Hidden Y Chromosome Material and Congenital Cardiovascular Malformations in a Cohort of Turner Syndrome Patients with 45,X Blood Karyotype.

INTRODUCTION: Bicuspid aortic valve is the most common congenital cardiac malformation (CCM) in adults and is 30-50 times more frequent in Turner syndrome (TS). We hypothesize that both X and Y chromosome dosages contribute to the prevalence of CCM in TS. The recognition of genotype-phenotype correlations may improve risk stratification of patients with 45,X karyotypes who have cryptic Y chromosome mosaicism. METHODS: Utilizing data and samples from the UTHealth Turner Syndrome Research Registry, we correlated Y chromosome DNA identified by multiplex quantitative PCR and SNP microarrays with the presence of congenital heart lesions. RESULTS: We identified Y chromosome DNA in more than 10% of registry participants, including 2 participants who had no detectable Y DNA by karyotype or SNP microarray. CONCLUSIONS: There were no significant correlations between the presence of Y DNA and CCM.

Dermatological concerns for women and girls with turner syndrome.

Introduction: Turner syndrome (TS) is associated with distinct manifestations in women and girls including short stature, cardiac abnormalities, premature ovarian failure as well as dermatological features, including lymphedema, keloids, onychodystrophy, and acne. Although many dermatological concerns present during the first few decades of life, the overwhelming majority of respondents are not provided with dermatology referrals at diagnosis. Methods: This cross-sectional study utilized an author designed survey to assess self-reported dermatological manifestations, dermatology referral experience, common therapies for select dermatological conditions, as well as a validated 10-question Dermatology Life Quality Index (DLQI) to assess quality-of-life impact in women and girls with Turner syndrome. Results: In our cohort, 64% (n = 149) had been referred to a dermatologist at some point in their life time. The majority of individuals self-identified their dermatological concern (79.6%) and were referred after a dermatological concern had already occurred (90.2%). The most common dermatological findings reported were xerosis cutis (78.7%), lymphedema (73%), and more than 20 acquired melanocytic nevi (70%). The overall mean DLQI score was 3.52, indicative of a small effect on the patient's life. Onychodystrophy, history of skin biopsy, and lymphedema were statistically significant to have a higher impact on quality of life. Discussion: Our data reveal that skin conditions are highly prevalent in the TS population during the early decades of life and affirm utilizing these conditions in the TS diagnostic process, as well as emphasize the need for specialized dermatology referrals to address the detrimental impacts related to skin concerns on quality of life.

A cranial implant for stabilizing whole-cell patch-clamp recordings in behaving rodents.

BACKGROUND: In vivo patch-clamp recording techniques provide access to the sub- and suprathreshold membrane potential dynamics of individual neurons during behavior. However, maintaining recording stability throughout behavior is a significant challenge, and while methods for head restraint are commonly used to enhance stability, behaviorally related brain movement relative to the skull can severely impact the success rate and duration of whole-cell patch-clamp recordings. NEW METHOD: We developed a low-cost, biocompatible, and 3D-printable cranial implant capable of locally stabilizing brain movement, while permitting equivalent access to the brain when compared to a conventional craniotomy. RESULTS: Experiments in head-restrained behaving mice demonstrate that the cranial implant can reliably reduce the amplitude and speed of brain displacements, significantly improving the success rate of recordings across repeated bouts of motor behavior. COMPARISON WITH EXISTING METHOD(S): Our solution offers an improvement on currently available strategies for brain stabilization. Due to its small size, the implant can be retrofitted to most in vivo electrophysiology recording setups, providing a low cost, easily implementable solution for increasing intracellular recording stability in vivo. CONCLUSIONS: By facilitating stable whole-cell patch-clamp recordings in vivo, biocompatible 3D printed implants should accelerate the investigation of single neuron computations underlying behavior.

Combined effects of high temperature and pesticide mixture exposure on free-swimming behaviors and hepatic cytochrome P450 1A expression in goldfish, Carassius auratus.

The synergy between multiple compounds and other stressors, including heat, creates volatility and greater unpredictability than standard single-chemical toxicity testing, especially in the case of pesticides and metabolites which might contain several noxious ingredients resulting in adverse ecological effects. To address this, the aim of this study was to examine the dose- and time-dependent effects of low- and high-dose pesticide mixture (metalachlor, linuron, isoproturon, tebucanazole, aclonifen, atrazine, pendimethalin, azinphos-methyl) and heat stress co-exposure (22°C control/32°C treatment for 4-week) on free-swimming behaviors and cumulative actionless time (CAT) of goldfish. Behavioral analysis showed a dose- and time-dependent decrease in distance swam, as well as a subsequent increase in CAT. Vertical and horizontal spatial behavioral use were affected under heat and pesticides co-exposure conditions. In 3- and 4-week(s) exposure groups, horizontal spatial behavioral use demonstrated elevated time spent in the lower third of the aquarium. Similarly, during 3- and 4-week(s) exposure (32°C control and 32°C high doses) vertical spatial behavioral use was found to increase time spent in the outermost edges of the aquarium. In all treatment groups, the final condition factor (KM) showed significant attenuation when compared to the initial KM. However, there was an unclear relationship between heat/pesticide co-exposure and growth most notably in 32°C high-dose groups. In addition, the expression of hepatic cytochrome P450 1A mRNA was significantly higher in pesticide-exposed groups. Taken together, data demonstrated that co-exposure with low- or high-dose pesticide mixture and heat stress significantly impacted natural swimming patterns, which over time might result in the broader population and ecological effects.

Siderosis idiopática del sistema nervioso central y asociación con atrofia óptica e infarto cerebral. Caso clínico / Superficial siderosis of the central nervous system. Report of one case

Superficial siderosis of the central nervous system is produced by the deposit of hemosiderin within the subpial layers of the central nervous system and central parts of the cranial nerves, leading to progressive degeneration. We report a 55-year-old male who consulted for hearing loss and long-standing progressive decrease in visual acuity, associated with sudden onset of left hemiparesis. A brain CAT scan showed subacute ischemic lesions in the territory of the right posterior cerebral artery (thalamus and right subcortical temporal regions), old ischemic lesions in the right subcortical occipital regions and cerebellar atrophy. A magnetic resonance confirmed the lesions and the presence of superficial diffuse siderosis. A cerebrospinal fluid analysis showed slight xanthochromia, 26 leukocytes/mm3, glucose 51 mg/dL and proteins 1.23 g/L. He was managed with aspirin in low doses and statins. His motor function improved and was discharged two weeks after admission.

Community perspectives on pharmacist-prescribed hormonal contraception in rural California.

OBJECTIVES: In the United States, numerous states have enabled pharmacists to prescribe hormonal contraception. Little research focuses on the perspectives of potential users of this service in rural communities. This study sought to describe awareness of, interest in, acceptability of, and support for pharmacist-prescribed contraception in a rural California county. STUDY DESIGN: We conducted a community-based survey in 2019-20 in Tulare County, California. Researchers partnered with community members to design, implement, and analyze the survey. We recruited respondents who were ages 15 to 44 and assigned female sex at birth, using passive community-based approaches, social media advertisements, and social networks. Analyses focused on 177 respondents with a potential future need for contraception. RESULTS: Thirty-one percent of respondents were aware that pharmacists could prescribe hormonal contraception in California, with more accurate knowledge among older respondents (p = 0.015). After receiving brief educational information about pharmacist-prescribed contraception, respondents expressed high levels of support and acceptability: they perceived pharmacist-prescribed contraception to be safe, time saving, and more convenient. Respondents were more comfortable talking about contraception with traditional contraceptive care providers compared to asking pharmacists questions about contraception. Fifty-seven percent were somewhat or very interested in obtaining contraception from a pharmacist, with higher levels of interest among those who preferred to use a different method. CONCLUSION: Awareness of pharmacist-prescribed contraception in a rural California community was low, though people are supportive of and interested in utilizing this service. This research suggests that increased availability of pharmacist-prescribed contraception could support individuals' reproductive self-determination and address gaps in access. IMPLICATIONS: Despite limited awareness of pharmacist-prescribed contraception, interest in using and community support for this service was high in a rural California community. This analysis suggests that increased availability of pharmacist-prescribed contraception could support reproductive self-determination and address access barriers, particularly for people whose contraceptive needs are not currently being met.

[Superficial siderosis of the central nervous system. Report of one case]. / Siderosis idiopática del sistema nervioso central y asociación con atrofia óptica e infarto cerebral. Caso clínico.

Superficial siderosis of the central nervous system is produced by the deposit of hemosiderin within the subpial layers of the central nervous system and central parts of the cranial nerves, leading to progressive degeneration. We report a 55-year-old male who consulted for hearing loss and long-standing progressive decrease in visual acuity, associated with sudden onset of left hemiparesis. A brain CAT scan showed subacute ischemic lesions in the territory of the right posterior cerebral artery (thalamus and right subcortical temporal regions), old ischemic lesions in the right subcortical occipital regions and cerebellar atrophy. A magnetic resonance confirmed the lesions and the presence of superficial diffuse siderosis. A cerebrospinal fluid analysis showed slight xanthochromia, 26 leukocytes/mm3, glucose 51 mg/dL and proteins 1.23 g/L. He was managed with aspirin in low doses and statins. His motor function improved and was discharged two weeks after admission.

Natural Progression of Non-Alcoholic Steatohepatitis to Hepatocellular Carcinoma.

Non-alcoholic steatohepatitis (NASH) is a chronic and progressive form of non-alcoholic fatty liver disease (NAFLD). Its global incidence is increasing which makes NASH an epidemic and a public health threat. Due to repeated insults to the liver, patients are at risk for developing hepatocellular carcinoma (HCC). The progression of NASH to HCC was initially defined according to a two-hit model which involved the development of steatosis, followed by lipid peroxidation and inflammation. However, current research defines a "multi-hit" or "multi-parallel hit" model which synthesizes several contributing pathways involved in progressive fibrosis and oncogenesis. This perspective considers the effects of cellular, genetic, immunologic, metabolic, and endocrine pathways leading up to HCC which underscores the complexity of this condition. This article will provide an updated review of the pathogenic mechanisms leading from NASH to HCC as well as an exploration of the role of biomarkers and screening.

No Effect of Assisted Hip Rotation on Bat Velocity.

Softball and baseball are games that require multiple skill sets such as throwing, hitting and fielding. Players spend a copious amount of time in batting practice in order to be successful hitters. Variables commonly associated with successful hitting include bat velocity and torso rotation. The concept of overspeed bodyweight assistance (BWA) has shown increases in vertical jump and sprint times, but not hip rotation and batting. The purpose of this study was to examine the effects of assisted hip rotation on bat velocity. Twenty-one male and female recreational softball and baseball players (15 males, age 23.8 ± 3.1yrs; height 177.67 ± 6.71cm; body mass 85.38 ± 14.83kg; 6 females, age 21.5 ± 2.1yrs; height 162.20 ± 9.82cm; body mass 60.28 ± 9.72kg) volunteered to participate. Four different BWA conditions (0%, 10%, 20%, and 30%) were randomly applied and their effects on bat velocity were analyzed. Subjects performed three maximal effort swings under each condition in a custom measurement device and average bat velocity (MPH) was used for analysis. A mixed factor ANOVA revealed no interaction (p=0.841) or main effect for condition, but there was a main effect for sex where males had greater bat velocity (43.82±4.40 - 0% BWA, 41.52±6.09 - 10% BWA, 42.59±7.24 - 20% BWA, 42.69±6.42 - 30% BWA) than females (32.57±5.33 - 0% BWA, 31.69±3.40 - 10% BWA, 32.43±5.06 - 20% BWA, 32.08±4.83 - 30% BWA) across all conditions Using the concept of overspeed training with assisted hip rotation up to 30% BWA did not result in an increase in bat velocity. Future research should examine elastic band angle and hip translation at set-up.

Views on HPV and HPV Vaccination: The Experience at a Federal Qualified Clinic in Puerto Rico.

OBJECTIVE: The purpose of this study was to understand through a quantitative assessment, the views of HPV and HPV vaccination among parents of sons from a FQHC in PR. METHODS: A self-administered questionnaire was given to a convenience sample of 200 parents of sons 9-17 years old. RESULTS: Nearly 30% of the parents reported that their sons had initiated the HPV vaccine regimen. Health care provider recommendation was significantly associated with vaccine initiation. Among parents of unvaccinated sons, the main reason for not getting the HPV vaccine was they did not know that boys were allowed to get the vaccine. CONCLUSIONS: Future efforts should focus on multilevel interventions aimed to increase knowledge as well as other modified behavioral determinants in parents of young males about HPV and the vaccine. Capacity building efforts should be targeted also to increase health providers' education and communication skills to promote HPV vaccination effectively.

Latent effects of early life stage exposure to triclosan on survival in fathead minnows, Pimephales promelas.

The objective of this study was to evaluate the effects of early life stage triclosan (5-chloro-2-(2,4, dichlorophenoxy)phenol, TCS) exposure on hatching, development, and survival in the fathead minnow, Pimephales promelas. Embryonic minnows were exposed to TCS (50 and 100 µg L-1) for 10 days followed by 6 weeks depuration. Mortality and morphological deformities were recorded and quantified during exposure and at the end of depuration. No significant effects on embryonic survival, time to reach the eyed stage, or hatching were found. However, at the conclusion of the depuration period, survival was significantly reduced in TCS exposed fish depending on the concentration. Visual inspection of the exposed fish suggests that mortality is related to spinal deformities, emaciation, and reduced foraging ability. Triclosan exhibits deleterious effects in fish at lower concentrations over longer durations than previously reported. Further, mortality in exposed fish 6 weeks after exposure demonstrates the need for various exposure assays to evaluate effects of TCS.

Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity.

A relationship between Epstein-Barr virus (EBV) infection and cancer of lymphoid and epithelial tissues such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), gastric carcinoma, and oral cancer has been reported. EBV is transmitted orally and infects B cells and epithelial cells. However, it has remained uncertain whether EBV plays a role in carcinogenesis of oral mucosal tissue. In the present study, we detected the EBV genome and latent EBV gene expression in normal mucosal epithelia, epithelial dysplasia, and oral squamous cell carcinoma (OSCC) to clarify whether EBV is involved in carcinogenesis of the oral cavity. We examined 333 formalin-fixed, paraffin-embedded tissue samples (morphologically normal oral mucosa 30 samples, gingivitis 32, tonsillitis 17, oral epithelial dysplasia 83, OSCC 150, and NPC 21). EBV latent infection genes (EBNA-2, LMP-1) were detected not only in OSCC (50.2 %, 10.7 %) but also in severe epithelial dysplasia (66.7 %, 44.4 %), mild to moderate epithelial dysplasia (43.1 %, 18.5 %), gingivitis (78.1 %, 21.9 %), and normal mucosa (83.3 %, 23.3 %). Furthermore, the intensity of EBV latent infection gene expression (EBER, LMP-1) was significantly higher in severe epithelial dysplasia (94.4 %, 72.2 %) than in OSCC (34.7 %, 38.7 %). These results suggest that EBV latent infection genes and their increased expression in severe epithelial dysplasia might play an important role in the dysplasia-carcinoma sequence in the oral cavity.

HPV Awareness and Vaccine Willingness Among Dominican Immigrant Parents Attending a Federal Qualified Health Clinic in Puerto Rico.

The purpose of this study was to describe the socio-demographic characteristics, awareness of human papillomavirus (HPV), and willingness to vaccinate among a convenience sample of 60 immigrant Dominican parents of adolescent sons in a Federal Qualified Health Clinic in Puerto Rico. Participation involved completing a self-administered survey. Even though more than half of the parents had not received proper HPV vaccine orientation from healthcare provider (58.3 %) nor asked provider for vaccination recommendation for their adolescent sons (56.7 %), most parents were aware of HPV (91.7 %) and HPV vaccination among males (55.0 %). Among those with unvaccinated sons, willingness to vaccinate the son within the next year was high (83.8 %). The low vaccination percentage (31.7 %) and information exchange between the parents and the son's healthcare provider indicates an opportunity for future culturally tailored interventions to target HPV vaccination among healthcare providers and parents of foreign descent in order to increase HPV vaccine uptake among males.

Resistance and gain-of-resistance phenotypes in cancers harboring wild-type p53.

Chemotherapy is the bedrock for the clinical management of cancer, and the tumor suppressor p53 has a central role in this therapeutic modality. This protein facilitates favorable antitumor drug response through a variety of key cellular functions, including cell cycle arrest, senescence, and apoptosis. These functions essentially cease once p53 becomes mutated, as occurs in ∼50% of cancers, and some p53 mutants even exhibit gain-of-function effects, which lead to greater drug resistance. However, it is becoming increasingly evident that resistance is also seen in cancers harboring wild-type p53. In this review, we discuss how wild-type p53 is inactivated to render cells resistant to antitumor drugs. This may occur through various mechanisms, including an increase in proteasomal degradation, defects in post-translational modification, and downstream defects in p53 target genes. We also consider evidence that the resistance seen in wild-type p53 cancers can be substantially greater than that seen in mutant p53 cancers, and this poses a far greater challenge for efforts to design strategies that increase drug response in resistant cancers already primed with wild-type p53. Because the mechanisms contributing to this wild-type p53 "gain-of-resistance" phenotype are largely unknown, a concerted research effort is needed to identify the underlying basis for the occurrence of this phenotype and, in parallel, to explore the possibility that the phenotype may be a product of wild-type p53 gain-of-function effects. Such studies are essential to lay the foundation for a rational therapeutic approach in the treatment of resistant wild-type p53 cancers.

Influence of four systems for dental bleaching on the bond strength of orthodontic brackets.

OBJECTIVE: To compare the influence of four systems for dental bleaching on the shear bond strength (SBS) of orthodontic brackets. MATERIALS AND METHODS: One-hundred and fifty freshly extracted bovine teeth were randomly divided into five groups. In group I the teeth were untreated (control). In the remaining groups the teeth were bleached, as follows: group II: 38% hydrogen peroxide; group III: 10% carbamide peroxide; group IV: resin-based coating material (RBCM), Beauty Coat; and group V: RBCM, White Coat. In all groups the enamel was conditioned with a self-etching primer and brackets were bonded with composite resin. Samples were stored (37°C, 24 hours), tested, and statistically analyzed, with significance predetermined at P ≤ .05. The adhesive remnant index (ARI) was also evaluated and analyzed. RESULTS: The SBS of group V (22.49 ± 5.34 MPa) was significantly higher than that of all other groups (I: 17.1 ± 5.11 MPa; II: 14.72 ± 5.42 MPa; III: 12.04 ± 5.29 MPa; and IV: 18.23 ± 5.58 MPa). In contrast, the SBS of group III was significantly lower than that of all groups (except group II). Significant differences in the ARI scores were present between groups. CONCLUSIONS: The use of RBCM for dental bleaching before bonding orthodontic brackets did not reduce the SBS. In contrast, hydrogen and carbamide peroxides negatively affected the SBS. The SBS yielded after bleaching with carbamide peroxide was significantly lower.

Comparison of the fecal microbiota in feral and domestic goats.

Animals have co-evolved with mutualistic microbial communities, known as the microbiota, which are essential for organ development and function. We hypothesize that modern animal husbandry practices exert an impact on the intestinal microbiota. In this study, we compared the structure of the fecal microbiota between feral and domestic goats using the G2 PhyloChip and assessed the presence of five tetracycline resistance genes [tet(M), tet(S), tet(O), tet(Q) and tet(W)] by PCR. Feces were collected from 10 goats: 5 domestic from a farm in the main island of Puerto Rico and 5 feral from the remote dry island of Mona. There were 42 bacterial phyla from 153 families detected in the goats' feces. A total of 84 PhyloChip-OTUs were different in the fecal microbiota of feral and domestic goat. Both feral and domestic goats carried antibiotic resistance genes tet(O) and tet(W), but domestic goats additionally carried tet(Q). Diet, host genetics and antibiotic exposure are likely determinant factors in shaping the intestinal microbiota and may explain the differences observed between feral and domestic goats fecal microbiota.

Myasthenia gravis in an adolescent patient presenting to the pediatric emergency department.

Myasthenia gravis is a rare, chronic, autoimmune disorder characterized by postsynaptic dysfunction at the neuromuscular junction. The disease affects more females than males. We describe the case of a 17-year-old female adolescent with recurrent episodes of dysarthria and dysphagia and a history of aspiration pneumonia. A bedside edrophonium (Tensilon) test in our emergency department confirmed the diagnosis of myasthenia gravis.

Albuterol nebulized in heliox in the initial ED treatment of pediatric asthma: a blinded, randomized controlled trial.

OBJECTIVE: A prospective blinded, randomized controlled trial was undertaken to compare the initial response of albuterol nebulized in heliox or control in the treatment of moderately severe asthma in children presenting to a pediatric ED. METHODS: Patients were randomized to receive heliox (n = 20) or control (n = 21). The primary outcome was to compare a modified dyspnea index score at 10 and 20 minutes after randomization. Secondary outcomes were to determine if heliox decreased admission rates or endotracheal intubation. RESULTS: There was no statistically significant difference found at 10 or 20 minutes after randomization with heliox (P = .169 and P = .062, respectively). No statistical difference in admission rate was found, and no patients required endotracheal intubation in either group. CONCLUSIONS: Our results demonstrate that albuterol nebulized with heliox offered no clinical benefit over standard therapy in the initial treatment of moderately severe asthma in the ED.

The role of supervision in child injury risk: definition, conceptual and measurement issues.

The purpose of this paper was to examine caregiver supervision and its role as an active strategy in childhood injury prevention. Through a review of the literature, the authors addressed conceptual and methodological issues related to supervision, such as the question of how to define 'adequate supervision.' Three critical dimensions (attention, proximity and continuity) of caregiver supervisory behaviors are identified as important areas for measurement. Presented is a framework for understanding the role of passive and active supervisory behaviors within the social context. The framework includes family and community characteristics and policies/regulations that may be important in caregiver decisions to use active or passive injury prevention strategies. Future research directions are discussed.