Mycobacterium tuberculosis subverts the differentiation of human monocytes into dendritic cells

Intracellular pathogens have developed strategies for evading elimination by the defenses of the host immune system. Here we describe an escape mechanism utilized by Mycobacterium tuberculosis that involves the interference with the generation of fully competent DC from monocytes. We show that monocytes infected with live M. tuberculosis differentiated into mature, CD83+ and CCR7+ DC (Mt-MoDC), but were characterized by a selective failure in the expression of the family of CD1 molecules. These cells also showed levels of MHC class II and CD80 (B7.1) that were reduced in comparison with LPS-matured DC. In addition, Mt-MoDC produced TNF-alpha and IL-10, but were unable to secrete IL-12. The generation of Mt-MoDC required the infection of monocytes with live M. tuberculosis, since infection with heat-killed bacteria partially abrogated the effects on monocyte differentiation. Interestingly, Mt-MoDC revealed an impaired antigen-presentation function as assessed by the reduced capability to induce proliferation of cord blood T lymphocytes. Further, naive T lymphocytes expanded by Mt-MoDC were unable to secrete cytokines, in particular IL-4 and IFN-gamma, suggesting that they could be ineffective in helping the macrophage-mediated killing of intracellular mycobacteria. Our results suggest that the interference with monocyte differentiation into fully competent DC is an evasion mechanism of M. tuberculosis that could contribute to its intracellular persistence by avoiding immune recognition.     

A case of carcinoid with multiple sites in the jejunum and distal ileum

Multiple carcinoid tumors of the small bowel with more than 3 lesions are very unusual. The authors report a case with 4 lesions, 2 of those localized in the jejunum with more advanced infiltration of the wall and extension to regional mesenteric lymph nodes, revealed by ultrasonography. The relative low incidence and particularly the vague, nonspecific clinical presentation, the unusual site in the jejunum, and failure of the radiological examine of one year before lead to not suspect this condition prior to US examination. However, the feature of asymmetric, concentric thickening of the bowel wall requiring a more accurate exam by CT with oral contrast was able to confirm the suspect of the intestinal tumor. The patient, 80 year old, underwent radical surgery with a wide lymph nodes dissection as well as double resection of the jejunum and distal ileum. The post-surgical outcome was uneventful. A 12-month follow-up is free of the disease.     

Varicocele sclerotherapy improves serum inhibin B levels and seminal parameters

The usefulness of treating varicocele in order to improve fertility is still a matter of debate. The aim of this study was to evaluate variations in seminal parameters and inhibin B concentrations in a group of males affected by varicocele and treated by percutaneous retrograde sclerotherapy in comparison with a group of patients who did not undergo varicocele treatment. Thirty-eight patients with left varicocele underwent spermatic vein phlebography and percutaneous retrograde sclerotherapy with hydroxy-polyaethoxy-dodecanol. Serum inhibin B, follicle-stimulating hormone (FSH), testosterone levels and seminal parameters (sperm concentration, motility and morphology) were performed before and 6 months after sclerotherapy. Forty patients with left varicocele who did not undergo sclerotherapy were studied as controls. A significant increase (p < 0.01) in serum inhibin B levels and a significant decrease (p < 0.05) in FSH levels were observed 6 months after treatment. Semen analysis showed a significant improvement in sperm concentration (p < 0.05) and progressive motility (p < 0.01) after treatment. In control group no significant variations in hormonal and seminal parameters were observed 6 months after the basal examination. Six months after the basal evaluation, inhibin B levels were significantly higher in treated subjects than in controls (p < 0.05) whereas FSH levels were significantly lower (p < 0.05). Sperm concentration and progressive motility were significantly increased (p < 0.05 and p < 0.001, respectively) in treated subjects in comparison with controls. In conclusion, varicocele sclerotherapy improves inhibin B levels and seminal parameters, confirming the positive effect of this treatment on spermatogenesis and Sertoli cell function.     

Amelioration of Neurosensory Structure and Function in Animal and Cellular Models of a Congenital Blindness

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Parechovirus Genotype 3 Outbreak among Infants,New South Wales,Australia, 2013–2014

From October 2013 through February 2014, human parechovirus genotype 3 infection was identified in 183 infants in New South Wales, Australia. Of those infants, 57% were male and 95% required hospitalization. Common signs and symptoms were fever >38°C (86%), irritability (80%), tachycardia (68%), and rash (62%). Compared with affected infants in the Northern Hemisphere, infants in New South Wales were slightly older, both sexes were affected more equally, and rash occurred with considerably higher frequency. The New South Wales syndromic surveillance system, which uses near real-time emergency department and ambulance data, was useful for monitoring the outbreak. An alert distributed to clinicians reduced unnecessary hospitalization for patients with suspected sepsis.     

Pre-Menopausal Breast Fat Density Might Predict MACE During 10 Years of Follow-Up: The BRECARD Study

ObjectivesThis study sought to determine whether the breast gland adipose tissue is associated with different rates of major adverse cardiac events (MACEs) in pre-menopausal women.BackgroundTo our knowledge, no study investigated the impact of breast adipose tissue infiltration on MACEs in pre-menopausal women.MethodsProspective multicenter cohort study conducted on pre-menopausal women >40 years of age without cardiovascular disease and breast cancer at enrollment. The study started in January 2000 and ended in January 2009, and the end of the follow-up for the evaluation of MACEs was in January 2019. Participants underwent mammography to evaluate breast density and were divided into 4 groups according to their breast density. The primary endpoint was the probability of a MACE at 10 years of follow-up in patients staged for different breast deposition/adipose tissue deposition.ResultsThe propensity score matching divided the baseline population of 16,763 pre-menopausal women, leaving 3,272 women according to the category of breast density from A to D. These women were assigned to 4 groups of the study according to baseline breast density. At 10 years of follow-up, we had 160 MACEs in group 1, 62 MACEs in group 2, 27 MACEs in group 3, and 16 MACEs in group 4. MACEs were predicted by the initial diagnosis of lowest breast density (hazard ratio: 3.483; 95% confidence interval: 1.476 to 8.257). Further randomized clinical trials are needed to translate the results of the present study into clinical practice. The loss of ex vivo breast density models to study the cellular/molecular pathways implied in MACE is another study limitation.ConclusionsAmong pre-menopausal women, a higher evidence of adipose tissue at the level of breast gland (lowest breast density, category A) versus higher breast density shows higher rates of MACEs. Therefore, the screening mammography could be proposed in overweight women to stage breast density and to predict MACEs. (Breast Density in Pre-menopausal Women Is Predictive of Cardiovascular Outcomes at 10 Years of Follow-Up [BRECARD]; NCT03779217)