:Individual and Cohort Dynamics Between Two Censuses 2001–2011

Religious identification has historically been salient in Northern Ireland as an ethnic‐national identity marker. Thirteen years after the Good Friday Agreement that marked the start of the peace process in the country, the question arises whether religious affiliation in Northern Ireland has become less of an ethnonational identity marker and more of a personal choice. This article analyzes religious switching and apostasy between 2001 and 2011, using data from the Northern Ireland Longitudinal Study, a representative sample of approximately 28 percent of the population, linked to the 2001 and 2011 censuses. We found that the vast majority retained their self‐reported religious affiliation, a tiny minority switched between Protestantism and Catholicism, and a significant minority, particularly among the young, switched to “none/not stated” or between Protestant denominations. Religious switching is associated with young age, higher education, and also socioeconomic deprivation. Experiences of social frustration appear to drive many to leave their faith

Methylphenidate and \u3ci\u3eMemory and Attention Adaptation Training\u3c/i\u3e for persistent cognitive symptoms after traumatic brain injury: a randomized, placebo-controlled trial

The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacologic enhancement (i.e., with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least four months prior to study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after six weeks of treatment (post-treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (p\u3c0.05) treatment-related improvements in cognitive functioning were found for word list learning (MAAT/placebo\u3eABT/placebo), nonverbal learning (MAAT/MPH\u3eMAAT/placebo and MAAT/MPH\u3eABT/MPH), and auditory working memory and divided attention (MAAT/MPH\u3eABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI

Methylphenidate and \u3ci\u3eMemory and Attention Adaptation Training\u3c/i\u3e for persistent cognitive symptoms after traumatic brain injury: a randomized, placebo-controlled trial

The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacologic enhancement (i.e., with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least four months prior to study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after six weeks of treatment (post-treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (p\u3c0.05) treatment-related improvements in cognitive functioning were found for word list learning (MAAT/placebo\u3eABT/placebo), nonverbal learning (MAAT/MPH\u3eMAAT/placebo and MAAT/MPH\u3eABT/MPH), and auditory working memory and divided attention (MAAT/MPH\u3eABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI

Methylphenidate and Memory and Attention Adaptation Training for persistent cognitive symptoms after traumatic brain injury: a randomized, placebo-controlled trial

The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacological enhancement (ie, with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least 4 months before study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after 6 weeks of treatment (post treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (PABT/placebo), nonverbal learning (MAAT/MPH>MAAT/placebo and MAAT/MPH>ABT/MPH), and auditory working memory and divided attention (MAAT/MPH>ABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI