Development of fluridil,a topical suppressor of the androgen receptor in androgenetic alopecia

Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topical treatment of AGA was synthesized from (3‐amino‐2‐hydroxy‐2‐methyl‐N‐(4‐nitro‐3‐trifluoromethyl)phenyl) propanamide (BP‐34), to contain perfluoroalkyl moieties. The trifluoromethyl derivative (fluridil) at 10 μM decreased expression of the AR in LNCaP human cells by 95%, its serum half‐life was 6 h; it decomposes hydrolytically to BP‐34 and trifluoroacetic acid. Acute intraperitoneal maximum tolerated dose (MTD) of fluridil in mice is 270–300 mg/kg/d and the subacute MTD is 450 mg/kg/d. The oral LD₅₀ in mice was 2,872 mg/kg in males, 2,232 mg/kg in females, and >2,500 mg/kg in rats. Fluridil solution in isopropanol was not cutaneously absorbed in rabbits, did not sensitize or show any phototoxic or photoallergic effects on guinea pig skin, and demonstrated no skin irritation potential in rabbits and humans. Fluridil solid induced only slight and reversible eye irritancy in rabbits and displayed no cytotoxicity to rabbit corneal fibroblasts in vitro. Fluridil demonstrated no significant mutagenicity potential by Ames method. In a double‐blind study, 43 males with AGA, Norwood grade II to Va, used topical 2% fluridil in isopropanol or the vehicle daily for 12 months. Anagens (growing hairs) increased in the fluridil group from 76% to 89%. All hematological and biochemistry values remained within normal range, including testosterone, which varied but seasonally. No fluridil or its decomposition product (BP‐34) was detected in serum. No adverse side effects were reported. Drug Dev. Res. 59:292–306, 2003. © 2003 Wiley‐Liss, Inc.     

Cutaneous malignant melanoma incidence is strongly associated with European depigmented skin type regardless of ambient ultraviolet radiation levels: evidence from Worldwide population-based data

Current public health advice is that high ultraviolet radiation (UVR) exposure is the primary cause of Malignant Melanoma of skin (CMM), however, despite the use of sun-blocking products incidence of melanoma is increasing. To investigate the UVR influence on CMM incidence worldwide WHO, United Nations, World Bank databases and literature provided 182 country-specific melanoma incidence estimates, daily UVR levels, skin colour (EEL), socioeconomic status (GDP PPP), magnitude of reduced natural selection (Ibs), ageing, urbanization, percentage of European descendants (Eu%), and depigmentation (blonde hair colour), for parametric and non-parametric correlations, multivariate regressions and analyses of variance. Worldwide, UVR levels showed negative correlation with melanoma incidence (“rho” = −0.515, p < 0.001), remaining significant and negative in parametric partial correlation (r = −0.513, p < 0.001) with other variables kept constant. After standardising melanoma incidence for Eu%, melanoma correlation with UVR disappeared completely (“rho” = 0.004, p = 0.967, n = 127). The results question classical views that UVR causes melanoma. No correlation between UVR level and melanoma incidence was present when Eu% (depigmented or light skin type) was kept statistically constant, even after adjusting for other known variables. Countries with lower UVR levels and more Eu% (depigmented or light skin people) have higher melanoma incidence. Critically, this means that individual genetic low skin pigmentation factors predict melanoma risk regardless of UVR exposure levels, and even at low-UVR levels.     

Concurrent optic disc pit and retinal cavernous hemangioma

Letter to the editor     

Use of ginger to control nausea and vomiting caused by chemotherapy in patients with cervical cancer undergoing treatment: An experiment

Introduction:Uterine cervix tumors have an invasive nature, with the capacity to proliferate to surrounding organs such as the vagina, bladder, and rectum, as well as the capacity for dissemination and involvement of structures distant from its place of origin. According to the International Federation of Gynecology and Obstetrics, patients with stages IB I, IB I microscopic (small dimension <4 cm) are indicated for radiotherapy or adjuvant chemoradiotherapy with cisplatin (40 mg/m²). However, cisplatin has side effects such as hematological implications (anemia, neutropenia, and thrombocytopenia), gastrointestinal disorders (nausea, vomiting, diarrhea, constipation), and fatigue. Zingiber officinale contains bioactive compounds that act on pregnancy and postoperative nausea, chemotherapy-induced nausea and vomiting, and also in the management of fatigue, myalgia, and insomnia. This study aimed to evaluate the effects of ginger on chemotherapy-induced nausea and vomiting in patients with cervical cancer undergoing treatment with cisplatin and radiotherapy.Methods and analyses:A randomized intervention clinical and controlled trial with a triple-blind design is described, comparing the effects of institutional antiemetic therapy alone, as well as in combination with 2 different ginger concentrations.Ethics and dissemination:Due to the nature of the study, we obtained approval from the Division Ethics Committee of Liga Contra o Câncer. All participants signed an informed consent form prior to randomization. The results of this study will be published in peer-reviewed journals. The data collected will also be available in a public repository of data.Trial registration number:This study is registered in the Brazilian Registry of Clinical Trials under number RBR-47yx6p9. This study was approved by the Division Ethics Committee of Liga Contra o Câncer under CAAE 40602320.0.0000.5293.     

Chest pain in the emergency department: From score to core—A prospective clinical study

High-sensitivity troponin assay brought new challenges as we detect elevated concentration in many other diseases, and it became difficult to distinguish the real cause of this elevation. In this notion, diagnosis of acute coronary syndrome (ACS) remains a challenge in emergency department (ED).We aim to examine different approaches for rule-in and rule-out of ACS using risk scores, copeptin, and coronary computed tomography angiography (CCTA).A prospective observational study was designed to evaluate chest pain patients. Consecutive adult patients admitted to the ED with a chief complaint of chest pain due to any cause were included.All patients were followed-up for 6 months after discharge for major adverse cardiovascular events and readmissions. Admission data, ED processes, and diagnoses were analyzed.One hundred forty-six patients were included, average age was 63 ± 13.4 years, and 95 (65.1%) were male. Global Registry of Acute Coronary Events (GRACE) and History, ECG, Age, Risk factors, Troponin (HEART) scores showed good prognostic abilities, but HEART combination with copeptin improves diagnoses of myocardial infarction (area under the curve [AUC] 0.764 vs AUC 0.864 P = .0008). Patients with elevated copeptin were older, had higher risk scores, and were more likely to be admitted to hospital and diagnosed with ACS in ED. For copeptin, AUC was 0.715 (95% confidence interval 0.629–0.803), and for combination with troponin, AUC of 0.770 (0.703–0.855) did not improve rule-in of myocardial infarction. High-sensitivity troponin I assay alongside prior stroke, history of carotid stenosis, dyslipidemia, use of diuretics, and electrocardiogram changes (left bundle branch block or ST depression) are good predictors of myocardial infarction (χ² = 52.29, AUC = 0.875 [0.813–0.937], P < .001). The regression analysis showed that combination of copeptin and CCTA without significant stenosis can be used for ACS rule-out (χ² = 26.36, P < .001, AUC = 0.772 [0.681–0.863], negative predictive value of 96.25%).For rule-in of ACS, practitioner should consider not only scores for risk stratification but carefully analyze medical history and nonspecific electrocardiogram changes and even with normal troponin results, we strongly suggest thorough evaluation in chest pain unit. For rule-out of ACS combination of copeptin and CCTA holds great potential.     

The construction of the Split Sleep Questionnaire on sleep habits during the COVID-19 pandemic in the general population

AimTo construct a single-format questionnaire on sleep habits and mood before and during the COVID-19 pandemic in the general population.MethodsWe constructed the Split Sleep Questionnaire (SSQ) after a literature search of sleep, mood, and lifestyle questionnaires, and after a group of sleep medicine experts proposed and assessed questionnaire items as relevant/irrelevant. The study was performed during 2021 in 326 respondents distributed equally in all age categories. Respondents filled out the SSQ, the Pittsburgh Sleep Quality Index (PSQI), and State Trait Anxiety Inventory (STAI), and kept a seven-day sleep diary.ResultsWorkday and work-free day bedtime during the COVID-19 pandemic assessed with SSQ were comparable to the sleep diary assessment (P = 0.632 and P = 0.203, respectively), as was the workday waketime (P = 0.139). Work-free day waketime was significantly later than assessed in sleep diary (8:19 ± 1:52 vs 7:45 ± 1:20; P < 0.001). No difference in sleep latency was found between the SSQ and PSQI (P = 0.066). Cronbach alpha for Sleep Habits section was 0.819, and 0.89 for Mood section. Test-retest reliability ranged from 0.45 (P = 0.036) for work-free day bedtime during the pandemic to 0.779 (P < 0.001) for sleep latency before the pandemic.ConclusionThe SSQ provides a valid, reliable, and efficient screening tool for the assessment of sleep habits and associated factors in the general population during the COVID-19 pandemic.

The COVID-19 pandemic, along with its multiple adverse effects on various aspects of mental health, has significantly affected sleep. Sleep habits alterations and newly developed sleep disturbances during the COVID-19 pandemic may influence the overall well-being and health (1). Since the beginning of the pandemic, several studies reported a delay in bedtimes and waketimes, and an associated shift in chronotype toward eveningness (2-5).Even though actigraphy and sleep diaries provide a valid and reliable assessment of sleep habits (6,7), to achieve the highest reliability and validity, these methods require an assessment during seven consecutive days including weekends (8). Daily reporting may be perceived by the respondents as an additional burden (6,9), a limitation that may be overcome by the use of single-administration questionnaires (9,10). Since sleep disturbances recognized in the first pandemic outbreak remained stable during new waves of the COVID-19 pandemic (5), single-administration questionnaires may enable screening of large population groups and an extended assessment of sleep disturbances during the pandemic.So far, validated sleep questionnaires have most often aimed at sleep disorders or symptoms associated with sleep disorders (9). Studies commonly report the Pittsburgh sleep Quality Index (PSQI) (11), which provides data on sleep duration, sleep disturbances, and sleep latency during the previous month. However, PSQI reflects mainly sleep quality on workdays (12), while not collecting information on sleep habits on weekends. The Sleep Timing Questionnaire (STQ) has been developed as an alternative to the sleep diary for the healthy adult population, showing good reliability and validity (10). Still, although sleep habits are associated with mood (13), social media use (14-16), learning time in students (17-19), sports or exercise (20), and symptoms of insomnia (21), the STQ does not assess variables such as mood and lifestyle habits.Large studies objectively assessing sleep with wearable devices have recognized sleep timing and sleep duration to be modifiable risk factors for adverse mental health during the current pandemic (22). Young adults are especially at risk for increased mood disorder symptoms, higher levels of perceived stress, and more common alcohol use during the pandemic (23). Even though mood disorders are often reported in pandemic studies on sleep habits, mood itself has been less commonly measured and associated with sleep parameters (24). A review of the literature showed a transactional relationship between mood and emotion (25), indicating that mood is characterized by longer duration than emotion (26). Mood is often assessed with the Brief Mood Introspection Scale (27), the Profile of Mood States (28), or the Visual Analogue Mood Scale (29). A relevant aspect of mood measurement is a hierarchical structure with two broad dimensions in positive and negative affect, and multiple specific states (30). Commonly used mood assessment scales evaluate the basic negative mood of fear/anxiety, sadness/depression, and anger/hostility, as well as at least one positive mood. Therefore, it has been strongly recommended that mood researchers assess a broad range of both positive and negative emotions (30).Linking mood changes and lifestyle habits during the pandemic has been relevant in order to recognize possible predictors of mood changes, especially due to a reported increase in depression (31). Since sleep is often intertwined with mood and lifestyle changes (31), we assumed that a single-format questionnaire comprehensively assessing these variables and sleep may be applicable and timely.The aim of this study was to construct a single-format Split Sleep Questionnaire (SSQ) comprehensively assessing sleep habits, lifestyle habits, and mood changes, as well as to evaluate its reliability and validity in the general population. Sleep habits were validated by using standard instruments such as sleep diary, PSQI, and STAI questionnaires as the measures of construct validity. Additionally, we aimed to assess the psychometric properties of the Mood section and to explore the effects of the COVID-19 pandemic on sleep habits and mood alterations in the general population of Croatia.     

Sex-Dependent Effects of the Intake of NOVA Classified Ultra-Processed Foods on Syndrome Metabolic Components in Brazilian Adults

Longitudinal studies evaluating the relationship between UPF consumption and the incidence of Metabolic Syndrome (MetS) and its components are still scarce. This study aimed to evaluate the effect of UPF consumption on the incidence of MetS and its components in adults. A prospective study was conducted with 896 participants from the 1978/79 Ribeirão Preto cohort, São Paulo, Brazil. UPF consumption was evaluated in %kcal and %g at ages 23–25 years. Incidence of MetS and its components were estimated at ages 37–39 years, according to the Joint Interim Statement criteria. Poisson regression was used to assess associations, and interactions with sex were investigated. UPF consumption had no association with MetS (%kcal Adjusted PR: 1.00; 95% CI: 0.99–1.01; %g Adjusted PR: 1.00; 95% CI: 0.99–1.01). However, women with higher UPF consumption, in %kcal and %g, had a higher risk of abdominal obesity (%kcal: p = 0.030; %g: p = 0.003); and women with higher UPF consumption, in %g, had a higher risk of low HDL-cholesterol (p = 0.041). For the other components of MetS, no significant associations were observed in either sex. These findings suggest evidence of no association between UPF consumption and MetS; however, consumption of UPF was associated with increased WC and low HDL-c, but only in women.     

Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network

Background

Spinal myxopapillary ependymomas (MPEs) are slowly growing ependymal gliomas with preferential manifestation in young adults. The aim of this study was to assess the outcome of patients with MPE treated with surgery, radiotherapy (RT), and/or chemotherapy.

Methods

The medical records of 183 MPE patients (male: 59%) treated at the MD Anderson Cancer Center and 11 institutions from the Rare Cancer Network were retrospectively reviewed. Mean patient'' age at diagnosis was 35.5 ± 15.8 years. Ninety-seven (53.0%) patients underwent surgery without RT, and 86 (47.0%) were treated with surgery and/or RT. Median RT dose was 50.4 Gy. Median follow-up was 83.9 months.

Results

Fifteen (8.2%) patients died, 7 of unrelated cause. The estimated 10-year overall survival was 92.4% (95% CI: 87.7–97.1). Treatment failure was observed in 58 (31.7%) patients. Local failure, distant spinal relapse, and brain failure were observed in 49 (26.8%), 17 (9.3%), and 11 (6.0%) patients, respectively. The estimated 10-year progression-free survival was 61.2% (95% CI: 52.8–69.6). Age (<36 vs ≥36 y), treatment modality (surgery alone vs surgery and RT), and extent of surgery were prognostic factors for local control and progression-free survival on univariate and multivariate analysis.

Conclusions

In this series, treatment failure of MPE occurred in approximately one third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression.     

The role of high-risk HPV-DNA testing in the male sexual partners of women with HPV-induced lesions

OBJECTIVES: The objectives were to assess the prevalence of high-risk HPV in the male sexual partners of women with HPV-induced lesions, and correlate it with biopsies guided by peniscopy. STUDY DESIGN: Fifty-four asymptomatic male sexual partners of women with low-grade squamous intra-epithelial lesions (LSIL) associated with high-risk HPV were examined between April 2003 and June 2005. The DNA-HPV was tested using a second-generation hybrid capture technique in scraped penile samples. Peniscopy identified acetowhite lesions leading to biopsy. RESULTS: High-risk HPV was present in 25.9% (14 out of 54) of the cases. Peniscopy led to 13 biopsies (24.07%), which resulted in two cases of condyloma, two cases of intra-epithelial neoplasia (PIN) I, one case of PIN II, and eight cases of normal tissue. The high-risk HPV test demonstrated 80% sensitivity, 100% specificity, 100% positive predictive value, and 88.9% negative predictive value for the identification of penile lesions. There was a greater chance of finding HPV lesions in the biopsy in the positive cases of high-risk HPV with abnormal peniscopy (p=0.007); OR=51 (CI 1.7-1527.1). CONCLUSION: Among asymptomatic male sexual partners of women with low-grade intra-epithelial squamous lesions, those infected by high-risk HPV have a higher chance of having abnormal penile tissue compared with male partners without that infection.