Background: Streptococcus pneumoniae is the leading cause of bacterial meningitis. Pneumococcal meningitis is associated with the highest mortality among bacterial meningitis and it may also lead to neurological sequelae despite the use of antibiotic therapy. Experimental animal models of pneumococcal meningitis are important to study the pathogenesis of meningitis, the host immune response induced after infection, and the efficacy of novel drugs and vaccines. Results: In the present work, we describe in detail a simple, reproducible and efficient method to induce pneumococcal meningitis in outbred mice by using the intracranial subarachnoidal route of infection. Bacteria were injected into the subarachnoid space through a soft point located 3.5 mm rostral from the bregma. The model was tested with several doses of pneumococci of three capsular serotypes (2, 3 and 4), and mice survival was recorded. Lethal doses killing 50 % of animals infected with type 2, 3 and 4 S. pneumoniae were 3.2 × 10, 2.9 × 10 and 1.9 × 10² colony forming units, respectively. Characterisation of the disease caused by the type 4 strain showed that in moribund mice systemic dissemination of pneumococci to blood and spleen occurred. Histological analysis of the brain of animals infected with type 4 S. pneumoniae proved the induction of meningitis closely resembling the disease in humans. Conclusions: The proposed method for inducing pneumococcal meningitis in outbred mice is easy-to-perform, fast, cost-effective, and reproducible, irrespective of the serotype of pneumococci used.

Pneumococcal meningitis (PM) is a life-threatening disease with a high case-fatality rate and elevated risk for serious neurological sequelae. In this study, we investigated the contribution of three major virulence factors of Streptococcus pneumoniae, the capsule, pneumococcal surface protein A (PspA) and C (PspC), to the pathogenesis of experimental PM.

Deep learning is widely applied in bioinformatics and biomedical imaging, due to its ability to perform various clinical tasks automatically and accurately. In particular, the application of deep learning techniques for the automatic identification of glomeruli in histopathological kidney images can play a fundamental role, offering a valid decision support system tool for the automatic evaluation of the Karpinski metric. This will help clinicians in detecting the presence of sclerotic glomeruli in order to decide whether the kidney is transplantable or not. In this work, we implemented a deep learning framework to identify and segment sclerotic and non-sclerotic glomeruli from scanned Whole Slide Images (WSIs) of human kidney biopsies. The experiments were conducted on a new dataset collected by both the Siena and Trieste hospitals. The images were segmented using the DeepLab V2 model, with a pre-trained ResNet101 encoder, applied to 512 × 512 patches extracted from the original WSIs. The results obtained are promising and show a good performance in the segmentation task and a good generalization capacity, despite the different coloring and typology of the histopathological images. Moreover, we present a novel use of the CD10 staining procedure, which gives promising results when applied to the segmentation of sclerotic glomeruli in kidney tissues.

Angioimmunoblastic T-cell lymphoma is one of the most common subtypes of peripheral T-cell lymphoma (15-20% of all cases), accounting for approximately 1-2% of all non-Hodgkin lymphomas. It often presents autoimmune phenomena including hemolytic anemia, thrombocytopenia, glomerulonephrities and circulating immune complexes. Polyarteritis nodosa is an autoimmune disease characterized by necrotizing vasculitis of medium vessels, which rarely develops in association with hematological malignant disorders. Herein we report the case of a 40-year-old man who underwent lymph node biopsy in the suspicious of sarcoidosis. On the basis of histological and immunohistochemical findings, the diagnosis of angioimmunoblastic T-cell lymphoma was performed. The patient was successfully treated with cytarabine-based regimen for 6 cycles. Three months after the initial diagnosis of angioimmunoblastic T-cell lymphoma, a whole body computed tomography showed a lesion in the lower pole of the left kidney. Renal cell carcinoma was suspected, thus a nephrectomy was carried out. The histological findings were compatible with polyarteritis nodosa. To the best of our knowledge, the association between polyarteritis nodosa and angioimmunoblastic T-cell lymphoma has been described only once. This relation may be secondary to the induction of an autoimmune phenomenon by the lymphoma with the formation of circulating immune complexes, leading to vessels walls injury. A careful evaluation is needed in the management of angioimmunoblastic T-cell lymphoma patients with signs of renal failure in order to avoid delay of treatment and organ damage.

Purpose: Omentin-1/intelectin (ITLN)1 is an adipocytokine with both anti-inflammatory and anti-oxidative stress properties, and little is known about its role in male reproduction. This study was aimed at exploring the relationships among omentin-1/ITLN1, semen parameters and F₂-isoprostanes (F₂-IsoPs), a maker of oxidative stress, in groups of patients affected by different pathologies. In addition, omentin-1/ITLN1 immunolocalization was assessed in ejaculated spermatozoa and in tissues of male reproductive system. Patients and Methods: Semen samples of infertile patients with varicocele (n = 27), genitourinary infections (n = 17), idiopathic infertility (n = 15) and fertile men (n = 21) were analyzed following WHO guidelines, and seminal plasma were used to determine omentin-1/ITLN1 by ELISA and F₂-IsoP levels by gas chromatography/negative-ion chemical ionization tandem mass spectrometry. Omentin-1/ITLN1 was localized in human sperm and in the tissue of male reproductive system. Results: Considering all participants, F₂-IsoP and omentin-1/ITLN1 levels were positively correlated (p = 0.000), and both these indices were negatively correlated with sperm parameters. Infertile patients showed lower sperm parameters than fertile ones; varicocele and infection groups had significantly increased levels of F₂-IsoPs (both p = 0.000) and omentin-1/ITLN1 (p = 0.000 and p = 0.001, respectively). Omentin-1/ITLN1 signal was located as a spot in the connecting piece (in 43.5% of cases midpiece was also labeled) of sperm from fertile men and in cytoplasmic residue and in the entire tail in sperm of patients with varicocele and genitourinary infections. A focal omentin-1/ITLN1 immunolabelling was evident in the basal area of epididymal tubule, and a diffuse signal was present in the seminal vesicle epithelium. Conclusion: Semen omentin-1/ITLN1 originates from seminal vesicles, its levels increase in inflammatory conditions and are negatively correlated with sperm parameters. For this reason, a sort of protective role of omentin-1/ITLN1 can be postulated, as this adipokine shows anti-inflammatory properties also in many other biological systems. Graphical Abstract:

Nerve growth factor (NGF) signalling affects spermatogenesis and mature sperm traits. In this paper, we aimed to evaluate the distribution and the role of NGF and its receptors (p75^NTR and TrKA) on the reproductive apparatus (testis and epididymis) and sperm of fertile men (F) and men with different pathologies, namely varicocele (V) and urogenital infections (UGIs). We collected semen samples from 21 individuals (31–40 years old) subdivided as follows: V (n = 7), UGIs (n = 7), and F (n = 7). We submitted the semen samples to bacteriological analysis, leucocyte identification, and analysis of sperm parameters (concentration, motility, morphology, and viability). We determined the seminal plasma levels of NGF, interleukin 1β (IL-1β), and F₂-isoprostanes (F₂-IsoPs), and the gene and protein expression of NGF receptors on sperm. We also used immunofluorescence to examine NGF receptors on ejaculated sperm, testis, and epididymis. As expected, fertile men showed better sperm parameters as well as lower levels of NGF, F_2-IsoPs, and IL-1β compared with men with infertility. Notably, in normal sperm, p75^NTR and TrKA were localised throughout the entire tail. TrKA was also found in the post-acrosomal sheath. This localisation appeared different in patients with infertility: in particular, there was a strong p75^NTR signal in the midpiece and the cytoplasmic residue or coiled tails of altered ejaculated sperm. In line with these findings, NGF receptors were intensely expressed in the epididymis and interstitial tissue of the testis. These data suggest the distinctive involvement of NGF and its receptors in the physiology of sperm from fertile men and men with infertility, indicating a possible role for new targeted treatment strategies.