Tildrakizumab in the treatment of psoriasis: latest evidence and place in therapy.

Psoriasis is a chronic inflammatory disorder that is clinically characterized by scaly cutaneous plaques. New evidence suggests that dysregulation of interleukin (IL)-23, a key cytokine in the T-helper-17 pathway, plays a vital role in the development of psoriatic systemic inflammation. The novel biologic medication tildrakizumab is among the first drugs with specific action against IL-23 that has recently been approved by the United States Food and Drug Administration and the European Medicines Agency for moderate-to-severe psoriasis. Tildrakizumab has been shown in large randomized controlled trials to be effective in improving skin manifestations as well as enhancing quality of life outcomes in patients with psoriasis. Its simple dosing, prolonged duration of action, and mild adverse event profile make it a practical option for patients; however, only a small number of trials have investigated the clinical effectiveness of tildrakizumab, and long-term data regarding the drug's efficacy and safety are currently limited. Hence, further research is needed to better understand the risks and benefits of tildrakizumab. This review summarizes and analyzes phase I, phase II, and phase III clinical trials that investigate the mechanism, pharmacokinetics, efficacy, and safety of tildrakizumab. It also identifies areas in which additional studies are warranted to further elucidate the advantages of tildrakizumab over other biologic therapies

The virtual peripheral nerve academy: education for the identification and treatment of peripheral nerve disorders

Millions of people around the globe suffer peripheral nerve injuries caused by trauma and medical disorders. However, medical school curricula are profoundly deficient in peripheral nerve education. This lack of knowledge within the healthcare profession may cause inadequate patient care. We developed the Virtual Peripheral Nerve Academy (VPNA) as a reusable virtual learning environment to provide medical students with detailed education on the peripheral nervous system (PNS). Students are introduced to the PNS through virtual 3D rendering of the human body, wherein they visualize individual nerves through dissection and observe normal motor and sensory function associated with each nerve. PNS structures that are absent from traditional texts are included in this visualization, ranging from the innervation of joints to the normal anatomic variation required for differential diagnosis of pain after an injury. Detailed modules on peripheral nerve disorders allow students to observe pathophysiological mechanisms, associated symptomatology, and appropriate treatments. Students are briefed on a patient clinical case, then interact with a patient avatar to learn the appropriate diagnostics, including physical exam maneuvers and electrodiagnostic testing. Interactive modules on peripheral nerve surgeries detail surgical techniques. The VPNA data and analytics dashboards allow medical students and course instructors to assess skill improvement and identify specific learning needs. The built-in learner management system and availability on both computer-based and virtual reality platforms facilitate integration into any existing medical school curricula. Ultimately, this immersive technology enables every medical student to learn about the peripheral nervous system and gain competency in treating real-life nerve pathologies

Results of a Second Year of Therapy with the 12-Month Histrelin Implant for the Treatment of Central Precocious Puberty

Background. Gonadotropin releasing hormone analogs (GnRHas) are standard of care for central precocious puberty (CPP). The histrelin subcutaneous implant is safe and effective in the treatment of CPP for one year. Objective. The study evaluates a second year of therapy in children with CPP who received a new implant after one year of treatment. Methods. A prospective one-year study following an initial 12-month treatment period was conducted. Results. Thirty-one patients (29 girls) aged 7.7 ± 1.5 years received a second implant. Eighteen were naïve to GnRHa therapy at first implantation. Peak LH declined from 0.92 ± 0.58 mIU/mL at 12 months to 0.51 ± 0.33 mIU/mL at 24 months (P < .0001) in naïve subjects, and from 0.74 ± 0.50 mIU/mL at 12 months to 0.45 ± 0.35 mIU/mL at 24 months (P = .0081) in previously treated subjects. Predicted adult height increased by 5.1 cm at 24 months (P = .0001). Minor implant site reactions occurred in 61%, while minor difficulties with explantation occurred in 32.2% of subjects. Conclusion. The histrelin implant demonstrates profound hypothalamic-pituitary-gonadal axis suppression when a new implant is placed for a second year of treatment. Prospective follow-up of this therapeutic modality for the treatment of CPP is needed

Food insecurity and the role of food assistance programs in supporting diet quality during the COVID-19 pandemic in Massachusetts

BackgroundEconomic and supply chain shocks resulting from the COVID-19 pandemic in 2020 led to substantial increases in the numbers of individuals experiencing food-related hardship in the US, with programs aimed at addressing food insecurity like the Supplemental Nutrition Assistance Program (SNAP) and food pantries seeing significant upticks in utilization. While these programs have improved food access overall, the extent to which diet quality changed, and whether they helped mitigate diet quality disruptions, is not well understood.ObjectiveTo evaluate food insecurity, food pantry and/or SNAP participation associations with both diet quality as well as perceived disruptions in diet during the COVID-19 pandemic among Massachusetts adults with lower incomes.MethodsWe analyzed complete-case data from 1,256 individuals with complete data from a cross-sectional online survey of adults (ages 18 years and above) living in Massachusetts who responded to “The MA Statewide Food Access Survey” between October 2020 through January 2021. Study recruitment and survey administration were performed by The Greater Boston Food Bank. We excluded respondents who reported participation in assistance programs but were ineligible (n = 168), those who provided straightlined responses to the food frequency questionnaire component of the survey (n = 34), those with incomes above 300% of the federal poverty level (n = 1,427), those who completed the survey in 2021 (n = 8), and those who reported improved food insecurity (n = 55). Current dietary intake was assessed via food frequency questionnaire. Using Bayesian regression models, we examined associations between pandemic food insecurity, perceived disruption in diet, diet quality, and intakes of individual foods among those who completed a survey in 2020. We assessed interactions by pantry and SNAP participation to determine whether participation moderated these relationships.ResultsIndividuals experiencing food insecurity reported greater disruption in diet during the pandemic and reduced consumption of healthy/unhealthy foods. Pantry participation attenuated significant associations between food insecurity and lower consumption of unhealthy (b = −1.13 [95% CI −1.97 to −0.31]) and healthy foods (b = −1.07 [−1.82 to −0.34]) to null (unhealthy foods: −0.70 [−2.24 to 0.84]; healthy foods: 0.30 [−1.17 to 1.74]), whereas SNAP participation attenuated associations for healthy foods alone (from −1.07 [−1.82 to −0.34] to −0.75 [−1.83 to 0.32]). Results were robust to choice of prior as well as to alternative modeling specifications.ConclusionAmong adults with lower incomes, those experiencing food insecurity consumed less food, regardless of healthfulness, compared to individuals not experiencing food insecurity. Participation in safety-net programs, including SNAP and pantry participation, buffered this phenomenon. Continued support of SNAP and the food bank network and a focus on access to affordable healthy foods may simultaneously alleviate hunger while improving nutrition security

Daily to decadal modulation of jet variability

The variance of a jet’s position in latitude is found to be related to its average speed: when a jet becomes stronger its variability in latitude decreases. This relationship is shown to hold for observed midlatitude jets around the world and also across a hierarchy of numerical models. North Atlantic jet variability is shown to be modulated on decadal timescales, with decades of a strong, steady jet being interspersed with decades of a weak, variable jet. These modulations are also related to variations in the basin-wide occurrence of high-impact blocking events. A picture emerges of complex multidecadal jet variability in which recent decades do not appear unusual. We propose an underlying barotropic mechanism to explain this behaviour, related to the change in refractive properties of a jet as it strengthens, and the subsequent effect on the distribution of Rossby wave breaking

Efficacy of novel recombinant fowlpox vaccine against recent Mexican H7N3 highly pathogenic avian influenza virus

Since 2012, H7N3 highly pathogenic avian influenza (HPAI) has produced negative economic and animal welfare impacts on poultry in central Mexico. In the present study, chickens were vaccinated with two different recombinant fowlpox virus vaccines (rFPV-H7/3002 with 2015 H7 hemagglutinin [HA] gene insert, and rFPV-H7/2155 with 2002 H7 HA gene insert), and were then challenged three weeks later with H7N3 HPAI virus (A/chicken/Jalisco/CPA-37905/2015). The rFPV-H7/3002 vaccine conferred 100% protection against mortality and morbidity, and significantly reduced virus shed titers from the respiratory and gastrointestinal tracts. In contrast, 100% of sham and rFPV-H7/2155 vaccinated birds shed virus at higher titers and died within 4 days. Pre- (15/20) and post- (20/20) challenge serum of birds vaccinated with rFPV-H7/3002 had antibodies detectable by hemagglutination inhibition (HI) assay using challenge virus antigen. However, only a few birds (3/20) in the rFPV-H7/2155 vaccinated group had antibodies that reacted against the challenge strain but all birds had antibodies that reacted against the homologous vaccine antigen (A/turkey/Virginia/SEP-66/2002) (20/20). One possible explanation for differences in vaccines efficacy is the antigenic drift between circulating viruses and vaccines. Molecular analysis demonstrated that the Mexican H7N3 strains have continued to rapidly evolve since 2012. In addition, we identified in silico three potential new N-glycosylation sites on the globular head of the H7 HA of A/chicken/Jalisco/CPA-37905/2015 challenge virus, which were absent in 2012 H7N3 outbreak virus. Our results suggested that mutations in the HA antigenic sites including increased glycosylation sites, accumulated in the new circulating Mexican H7 HPAIV strains, altered the recognition of neutralizing antibodies from the older vaccine strain rFPV-H7/2155. Therefore, the protective efficacy of novel rFPV-H7/3002 against recent outbreak Mexican H7N3 HPAIV confirms the importance of frequent updating of vaccines seed strains for long-term effective control of H7 HPAI virus.info:eu-repo/semantics/publishedVersio

Independent and joint cross-sectional associations of statin and metformin use with mammographic breast density

Background Well-tolerated and commonly used medications are increasingly assessed for reducing breast cancer risk. These include metformin and statins, both linked to reduced hormone availability and cell proliferation or growth and sometimes prescribed concurrently. We investigated independent and joint associations of these medications with mammographic breast density (MBD), a useful biomarker for the effect of chemopreventive agents on breast cancer risk. Methods Using data from a cross-sectional study of 770 women (78% Hispanic, aged 40–61 years, in a mammography cohort with high cardiometabolic burden), we examined the association of self-reported “ever” use of statins and metformin with MBD measured via clinical Breast Imaging Reporting and Data System (BI-RADS) density classifications (relative risk regression) and continuous semi-automated percent and size of dense area (Cumulus) (linear regression), adjusted for age, body mass index, education, race, menopausal status, age at first birth, and insulin use. Results We observed high statin (27%), metformin (13%), and combination (9%) use, and most participants were overweight/obese (83%) and parous (87%). Statin use was associated with a lower likelihood of high density BI-RADS (RR = 0.60, 95% CI = 0.45 to 0.80), percent dense area (PD) (β = − 6.56, 95% CI = − 9.05 to − 4.06), and dense area (DA) (β = − 9.05, 95% CI = − 14.89 to − 3.22). Metformin use was associated with lower PD and higher non-dense area (NDA), but associations were attenuated by co-medication with statins. Compared to non-use of either medication, statin use alone or with metformin were associated with lower PD and DA (e.g., β = − 6.86, 95% CI: − 9.67, − 4.05 and β = − 7.07, 95% CI: − 10.97, − 3.17, respectively, for PD) and higher NDA (β = 25.05, 95% CI: 14.06, 36.03; β = 29.76, 95% CI: 14.55, 44.96, respectively). Conclusions Statin use was consistently associated with lower MBD, measured both through clinical radiologist assessment and continuous relative and absolute measures, including dense area. Metformin use was associated with lower PD and higher NDA, but this may be driven by co-medication with statins. These results support that statins may lower MBD but need confirmation with prospective and clinical data to distinguish the results of medication use from that of disease

Spectroscopic Characterization of Galaxy Clusters in RCS-1: Spectroscopic Confirmation, Redshift Accuracy, and Dynamical Mass–Richness Relation

We present follow-up spectroscopic observations of galaxy clusters from the first Red-sequence Cluster Survey (RCS-1). This work focuses on two samples, a lower redshift sample of ∼30 clusters ranging in redshift from z ∼ 0.2–0.6 observed with multiobject spectroscopy (MOS) on 4–6.5-m class telescopes and a z ∼ 1 sample of ∼10 clusters 8-m class telescope observations. We examine the detection efficiency and redshift accuracy of the now widely used red-sequence technique for selecting clusters via overdensities of red-sequence galaxies. Using both these data and extended samples including previously published RCS-1 spectroscopy and spectroscopic redshifts from SDSS, we find that the red-sequence redshift using simple two-filter cluster photometric redshifts is accurate to σz ≈ 0.035(1 + z) in RCS-1. This accuracy can potentially be improved with better survey photometric calibration. For the lower redshift sample, ∼5 per cent of clusters show some (minor) contamination from secondary systems with the same red-sequence intruding into the measurement aperture of the original cluster. At z ∼ 1, the rate rises to ∼20 per cent. Approximately ten  per cent of projections are expected to be serious, where the two components contribute significant numbers of their red-sequence galaxies to another cluster. Finally, we present a preliminary study of the mass–richness calibration using velocity dispersions to probe the dynamical masses of the clusters. We find a relation broadly consistent with that seen in the local universe from the WINGS sample at z ∼ 0.05