Medical research

The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis, first emerged in the 1980s, but only in the last decade has recognition of “mast cell activation syndrome” (MCAS) grown significantly. Two principal proposals for diagnostic criteria have emerged. One, originally published in 2012, is labeled by its authors as a “consensus” (re-termed here as “consensus-1”). Another sizable contingent of investigators and practitioners favor a different approach (originally published in 2011, newly termed here as “consensus-2”), resembling “consensus-1” in some respects but differing in others, leading to substantial differences between these proposals in the numbers of patients qualifying for diagnosis (and thus treatment). Overdiagnosis by “consensus-2” criteria has potential to be problematic, but underdiagnosis by “consensus-1” criteria seems the far larger problem given (1) increasing appreciation that MCAS is prevalent (up to 17% of the general population), and (2) most MCAS patients, regardless of illness duration prior to diagnosis, can eventually identify treatment yielding sustained improvement. We analyze these proposals (and others) and suggest that, until careful research provides more definitive answers, diagnosis by either proposal is valid, reasonable, and helpful.

Objective: To describe the pharmacokinetic parameters of oral pregabalin in normal cats after single oral dosing.Animals: Six healthy adult research cats.Procedures: Following sedation and indwelling catheter placement, one oral (4 mg/kg) dose of pregabalin was administered. Blood samples were collected at 0, 15 and 30 min and 1, 1.5, 2, 3, 4, 6, 8, 12, 24, and 36 h after administration. Plasma pregabalin concentrations were measured by high-performance liquid chromatography and subjected to pharmacokinetic analysis using commercial software.Results: Four of six cats developed moderate sedation after pregabalin administration. The peak pregabalin concentration was 8.3 ± 1.6 μg/ml which occurred at 2.9 ± 1.2 h. Elimination half-life was 10.4 ± 2.6 h and area under the curve was 133.9 ± 71.5 μg-h/ml. Time above the minimum therapeutic concentration for seizure control in dogs and people (2.8 μg/ml) was 17.6 ± 6.2 h. Using these data, predicted minimum, maximum and average steady state concentrations were calculated for 12 and 24 h dosing intervals.Conclusions and Clinical Relevance: Pregabalin (4 mg/kg) administered orally to cats results in plasma concentrations within the range considered to be efficacious for seizure control in dogs and humans between 1.5 and at least 12 h. Because of moderate sedative side effects in the majority of cats at this dose and high calculated maximum steady state concentrations, a lower dose, given more frequently (1–2 mg/kg q 12 h), should be...

Lockdowns imposed during the COVID-19 pandemic had an impact on the gut microbiome development of babies born during these periods according to new research from RCSI University of Medicine and Health Sciences, Children’s Health Ireland and APC Microbiome Ireland. More ...

Inadequate titers of pneumococcal antibody (PA) are commonly present among patients with recurrent respiratory infections.We sought to determine the effect of the degree of inadequacy in baseline PA titers on the subsequent polysaccharide vaccine response, ...

Considerable interest has arisen concerning the relationship between hereditary connective tissue disorders such as the Ehlers-Danlos syndromes (EDS)/hypermobility spectrum disorders (HSD) and autism, both in terms of their comorbidity as well as co-occurrence ...

Substantial age-related differences in the proportions of people diagnosed suggest an urgent need to improve access to adult autism diagnostic services.

Background Little is known about the frequency with which different combinations of phytochemicals (chemovars) arise in Cannabis flower or whether common chemovars are associated with distinct pharmacodynamics and patient health outcomes. This study created a clinically relevant, user-friendly, scalable chemovar indexing system summarizing primary cannabinoid and terpene contents and tested whether the most frequently consumed chemovars differ in their treatment effectiveness and experienced side effects. Methods Between 09/10/2016 and 03/11/2021, 204 people used the freely available, educational mobile software application, Releaf App, to record 6309 real-time consumption sessions using 633 distinct Cannabis flower products, unique at the user level, with terpene and cannabinoid potency information. The indexing system is based on retrospective data analysis of the products’ primary and secondary terpene contents and tetrahydrocannabinol (THC) and cannabidiol (CBD) potencies and yielded a total of 478 distinct chemovars. Analyses of covariances (ANCOVAs) were used to compare symptom levels and side effects experienced across the five most common chemovars before and after cannabis consumption for app users overall and for those treating chronic pain and depression or anxiety. Results Examination of the five most frequently consumed chemovars showed significant differences in symptom treatment effectiveness for chronic pain and for depression and anxiety (ps  .001). While the effects varied in magnitude, the five chemovars were effective across conditions except for MC61 (mercene .01–0.49%/beta-caryophyllene .01 to 0.49%/THC 20–25%/CBD 0.01–1.0%), which exacerbated feelings of anxiety or depression. The chemovars also differed in their association with experiencing positive, negative, and context-specific side effects, with two chemovars, MC61 and MC62 (mercene .01–0.49%/beta-caryophyllene .01–0.49%/THC 20–25%/CBD 1–5%), generating two to three fewer positive side effects and as much as one more negative and two more context-specific side effects than the other three chemovars. Conclusions The findings provide “proof-of-concept” that a simple, yet comprehensive chemovar indexing system can be used to identify systematic differences in clinically relevant patient health outcomes and other common experiences across Cannabis flower products, irrespective of the product’s commercial or strain name. This study was limited by self-selection into cannabis and app use and a lack of user-specific information. Further research using this chemovar indexing system should assess how distinct combinations of phytochemicals interact with user-level characteristics to produce general and individualized Cannabis consumption experiences and health outcomes, ideally using randomized methods to assess differences in effects across chemovars.

The classical approach to autism spectrum disorders (ASD) is often limited to considering their neuro-functional aspects. However, recent scientific literature has shown that ASDs also affect many body systems and apparatuses such as the immune system, the sensory-motor system, and the gut-brain axis. The connective tissue, a common thread linking all these structures, may have a pathogenetic role in the multisystem involvement of ASD. Depending on its different anatomical sites, the connective tissue performs functions of connection and support; furthermore, it acts as a barrier between the external and internal environments, regulating the interchange between the two and performing immunological surveillance. The connective tissue shares a close relationship with the central nervous system, the musculoskeletal system and the immune system. Alterations in brain connectivity are common to various developmental disorders, including ASD, and for this reason here we put forward the hypothesis that alterations in the physiological activity of microglia could be implicated in the pathogenesis of ASD. Also, muscle hypotonia is likely to clinically correlate with an altered sensoriality and, in fact, discomfort or early muscle fatigue are often reported in ASDs. Furthermore, patients with ASD often suffer from intestinal dysfunctions, malabsorption and leaky gut syndrome, all phenomena that may be linked to reduced intestinal connectivity. In addition, at the cutaneous and subcut...

How synaptic pruning shapes neural wiring during development and, possibly, in disease

Jacques Courseault, MD, CAQSM, FAAPMR August 26, 2022 - The area of hypermobility and Ehlers-Danlos research is gaining more traction with the recognition of peculiar clinically presenting patterns in flexible patients. Because of the thorough evaluation performed at the Tulane Hypermobility and Ehlers-Danlos Clinic, we noticed a trend of high folate levels during the screening. To

ABSTRACT: Lower extremity soft tissues injuries account for a large proportion of musculoskeletal injuries. In cases where medication, physical therapy and cortisone injections do not provide complete relief, dextrose prolotherapy is a viable treatment option that has been available for many decades. In our clinic, dextrose prolotherapy is particularly effective in patients who are hypermobile

Background Ehlers–Danlos syndromes are hereditary disorders of connective tissue that are characterized by joint hypermobility, skin hyperextensibility and tissue fragility. The most common subtype ...

J Sports Sci. 2004 Oct;22(10):946-65; discussion 965-6. Review

Alternative medicine gurus are analyzing patients' genetic data and divining health information to sell nutritional supplements. Is this modern-day snake oil?

Linked Editorial: Steele and O’Toole. Br J Dermatol 2020; 182:521–522. Linked Comment: Hausser. Br J Dermatol 2020; 182:535–536. Respond to this article

How to download academic papers and books for free pic.twitter.com/slxtHkbFRs— Alex Strasser (@AStrasser116) October 2, 2022

The need of this study is to assess the role of collagen III in all hernias which include primary inguinal hernias ventral and recurrent abdominal hernias.Collagen type III represents the mechanically instable, less cross-linked collagen synthesized during ...

The serotonin type 4 (5-HT4) receptor agonists are potent prokinetic agents that act on serotonin receptors in the intestine and promote intestinal peristalsis, increase gastric emptying and decrease esophageal reflux. Two 5-HT4 receptor agonists have been developed and were approved for use in the United States, but both were found to have significant serious adverse effects and have been withdrawn (cisapride) or placed under restricted use (tegaserod). Both cisapride and tegaserod have been associated with a low rate of transient serum enzyme elevations during therapy, but neither has been implicated convincing in cases of clinically apparent liver injury with jaundice.

Trintellix (vortioxetine) is a brand-name prescription drug that’s used to treat depression. Learn about side effects, dosage, uses, and more.

Coffee is one of the most popular beverages consumed worldwide. Roasted coffee is a complex mixture of thousands of bioactive compounds, and some of them have numerous potential health-promoting properties that have been extensively studied in the cardiovascular and central nervous systems, with rel …

There is a much greater prevalence of obstetric and gynecologic issues reported by women with Ehlers-Danlos syndrome than in the general population. Additionally, rates differed significantly among the three most common types of Ehlers-Danlos syndrome with vascular type having the highest rates of a …

A summary of clinical studies from 2021 and 2022 show that NMN treatment impacts exercise capacity, sleep, and fatigue, and provide insight into safety and dosing strategies.

To characterize the natural history and clinical features of myopathies caused by mono‐allelic, dominantly acting pathogenic variants in COL12A1. Patients with dominant COL12A1‐related myopathies were characterized by history and clinical ...

The study aimed to determine the impact of 6-month rigid brace on back muscle strength and endurance in adolescents with idiopathic scoliosis. Sixty-one girls, aged 7.0-16.0, were analyzed in two groups: the study group (6-month rigid brace wear) vs. the control group (no brace treatment), recruited …

In this month’s “Hot Topic,” Brad Karon, M.D., Ph.D., will discuss recent information on the advantages and disadvantages of using butterfly needles for blood collection.

Previously reported levels of iron absorption from common Southeast Asian meals composed of rice, vegetables, and spices were too low to be consistent with the known prevalence of iron deficiency. In the present paper the cause of the low absorption was systematically sought. Variables investigated …

The amygdala is a highly interconnected region of the brain that is critically important to emotional processing and affective networks. Previous studies have shown that the response of the amygdala to emotionally arousing stimuli can be modulated by sex hormones. Because oral contraceptive pills dr …

Exogenous cortisol administration has been used to test the influence of glucocorticoids on a variety of outcomes, including memory and affect. Careful control of factors known to influence cortisol and other endogenous hormone levels is central to the success of this research. While the use of horm …