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

Bacterial coinfections in dengue virus disease: what we know and what is still obscure about an emerging concern

Dengue virus is the most frequent arthropod-borne viral infection worldwide. Simultaneously to the growth of its incidence, cases of bacterial coinfection in dengue have been increasingly reported. The clinical course of dual infections may worsen for reciprocal interactions and delays in the diagnosis, so that clinicians should be aware of this eventuality. Therefore, we reviewed literature to provide an overview of the epidemiological, clinical, and physiopathological issues related to bacterial coinfections and bacteremia in dengue.Clinical studies and case reports regarding bacteremia and bacterial coinfections in dengue and the interactions between the pathogens published on PubMed were reviewed.We found 26 case reports, only 3 studies on concurrent bacteremia and 12 studies reporting data on bacterial coinfections in dengue. According to the three available studies, the 0.18-7 % of dengue infections are accompanied by concurrent bacteremia, while the 14.3-44.4 % of dengue-related deaths seem associated to bacterial coinfections. Comorbidities, advanced age, and more severe dengue manifestations could be risk factors for dual infections. A longer duration of fever and alterations in laboratory parameters such as procalcitonin, hyponatremia, leukocyte count, and renal function tests can raise the suspicion.Despite the real burden and consequences of this emerging concern is still not computable accurately due to the lack of a significant number of studies on large cohorts, clinicians need a greater awareness about it to early recognize warning signs, to properly use available diagnostic tools and to readily start antibiotic treatment able to prevent worsening in mortality and morbidity

Design of additively manufactured moulds for expanded polymers

The traditional tools used in steam-chest moulding technologies for the shaping of expanded polymers can be replaced today by lighter moulds, accurately designed and produced exploiting the additive manufacturing technology. New paradigms have to be considered for mould design, assuming that additive manufacturing enables the definition of different architectures that are able to improve the performance of the moulding process. This work describes the strategies adopted for the design and manufacturing by Laser powder bed fusion of the moulds, taking into specific consideration their functional surfaces, which rule the heat transfer to the moulded material, hence the quality of the products and the overall performance of the steamchest process. The description of a case study and the comparison between the performance of the traditional solution and the new moulds are also presented to demonstrate the effectiveness of the new approach. This study demonstrates that the redesign and optimization of the mould shape can lead to a significant reduction of the energy demand of the process, thanks to a homogeneous delivery of the heating steam throughout the part volume, which also results in a remarkable cutting of the cycle time

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

Cancer and HIV-1 Infection: Patterns of Chronic Antigen Exposure.

The main role of the human immune system is to eliminate cells presenting foreign antigens and abnormal patterns, while maintaining self-tolerance. However, when facing highly variable pathogens or antigens very similar to self-antigens, this system can fail in completely eliminating the anomalies, leading to the establishment of chronic pathologies. Prototypical examples of immune system defeat are cancer and Human Immunodeficiency Virus-1 (HIV-1) infection. In both conditions, the immune system is persistently exposed to antigens leading to systemic inflammation, lack of generation of long-term memory and exhaustion of effector cells. This triggers a negative feedback loop where effector cells are unable to resolve the pathology and cannot be replaced due to the lack of a pool of undifferentiated, self-renewing memory T cells. In addition, in an attempt to reduce tissue damage due to chronic inflammation, antigen presenting cells and myeloid components of the immune system activate systemic regulatory and tolerogenic programs. Beside these homologies shared between cancer and HIV-1 infection, the immune system can be shaped differently depending on the type and distribution of the eliciting antigens with ultimate consequences at the phenotypic and functional level of immune exhaustion. T cell differentiation, functionality, cytotoxic potential and proliferation reserve, immune-cell polarization, upregulation of negative regulators (immune checkpoint molecules) are indeed directly linked to the quantitative and qualitative differences in priming and recalling conditions. Better understanding of distinct mechanisms and functional consequences underlying disease-specific immune cell dysfunction will contribute to further improve and personalize immunotherapy. In the present review, we describe relevant players of immune cell exhaustion in cancer and HIV-1 infection, and enumerate the best-defined hallmarks of T cell dysfunction. Moreover, we highlight shared and divergent aspects of T cell exhaustion and T cell activation to the best of current knowledge

A Practical Approach to Fatigue Management in Colorectal Cancer.

Cancer-related fatigue is serious and complex, as well as one of the most common symptoms experienced by patients with colorectal cancer, with the potential to compromise quality of life, activities of daily living, and ultimately survival. There is a lack of consensus about the definition of cancer-related fatigue; however, definitions have been put forward by the European Association for Palliative Care (EAPC) and the National Comprehensive Cancer Network (NCCN). Numerous cancer- and treatment-related factors can contribute to fatigue, including disease progression, comorbidities, medical complications such as anemia, side effects of other medications, and a number of physical and psychologic factors. This underlines the importance of tackling factors that may contribute to fatigue before reducing the dose of treatment. NCCN guidelines and the EAPC have proposed approaches to managing fatigue in cancer patients; however, relatively few therapeutic agents have been demonstrated to reduce fatigue in randomized controlled trials. It is recognized that physical activity produces many beneficial physiologic modifications to markers of physical performance that can help to counteract various causes of fatigue. In appropriately managed and monitored patients with colorectal cancer, emerging evidence indicates that exercise programs may have a favorable influence on cancer-related fatigue, quality of life, and clinical outcomes, and therefore may help patients tolerate chemotherapy. This review assesses fatigue in patients with colorectal cancer and proposes updates to a treatment algorithm that may help clinicians manage this common problem

Time to redefine endometriosis including its pro-fibrotic nature

Endometriosis is currently defined as presence of endometrial epithelial and stromal cells at ectopic sites. This simple and straightforward definition has served us well since its original introduction. However, with advances in disease knowledge, endometrial stromal and glands have been shown to represent only a minor component of endometriotic lesions and they are often absent in some disease forms. In rectovaginal nodules, the glandular epithelium is often not surrounded by stroma and frequently no epithelium can be identified in the wall of ovarian endometriomas. On the other hand, a smooth muscle component and fibrosis represent consistent features of all disease forms. Based on these observations, we believe that the definition of endometriosis should be reconsidered and reworded as 'A fibrotic condition in which endometrial stroma and epithelium can be identified'. The main reasons for this change are: (1) to foster the evaluation of fibrosis in studies on endometriosis pathogenesis using animal models; (2) to limit potential false negative diagnoses if pathologists stick stringently to the current definition of endometriosis requiring the demonstration of endometrial stromal and glands; (3) to consider fibrosis as a potential target for treatment in endometriosis. This opinion article is aimed at boosting the attention paid to a largely neglected aspect of the disease. We hope that targeting the fibrotic process might increase success in developing new therapeutic approaches

Disarming the guarded prognosis: predicting survival in newly referred patients with incurable cancer

People affected by cancer want information about their prognosis but clinicians have trouble estimating and talking about it. We sought to determine the nature and accuracy of medical oncologists' estimates of life expectancy in newly referred patients with incurable cancer. With reference to each patient, medical oncologists estimated how long they thought 90, 50, and 10% of similar patients would live. These proportions were chosen to reflect worst case, predicted, and best case scenarios suitable for discussions. After a median follow-up of 35 months, 86 of the 102 patients had died with an observed median survival of 12 months. Oncologists' estimates of each patient's worst case, predicted and best case scenarios were well-calibrated: 10% of patients lived for fewer months than estimated for the worst 10% of similar patients; 50% lived for at least as long as estimated for 50% of similar patients (predicted survival), and 17% lived for more months than estimated for the best 10% of similar patients. Oncologists' estimates of each patient's predicted survival were imprecise: 29% were within 0.67–1.33 times the patient's actual survival, 35% were too optimistic (>1.33 times the actual survival), and 39% were too pessimistic (<0.67 times the actual survival). The proportions of patients with actual survival times bounded by simple multiples of their predicted survival were as follows: 61% between half to double their predicted, 6% at least three to four times their predicted, and 4% no more than 1/6 of their predicted; similar to the proportions in an exponential distribution (about 50%, 10% and 10% respectively). Ranges based on simple multiples of the predicted survival time appropriately convey prognosis and its uncertainty in newly referred people with incurable cancer

ASO Author Reflections: The Liver-First Approach: A New Standard for Patients with Multiple Bilobar Colorectal Metastases?

The best surgical strategy for patients with colorectal cancer and synchronous liver metastases is a matter of endless debate. Technical and oncological issues must be considered but have often been confounded. In 2006, Mentha et al.1 proposed an innovative and convincing oncosurgical approach, whereby they reversed the strategy, focusing attention on the prognostically most relevant target, i.e. the liver. Even if appealing, the liver-first approach struggled to find its role and failed to demonstrate a benefit, except for the inclusion of chemoradiotherapy in the treatment schedule of patients with locally advanced rectal tumors. The proposers themselves reported non-inferiority (and not superiority) of the reverse strategy in comparison with the standard primary-first approach.2 A recent network meta-analysis ranked the liver-first approach as the best treatment option for its relative efficacy based on 5-year overall survival outcomes,3 but the evidence is too weak to impact current clinical practice

A strongly magnetized pulsar within grasp of the Milky Way's supermassive black hole

The center of our Galaxy hosts a supermassive black hole, Sagittarius (Sgr) A*. Young, massive stars within 0.5 pc of SgrA* are evidence of an episode of intense star formation near the black hole a few Myr ago, which might have left behind a young neutron star traveling deep into SgrA*'s gravitational potential. On 2013 April 25, a short X-ray burst was observed from the direction of the Galactic center. Thanks to a series of observations with the Chandra and the Swift satellites, we pinpoint the associated magnetar at an angular distance of 2.4+/-0.3 arcsec from SgrA*, and refine the source spin period and its derivative (P=3.7635537(2) s and \dot{P} = 6.61(4)x10^{-12} s/s), confirmed by quasi simultaneous radio observations performed with the Green Bank (GBT) and Parkes antennas, which also constrain a Dispersion Measure of DM=1750+/-50 pc cm^{-3}, the highest ever observed for a radio pulsar. We have found that this X-ray source is a young magnetar at ~0.07-2 pc from SgrA*. Simulations of its possible motion around SgrA* show that it is likely (~90% probability) in a bound orbit around the black hole. The radiation front produced by the past activity from the magnetar passing through the molecular clouds surrounding the Galactic center region, might be responsible for a large fraction of the light echoes observed in the Fe fluorescence features.Comment: ApJ Letters in pres