Did Going North Give Us Migraine? An Evolutionary Approach on Understanding Latitudinal Differences in Migraine Epidemiology

This commentary discusses a recent publication by evolutionary biologists with strong implications for migraine experts. The Authors showed that a gene polymorphism associated with migraine gave our ancestors an evolutionary advantage when colonizing northern, and thus colder, territories. They then highlight that the prevalence of migraine may differ among countries because of climatic adaptation. These results may prove useful in planning both epidemiological and physiological studies in the field of migraine

Evaluation of the weight loss of raw beef cuts vacuum-packaged with two different techniques

In the present study, 25 cuts of shank form adult cattle coming from the same slaughtering batch, were withdrawn just after manual sectioning/deboning, and each divided into two pieces (Prox and Dist) of approximately the same weight, that were vacuum packaged by using two different packaging systems: vacuum chamber machine with a bag material and a thermo-forming packaging machine with top and bottom webs named BAG and THF respectively. The packed cuts were stored at 2-3\ub0C for 20 days. The drip loss was calculated at the end of the storage as the difference between drained weight and net. Internal muscle pH and pH of the exudate present in the package and microbiological analyses (by pooling the samples) were performed at T0 and at the end of the storage. The drip loss, was significantly lower with BAG packaging: this difference was evident after 20 days of storage (average \ub1 STD BAG vs THF = 1.04\ub10.36% vs 1.71\ub10.42%; P<0.01). The values were, in general, low for both the packaging systems, never above 2%. Moreover, shrink bag packages are characterized by better overall pack appearance and less plastic weight per pack. Forming step reduce the thickness of ther-moforming material lowering the mechanical resistance and the barrier to oxygen, on the contrary after shrinking bag materials are thickened. The pH of muscles was stable, although a slight increase was evidenced after 20 (average \ub1 STD BAG vs THF= 5.73\ub10.05 vs 5.78\ub10.09; P<0.01), due to the ageing of meat. The pH of the exudate was equal at T20 (average \ub1 STD BAG vs THF = 5.34\ub10.20 vs 5.33\ub10.17). The drip loss didn\u2019t influence the development of all the microflora; in particular LAB, that represented the main microbial population, showed a gradual increase from T0 (2.20\ub10.41 Log CFU/g) to T20 (average \ub1 STD BAG vs THF= 4.76\ub10.29 Log CFU/g vs 4.75\ub10.0.15 Log CFU/g). No Enterobacteriaceae showed an increase, if compared to the initial counts, due to the prolonged storage and the gradual growth of ephemeral microorganisms, without differences among the two series (Enterobacteriaceae: T0=<1.7 Log CFU/g to T20 average \ub1 STD BAG vs THF = 2.83\ub10.77 Log CFU/g vs 3.09\ub10.0.70 Log CFU/g). In conclusion, the use of the BAG system demonstrated to have an effect in reducing the drip loss of beef cuts during the refrigerated storage, with only slight influence on the other characteristics of raw meat

Short-term effects of focal muscle vibration on motor recovery after acute stroke: a pilot randomized sham-controlled study

Repetitive focal muscle vibration (rMV) is known to promote neural plasticity and long-lasting motor recovery in chronic stroke patients. Those structural and functional changes within the motor network underlying motor recovery occur in the very first hours after stroke. Nonetheless, to our knowledge, no rMV-based studies have been carried out in acute stroke patients so far, and the clinical benefit of rMV in this phase of stroke is yet to be determined. The aim of this randomized double-blind sham-controlled study is to investigate the short-term effect of rMV on motor recovery in acute stroke patients. Out of 22 acute stroke patients, 10 were treated with the rMV (vibration group–VG), while 12 underwent the sham treatment (control group–CG). Both treatments were carried out for 3 consecutive days, starting within 72 h of stroke onset; each daily session consisted of three 10-min treatments (for each treated limb), interspersed with a 1-min interval. rMV was delivered using a specific device (Cro®System, NEMOCO srl, Italy). The transducer was applied perpendicular to the target muscle's belly, near its distal tendon insertion, generating a 0.2–0.5 mm peak-to-peak sinusoidal displacement at a frequency of 100 Hz. All participants also underwent a daily standard rehabilitation program. The study protocol underwent local ethics committee approval (ClinicalTrial.gov NCT03697525) and written informed consent was obtained from all of the participants. With regard to the different pre-treatment clinical statuses, VG patients showed significant clinical improvement with respect to CG-treated patients among the NIHSS (p < 0.001), Fugl-Meyer (p = 0.001), and Motricity Index (p < 0.001) scores. In addition, when the upper and lower limb scales scores were compared between the two groups, VG patients were found to have a better clinical improvement at all the clinical end points. This study provides the first evidence that rMV is able to improve the motor outcome in a cohort of acute stroke patients, regardless of the pretreatment clinical status. Being a safe and well-tolerated intervention, which is easy to perform at the bedside, rMV may represent a valid complementary non-pharmacological therapy to promote motor recovery in acute stroke patients

Investigating Employees’ Concerns and Wishes Regarding Digital Stress Management Interventions With Value Sensitive Design: Mixed Methods Study

Background: Work stress places a heavy economic and disease burden on society. Recent technological advances include digital health interventions for helping employees prevent and manage their stress at work effectively. Although such digital solutions come with an array of ethical risks, especially if they involve biomedical big data, the incorporation of employees' values in their design and deployment has been widely overlooked. Objective: To bridge this gap, we used the value sensitive design (VSD) framework to identify relevant values concerning a digital stress management intervention (dSMI) at the workplace, assess how users comprehend these values, and derive specific requirements for an ethics-informed design of dSMIs. VSD is a theoretically grounded framework that front-loads ethics by accounting for values throughout the design process of a technology. Methods: We conducted a literature search to identify relevant values of dSMIs at the workplace. To understand how potential users comprehend these values and derive design requirements, we conducted a web-based study that contained closed and open questions with employees of a Swiss company, allowing both quantitative and qualitative analyses. Results: The values health and well-being, privacy, autonomy, accountability, and identity were identified through our literature search. Statistical analysis of 170 responses from the web-based study revealed that the intention to use and perceived usefulness of a dSMI were moderate to high. Employees' moderate to high health and well-being concerns included worries that a dSMI would not be effective or would even amplify their stress levels. Privacy concerns were also rated on the higher end of the score range, whereas concerns regarding autonomy, accountability, and identity were rated lower. Moreover, a personalized dSMI with a monitoring system involving a machine learning-based analysis of data led to significantly higher privacy (P=.009) and accountability concerns (P=.04) than a dSMI without a monitoring system. In addition, integrability, user-friendliness, and digital independence emerged as novel values from the qualitative analysis of 85 text responses. Conclusions: Although most surveyed employees were willing to use a dSMI at the workplace, there were considerable health and well-being concerns with regard to effectiveness and problem perpetuation. For a minority of employees who value digital independence, a nondigital offer might be more suitable. In terms of the type of dSMI, privacy and accountability concerns must be particularly well addressed if a machine learning-based monitoring component is included. To help mitigate these concerns, we propose specific requirements to support the VSD of a dSMI at the workplace. The results of this work and our research protocol will inform future research on VSD-based interventions and further advance the integration of ethics in digital health

Methane flux, vertical gradient and mixing ratio measurements in a tropical forest

Measurements of CH<sub>4</sub> mixing ratio, vertical gradients and turbulent fluxes were carried out in a tropical forest (Reserva Biológica Cuieiras), about 60 km north of Manaus, Brazil. The methane mixing ratio and flux measurements were performed at a height of 53 m (canopy height 35 m). In addition, vertical CH<sub>4</sub> gradients were measured within the canopy using custom made air samplers at levels of 2, 16 and 36 m above ground. The methane gradients within the canopy reveal that there is a continuous methane source at the surface. No clear evidence for aerobic methane emission from the canopy was found. The methane fluxes above the canopy are small but consistently upwards with a maximum early in the morning. The measured fluxes are in agreement with the observed CH<sub>4</sub> gradient in the canopy. In the morning hours, a strong canopy venting peak is observed for both CH<sub>4</sub> and CO<sub>2</sub>, but for CO<sub>2</sub> this peak is then superimposed by photosynthetic uptake, whereas the peak lasts longer for CH<sub>4</sub>. Monthly averaged diurnal cycles of the CH<sub>4</sub> mixing ratio show a decrease during daytime and increase during nighttime. The magnitude of the difference in CH<sub>4</sub> mixing ratio between day and night gradually increases throughout the wet season. The fluxes required to explain the nighttime increase are in agreement with the nighttime fluxes measured above the canopy, which implies that the CH<sub>4</sub> increase in the nighttime boundary layer originates from local sources

Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis

Background: Obsessive–compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats. Results: Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure. Conclusions: This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies

Human Chorionic Gonadotrophin as a Possible Mediator of Leiomyoma Growth during Pregnancy : Molecular Mechanisms

Uterine fibroids are the most common gynecologic benign tumors. Studies supporting a strong pregnancy-related growth of leiomyomas generally claimed a crucial role of sex steroid hormones. However, sex steroids are unlikely the unique actors involved as estrogen and progesterone achieve a pick serum concentration in the last trimester while leiomyomas show a typical increase during the first trimester. Given the rapid exponential raise in serum human Chorionic Gonadotrophin (hCG) at the beginning of gestation, we conducted a review to assess the potential role of hCG in the striking growth of leiomyomas during initial pregnancy. Fibroid growth during initial pregnancy seems to correlate to the similar increase of serum hCG levels until 12 weeks of gestation. The presence of functional Luteinizing Hormone/human Chorionic Gonadotropin (LH/hCG) receptors was demonstrated on leiomyomas. In vitro treatment of leiomyoma cells with hCG determines an up to 500% increase in cell number after three days. Expression of cyclin E and cyclin-dependent kinase 1 was significantly increased in leiomyoma cells by hCG treatment. Moreover, upon binding to the receptor, hCG stimulates prolactin secretion in leiomyoma cells, promoting cell proliferation via the mitogen-activated protein kinase cascade. Fibroid enlargement during initial pregnancy may be regulated by serum hCG

Combined Use of Mycobacterium tuberculosis-Specific CD4 and CD8 T-Cell Responses Is a Powerful Diagnostic Tool of Active Tuberculosis.

Immune-based assays are promising tools to help to formulate diagnosis of active tuberculosis. A multiparameter flow cytometry assay assessing T-cell responses specific to Mycobacterium tuberculosis and the combination of both CD4 and CD8 T-cell responses accurately discriminated between active tuberculosis and latent infection

Regulatory T cells from patients with end-stage organ disease can be isolated, expanded and cryopreserved according good manufacturing practice improving their function

Background Here, we isolated, expanded and functionally characterized regulatory T cells (Tregs) from patients with end stage kidney and liver disease, waiting for kidney/liver transplantation (KT/LT), with the aim to establish a suitable method to obtain large numbers of immunomodulatory cells for adoptive immunotherapy post-transplantation. Methods We first established a preclinical protocol for expansion/isolation of Tregs from peripheral blood of LT/KT patients. We then scaled up and optimized such protocol according to good manufacturing practice (GMP) to obtain high numbers of purified Tregs which were phenotypically and functionally characterized in vitro and in vivo in a xenogeneic acute graft-versus-host disease (aGVHD) mouse model. Specifically, immunodepressed mice (NOD-SCID-gamma KO mice) received human effector T cells with or without GMP-produced Tregs to prevent the onset of xenogeneic GVHD. Results Our small scale Treg isolation/expansion protocol generated functional Tregs. Interestingly, cryopreservation/thawing did not impair phenotype/function and DNA methylation pattern of FOXP3 gene of the expanded Tregs. Fully functional Tregs were also isolated/expanded from KT and LT patients according to GMP. In the mouse model, GMP Tregs from LT or KT patient proved to be safe and show a trend toward reduced lethality of acute GVHD. Conclusions These data demonstrate that expanded/thawed GMP-Tregs from patients with end-stage organ disease are fully functional in vitro. Moreover, their infusion is safe and results in a trend toward reduced lethality of acute GVHD in vivo, further supporting Tregs-based adoptive immunotherapy in solid organ transplantation