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A diagnosis of late-stage melanoma is associated with significant mortality. From a public health perspective, the knowledge of geographic disparities in late-stage diagnoses can inform efforts to facilitate the diagnosis of the earlier stage, highly curable melanomas. We conducted a county-level analysis of melanoma in New York state to identify communities that may benefit from pilot health interventions to reduce the burden of late-stage melanoma. From 1995 to 2016, late-stage melanoma incidence increased from 1.5 to 2.8 cases per 100,000 in New York state. We found statistically significant associations between decreased county-level health system access (including physician density and resident educational status) and increased county incidence and proportion of late-stage disease among diagnosed cases (P less then 0.001 for both). Increased county-level socioeconomic status, including measures of resident wealth and medical insurance status, was positively associated with greater late-stage incidence (P less then 0.001). However, decreased county-level socioeconomic status was positively associated with a greater proportion of late-stage disease among cases at diagnosis (P = 0.009). Counties with reduced access to physician services and lower socioeconomic status may be suitable for pilot interventions promoting the recognition and diagnosis of early-stage melanomas to reduce late-stage diagnoses and associated mortality.
In 2000, the FDA began issuing advice about treatments for hypoactive sexual desire disorder (HSDD) in women. How its recommendations have evolved has not been reviewed. Its consistent preference for self-rating by patients over evaluation by an examining clinician has not been addressed.
Recount the changes in FDA's proposals about patient-reported outcomes and diagnostics. Compare the value of patient-reported measures and clinical interviews.
Historical review is based on draft guidances, publications, meetings, and prescribing information.
The FDA has avoided clinician input into diagnosis and evaluation of the severity of HSDD in women. It abandoned its initial (2000) insistence on counts of satisfying sexual events to define efficacy in favor of symptom-related scales to evaluate desire and distress with daily self-ratings. By 2015, the FDA accepted the self-rated Female Sexual Function Index-Desire Domain (FSFI-D) to measure desire and the most relevant item of the Female Sexual Distress Scale-nd are recommended for clinical practice. Pyke RE. FDA Decisions on Measures of Hypoactive Sexual Desire Disorder in Women A History, With Grounds to Consider Clinical Judgment. Sex Med Rev 2021;9186-193.
FDA's decisions on how to measure HSDD in women may have stabilized on accepting 2 co-primary measures the FSFI-D and the FSDS-R item on bother about low desire, and on accepting the DSDS for diagnosis. FDA's rejection of clinician ratings of severity through interviews in clinical trials seems unsound because interviews can give broader assessments than (brief) self-ratings, although the agency's logic was to avoid diagnostic controversies and help avoid overcommercialization. Semistructured clinical interviews for diagnosis (DSDS) and severity-rating (SIDI-F) are well validated and are recommended for clinical practice. Pyke RE. FDA Decisions on Measures of Hypoactive Sexual Desire Disorder in Women A History, With Grounds to Consider Clinical Judgment. Sex Med Rev 2021;9186-193.
Although testosterone therapy (TTh) is the standard practice in otherwise healthy hypogonadal men, this therapy has historically been contraindicated in men with a history of prostate cancer. Recent evidence suggests that there is minimal or no prostate cancer growth in the setting of TTh administration in men definitively treated for non-metastatic prostate cancer.
To review the evidence supporting the safety and efficacy of TTh in patients previously treated for localized prostate cancer.
A literature review of the PubMed database was performed to identify studies evaluating the safety and efficacy of TTh in patients with a history of prostate cancer. Search terms included Testosterone Therapy, Testosterone Replacement Therapy and Radical Prostatectomy, Radiotherapy, External Beam Radiation Therapy, EBRT, Brachytherapy; Prostate Cancer and Hypogonadism, Low Testosterone; Bipolar Androgen Therapy.
Available literature provides evidence for the safe application of TTh in patients previously treated fotment A Review of Literature. selleck products Sex Med Rev 2021; XXXXX-XXX.
TTh should be offered to select hypogonadal patients who have a history of definitively treated prostate cancer. Adequately designed randomized controlled trials are necessary to confirm the safety and efficacy of TTh in this population. Natale C, Carlos C, Hong J, et al. Testosterone Replacement Therapy After Prostate Cancer Treatment A Review of Literature. Sex Med Rev 2021; XXXXX-XXX.
The purpose of this study was to retrospectively assess the safety profile of percutaneous image-guided screw fixation (PIGSF) for insufficiency, impending or pathological fractures.
From July 2012 to April 2020, all consecutive patients who underwent PIGSF were retrospectively included in the study. Patient characteristics, fracture type, procedural data and complications were analyzed. Complications were divided into per-procedural, early (<24hours) and delayed (>24hours) and classified into minor (grade 1-2) and major complications (grade 3-5) according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
A total of 110 fractures (40 insufficiency [36%], 53 pathological [48.5%] and 17 impending [15.5%] fractures) in 94 patients (48 women, 46 men; mean age, 62.7±12.7 [SD] years; age range 32-88 years) were treated with PIGSF during 95 procedures. Twenty-four-hours follow-up was available for all patients, and>24-hours follow-up was available for 79 (79/110; 71.8%) fractures in 69 (69/94; 73.4%) patients. Per-procedural complications occurred in 3/110 fractures (2.7%, all minor). Early complications were reported in 4/110 fractures (3.6%, 1 major and 3 minor) and delayed ones in 14/79 fractures (17.7%, 5 major and 9 minor). The most frequent major delayed complication was infection (3/79; 3.8%).
The rate of per-procedural and early (within 24hours) complications following PIGSF is extremely low with most complications being minor, with major complications being delayed ones (>24hours).
24hours).Mast cells (MCs) exist intracranially and have been reported to affect higher brain functions in rodents. However, the role of MCs in the regulation of emotionality and social behavior is unclear. In the present study, using male mice, we examined the relationship between MCs and social behavior and investigated the underlying mechanisms. Wild-type male mice intraventricularly injected with a degranulator of MCs exhibited a marked increase in a three-chamber sociability test. In addition, removal of MCs in Mast cell-specific Toxin Receptor-mediated Conditional cell Knock out (Mas-TRECK) male mice showed reduced social preference levels in a three-chamber sociability test without other behavioral changes, such as anxiety-like and depression-like behavior. link2 Mas-TRECK male mice also had reduced serotonin content and serotonin receptor expression and increased oxytocin receptor expression in the brain. These results suggested that MCs may contribute to the regulation of social behavior in male mice. This effect may be partially mediated by serotonin derived from MCs in the brain.Neuropathic pain develops due to injury to the somatosensory system, affecting the patient's quality of life. In view of the ineffectiveness of the current pharmacotherapy, substances obtained from natural products (NPs) are a promising alternative. One NP that has been discussed in the literature is hecogenin acetate (HA), a steroidal sapogenin with anti-inflammatory and antinociceptive activity. However, HA has low water solubility, which affects its bioavailability. Thus, the objective of this study was to evaluate the anti-hyperalgesic activity of pure and complexed hecogenin acetate (HA/βCD) in an animal model of chronic neuropathic and inflammatory pain. The inclusion complex was prepared at a molar ratio of 12 (HAβCD) by the lyophilization method. For the induction of chronic inflammatory pain, the mice received an intraplantar injection of CFA (complete Freund's adjuvant), and were evaluated for mechanical hyperalgesia and for the levels of myeloperoxidase (MPO) in the skin of the paw after eight dayspotential for use in the treatment of chronic pain.Huntington's disease (HD) is due to a mutation in the gene encoding for Huntingtin protein generating polyQ domain extension. Mutant Htt (mHtt) leads to important dysfunction of the BDNF/TrkB signaling. We previously described the 23aa Htt fragment P42, that attenuated the pathological phenotypes induced by mHtt. We reported that, in the R6/2 mouse model of HD, P42 rescued striatal TrkB level but marginally increased cortical BDNF. In the present study, our aim was to address P42 neuroprotection in presence of an external input of BDNF. We combined P42 administration with environmental enrichment (EE), induced by training in the Hamlet test. We examined the consequences of P42 + EE combination on different phenotypes in R6/2 HD mice motor and cognitive performances, recorded at early and late pathological stages, and analyzed aggregated mHtt and BDNF levels in forebrain structures. Hamlet exploration (i.e., entries in Run, Hide, Eat, Drink and Interact houses) was gradually impaired in R6/2 mice, but maintained by P42 treatment until week 8. Topographic memory alteration measured at week 7 was attenuated by P42. Motor performances (rotarod) were significantly ameliorated by the P42 + EE combination until late stage (week 12). link3 The P42 + EE combination also significantly decreased aggregated Htt levels in the hippocampus, striatum and cortex, and increased BDNF levels in the cortex and striatum. We concluded that combination between P42 treatment, known to increase TrkB striatal expression, and a BDNF-enhancing therapy such as EE efficiently delayed HD pathology in R6/2 mice. Use of dual therapies might be a pertinent strategy to fight neurodegeneration in HD.
To develop and evaluate a modified four vessel occlusion (4VO) model of global cerebral ischemia-reperfusion (GCI/R) in rats based on the Pulsinelli and Brierley's method.
Vertebral arteries (VAs) were isolated and then permanently ligated with 5-0 nylon surgical sutures under visual conditions. A total of 24 h later, GCI was induced by transient clipping of the bilateral common carotid artery for 20 min. Cognitive function and visual perception were then evaluated by behavioral and histopathological approaches.
There was no significant difference in the survival rates between the groups. The modified 4VO group had a significantly lower body weight at each time point assessed. In the Y-maze test, the percentage of time spent and distance traveled in the III arm was significantly decreased on day 28, suggesting that cognitive function may have been impaired by the modified 4VO model. The modified 4VO procedure induced severe hippocampal damage but did not result in noticeable changes in visual perception, as indicated by the light-dark box test, and analysis of the optic tract and retinal structures.