Coactivation of the elbow antagonist muscles is not affected by the speed of movement in isokinetic exercise

Since muscle coactivation increases the stiffness and stability of a joint, greater coactivation is likely during faster than slower movements. Very few studies, though, have been conducted to verify this hypothesis. Moreover, a large number of studies have examined coactivation of muscles surrounding the knee joint whereas there are few reports on the elbow joint. The aim of this study was therefore to compare the antagonist activation of the elbow flexors and extensors during isokinetic concentric exercises and to investigate the influence of angular velocity on their activation. Twelve men participated in the study. The surface electromyographic signals (sEMG) were recorded from the biceps brachii (BB) and triceps brachii (TB) muscles during three maximal voluntary isometric contractions (MVC) of elbow flexors and extensors and a set of three maximal elbow flexions and extensions each at 15 degrees, 30 degrees , 60 degrees, 120 degrees, 180 degrees, and 240 degrees.s(-1). Normalized root mean square (RMS) of sEMG was calculated during the isokinetic phase of movement as an index of sEMG amplitude. During elbow flexion, the antagonist activation of BB averaged 16.2% lower than TB, and this difference was statistically significant at all angular velocities. The normalized RMS values ranged from 26.0% +/- 19.0 at MVC to 37.8% +/- 13.9 at 240 degrees.s(-1) for antagonist TB activation, and from 5.7% +/- 5.2 at MVC to 18.9% +/- 8.6 at 240 degrees.s(-1) for antagonist BB activation. No influence of angular velocity on agonist and antagonist activity was found. Moreover, flexion and extension torques were both strongly affected by the amount of antagonist activation. The functional specialization of the two muscle groups could be responsible for the different levels of antagonist activation. The frequent use of BB, which is not assisted by gravity during daily activities, could lead to reduced coactivation due to a better functioning of the control system based upon reciprocal innervation. These findings may have significant implications in the design of rehabilitation programs directed to the elbow joint.     

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.     

AGEs/RAGE complex upregulates BACE1 via NF-κB pathway activation

Although the pathogenesis of sporadic Alzheimer disease (AD) is not clearly understood, it is likely dependent on several age-related factors. Diabetes is a risk factor for AD, and multiple mechanisms connecting the 2 diseases have been proposed. Hyperglycemia enhances the formation of advanced glycation end products (AGEs) that result from the auto-oxidation of glucose and fructose. The interaction of AGEs with their receptor, named RAGE, elicits the formation of reactive oxygen species that are also believed to be an early event in AD pathology. To investigate a functional link between the disorders diabetes and AD, the effect of 2 AGEs, pentosidine and glyceraldehydes-derived pyridinium (GLAP), was studied on BACE1 expression both in vivo, in streptozotocin treated rats, and in vitro in differentiated neuroblastoma cells. We showed that pentosidine and GLAP were able to upregulate BACE1 expression through their binding with RAGE and the consequent activation of NF-κB. In addition, both pentosidine and GLAP were found to be increased in the brain in sporadic AD patients. Our findings demonstrate that activation of the AGEs/RAGE axis, by upregulating the key enzyme for amyloid-β production, provides a pathologic link between diabetes mellitus and AD.     

Is the anteroposterior and transverse diameter ratio of nonpalpable thyroid nodules a sonographic criteria for recommending fine‐needle aspiration cytology?

BACKGROUND: As a consequence of the increasing application of ultrasound (US) technology, the detection of asymptomatic nonpalpable thyroid nodules has generally increased. The aim of our study was to assess if the anteroposterior and transverse diameter ratio of nonpalpable thyroid nodules (A/T) > or = 1 could be a sonographic criterion for recommending fine-needle aspiration cytology (FNAC). METHODS: From January 2002 to January 2004, 828 consecutive solid nonpalpable thyroid nodules were evaluated by ultrasonography, colour-Doppler and FNAC in our department. Cases were selected from 2217 patients, referred to our thyroid unit for US-guided FNAC from the greater Brescia area, an endemic zone for goitre. Entry criteria included the presence at US of a solid thyroid nodule that was nonpalpable at physical examination, euthyroid condition and no previous diagnosis of thyroid malignancy. All patients with suspicious or malignant cytology underwent surgery. RESULTS: One hundred and twenty-seven nodules with inadequate cytology were excluded from the study. Thyroid malignancy was observed in 67 (9.6%) nodules. At US, cancers presented a solid hypoechoic appearance in 79.1% of cases, blurred margins in 47.8%, microcalcification in 73.1%, intranodular vascular pattern in 56.7% and A/T > or = 1 in 83.6%. A hypoechoic appearance (OR 4.3), blurred margins (OR 2.6), microcalcification (OR 6.1), intranodular vascular pattern (OR 10.2) and A/T > or = 1 (OR 22.4) were independent risk factors of malignancy. CONCLUSIONS: A/T > or = 1 in conjunction with at least one other sonographic risk factor is able to detect the majority of carcinoma and, moreover, it limits the FNAC procedures to only 15.9% of all the nodules.     

How I investigate chronic myelomonocytic leukemia

The 2016 revised 4th edition of the World Health Organization classification of hematopoietic neoplasms updated the diagnostic criteria for chronic myelomonocytic leukemia (CMML). Persistent peripheral blood monocytosis of at least 1 × 10⁹/L and a percentage of monocytes ≥10% of the circulating white blood cell count (WBC) are both prerequisite criteria for this diagnosis. CMML represents the prototype of “overlapping” myeloid neoplasms with concurrent myeloproliferative and myelodysplastic features. However, clinical presentation is heterogeneous, with cases showing prevailing “dysplastic” features and others a predominant “proliferative” phenotype. Accounting for this diversity, two variants of CMML are recognized: “dysplastic” CMML defined by WBC < 13 × 10⁹/L and “proliferative” CMML with WBC ≥ 13 × 10⁹/L often showing features mimicking a myeloproliferative neoplasm. Although not an official WHO category, the “oligomonocytic” variant of CMML is defined by relative monocytosis with an absolute monocyte count of 0.5‐0.9 × 10⁹/L. It can be considered a “pre‐phase,” as it frequently anticipates the development of an overt, classic CMML. In an attempt at improving disease prognostication, the blast count based grading system for CMML of the WHO 2008 Classification has been expanded in 2016 to include a new “CMML‐0” category. Lastly, the large body of knowledge on the molecular events occurring in CMML has been used to assist diagnosis and assess prognosis. Despite the step forwards, diagnosis of CMML still remains one of exclusion as no clinical, pathologic or molecular findings are specific for this disease. The current review brings insight into the spectrum of CMML and provides practical advice to approach suspected cases of CMML.     

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.     

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.