Notes

[Studies upon Monoamine Transporter Occupancy involving Anti-depressants making use of PET: Emphasizing SERT as well as NET].
While preclinical stroke studies have shown that mesenchymal stem cells (MSCs) promote recovery, few randomized controlled trials (RCT) have assessed cell therapy in humans. In this RCT, we assessed the safety, feasibility, and efficacy of intravenous autologous bone marrow-derived MSCs in subacute stroke. ISIS-HERMES was a single-center, open-label RCT, with a 2-year follow-up. We enrolled patients aged 18-70 years less than 2 weeks following moderate-severe ischemic carotid stroke. Patients were randomized 21 to receive intravenous MSCs or not. Primary outcomes assessed feasibility and safety. Secondary outcomes assessed global and motor recovery. Passive wrist movement functional MRI (fMRI) activity in primary motor cortex (MI) was employed as a motor recovery biomarker. We compared "treated" and "control" groups using as-treated analyses. Of 31 enrolled patients, 16 patients received MSCs. Treatment feasibility was 80%, and there were 10 and 16 adverse events in treated patients, and 12 and 24 in controls at 6-month and 2-year follow-up, respectively. Using mixed modeling analyses, we observed no treatment effects on the Barthel Index, NIHSS, and modified-Rankin scores, but significant improvements in motor-NIHSS (p = 0.004), motor-Fugl-Meyer scores (p = 0.028), and task-related fMRI activity in MI-4a (p = 0.031) and MI-4p (p = 0.002). Intravenous autologous MSC treatment following stroke was safe and feasible. Motor performance and task-related MI activity results suggest that MSCs improve motor recovery through sensorimotor neuroplasticity.ClinicalTrials.gov Identifier NCT00875654.Multicellular eukaryotes emerged late in evolution from an ocean of viruses, bacteria, archaea, and unicellular eukaryotes. These macroorganisms are exposed to and infected by a tremendous diversity of microorganisms. Those that are large enough can even be infected by multicellular fungi and parasites. Each interaction is unique, if only because it operates between two unique living organisms, in an infinite diversity of circumstances. This is neatly illustrated by the extraordinarily high level of interindividual clinical variability in human infections, even for a given pathogen, ranging from a total absence of clinical manifestations to death. Daclatasvir in vitro We discuss here the idea that the determinism of human life-threatening infectious diseases can be governed by single-gene inborn errors of immunity, which are rarely Mendelian and frequently display incomplete penetrance. We briefly review the evidence in support of this notion obtained over the last two decades, referring to a number of focused and thorough reviews published by eminent colleagues in this issue of Human Genetics. It seems that almost any life-threatening infectious disease can be driven by at least one, and, perhaps, a great many diverse monogenic inborn errors, which may nonetheless be immunologically related. While the proportions of monogenic cases remain unknown, a picture in which genetic heterogeneity is combined with physiological homogeneity is emerging from these studies. A preliminary sketch of the human genetic architecture of severe infectious diseases is perhaps in sight.Objective To compare incidental fragility fractures in psoriatic arthritis (PsA) patients with matched controls from a university hospital. Methods Consecutive PsA patients were matched (age and sex) with controls (12). Follow-up began at index date, defined as the date of PsA diagnosis for cases and their respective controls, until the last hospital visit, death or the end of the study (31 December 2017). Electronic medical records were reviewed for osteoporotic fractures. Incidence rates per 100,000 persons-years (PY) of distinct types of fractures after index dates were calculated and compared between groups. A multivariate Cox regression analysis was performed to investigate determinants of fractures. Results Ninety-two PsA patients and 184 controls were included. No difference was found in the overall fracture incidence rate per 100,000 PY between PsA and controls (1020 95% CI 510-1930, vs 870 95% CI 520-1390, p = 0.36). Vertebral fractures were numerically more frequent in PsA patients with an incidence rate of 1020 (95% CI 510-1930) per 100,000 PY versus 460 (95% CI 240-920), per 100,000 PY in the control group but it did not reach statistical significance (p = 0.06). In the Cox regression analysis, after adjusting for bisphosphonate use, only age (HR 1.10, 1.05-1.16, p less then 0.001) and female sex (HR 3.94, 1.11-13.91, p = 0.03) were associated with fractures while PsA diagnosis and use of glucocorticoids were not. Conclusion In this cohort of PsA patients, no overall increased risk of fractures was found in comparison with matched controls.Key Points• PsA could have different effects on bone, leading to confusing results in bone densitometry readings contributing to the difficulty in establishing the real prevalence of OP in PsA.• Vertebral fractures were more frequent in PsA patients compared to controls, but it did not reach statistical significance. No difference was found in the overall fracture incidence rate.COVID-19 outbreak has quickly spread worldwide, causing a high pressure on the health-care system. In Italy, from March 8, 2020, all the deferrable clinical activities have been suspended to increase the health care offer for COVID-19 patients. The hospital organization has been modified also in order to assure non-COVID-19 patients assistance. The Scleroderma Unit of ASST Pini-CTO Hospital, in Milan, in the region mostly hit by SARS-CoV-2 in Italy, follows more than 600 patients affected by systemic sclerosis (SSc). Patients with SSc need a close follow-up with a regular screening of organ involvement and frequent intravenous treatments. All SSc patients have been educated about ministerial directives to limit COVID-19 spread. The organization of our Scleroderma Unit has been quickly rethought to assure SSc patients assistance in safety for them and for health-care workers during urgent visits or infusion therapies. Using electronic way of communication with frequent virtual contact and guarantying home deliveries of some therapies, we allowed a continuity of care also outside the Hospital.Insects are the most abundant and diverse organisms on Earth and provide essential ecosystem services. However, Brazilian society rarely consider the importance of insects in their diverse country. Therefore, in this review, we provide an overview of ecosystem services provided by insects in Brazil. A database search returned 136 articles, published in English or Portuguese, on ecosystem services provided by insects in Brazil. The first article was published in 1982, and majority of the studies were conducted in the Atlantic Forest or the Cerrado biomes. The most frequently studied insect-provided ecosystem services were pollination, decomposition, and biological control of pests. The studies focused primarily on natural and anthropic ecosystems, and most followed an experimental approach. We noted that the term "ecosystem services" was not used frequently in studies on insects in Brazil. The information available was mostly taxon-biased. We discuss the implications of these findings in relation to reconciling economic interests and the need for insect conservation for continued provision of ecosystem services in a broader perspective. In conclusion, we argue that the scientific community should focus on understanding the ecosystem services provided by insects other than those strictly related to economic activities, and on improving communication with policymakers and citizens. As a tropical and megadiverse country, Brazil has the potential to become a protagonist in conserving and using the ecosystem services provided by insects, both locally and internationally, by providing scientific information to policymakers and citizens.Interleukin-17 (IL-17) is a pro-inflammatory cytokine found in various cancers. Current evidence indicates that IL-17 plays a vital role in tumour initiation and progression in colorectal carcinoma (CRC) via binding with its receptor, IL-17RA. However, the association between clinicopathological features and presence of IL-17 and IL-17RA protein in primary CRC tissues remains unclear. This study also investigates the difference between the presence of IL-17 and IL-17RA in the paired tumour tissues versus adjacent normal tissues. The presence of IL-17RA and IL-17 protein in primary CRC tissues was determined by immunohistochemistry. Associations between clinicopathological features and IL-17RA and IL-17 immunoreactivity, were analyzed by χ2 tests. We found that both IL-17RA (p = 0.001) and IL-17 (p = 0.025) in tumour cells of primary CRC tissues was significantly lower as compared to adjacent normal tissue. Positive immunoreactivity for IL-17RA and IL-17 were detected in 51.0% and 16.8% of tumour tissues, respectively. Furthermore, negative immunoreactivity of IL-17R was significantly associated with advanced stage according to TNM classifier (p = 0.027), high grade of tumour (p = 0.019), increased depth of tumour invasion (p = 0.023) and vascular invasion (p = 0.039). Positive IL-17 immunoreactivity was associated with advanced stage (p = 0.008) and lymph node metastasis (p = 0.008). Thus, this study suggests that the loss of IL-17RA expression occurs as tumour progresses and this may predict the aggressiveness of tumour whilst expression of IL-17 promotes tumour progression and lymph node metastasis. Thus, loss of IL-17RA could be a useful prognostic biomarker for tumour progression in CRC patients.To investigate the diagnostic performance of relative telomere length (RTL) in cell-free DNA (cfDNA) for endometrioid endometrial cancer (EC). We measured RTL in cfDNA of 40 EC patients (65 ± 12 years) and 31 healthy controls (HC) (63 ± 13 years), excluding in both groups other oncologic and severe non-oncologic diseases to limit confounders. Circulating cfDNA was extracted from serum using the QIAamp DNA Blood Mini kit (Qiagen, Hilden, Germany). After the quantitative real-time polymerase chain reaction, telomere repeat copy number to single-gene copy number ratio was calculated. RTL in cfDNA was found to be significantly lower in EC patients than in HC (p less then 0.0001). The diagnostic performance of cfDNA RTL was estimated with receiver operating characteristics (ROC) curve analysis, which showed a diagnostic accuracy for EC of 0.87 (95% CI 0.79-0.95, p less then 0.0001). The cutoff cfDNA RTL value of 2.505 (T/S copy ratio) reported a sensitivity of 80.0% (95% CI 64.35-90.95) and a specificity of 80.65% (95% CI 62.53-92.55). Significant differences of RTL among EC stages or grades (p = 0.85 and p = 0.89, respectively) were not observed. Our results suggest that cfDNA RTL analysis may be a diagnostic tool for EC detection since the early stage, whilst its diagnostic performance seems unsatisfactory for cancer progression, staging, and grading. However, further studies are needed to confirm these preliminary findings. In particular, future investigations should focus on high-risk patients (such as those with atypical endometrial hyperplasia) that may benefit from this tool, because TL shortening is not specific for EC and is influenced by other oncologic and non-oncologic diseases.
Homepage: https://www.selleckchem.com/products/BMS-790052.html