Functional consequences of a novel uromodulin mutation in a family with familial juvenile hyperuricaemic nephropathy

Background. Familial juvenile hyperuricaemic nephropathy (FJHN)is an autosomal-dominant disorder featuring hyperuricaemia,low fractional urate excretion, interstitial nephritis and chronicrenal failure. The responsible gene UMOD was recently identified.UMOD encodes for uromodulin or Tamm–Horsfall glycoprotein,the most abundant protein in normal urine. We encountered afamily with FJHN and identified a novel UMOD mutation in exon6. Methods. We sequenced the gene in all family members, identifiedthe mutation, and verified its presence in the affected members.We next performed functional studies of the mutant protein byimmunofluorescence and FACS analysis on transfected cells. Results. The mutation p.C347G (c.1039T>G) results in a conservedcysteine to glycine amino acid substitution in the uromodulinzona pellucida (ZP) domain. The cell studies showed that thenovel uromodulin mutation causes a delay in protein export tothe plasma membrane due to its retention in the endoplasmicreticulum. Conclusions. We describe the first reported mutation mappingin the ZP uromodulin domain. Our data provide further evidenceshowing why the excretion of uromodulin is reduced in this syndrome.     

Evaluation of prognostic factors and clinicopathological patterns of recurrence after curative surgery for colorectal cancer

BACKGROUNDColorectal cancer is a common tumor with a quite high-related mortality. Despite the used curative treatments, patients will develop cancer recurrence in up to 50% of the cases and/or other primary neoplasms. Although most of the recurrences are discovered within 3 years from the first treatment, a small percentage is found after 5 years. The early detection of recurrence is crucial to allow further therapies improving patients’ survival. Several follow-up programs have been developed but the optimal one is far from being established.AIMTo evaluation of potential prognostic factors for timing and patterns of recurrence in order to plan tailored follow-up programs.METHODSPerioperative and long-term data of all consecutive patients surgically treated with curative intent, from January 2006 to June 2009, for colorectal adenocar-cinoma, were retrospectively reviewed to find potential prognostic factors associated with: (1) Recurrence incidence; (2) Incidence of an early (within 3 years from surgery) or late recurrence; and (3) Different sites of recurrence. In addition, the incidence of other primary neoplasms has been evaluated in a cohort of patients with a minimum potential follow-up of 10 years.RESULTSOur study included 234 patients. The median follow-up period has been 119 ± 46.2 mo. The recurrence rate has been 25.6%. Patients with a higher chance to develop recurrence had also the following characteristics: Higher levels of preoperative glycemia and carcinoembryonic antigen, highest anaesthesiologists Score score, occlusion, received a complex operation performed with an open technique, after a longer hospital stay, and showed advanced tumors. The independent prognostic factors for recurrence were the hospital stay, N stage 2, and M stage 1 (multivariate analysis). Younger ages were significantly associated with an early recurrence onset. Patients that received intermediate colectomies or segmental resections, having an N stage 2 or American Joint Committee on Cancer stage 3 tumors were also associated with a higher risk of liver recurrence, while metastatic diseases at diagnosis were linked with local recurrence. Neoadjuvant treatments showed lung recurrence. Finally, bigger tumors and higher lymph node ratio were associated with peritoneal recurrence (marginally significant). Thirty patients developed a second malignancy during the follow-up time.CONCLUSIONSeveral prognostic factors should be considered for tailored follow-up programs, eventually, beyond 5 years from the first treatment.     

Music Provided Through a Portable Media Player (iPod) Blunts Pain During Physical Therapy

This research studied, 25 adult patients who underwent physical therapy to assess the analgesic effect of distraction with the use of music during physical therapy. Patients randomly underwent physical therapy once with music provided by an iPod and once without music. In both sessions patients underwent identical physical procedures. At end of both sessions patients filled in 5-item questionnaire where they scored pain and other parameters, such as stress, enjoyment, interaction, and satisfaction, on 10-cm visual analog scale. The mean scores (range, 0-10) of the two sessions were statistically compared. Mean pain scores were significantly lower (p = .031) during the session in which patients received music (4.8 ± 2.5) than during the session without music (5.8 ± 2.3). The other items of the questionnaire did not disclose any statistically significant difference when the sessions with versus without music were compared. Enjoyment (8.5 ± 1.6), interaction (8.3 ± 1.9), and satisfaction (8.6 ± 1.7) scores with music did not significantly differ in the sessions without music (8.5 ± 2.1, 8.5 ± 1.9, and, 8.5 ± 1.5, respectively); mean stress score was, 3.9 in both sessions. The conclusion of the study is that music provided through a portable media player has an analgesic effect. This can be an effective analgesic strategy during painful physical therapy.     

Asthma and rhinitis in cleaning workers: a systematic review of epidemiological studies

Objective: This article presents a systematic review of epidemiological studies linking cleaning work and risk of asthma and rhinitis. Methods: Published reports were identified from PubMed covering the years from 1976 through June 30, 2012. In total, we identified 24 papers for inclusion in the review. The quality of studies was evaluated using the Strengthening of the Reporting of Observational Studies in Epidemiology (STROBE) statement checklist of 22 items for cross-sectional, cohort and case–control studies. Results: Increased risk of asthma or rhinitis has been shown in 79% of included epidemiological studies. In four studies the increased risk of asthma in cleaning workers was confirmed by objective tests, such as bronchial hyper-reactivity or airflow obstruction. Level of exposure to cleaning products, cleaning sprays, bleach, ammonia, mixing products and specific job tasks has been identified as specific causes of asthma and rhinitis. Conclusions: Possible preventive measures encompass the substitution of cleaning sprays, bleach and ammonia, avoidance of mixing products, the use of respiratory protective devices, worker education and medical surveillance.     

Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin‐1β

Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti‐inflammatory activities of melatonin in an in vitro model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL‐1β‐stimulated Caco‐2 cells. Differentiated monolayers of Caco‐2 cells were preincubated with melatonin (1 nmol/L‐50 μmol/L) and then exposed to IL‐1β. After each treatment, different inflammatory mediators, DNA‐breakage, and global DNA methylation status were assayed. To evaluate the involvement of melatonin membrane receptors, we also exposed differentiated monolayers to melatonin in the presence of luzindole, a MT1 and MT2 antagonist. Our results showed that melatonin, at concentrations similar to those obtained in the lumen gut after ingestion of dietary supplements for the treatment of sleep disorders, was able to attenuate the inflammatory response induced by IL‐1β. Anti‐inflammatory effects were expressed as both a decrease of the levels of inflammatory mediators, including IL‐6, IL‐8, COX‐2, and NO, and a reduced increase in paracellular permeability. Moreover, the protection was associated with a reduced NF‐κB activation and a prevention of DNA demethylation. Conversely, luzindole did not reverse the melatonin inhibition of stimulated‐IL‐6 release. In conclusion, our findings suggest that melatonin, through a local action, can modulate inflammatory processes at the intestinal level, offering new opportunities for a multimodal management of IBD.     

Clinical outcome of neurological patients with COVID-19: the impact of healthcare organization improvement between waves

Neurological Sciences - The aim of this study is to evaluate the differences in clinical presentations and the impact of healthcare organization on outcomes of neurological COVID-19 patients...     

Neurological involvement associated with COVID-19 disease: a study on psychosocial factors

Neurological Sciences - Several people affected by COVID-19 experienced neurological manifestations, altered sleep quality, mood disorders, and disability following hospitalization for a long time....     

Plasma or serum samples: measurements of cardiac troponin T and of other analytes compared.

Conflicting data in the literature concern possible differences in the immunochemical measurement of cardiac troponins, either in plasma or in serum. In order to address this specific point, 96 serum and heparin-plasma pairs were obtained for cardiac marker measurement [cardiac troponin T (cTnT); myoglobin (Myo) and creatine kinase-MB isoenzyme (CK-MB)]; 29 additional "common" analytes were measured in 77 such samples. The cardiac markers were measured by electrochemiluminescence (Elecsys 2010, Roche); the other analytes by established automated methods (Modular, Roche). Mean plasma/serum ratios for cTnT (0.95), creatine kinase-MB (1.01) and myoglobin (0.99) were comparable with those of the 29 common analytes (interval of means 0.83-1.05). The distribution of the plasma-serum differences also showed similarities between cardiac markers and other analytes. A few outlier plasma-serum differences (3-5%) were measured for both categories of analytes. Addition of heparin to serum (51 samples) caused decreased cTnT (mean ratio 0.92). In 3 of 51 such samples the cTnT decrease was more marked, but in a second sample from the same subjects (1 week later) such a prominent, heparin-induced loss of cTnT no longer appeared. In conclusion, plasma-serum differences in immuno-reactive cTnT compare with those observed for other analytes. In occasional heparin-plasma samples immunochemical measurement of cTnT may give exceptionally low values. However, in our sample group of 96 patients (cTnT lower or higher than the cut-off in, respectively, 24 and 72 patients), no misclassification occurred if plasma instead of serum cTnT values were considered.     

Aortic root dilation in associated with the reduction in capillary density observed at nailfold capillaroscopy in SSc patients

Clinical Rheumatology - Systemic sclerosis (SSc) is an autoimmune disease characterized by endothelial dysfunction and fibroblasts activation. Microvascular disease may be easily observed by means...