(1) Background: There are links between tension-type headache and/or migraine with dysfunctions of the cervical and masticatory muscles and with psychosocial factors. The study aims to highlight the connections between primary headaches, bruxism and psychosocial issues, the effectiveness of a multidisciplinary approach in decreasing the intensity and frequency of the headache episodes and bruxism. (2) Methods: 67 patients with primary headache and bruxism were divided into two equal groups. The subjects attended manual therapy sessions twice a week and a weekly counselling session for three months. (3) Results: an overall comparison before and after three months show a significant decrease of the qualitative variables (tension-type headache, migraine, awake bruxism, limited jaw opening, anxiety and stress) after 3 months. Comparing the efficiency of the procedures after 3 months between the two groups, awake bruxism and perceived stress are significantly different. (4) Conclusions: Although the differences are not radical when comparing MT with MT+C at three months, the patients who received either manual therapy or this treatment combination showed an improvement in pain relief, in the frequency and complexity of their symptoms, a reduction in functional disability and an overall improvement of the quality of their lives after three months of treatment.

Secondary metabolites such as flavonoids are considered to be promising in the treatment of NAFLD, which is one of the complications of diabetes due to oxidative stress and inflammation. Some plants, such as Eryngium carlinae, have been investigated with regard to their medicinal properties in in vitro and in vivo assays, showing favorable results for the treatment of various diseases such as diabetes and obesity. The present study examined the antioxidant and anti-inflammatory effects of the phenolic compounds present in an ethyl acetate extract of the inflorescences of Eryngium carlinae on liver homogenates and mitochondria from STZ-induced diabetic rats. Phenolic compounds were identified and quantified by UHPLC-MS. In vitro assays were carried out to discover the antioxidant potential of the extract. Male Wistar rats were administered with a single intraperitoneal injection of STZ (45 mg/kg) and were given the ethyl acetate extract at a level of 30 mg/kg for 60 days. Phytochemical assays showed that the major constituents of the extract were flavonoids; in addition, the in vitro antioxidant activity was dose-dependent with IC50 = 57.97 mg/mL and IC50 = 30.90 mg/mL in the DPPH and FRAP assays, respectively. Moreover, the oral administration of the ethyl acetate extract improved the effects of NAFLD, decreasing serum and liver TG levels and oxidative stress markers and increasing the activity of the antioxidant enzymes. Likewise, it attenuated liver damage by decreasing the expression of NF-κB and iNOS, which lead to inflammation and liver damage. These results suggest that the phenolic compounds of the ethyl acetate extract of E. carlinae have antioxidant, anti-inflammatory, hypolipidemic, and hepatoprotective activity.

Synthetic antivirals and corticosteroids have been used to treat both influenza and the SARS-CoV-2 disease named COVID-19. However, these medications are not always effective, produce several adverse effects, and are associated with high costs. Medicinal plants and their constituents act in several different targets and signaling pathways involved in the pathophysiology of Influenza and COVID-19. This study aimed to perform a review to evaluate the effects of medicinal plants on Influenza and COVID-19 and to investigate the potential delivery systems for new antiviral therapies. EMBASE, PubMed, GOOGLE SCHOLAR, and COCHRANE databases were searched. The studies included in this review showed that medicinal plants, in different formulations, can help decrease viral spread and time of full recovery. Plants reduced the incidence of acute respiratory syndromes and the symptom scores of the illnesses. Moreover, plants are related to few adverse effects and have low costs. In addition to their significance as natural antiviral agents, medicinal plants and their bioactive compounds may exhibit low bioavailability. This highlights the need for alternative delivery systems, such as metal nanoparticles, that can effectively transport these compounds to infected tissues.

Euryale ferox, which belongs to the family of Nymphaeaceae, has been widely distributed in China, India, Korea, and Japan. The seeds of E. ferox (EFS) have been categorized as superior food for 2000 years in China, based on its abundant nutrients including polysaccharides, polyphenols, sesquineolignans, tocopherols, cyclic dipeptides, glucosylsterols, cerebrosides, and triterpenoids. These constituents exert multiple pharmacological effects, such as antioxidant, hypoglycemic, cardioprotective, antibacterial, anticancer, antidepression, and hepatoprotective properties. There are very few summarized reports on E. ferox, albeit with its high nutritional value and beneficial activities. Therefore, we collected the reported literatures (since 1980), medical classics, databases, and pharmacopeia of E. ferox, and summarized the botanical classification, traditional uses, phytochemicals, and pharmacological effects of E. ferox, which will provide new insights for the further research and development of EFS-derived functional products.

Rice bran arabinoxylan compound (RBAC) is a polysaccharide modified by Lentinus edodes mycelial enzyme widely used as a nutraceutical. To explore translational research on RBAC, a scoping review was conducted to synthesise research evidence from English, Japanese, Korean, and Chinese sources while combining bibliometrics and network analyses for data visualisation. Ninety-eight articles on RBAC and the biological activities related to human health or disease were included. Research progressed with linear growth (median=3/year) from 1998 to 2022, predominantly on Biobran MGN-3 (86.73%) and contributed by 289 authors from 100 institutions across 18 countries. Clinical studies constitute 61.1% of recent articles (2018 to 2022). A shifting focus from immuno-cellular activities to human translations over the years was shown via keyword visualisation. Beneficial effects of RBAC include immunomodulation, synergistic anticancer properties, hepatoprotection, antiinflammation, and antioxidation. Cancer patients reported reduced side effects from chemoradiotherapy and improved quality of life in human studies, indicating RBAC’s impact on the psycho-neuro-immune axis. RBAC has been studied in 17 conditions, including cancer, liver diseases, HIV, allergy, chronic fatigue, gastroenteritis, cold/flu, diabetes, and in healthy participants. Further translational research on the impact on patient and community health is required for the evidence-informed use of RBAC in health and disease.

Currently, some non-conventional therapies (NCT), such as acupuncture, homeopathy, osteopathy, naturopathy, herbology, and Traditional Chinese Medicine are structured and well-regulated for a market of teaching and clinical practice in Portugal, among which acupuncture has become one of the most appealing and functional branches. Through investigation of acupuncture laws, field surveys, teaching work and interviews with people from NCT field in Portugal, we showed the current acupuncture education in Portugal and found that according to the academic norms and rules of education in Portugal, there is a gradual difficulty in the progression and maintenance of the degree training dynamics, due to the lack of more tolerant transitional measures and also, a timid commitment on the part of the institutions that embark on these complementary programs. Therefore, it will be necessary to promote additional programs and measures that avoid a total emptiness of the teaching of acupuncture and at the same time losses of clinicians, competencies and quality of information that are difficult to recover. It could be very meaningful and thought-provoking to the future development and improvement of acupuncture in Portugal and in other countries that welcome acupuncture and intend to have a better legislation and application.

Abstract: Five patients with standard medical treatment-resistant symptoms of skin lesions, ear infections, allergic rhinitis, nasal congestion, asthma, heartburn, and failure to thrive were success- fully treated with an integrative medicine assessment and integrative medicine treatment approach. The integrative medicine assessment method of autonomic response testing enabled the identifica- tion of nickel sensitivity as a common element in these patients. It guided the use of the integrative medicine therapies of low dose immunotherapy, gamma linoleic acid supplementation, chelation, dietary nickel restriction, and removal of nickel containing dental and cosmetic appliances. A chart review of 151 patients indicated a strong association of nickel and the simultaneous presence of skin lesions.

Today, enterococci (mainly Enterococcus faecalis) are one of the main causes of infective endocarditis in the world, generally affecting an elderly and fragile population, with a high mortality rate. enterococci are intrinsically resistant to many commonly used antimicrobial agents. All enterococci exhibit decreased susceptibility to penicillin and ampicillin, as well as high-level resistance to most cephalosporins and all semi-synthetic penicillins, as the result of expression of low-affinity penicillin-binding proteins, that precludes an unacceptable number of therapeutic failures with monotherapy with these drugs. For years, the synergistic combination of penicillins and aminoglycosides was the cornerstone of treatment, but the emergence of strains with high resistance to aminoglycosides led to the search for new alternatives, such as dual beta-lactam therapy. The development of multi-drug resistant strains of Enterococcus faecium is a matter of considerable concern due to its probable spread to E. faecalis and have forced the search of new alternatives with the combination of daptomycin, fosfomycin or tigecycline. Some of them have scarce clinical experience and others are still under investigation and will be analyzed in this review. In addition, the need for prolonged treatment (6-8 weeks) to avoid relapses has led to the consideration of viable options such as outpatient parenteral therapies or long-acting administrations with the new lipoglycopeptides (dalbavancin or oritavancin), and sequential oral treatments, which will also be discussed.

Different hypotheses of carcinogenesis have been proposed based on local genetic factors and physiologic mechanisms. It is assumed that changes of the metric invariants of a biologic system (BS) determine general mechanisms of cancer development. Numerous data demonstrate an existence of three invariant feedback patterns of BS: negative feedback (NFB), positive feedback (PFB) and reciprocal links (RL). These base patterns represent basis elements of a Lie algebra and imaginary part of coquaternion. Considering coquaternion as a model of a functional core of a BS, conditions of the system can be identified with the points of three families of hypersurfaces in R⁴₂: hyperboloids of one sheet, hyperboloids of two sheets and double-cones. Corresponding quadratic form relates negative and positive entropy contributions of base elements to the energy level of the system, so that anabolic states of the system will correspond to the points of a hyperboloid of one sheet, while catabolic conditions to the points of a hyperboloid of two sheets. Equilibrium states will lie in a double cone. Hypothetically anabolic and catabolic states dominate intermittently oscillating around the equilibrium. Deterioration of base elements increases positive entropy and causes domination of catabolic states which is the main metabolic determinant of cancer. Corresponding trajectory of a malfunctioning system will have a tendency to remain inside the double cone.

The emergence of multidrug-resistant bacterial strains, especially in the clinical setting, has renewed interest in alternative treatment methods. The utilization of prokaryotic viruses in phage therapy has demonstrated potential as a novel treatment method against multidrug-resistant bacterial infections. As the post-antibiotic era quickly approaches, the development and standardization of phage therapy is critically relevant to public health. This review serves to highlight the development of phage therapy against methicillin-resistant Staphylococcus aureus (MRSA), an antibiotic-resistant bacterial strain responsible for severe clinical infections.

Background: Menopause symptoms and hormone replacement therapy (HRT) are among the most common reasons patients seek gynecological advice. Although at least half of all women in developed countries will take HRT during their lifetime, the treatment is not without risk and guidance on HRT is mixed. Greater awareness of negative HRT health effects from extended use has piqued interest in ‘safer options’. Menopause reversal with autologous ovarian platelet-rich plasma (OPRP) has brought this restorative approach forward for consideration, but appropriateness and cost-effectiveness require examination. Methods: HRT and OPRP data from USA were projected to compare cumulative 1yr patient costs using stochastic Monte Carlo modeling. Results: Mean±SD cost-to-patient for HRT including initial consult plus pharmacy refills was estimated at about USD 576±246/yr. While OPRP included no pharmacy component, an estimated 4 visits over 1yr for OPRP maintenance entailed ultrasound, phlebotomy/sample processing, surgery equipment, and incubation/laboratory expense, yielding mean±SD cost for OPRP at USD 8,710±4,911/yr (p<0.0001 vs. HRT, by t-test). Upper-bound estimates for annual HRT and OPRP costs were USD 1,341 and USD 22,232, respectively. Conclusions: While HRT and OPRP may have similar efficacy and safety for menopause therapy, they diverge sharply in cost-effectiveness. Most patients would likely find OPRP too complex, invasive, and expensive to be competitive vs. HRT. Although OPRP is an interesting and cautiously useful technique for selected menopause patients reluctant to use HRT, repurposing this infertility treatment for wider use appears inefficient compared to standard HRT currently available.

Chronic diseases are still known as incurable diseases, and we suspect that the medical research model is unfit for characterizing chronic diseases. In this study, we examined accuracy and reliability required for characterizing chronic diseases, reviewed implied presumptions in clinical trials and assumptions used in statistical analysis, examined sources of variances normally encountered in clinical trials, and conducted numeric simulations by using hypothetical data for several theoretical and hypothetical models. We found that the sources of variances attributable to personal differences in clinical trials can distort hypothesis test outcomes, that clinical trials introduce too many errors and too much inaccuracies that tend to hide weak and slow effects of treatments, and that the means of treatments used in statistical analysis have little or no relevance to specific patients. We further found that a large number of uncontrolled co-causal or interfering factors normally seen in human subjects can greatly enlarge the means and the variances of the experimental errors, and the use of high rejection criteria (e.g., low p values) further raises the chances of failing to find treatment effects. As a whole, we concluded that the research model using clinical trials is wrong on multiple grounds, under any of our realistic theoretical and hypothetical models, and that misuse of statistical analysis is most probably responsible for failure to identify treatment effects for chronic diseases and to detect harmful effects of toxic substances in the environment. We proposed alternative experimental models involving the use of single-person or mini optimization trials for studying low-risk weak treatments.

Objective: To recommend how physicians can best respond to families whose hopes for a miracle via divine intervention influence their medical decisions, like, for example, making them not want to withdraw ventilatory support in cases of poor neurologic prognosis because they are still hoping for God to intervene. Methods: Auto-ethnographic analysis of chaplaincy experience in this clinical context yields a nuanced 90-second, point-of-care spiritual intervention physicians can use to address the religious aspect of families who base medical decisions on their hopes for a miracle via divine intervention. Explanation of how spiritual intervention dovetails with existing physician communication protocol for responding to families hoping for a miracle. Results: Spiritual intervention for religious aspect of miracle-hoping families is integrated into existing physician communication protocol for responding to families hoping for a miracle with recommendations for utilization of existing communication technology when necessary. Conclusion: Properly addressing the religious dimension of families hoping for a miracle may be helpful for physicians interested in decreasing their own stress levels, improving outcomes for this clinical context, and ensuring that unintentional discrimination does not perpetuate racial disparities in end-of-life care.

The aim of this document is to provide practical guidance on the choice of target difference used in the sample size calculation of a randomised controlled trial (RCT). Guidance is provided with a definitive trial, one that seeks to provide a useful answer, in mind and not those of a more exploratory nature. The term “target difference” is taken throughout to refer to the difference that is used in the sample size calculation (the one that the study formally “targets”). Please see the glossary for definitions and clarification with regards other relevant concepts. In order to address the specification of the target difference, it is appropriate, and to some degree necessary, to touch on related statistical aspects of conducting a sample size calculation. Generally the discussion of other aspects and more technical details is kept to a minimum, with more technical aspects covered in the appendices and referencing of relevant sources provided for further reading.The main body of this guidance assumes a standard RCT design is used; formally, this can be described as a two-arm parallel-group superiority trial. Most RCTs test for superiority of the interventions, that is, whether or not one of the interventions is superior to the other (See Box 1 for a formal definition of superiority, and of the two most common alternative approaches). Some common alternative trial designs are considered in Appendix 3. Additionally, it is assumed in the main body of the text that the conventional (Neyman-Pearson) approach to the sample size calculation of an RCT is being used. Other approaches (Bayesian, precision and value of information) are briefly considered in Appendix 2 with reference to the specification of the target difference.

Philip Morris International (PMI) has developed the Population Health Impact Model (PHIM) to quantify, in the absence of epidemiological data, the effects of marketing a candidate modified risk tobacco product (cMRTP) on the public health of a whole population. Various simulations were performed to understand the harm reduction impact on the U.S. population over a 20-year period under various scenarios. The overall reduction in smoking attributable deaths (SAD) over the 20-year period was estimated as 934,947 if smoking completely went away and between 516,944 and 780,433 if cMRTP use completely replaces smoking. The reduction in SADs was estimated as 172,458 for the World Health Organization (WHO) 2025 Target and between 70,274 and 90,155 for the gradual cMRTP uptake. Combining the scenarios (WHO 2025 Target and cMRTP uptake), the reductions were between 256,453 and 268,796, depending on the cMRTP effective dose. These results show how a cMRTP can reduce overall population harm additionally to existing tobacco control efforts.