Intra-articular Hymovis injection for managing hip OA in active sportsmen. A 24-month observational retrospective clinical investigation

BackgroundHip Osteoarthitis (OA) risk is sport-specific and depends on frequency, intensity, and type of mechanic stress the hip is subjected to. This retrospective observational study aims to investigate the safety and performance of Hymovis (HYADD-4) injection, a hexadecyl (C-16) HA-derivative, when used to manage symptomatic hip OA in active middle-aged sportsmen over a 24-month observation period.MethodsThe retrospective analysis included clinical records of active sportsmen, aged between 40 and 65 years, and suffering from symptomatic Kellgren-Lawrence grade II to III hip OA, treated with two (24 mg/3 ml) Hymovis injections, two weeks apart, every 3–4 months, for two years. When available, data on MRI examination were included in the analysis as well as Heidelberg Sports Activity Score (HAS) and Copenhagen Hip and Groin Outcome Score (HAGOS) questionnaires.ResultsThirty patients (56.4 ± 7.3 years) were included in the study, sixteen cyclists and 14 tennis players. For all patients, HAS and most HAGOS scores improved significantly (p < 0.05) at the first control visit (4 months) and further improved over time. For all other scores an important clinical benefit was experienced by more than 50% of participants. No adverse events were recorded.ConclusionTreatment of hip OA in active sportsmen with Hymovis seems a safe and effective approach for the management of OA symptoms, by potentially protecting cartilage and subchondral bone from further damage.     

Effects of exogenous factors on spatial accuracy in neurosurgery

The study aimed to assess the effect of exogenous factors such as surgeon posture, surgical instrument length, fatigue after a night shift, exercise and caffeine consumption on the spatial accuracy of neurosurgical manipulations. For the evaluation and simulation of neurosurgical manipulations, a testing device developed by the authors was used. The experimental results were compared using nonparametric analysis (Wilcoxon test) and multivariate analysis, which was performed using mixed models. The results were considered statistically significant at p < 0.05. The study included 11 first-year neurosurgery residents who met the inclusion criteria. Hand support in the sitting position (Wilcoxon test p value = 0.0033), caffeine consumption (p = 0.0058) and the length of the microsurgical instrument (p = 0.0032) had statistically significant influences on the spatial accuracy of surgical manipulations (univariate analysis). The spatial accuracy did not significantly depend on the type of standing position (Wilcoxon test p value = 0.2860), whether the surgeon was standing/sitting (p = 0.1029), fatigue following a night shift (p = 0.3281), or physical exertion prior to surgery (p = 0.2845).When conducting the multivariate analysis, the spatial accuracy significantly depended on the test subject (p < 0.0001), the use of support during the test (p = 0.0001), and the length of the microsurgical instrument (p = 0.0397). To increase the spatial accuracy of microsurgical manipulations, hand support and shorter tools should be used. Caffeine consumption in high doses should also be avoided prior to surgery.     

Measuring disease activity and response to treatment in rheumatoid arthritis

Introduction: Effective treatment of rheumatoid arthritis (RA) requires suppression of the underlying inflammation. Measurement of such inflammation, the disease activity, is mandatory to target treatment and maximize outcomes. However, this is not as straightforward as it may seem.

Areas covered: The many tools developed to measure disease activity in RA, from composite scores and patient-reported outcomes, to laboratory markers and imaging are discussed, with a focus on their utility in guiding therapy and assessing response. The complex issues in measuring disease activity in RA, whether in clinical trials or normal clinical practice, and in the context of national guidelines and recommendations, available time, and resources are considered.

Expert commentary: The key to effective management of RA is the rapid suppression of inflammation, ideally to remission, with maintenance of such remission. The aim is to prevent disability and maximize quality of life. Central to this is the ability to determine disease activity (potentially open to suppression) as opposed to damage (irreversible). A variety of measures are currently available, allowing better assessment of response to treatment. In the future, the development of predictive biomarkers allowing targeting of drugs may revolutionize this field and render the tools of today redundant.     

Making meaning of the virginity experience: young men's perceptions in the United States

ABSTRACT

A qualitative grounded theory approach was used to analyze 34 narratives from young men about their experience of retaining, losing, or giving away their virginity, where 7 said they were virgins, 26 said they were non-virgins, and one did not mention his virginity status. We found that virginity is a multidimensional concept, with two distinct dimensions: the experiential and the developmental. The experiential dimension refers to young men's perception and understanding of their virginity in four overlapping areas: physical, spiritual, relational, and emotional. The developmental dimension refers to young men's perception of their underlying sexual identity growth processes and the gendered and sexual double standards that influence this understanding. Clinical implications of this study are useful in education and counseling. They seek to empower young men with information relating to the multidimensional nature of virginity experience, and minimize the negative effects on romantic relationships, sexual adjustment, and self-identity development. The findings are helpful in designing interventions for young men and women who are at high risk for sexually transmitted infections and can help them negotiate mutually safe and pleasurable experiences regarding their virginity.     

Chalcone hybrids and their antimalarial activity

Malaria, one of the most striking, re-emerging infectious diseases caused by the genus Plasmodium, places a huge burden on global healthcare systems. A major challenge in the control and eradication of malaria is the continuous emergence of increasingly widespread drug-resistant malaria, creating an urgent need to develop novel antimalarial agents. Chalcone derivatives are ubiquitous in nature and have become indispensable units in medicinal chemistry applications due to their diverse biological profiles. Many chalcone derivatives demonstrate potential in vitro and in vivo antimalarial activity, so chalcone could be a useful template for the development of novel antimalarial agents. This review covers the recent development of chalcone hybrids as antimalarial agents. The critical aspects of the design and structure–activity relationship of these compounds are also discussed.     

Baroreflex activation in conscious rats modulates the joint inflammatory response via sympathetic function

The baroreflex is a critical physiological mechanism controlling cardiovascular function by modulating both the sympathetic and parasympathetic activities. Here, we report that electrical activation of the baroreflex attenuates joint inflammation in experimental arthritis induced by the administration of zymosan into the femorotibial cavity. Baroreflex activation combined with lumbar sympathectomy, adrenalectomy, celiac subdiaphragmatic vagotomy or splenectomy dissected the mechanisms involved in the inflammatory modulation, highlighting the role played by sympathetic inhibition in the attenuation of joint inflammation. From the immunological standpoint, baroreflex activation attenuates neutrophil migration and the synovial levels of inflammatory cytokines including TNF, IL-1β and IL-6, but does not affect the levels of the anti-inflammatory cytokine IL-10. The anti-inflammatory effects of the baroreflex system are not mediated by IL-10, the vagus nerve, adrenal glands or the spleen, but by the inhibition of the sympathetic drive to the knee. These results reveal a novel physiological neuronal network controlling peripheral local inflammation.     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.