The potential therapeutic role of Hericium erinaceus extract in pathologic conditions involving the urogenital-gut axis: insights into the involved mechanisms and mediators.

In this review we focused on the putative therapeutic effect of Hericium erinaceus extract in the treatment of pathologic conditions of the lower urinary tract in which intestinal inflammation may play a role. To this aim we reviewed the available evidence on pelvic cross-organ sensitization as a possible mechanism through which intestinal inflammation and dysbiosis may affect the lower urinary tract. Also, we reviewed the clinical and experimental evidence supporting the role of Hericium erinaceus extract as an anti-inflammatory agent highlighting the role of a number of putative mediators and mechanisms which might make this nutraceutical suitable for the management of 'difficult to treat' lower urinary tract disorders.

"A lactose-modified chitosan accelerates chondrogenic differentiation in mesenchymal stem cells spheroids".

Spheroids derived from human mesenchymal stem cells (hMSCs) are of limited use for cartilage regeneration, as the viability of the cells progressively decreases during the period required for chondrogenic differentiation (21 days). In this work, spheroids based on hMSCs and a lactose-modified chitosan (CTL) were formed by seeding cells onto an air-dried coating of CTL. The polymer coating can inhibit cell adhesion and it is simultaneously incorporated into spheroid structure. CTL-spheroids were characterized from a morphological and biological perspective, and their properties were compared with those of spheroids obtained by seeding the cells onto a non-adherent surface (agar gel). Compared to the latter, smaller and more viable spheroids form in the presence of CTL as early as 4 days of culture. At this time point, analysis of stem cells differentiation in spheroids showed a remarkable increase in collagen type-2 (COL2A1) gene expression (~700-fold compared to day 0), whereas only a 2-fold increase was observed in the control spheroids at day 21. These results were confirmed by histological and transmission electron microscopy (TEM) analyses, which showed that in CTL-spheroids an early deposition of collagen with a banding structure already occurred at day 7. Overall, these results support the use of CTL-spheroids as a novel system for cartilage regeneration, characterized by increased cell viability and differentiation capacity within a short time-frame. This will pave the way for approaches aimed at increasing the success rate of procedures and reducing the time required for tissue regeneration.

Golimumab improves health-related quality of life of patients with moderate-to-severe ulcerative colitis: Results of the go-care study.

BACKGROUND: In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy. METHODS: We report results from a multicenter prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment). RESULTS: Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (168.5) and w48 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48. CONCLUSIONS: GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment.

Genomic comparison of two strains of Mycobacterium avium subsp. paratuberculosis with contrasting pathogenic phenotype.

In a previous study, we evaluated the degree of virulence of Mycobacterium avium subsp. paratuberculosis (Map) strains isolated from cattle in Argentina in a murine model. This assay allowed us to differentiate between high-virulent MapARG1347 and low-virulent MapARG1543 strains. To corroborate whether the differences in virulence could be attributed to genetic differences between the strains, we performed Whole Genome Sequencing and compared the genomes and gene content between them and determined the differences related to the reference strain MapK10. We found 233 SNPs/INDELS in one or both strains relative to Map K10. The two strains share most of the variations, but we found 15 mutations present in only one of the strains. Considering NS-SNP/INDELS that produced a severe effect in the coding sequence, we focus the analysis on four predicted proteins, putatively related to virulence. Survival of MapARG1347 strain in bMDM was higher than MapARG1543 and was more resistant to acidic pH and H2O2 stresses than MapK10. The genomic differences between the two strains found in genes MAP1203 (a putative peptidoglycan hydrolase), MAP0403 (a putative serine protease) MAP1003c (a member of the PE-PPE family) and MAP4152 (a putative mycofactocin binding protein) could contribute to explain the contrasting phenotype previously observed in mice models.

Evaluation of stress response in black-tailed prairie dogs (Cynomys ludovicianus) in arid regions from colonies in Chihuahua Mexico.

Among all the regulatory homeostatic networks in vertebrates, the activation of the hypothalamic-pituitaryadrenal axis during the stress response, has gained considerable attention, and the measurement of fecal glucocorticoids (FGC) has become an invaluable tool to assess adrenocortical activity related to stressful events in wild and captive animals. However, the use of FGC requires the validation of measurement techniques and the proper selection of the specific hormone according to the study species. The main objective of this study was to identify the dominant glucocorticoid (GC) hormone in the stress response of black-tailed prairie dogs (Cynomys ludovicianus) in an arid grassland of Chihuahua, Mexico. A capture stress challenge in the field was developed to determine if the levels of glucocorticoids (cortisol and corticosterone) both in serum and fecal samples could be attributed to stress in Cynomys ludovicianus. The samples were analysed with the technique of liquid phase radioimmunoassay , and this study showed that both cortisol and corticosterone are present at measurable levels in serum and fecal samples of black-tailed prairie dogs. We found that both GCs were present in similar concentrations in serum, however, corticosterone concentration in fecal samples was higher than cortisol. Likewise, biochemical validations performed in this study to test the assay reached acceptable levels of reliability. Therefore, we confirm that fecal analysis can be implemented as a method to measure stress responses in wild prairie dogs.

Un hallazgo inesperado en hipocondrio derecho / An unexcepted finding in the right hypocondrium

A 90-years-old man comes to the emergency department with diffuse abdominal pain and fever three days. On physical examination, the abdomen is soft and depressible with air-fluid sound present and bilateral reductible inguinal hernias. A mass is palpated at the level of the roght hypochondrium with a positive Murphy´s sign whitout signs of peritoneal irritation. An abdominal CT with intravenous contrast is requested due to the suspicion of acute abdominal pathology, observing cholelithiasis and a markedly distended gallbladder with torsion. (AU)

Lesiones osteolíticas multifocales / Multifocal osteolytic lesions

A 79-year-old woman with multiple pathologies and multiple osteolytic lesions during the Covid-19 pandemic. Histopathological and radiological differential diagnosis of injuries. (AU)

Two-species totally asymmetric simple exclusion process model: From a simple description to intermittency and traveling traffic jams.

We extend the paradigmatic and versatile totally asymmetric simple exclusion process (TASEP) for stochastic 1D transport to allow for two different particle species, each having specific entry and exit rates. We offer a complete mean-field analysis, including a phase diagram, by mapping this model onto an effective one-species TASEP. Stochastic simulations confirm the results, but indicate deviations when the particle species have very different exit rates. We illustrate that this is due to a phenomenon of intermittency, and formulate a refined "intermittent" mean-field theory for this regime. We discuss how nonstationary effects may further enrich the phenomenology.

Bulto y molestias en región inguinal en gestante de 16 semanas / Lump and discomfort in the groin region in a 16-week pregnant woman 16 weeks

34-year-old woman, 16 weeks pregnant, with a personal history of cervical conization and previous cesarean section.Consultation for discomfort in the right groin region and signs of inflammation in the area, without a clear tumor. She refers that inthe first pregnancy she presented the same symptoms. In the intergestational period she has not noticed these symptoms. On physicalexamination, the 16-week pregnant abdomen did not reveal clear signs of hernia, although there was slight pain on palpation. It wasdecided to request a pelvic ultrasound to rule out the presence of hernia or other soft tissue lesions in the groin region. (AU)

Mujer de 34 años, gestante de 16 semanas, con antecedentes personales de conización cervical y cesárea anterior. Consultapor molestias en región inguinal derecha y signos de inflamación en la zona, sin clara tumoración. Refiere que en el primerembarazo presentaba la misma sintomatología. En el período intergestacional no ha notado estos síntomas. A la exploraciónfísica se palpa útero, con altura correspondiente a unas 16 semanas de gestación, no se demuestran signos evidentes de hernia,aunque si leve dolor a la palpación. Se decide solicitar ecografía pélvica para descartar la presencia de hernia u otras lesiones de partes blandas en región inguinal. (AU)

Intestinal microbiota, intestinal permeability and the urogenital tract: is there a pathophysiological link?

Human gut microbiome is related to different clinical conditions and diseases. Recently several hypotheses have been theorized about a link between gut microbiota and genitourinary disease including urinary tract infections, and benign prostatic hyperplasia. Despite several data, underlying mechanisms still remain unclear. The aim of this review is to report the current state of knowledge in relation to urinary tract infections, benign prostatic hyperplasia and intestinal microbiota with a focus on its role in the development of disease and the underlying pathophysiologic mechanisms.

COVID-19 y embolia pulmonar: una nueva entidad / Covid-19 and pulmonary embolism: a new entity

El SARS-CoV-2 es un virus emergente que se extendió por todo el mundo desde China a finales de 2019, generando en el individuo una respuesta inflamatoria sistémica con afectación severa de los principales órganos (pulmón, corazón, sistema nervioso central, etc.). A la enfermedad causada por el mismo, la denominamos COVID-19. Una de las complicaciones descritas en la literatura, más frecuentemente asociadas a la infección, es la enfermedad tromboembólica venosa (embolismo pulmonar y trombosis venosa profunda). Se cree que la causa es debida a la inflamación excesiva y un estado de hipercoagulabilidad, con activación plaquetaria, disfunción endotelial y estasis sanguínea, que favorece la adhesión plaquetaria y formación de trombos. Presentamos dos casos clínicos diagnosticados en nuestro centro durante el periodo de pandemia en los que se observó esta complicación (AU)

SARS-CoV-2 is an emerging virus spread over the world from China in late 2019, generating in the patient a systemic inflammatory response with severe involvement of the main organs (lung, heart, central nervous system, etc.). The disease produced by this virus is called COVID-19. Previous studies show that one of the most commonly associated complications with COVID-19 is venous thromboembolic disease (pulmonary embolism and deep vein thrombosis). The cause is thought to be due to excessive inflammation and hypercoagulability, with platelet activation, endothelial dysfunction and blood theses, which promotes platelet adhesion and thrombus formation. We present two clinical cases reported during the pandemic period in which this complication was reported (AU)

New and rapid strategies for the diagnosis of bovine paratuberculosis "in situ" using latex particles.

The chemical coupling of a protoplasmatic antigen from Mycobacterium avium subsp. paratubeculosis onto core-shell carboxylated particles was investigated with the aim of producing latex-protein complexes to be used in immunoagglutination assays capable of detecting bovine paratuberculosis disease. For this purpose, sensitizations were carried out using both colored and not colored carboxylated latexes as well as the protoplasmatic antigen at pH close to its isoelectric point to favor the antigenic protein to approach the particle surface. In all cases, higher fractions of proteins were chemically-bound to carboxyl groups on the surface of the particles. The assessment of the performance of the visual immunoagglutination assays consisted of evaluating 111 sera from healthy and infected bovines with Mycobacterium avium subsp. paratuberculosis. Complexes obtained from the colored latex allowed an acceptable visual discrimination between the studied positive and negative sera. Most of the positive samples showed strong to very strong agglutination and only a few samples reacted weakly, i.e. a sensitivity of 70%. The specificity of the assay, on the other hand, was 86%. Therefore, this rapid detection technique allows an easy and inexpensive identification of animals possibly infected with paratuberculosis "in situ" in the herds.

May chronic cough in chronic obstructive pulmonary disease be a contraindication of Percutaneous Endoscopic Gastrostomy placement: a case report.

BACKGROUND: Percutaneous Endoscopic Gastrostomy (PEG) can involve some complications, despite the good safety of its track record. The Buried Bumper Syndrome (BBS) is a rare, late and dangerous complication that consists in the erosion of the internal bumper through the gastric wall. Case presentation We report the development of BBS in a man with chronic obstructive pulmonary disease (COPD) who had a persistent chronic cough which was prevalently but not solely in the morning and required placement of a PEG tube for continuous infusion of Levodopa/carbidopa intestinal gel for advanced Parkinson's disease. CONCLUSION: We believe that COPD with chronic cough while not representing an absolute contraindication to PEG placement, may potentially cause BBS and therefore an appropriate regimen of tube care by expert personnel is mandatory in this setting.

Efficacy of ustekinumab in the treatment of patients with Crohn's disease with failure to previous conventional or biologic therapy: a prospective observational real-life study.

Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn's disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear. This study was performed on 92 subjects with confirmed diagnosis of moderate to severe Crohn's disease and no neoplasia. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy. All patients underwent endoscopic examination and bowel MRI and ultrasonography at baseline (T0). At week 52 (T52), patients underwent colonoscopy for assessment of mucosal healing and MRI or ultrasonography for assessment of transmural healing. CDAI was used for the assessment of clinical response and clinical remission. SES-CD was used to assess endoscopic response and remission. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period. Clinical response at week 52 was achieved in 38 (50.5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. We observed a reduction in SES-CD of at least 50% in 34 (45%) patients as well as an SES-CD ≤ 2 in 26 (35%) patients. All patients with mucosal healing also showed transmural healing. No major TRAEs were observed during treatment. In this multicenter, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing).

Quantification of immunoreactive testosterone and estradiol-17ß metabolites to identify the sex of Neotropical otters (Lontra longicaudis annectens) in the field.

Before there was use of ultrasonographic imaging, determination of the ratio of estrogens to androgens in the same individual was a technique used for differentiating the sex of monomorphic animals in captivity, with larger estrogen concentrations in the females. Due to species-specific differences in both concentration and changes throughout the year of these hormones, corroboration of the method is needed in each case. In this study, there was use of a chemo-immuno assay to quantify sex steroids in fecal samples collected from seven (five females and two males) Neotropical otters, Lontra longicaudis. The reproductive season for this species was determined to be between October and March, with increased estradiol in the females and relatively greater concentrations of testosterone in the males as compared with other seasons of the year. Results from utilization of a k-means analysis procedure indicated that the use of steroid ratios in fecal samples to differentiate otter sex is an effective technique when there are evaluations during the breeding season. The estrogen to androgen ratios during this period, however, are the inverse of what was expected, with there being larger testosterone concentrations in the female otters. The ratio of estrogens to androgens in feces of captive otters can be effectively used to determine the sex of otters in the field. We propose this method is reliable for sex determination in wild otter populations during the reproductive season.

Dutasteride combined with androgen receptor antagonists inhibit glioblastoma U87 cell metabolism, proliferation, and invasion capacity: Androgen regulation.

Glioblastoma (GB) is the most common and aggressive primary brain tumor in adult humans. Therapeutic resistance and tumor recurrence after surgical resection contributes to a poor prognosis for glioblastoma patients. Men are known to be more likely than women to develop an aggressive form of GB. Although the reasons for this disparity remain poorly understood, differences in sex steroids have emerged as a leading explanation. Studies indicate that GB-derived cells express androgen receptors (ARs) and synthesize androgens, suggesting that androgens may have a role in the tumor pathogenesis. Thus, our objective was to investigate the effects of the 5α-reductase enzyme inhibitor dutasteride, the AR antagonists cyproterone and flutamide, and combinations of these drugs on the metabolism, proliferation, and invasion capacity of GB-derived U87 cells. We also examined the effects of three natural androgens testosterone, androstenedione and dihydrotestosterone (T, A4, and DHT) on these cells. Cell metabolism was investigated by MTT assay, proliferation was assessed by the bromodeoxyuridine (BrdU) incorporation assay, and invasion was assessed by Boyden chamber assay. The results revealed that T and especially DHT, but not A4, increased U87 cell metabolism and proliferation. Following these findings, we examined the effect of adding dutasteride, cyproterone, or flutamide to the culture media and found that they all significantly decreased cell metabolism and proliferation. Dutasteride also significantly reduced cell invasion. Moreover, any combination of these drugs enhanced their inhibitory effects; the combination of dutasteride to flutamide was most effective at decreasing GB cell proliferation. Our results suggest that administering a combination of AR antagonists and enzyme blockers may be a more effective alternative treatment for GB.

Classifying the type of delivery from cardiotocographic signals: A machine learning approach.

BACKGROUND AND OBJECTIVE: Cardiotocography (CTG) is the most employed methodology to monitor the foetus in the prenatal phase. Since the evaluation of CTG is often visual, and hence qualitative and too subjective, some automated methods have been introduced for its assessment. METHODS: In this paper, a custom-made software is exploited to extract 17 features from the available CTG. A preliminary univariate statistical analysis is performed; then, five machine learning algorithms, exploiting ensemble learning, were implemented (J48, Random Forests (RF), Ada-boosting of decision tree (ADA-B), Gradient Boosting and Decorate) through Knime analytics platform to classify patients according to their delivery: vaginal or caesarean section. The dataset is composed by 370 signals collected between 2000 and 2009 in both public and private hospitals. The performance of the algorithms was evaluated using 10 folds cross validation with different evaluation metrics: accuracy, precision, sensitivity, specificity, area under the curve receiver operating characteristic (AUCROC). RESULTS: While only two features were significantly different (gestation week and power expressed by the high frequency band of FHR power spectrum), from the statistical point of view, machine learning results were great. The RF obtained the best results: accuracy (91.1%), sensitivity (90.0%) and AUCROC (96.7%). The ADA-B achieved the highest precision (92.6%) and specificity (93.1%). As expected, the lowest scores were obtained by J48 that was the base classifier employed in all the others empowered implementations. Excluding the J48 results, the AUCROC of all the algorithms was greater than 94.9%. CONCLUSION: In the light of the obtained results, that are greater than those ones found in the literature from comparable researches, it can be stated that the machine learning approach can actually help the physicians in their decision process when evaluating the foetal well-being.