Impact of physical activity on brain oxidative metabolism and intrinsic capacities in young swiss mice fed a high fat diet.

Type 2 diabetes and obesity characterized by hallmarks of insulin resistance along with an imbalance in brain oxidative metabolism would impair intrinsic capacities (ICs), a new concept for assessing mental and physical functioning. Here, we explored the impact of physical activity on antioxidant responses and oxidative metabolism in discrete brain areas of HFD or standard diet (STD) fed mice but also its consequences on specific domains of ICs. 6-week-old Swiss male mice were exposed to a STD or a HFD for 16 weeks and half of the mice in each group had access to an activity wheel and the other half did not. As expected HFD mice displayed peripheral insulin resistance but also a persistent inhibition of aconitase activity in cortices revealing an increase in mitochondrial reactive oxygen species (ROS) production. Animals with access to the running wheel displayed an improvement of insulin sensitivity regardless of the diet factor whereas ROS production remained impaired. Moreover, although the access of the running wheel did not influence mitochondrial biomass, in the oxidative metabolism area, it produced a slight decrease in brain SOD1 and catalase expression notably in HFD fed mice. At the behavioural level, physical exercise produced anxiolytic/antidepressant-like responses and improved motor coordination in both STD and HFD fed mice. However, this non-pharmacological intervention failed to enhance cognitive performance. These findings paint a contrasting landscape about physical exercise as a non-pharmacological intervention for positively orienting the aging trajectory.

Clinical, laboratory and evolutionary features of abdominal tuberculosis in comparison with other forms of extrapulmonary tuberculosis.

BACKGROUND/OBJECTIVES: Tuberculosis is a multisystem disease that might affect any organ. Abdominal tuberculosis (ABT) represents 5-17% from all extrapulmonary tuberculosis (EPT) sites. We aimed to study the clinical, laboratory and evolutionary features of ABT cases and to identify predictive factors associated with ABT. METHODS: We conducted a retrospective study including all patients hospitalized in the infectious diseases department for EPT between 1991 and 2019. We studied the characteristics of ABT cases, and we compared them with other EPT cases. RESULTS: We identified 519 patients with EPT, among whom 86 (16.6%) patients had ABT. There were 58 females (67.4%). Peritoneal tuberculosis was the most common clinical form of ABT (68.6%), followed by intestinal tuberculosis (18.6%). Patients aged 60 years and above were significantly less affected with ABT (odds ratio (OR) = 0.2; p = 0.001). The revealing systemic symptoms including fever (OR = 2.04; p = 0.006), weight loss (OR = 2.5; p < 0.001) and anorexia (OR = 1.7; p = 0.021) were significantly more frequent among ABT patients. Inflammatory markers including C-reactive protein levels (37 [10-89] mg/l vs 10 [4-57] mg/l; p < 0.001) and erythrocyte sedimentation rates (43 [15-95] mm/h vs 27 [15-60] mm/h; p = 0.044) were significantly higher among ABT cases. Multivariate logistic regression analysis showed that anorexia (adjusted OR (AOR) = 1.9; p = 0.015) and pulmonary involvement (AOR = 3.3; p = 0.002) were independent predictors of higher rate of ABT. Concomitant involvement of neuro-meningeal (AOR = 0.18; p = 0.001) and osteo-articular (AOR = 0.2; p = 0.01) sites, 40-59 (AOR = 0.2; p < 0.001) and ≥60 (AOR = 0.2; p < 0.001) age groups as well as hemoglobin rate (AOR = 0.7; p < 0.001) were independently associated with lower rate of ABT. CONCLUSIONS: Anorexia and pulmonary involvement were independent predictors of higher rate of ABT. Concomitant involvement of neuro-meningeal and osteo-articular sites, 40-59 and ≥60 age groups and hemoglobin rate were independently associated with lower rate of ABT.

Survival of an immuno-competent patient from splenic and gastric mucormycosis-case report and review of the literature.

Mucormycosis is a life-threatening disease responsible for a high mortality rate. The disease usually affects immuno-compromised patients. While all sites might be involved, gastrointestinal disease is rare, occurring for 5% to 13% of all mucormycosis cases. We report herein the fifth case of splenic and gastric mucormycosis revealed after gastric perforation and the first case occurring among an immuno-competent patient, and we review all reported cases of splenic mucormycosis by searching PubMed publications till October 2020. The literature search yielded 27 cases of splenic mucormycosis including our case. The majority of the cases had underlying immuno-compromised conditions, except for 6 cases, including ours. A male predominance was noted (22 cases). Involvement of the spleen and the stomach was rare, occurring among four immuno-compromised patients. The outcome was death in more than half of the cases. Splenic and gastric mucormycosis is a rare disease. The diagnosis of splenic mucormycosis should be considered in front of splenic lesions suggesting abscess or infarction, especially among immuno-compromised patients.

Comparative analysis between tuberculous meningitis and other forms of extrapulmonary tuberculosis.

INTRODUCTION: Tuberculosis is a multisystem disease that may affect any organ or tissue. Tuberculous meningitis (TBM) is the most severe form of tuberculosis and commonly affects the brain. We aimed to study the epidemiological, clinical, therapeutic and evolutionary features of TBM among adults and to compare them with other forms of extrapulmonary tuberculosis. METHODS: We conducted a retrospective study including all patients hospitalized for extrapulmonary tuberculosis in the infectious disease department in Sfax, Tunisia between 1993 and 2018. We specified the particularities of TBM cases, and we compared them with other extrapulmonary tuberculosis cases. RESULTS: We encountered 78 patients diagnosed with TBM, among 519 patients with extrapulmonary tuberculosis (15%). The median age was 36 years (23-50) years. There were 44 females (56.4%). In comparison with other forms of extrapulmonary tuberculosis, fever [odds ratio (OR)=4.4; p<0.001], asthenia (OR=3.4; p<0.001) and anorexia (OR=2.3; p=0.001) were significantly more frequent in TBM patients. Adverse effects of antitubercular therapy were more frequent among TBM patients (OR=3.1; p<0.001). The mean duration of antitubercular therapy was 15 (12-20) months. Recovery occurred in 66 cases (84.6%), complications in 44 cases (56.4%) and death in 7 cases (9%). Comparison of the disease evolution showed that complications (OR=7.4; p<0.001) and mortality rates (OR=10.7; p<0.001) were significantly more frequent in TBM patients, while recovery was significantly more frequent in other sites of extrapulmonary tuberculosis patients (OR=0.5; p=0.02). CONCLUSIONS: In our country, TBM remains a disabling disease. Despite antitubercular therapy, the prognosis was more severe with the occurrence of not only complications but also a high mortality rate in comparison with other forms of extrapulmonary tuberculosis. When clinical and laboratory features suggest the diagnosis of TBM, clinicians should look for tuberculosis elsewhere in the body.

Breast tuberculosis: a diagnosis not to be forgotten

Objective: To study the clinical characteristics and imaging features of breast tuberculosis (TB) and to describe treatment. Material and Methods: A retrospective study including all patients hospitalized in the infectious diseases department for breast TB between 1997 and 2018. Results: Twenty-two women, with a mean age of 39±12 years, were identified. In total, 18 patients were multiparous (81.8%). Both lump and mastalgia were the presenting symptoms in 19 cases (86.3%). Ipsilateral axillary lymphadenopathy was noted in 14 cases (63.6%). The most common finding on ultrasound was a well or poorly defined mass lesion, noted in 17 cases (77.2%), followed by fistulous tracts in seven cases (31.8%). Mammography showed focal, asymmetric breast density in 17 cases (89.5%) and diffuse in two cases (10.5%). The diagnosis was confirmed based on the presence of epithelioid cell granulomas and caseous necrosis in 13 cases (59.1%). Patients received antitubercular therapy for a mean duration of 11±5 months. The disease evolution was favorable in 20 cases (91%). There were two relapsing cases (9%). Conclusion: Breast TB should be considered in the differential diagnosis of young patients presenting with palpable lump with axillary lymphadenopathy, especially in endemic regions. The diagnosis confirmation usually requires an excision biopsy providing histological or bacteriological evidence.

The association between vitamin D deficiency and extrapulmonary tuberculosis: Case-control study.

Tuberculosis remains a public health issue worldwide. Identifying its risk factors, such as vitamin D deficiency, is mandatory so as to target the preventive strategies. We aimed to study the association between vitamin D deficiency and extrapulmonary tuberculosis. We conducted a case-control study including all cases of extrapulmonary tuberculosis hospitalized in the infectious diseases department over a two-year period from April 2017 until April 2019. We included 45 cases of extrapulmonary tuberculosis and 45 controls matched by gender and age. Vitamin D deficiency was significantly more frequent among cases (80% vs 37.7%; p < 0.001), with an odds ratio (OR) of 6.5 (IC95% = 2.5-16). The mean levels of vitamin D were significantly lower among cases (11.9 ± 8.8 vs 22.3 ± 11 ng/mL; p < 0.001). In the multivariate analysis, we found that vitamin D deficiency was an independent predictor of extrapulmonary tuberculosis (OR = 6.13; p < 0.001). The cutoff value of vitamin D predictor of extrapulmonary tuberculosis was 18.5 ng/mL which was associated with a sensitivity of 80% and a specificity of 62%. Our study provides strong evidence that vitamin D deficiency was an independent predictor of extrapulmonary tuberculosis. More studies are needed in order to evaluate the potential preventive role of vitamin D and the benefit of possible supplementation.

Tuberculous and Brucellar Spondylodiscitis: Comparative Analysis of Clinical, Laboratory, and Radiological Features.

STUDY DESIGN: This was a retrospective study. PURPOSE: The aim was to compare the clinical, laboratory, radiological, and evolutionary features of tuberculous spondylodiscitis (TS) and brucellar spondylodiscitis (BS). OVERVIEW OF LITERATURE: Clinical presentation of spondylodiscitis varies according to the underlying etiology, among which brucellosis and tuberculosis represent the primary cause, in endemic countries. Only a few studies have compared the characteristics between TS and BS. METHODS: A retrospective study was conducted using the data of all patients hospitalized for TS and BS in the infectious diseases department between 1991 and 2018. RESULTS: Among a total of 117 patients, 73 had TS (62.4%) and 44 had BS (37.6%). Females were significantly more affected with TS than males (56.2% vs. 22.7%, p<0.001). Fever (72.7% vs. 45.2%, p=0.004) and sweating (72.7% vs. 47.9%, p=0.009) were significantly more frequent among patients with BS. The median erythrocyte sedimentation rate was significantly higher in the TS group (median, 70 mm/hr; interquartile range [IQR], 45-103 mm/hr) than in the BS group (median, 50 mm/hr; IQR, 16-75 mm/hr) (p=0.003). Thoracic involvement was significantly more frequent in the TS group (53.4% vs. 34.1%, p=0.04), whereas lumbar involvement was significantly more frequent in the BS group (72.7% vs. 49.3%, p=0.01). Initial imaging findings revealed significantly higher frequencies of posterior vertebral arch involvement, vertebral compaction, and spinal cord compression in the TS group. Percutaneous abscess drainage (20.5% vs. 2.3%, p=0.005) and surgical treatment (17.8% vs. 2.3%, p=0.01) were more frequently indicated in the TS group, with a significant difference. CONCLUSIONS: A combination of clinical, laboratory, and radiological features can be used to distinguish between TS and BS while these patients await diagnosis confirmation.

Update on urogenital tuberculosis in Southern Tunisia: a review of a 26-year period.

INTRODUCTION: Tuberculosis affects commonly the lungs, but any other organs can be affected as well. Urogenital tuberculosis is usually misdiagnosed. In this perspective, we aimed to give an update on the epidemiological, clinical and evolutionary features of urogenital tuberculosis in Southern Tunisia. METHODS: We conducted a retrospective study including all patients with extrapulmonary tuberculosis notified during the period from 1992 to 2017 in Southern Tunisia. We specified the particularities of urogenital tuberculosis cases, and we compared them with other extrapulmonary tuberculosis cases. RESULTS: Overall, we analyzed 240 cases with urogenital tuberculosis, among 1702 patients with extrapulmonary tuberculosis (14.1%). There were 121 women (50.4%). The mean age was 49±17 years. Multifocal tuberculosis was noted in 29 cases (12.1%). There were 169 cases with urinary tract tuberculosis (70.4%). Chronological trends analysis showed that the median age at diagnosis increased significantly (Rho=0.41; p=0.039) and the number of urogenital tuberculosis declined during the study period, without a statistical significance (Rho = -0.07; p=0.721). Compared to other extrapulmonary tuberculosis sites, patients aged 60 years and above (OR=2.7; p<0.001) and coming from rural areas (OR=1.4; p=0.021) were more frequently diagnosed with urogenital tuberculosis. Treatment duration was significantly longer in patients with urogenital tuberculosis (10.13±3.79 vs 9.20±3.77 months; p<0.001). As for the disease evolution, relapse was significantly more frequent in patients with urogenital tuberculosis (OR=4.1; p=0.045). CONCLUSIONS: Although decreasing trends over time were noted, the prognosis of urogenital tuberculosis was more severe compared to other extrapulmonary tuberculosis sites.

Prognosis of urinary tract infections: predictive factors and role of Ramadan fasting.

BACKGROUND: The role of Ramadan fasting (RF) as a predictive factor of urinary tract infection (UTI) recurrence was controversially discussed in the literature. AIM: The present study aimed to identify the prognosis factors of recurrent UTIs. METHODS: Data were retrospectively collected from patients with UTI diagnosed at the infectious diseases department and its affiliated outpatient department in Hedi Chaker University Hospital, Sfax, Tunisia, between 2010 and 2017. Kaplan-Meier method was used to generate recurrence-free survival (RFS) curves for first episode of UTI diagnosed in two groups: during and outside Ramadan, which were compared using Log-rank test for statistical inference. Univariate and multivariate Cox proportional hazards regression models were used to identify UTI recurrence factors (sex, age, age group, season, comorbidities, first UTI episode diagnosed during Ramadan, UTI requiring hospitalization, length of hospital stay, nosocomial UTI, clinical presentation). RESULTS: During the follow up, among the 867 patients with UTI, 105 (12.1%) developed a recurrent UTI one. The RFS median [95% confidence interval] was 60 [40 to 82] days. Survival curves showed that patients with UTI diagnosed during Ramadan had shorter RFS compared with those diagnosed outside of Ramadan (32 vs. 60 days, respectively, p=0.002). RF (hazard ratio = 2.96; p = 0.033) and diabetes mellitus (hazard ratio =1.6; p = 0.033) were independently associated with UTI recurrence in multivariate Cox regression analysis. CONCLUSION: Recurrent UTI was a prevalent and challenging condition among patients with UTI. Diabetes mellitus and RF had a prognosis value for recurrence in UTI.

Performance of an Easy and Simple New Scoring Model in Predicting Multidrug-Resistant Enterobacteriaceae in Community-Acquired Urinary Tract Infections.

BACKGROUND: Multidrug resistance (MDR) is a growing global problem in bacterial community-acquired urinary tract infections (CUTIs). We aimed to propose an easy-to-use clinical prediction model to identify patients with MDR in CUTI. METHODS: We conducted a retrospective study including 770 patients with documented CUTI diagnosed during 2010-2017. Logistic regression-based prediction scores were calculated based on variables independently associated with MDR. Sensitivities and specificities at various cutoff points were determined, and the area under the receiver operating characteristic curve (AUROC) was computed. RESULTS: We found MDR Enterobacteriaceae in 372 cases (45.1%). Multivariate analysis showed that age ≥70 years (adjusted odds ratio [aOR], 2.5; 95% confidence interval [CI], 1.8-3.5), diabetes mellitus (aOR, 1.65; 95% CI, 1.19-2.3), history of urinary tract surgery in the last 12 months (aOR, 4.5; 95% CI, 1.22-17), and previous antimicrobial therapy in the last 3 months (aOR, 4.6; 95% CI, 3-7) were independent risk factors of MDR in CUTI. The results of Hosmer-Lemshow chi-square testing were indicative of good calibration of the model (χ2 = 3.4; P = .49). At a cutoff of ≥2, the score had an AUROC of 0.71, a sensitivity of 70.5%, a specificity of 60%, a positive predictive value of 60%, a negative predictive value of 70%, and an overall diagnostic accuracy of 65%. When the cutoff was raised to 6, the sensitivity dropped (43%), and the specificity increased appreciably (85%). CONCLUSIONS: We developed a novel scoring system that can reliably identify patients likely to be harboring MDR in CUTI.

Activation of nociceptin/orphanin FQ receptors inhibits contextual fear memory reconsolidation.

Several neuropeptidergic systems act as modulators of cognitive performances. Among them, nociceptin, an opioid-like peptide also known as orphanin FQ (N/OFQ), has recently gained attention. Stimulation of its receptor, the N/OFQ opioid receptor (NOP), which is expressed in brain regions involved in emotion, memory and stress response, has inhibitory effects on the acquisition and/or consolidation of spatial and emotional memory in rodents. Recently, N/OFQ was also proposed to be linked to the pathogenesis of Post-Traumatic Stress Disorder in humans. However, until now the effect of the activation of the N/OFQ-NOP system on already consolidated memory, such as during retrieval and reconsolidation phases, has never been explored. In the present study, we investigated the consequences of systemic injection of NOP agonists or i.c.v. injection of the N/OFQ peptide on the retrieval and the reconsolidation of contextual fear memory in mice. We demonstrate that the activation of the N/OFQ system impairs the reconsolidation of context-dependent but not cue-dependent aversive memories. We also show that this amnestic effect is associated with decreased c-Fos expression in the hippocampus and amygdala. Our data thus provide the first evidence that the NOP receptor could be targeted during the reconsolidation process to weaken maladaptive memories. The N/OFQ-NOP system might constitute in the future an interesting pharmacological target for interfering with so-called "pathological memories", in particular those involving maladaptive contextual memories.

Cognitive deficit in hippocampal-dependent tasks in Werner syndrome mouse model.

Mammalian aging is often characterized by metabolic disturbances, cognitive declines and DNA repairs deficiency, but the underlying molecular mechanisms are still not well understood. Alterations in DNA repair can significantly exacerbate aging. Mammalian neuronal cells which accumulate unrepaired DNA damage over time could potentially lead to brain functions disorders. Focusing on the ATP-dependent RecQ-type DNA helicase, an enzyme involved in repair of double strand DNA, a mouse model of Werner syndrome (WS) had been proposed as a model of accelerated aging. Until now, no study has investigated the impact of this premature aging syndrome on learning and memory. Spatial memory and cognitive flexibility are particularly affected by the aging process in both men and rodents. Studies have shown that aged mice exhibited similar performance than young adult mice on non-hippocampus dependent memory whereas their performances were decreased in hippocampus-dependent tasks. In this study, we have submitted 3, 5 and 8 month-old WS mice to several behavioral paradigms to evaluate hippocampus-dependent (spatial object location, Morris water maze and fear conditioning) and non hippocampus-dependent (object recognition) memories. No effect on the locomotion activity and anxiety level has been observed in adult WS mice. Interestingly, the 8 month-old WS mice exhibit long-term memory impairment similar to aged mice, suggesting that adult WS mice do develop some aspects of cognitive aging.

Involvement of protein degradation by the ubiquitin proteasome system in opiate addictive behaviors.

Plastic changes in the nucleus accumbens (NAcc), a structure occupying a key position in the neural circuitry related to motivation, are among the critical cellular processes responsible for drug addiction. During the last decade, it has been shown that memory formation and related neuronal plasticity may rely not only on protein synthesis but also on protein degradation by the ubiquitin proteasome system (UPS). In this study, we assess the role of protein degradation in the NAcc in opiate-related behaviors. For this purpose, we coupled behavioral experiments to intra-accumbens injections of lactacystin, an inhibitor of the UPS. We show that protein degradation in the NAcc is mandatory for a full range of animal models of opiate addiction including morphine locomotor sensitization, morphine conditioned place preference, intra-ventral tegmental area morphine self-administration and intra-venous heroin self-administration but not for discrimination learning rewarded by highly palatable food. This study provides the first evidence of a specific role of protein degradation by the UPS in addiction.