Are Serbian and English listeners insensitive to lexical pitch accents in Serbian?

The paper investigated possible perceptual insensitivity effects in the perception of lexical pitch accents by native and non-native listeners, that is, by Serbian and English listeners, respectively. The objective of the study was to explore which word-prosodic categories listeners used when they were required to contrast and recall sequences of lexical pitch accents. To that effect, Serbian and English listeners performed a Sequence Recall Task (SRT) in which they contrasted pairs of non-words with different Serbian lexical pitch accent types, and recalled the sequences of these non-words under different memory load conditions. Listeners' answers were coded correct and incorrect and the accuracy scores between the groups were compared and analyzed. Both groups had almost identical levels of accuracy and they performed well above chance level on each contrast. Neither group exhibited any effects of perceptual insensitivity to lexical pitch accents. English (non-native) listeners did not differ in their performance from native Serbian listeners, which, contrary to what previous research suggested, implied that one's native language word-prosodic category inventory did not preclude the encoding of non-native word-prosodic categories. Instead, non-native listeners were capable of deploying different prosodic resources such as post-lexical pitch accents to recall the sequences.

Weight-Bearing Physical Activity Influences the Effect of Vitamin D on Bone Turnover Markers in Patients with Intellectual Disability.

OBJECTIVES: Individuals with intellectual disabilities (IDs) are at increased risk for low bone mass and fragility fractures, and those who are nonambulatory may be at even higher risk. Patients with IDs often are vitamin D deficient, but there is little information concerning how vitamin D treatment of patients with IDs affects markers of bone formation and resorption. METHODS: We performed a retrospective analysis of 23 institutionalized individuals with IDs who were the subject of a performance improvement continuing medical education project designed to reduce risk for fracture by optimizing serum vitamin D levels. Patients were divided into those with normal weight-bearing (NWB) physical activity (15 patients: 14 men, 1 woman) and those with low weight-bearing (LWB) physical activity (8 patients: 7 men, 1 woman). All of the subjects received 50,000 IU of vitamin D3 weekly for 4 to 8 weeks, followed by a maintenance dose of 50,000 IU monthly for 3 to 6 months. Bone turnover markers (type 1 cross-linked C-telopeptide [CTX], type 1 N-terminal propeptide [P1NP], and parathyroid hormone [PTH]) and 25(OH)-vitamin D levels were measured before and after vitamin D supplementation. RESULTS: At baseline, there were no significant differences in the serum levels of 25OH-D, PTH, P1NP, or CTX between the two groups (NWB and LWB). Vitamin D levels were increased to a higher value in LWB subjects than in NWB subjects (61 ± 4.1 vs 48.4 ± 2.2 ng/mL, P < 0.001). Vitamin D treatment suppressed PTH (20.5% ± 14.3% vs 31.4% ± 7.7%, P = not significant) and P1NP (33.0% ± 6.2% vs 29.4% ± 6.9%, P = not significant) similarly in both groups. Although CTX levels declined by 26.4% ± 5.3% (P = 0.0002) in NWB individuals (as anticipated), vitamin D supplementation resulted in an unexpected 25.8% ± 8% increase (P = 0.01) in CTX in LWB individuals, suggesting osteoclast activation. CONCLUSIONS: Although high-dose vitamin D appeared to suppress osteoclast activity in NWB adults with IDs, the increase in serum CTX levels in those with LWB activity implies activation of osteoclasts that could exacerbate their unique low bone mass and increase fracture risk. The results support the use of a lower-dose vitamin D regimen in this patient group with LWB.

Clinical Significance of J Waves in Patients Undergoing Therapeutic Hypothermia for Out-of-Hospital Cardiac Arrest.

BACKGROUND: Hypothermia is associated with the development of J waves. However, little is known about the impact of these electrocardiogram (ECG) findings on the development of ventricular arrhythmias and patient outcomes during therapeutic hypothermia (TH) postresuscitation from out-of-hospital cardiac arrest (OHCA). We investigated the prevalence of J waves in OHCA patients prior to and during TH. Additionally, we explored the incidence of atrial and ventricular arrhythmias and in-hospital mortality for patients with and without J waves either at baseline, during TH, or both. METHODS: We conducted a retrospective analysis of patients who suffered OHCA and underwent TH (goal temperature of 32-34°C). Fifty-nine patients were stratified dependent upon the presence of or the development of J waves on surface ECGs. Descriptive analysis and logistic regression modeling were used to assess the population differences and mortality, respectively, between patients who developed J waves during TH and those who did not. RESULTS: There was no difference in the development of in-hospital atrial or ventricular arrhythmias between patients with J waves present during TH (16%) and those without (17.6%, P = 0.834). Compared to patients without J waves at baseline and during TH, those with J waves present both at baseline and during TH had significantly worse survival (hazard ratio = 12.42, P = 0.046). CONCLUSIONS: While J waves are common ECG findings during TH in patients resuscitated from OHCA, our study demonstrated an increase in mortality for patients with J waves present both at baseline and during TH.

MENSTRUAL AND REPRODUCTIVE FUNCTION IN WOMEN WITH TYPE 1 DIABETES.

OBJECTIVE: Menstrual irregularities, reproductive abnormalities, and androgen excess are reported to be more prevalent in women with type 1 diabetes (T1D). The objective of this study was to investigate the prevalence of menstrual irregularities, reproductive abnormalities, and androgen excess among women with T1D and their age-matched controls. METHODS: A survey requesting information regarding menstrual and reproductive histories was administered to all participants. Results were stratified according to age (18 to 40, 40 to 50, and >50 years). RESULTS: There were no significant differences between women with and without diabetes in age at menarche, cycle length, or androgen excess in any group. Women who self-reported difficulty with glycemic control were more likely to report irregular menses than controls (P = .04). Among women who reported ever being pregnant, there were fewer pregnancies (P = .02) and live births (P = .002) in women with T1D. Women with T1D reported a lower frequency of oral contraceptive use (P = .003), despite being less likely to smoke (P = .016). CONCLUSION: Menstrual and reproductive abnormalities were not observed more frequently in women with T1D in this study. Subtle but measurable differences in menstrual and reproductive function were confined to the subgroup of women who perceived poor control of their diabetes. Additional prospective studies of T1D and menstrual and reproductive function would be useful.

Electrophysiology testing and the National Cardiovascular Data Registry: stimulating, yet inconclusive.

In this issue of PACE, Cheng et al. do an impressive job in evaluating clinical variables associated with electrophysiology studies (EPS) performed within 1 month before implantable cardioverter defibrillator (ICD) placement in 33,786 individuals entered into the National Cardiovascular Data Registry for Implantable Cardioverter Defibrillators (NCDR®-ICD) over a 3-year period. Although of great interest, most of the conclusions are by necessity based on conjecture drawn from observations alone, since the inherent, point-in-time structure of the Registry limits the ability to assess accurate longitudinal clinical correlations and outcomes. The fact is, we really do not know why these patients underwent EPS or how the data from these tests were used. In addition to stimulating speculation on the role of EPS in ICD recipients, the present report should promote caution regarding what conclusions can and should be drawn from the NCDR®-ICD in its present format. As constructed, the Registry provides demographic data and clinical elements up to only a fixed point in time. Hence, the ability to draw conclusions is limited by the abundance of disconnected variables and snapshot quality of data in the NCDR.

Hypogonadism in Males With Genetic Neurodevelopmental Syndromes.

Genetic syndromes that affect the nervous system may also disrupt testicular function, and the mechanisms for these effects may be interrelated. Most often neurological signs and symptoms predominate and hypogonadism remains undetected and untreated, while in other cases, a thorough evaluation of a hypogonadal male reveals previously unrecognized ataxia, movement disorder, muscle weakness, tremor, or seizures, leading to a syndromic diagnosis. Androgen deficiency in patients with neurological diseases may aggravate muscle weakness and fatigue and predispose patients to osteoporosis and obesity. The purpose of this mini review is to provide a current understanding of the clinical, biochemical, histologic, and genetic features of syndromes in which male hypogonadism and neurological dysfunction may coexist and may be encountered by the clinical endocrinologist.

Low endogenous estradiol levels are associated with elevated risk of cardiovascular disease mortality in young and middle-aged men in the United States.

BACKGROUND AND AIMS: Evidence for the association of total estradiol (E2) with cardiovascular disease (CVD) in young men is limited. We investigated the association of total E2 or free estradiol (FE2) and CVD mortality in a nationally representative multiracial sample of young and middle-aged men in the United States. METHODS: Data were from 954 men without CVD, cancer, diabetes and not on androgen therapy or taking anabolic steroids, who participated in the National Health and Nutrition Examination Survey (1988-1991), for whom E2 was measured, and were followed for mortality through to 2015. Fasting serum levels of E2 were measured using competitive electrochemiluminescence immunoassays. Free estradiol was estimated from the levels of estradiol, sex hormone binding globulin, and albumin. International Classification of Diseases codes were used to define CVD mortality. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The average age of participants at baseline was 35.7 ± 11.6 years, with 11% and 6% reporting Black and Hispanic race and ethnicity, respectively. During a median follow-up of 25.2 years, 40 CVD deaths were recorded. Controlling for baseline demographic and CVD risk factors, and total testosterone levels, a 1 standard deviation decrement in log E2 (HR: 2.33, 95%CI: 1.11-5.00) or FE2 (HR: 1.89, 95%CI: 1.01-3.57) was associated with elevated risk of CVD mortality. This elevated risk was largely limited to non-Hispanic White men. CONCLUSIONS: In this study, low levels of E2 or FE2 were associated with elevated risk of CVD mortality.

Impact of Smoking, Obesity and Maternal Diabetes on SHBG Levels in Newborns.

BACKGROUND: Low levels of SHBG have become a marker for insulin resistance and diabetes. Babies born to mothers who are obese, have diabetes, or smoke during pregnancy are at greater risk of developing obesity and diabetes later in life. AIMS: To examine the impact of maternal obesity, diabetes and smoking on SHBG levels in newborns. STUDY DESIGN: This cross-sectional study is part of an ongoing multicenter, longitudinal study. SUBJECTS: 98 healthy newborns and their parents, including 16 mothers with diabetes and 31 mothers with a smoking history. OUTCOME MEASURES: Cord blood and second day venipuncture samples were collected for measurement of SHBG and insulin. RESULTS: Babies born to mothers with diabetes had lower SHBG levels in cord blood [14.0 (8.9-20.4) vs. 19.6 (14.9-25.1) nmol/L; p=0.011] and on day 2 [18.8 (12.6-21.2) vs. 22.9 (17.1-29.1) nmol/L; p=0.015] than controls. Maternal diabetes remained negatively associated with SHBG levels in cord blood (p=0.02) and on day 2 (p=0.04) when adjusted for mothers' age, smoking status, pre-pregnancy weight and weight gain during pregnancy. SHBG levels in cord blood and day 2 samples were similar in babies born to mothers who were overweight-obese but not diabetic vs. normal weight, or were smokers when compared to non-smokers. CONCLUSIONS: SHBG levels are lower in newborns born to mothers with diabetes than without diabetes, and may be a marker for babies' life-long risk for abnormal metabolic health. On the other hand, the adverse effects of tobacco smoke on the fetus do not appear to directly influence SHBG levels.

Temporal and Global Trends of the Incidence of Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

BACKGROUND: Since the initial clinical description of hypertrophic cardiomyopathy (HCM) over 60 years ago, sudden cardiac death (SCD) has been the most visible and feared complication of HCM. OBJECTIVES: This study sought to characterize the temporal, geographic, and age-related trends of reported SCD rates in adult HCM patients. METHODS: Electronic databases were systematically searched up to November 2021 for studies reporting on SCD event rates in HCM patients. Patients with SCD equivalents (appropriate implantable cardioverter-defibrillator [ICD] shocks and nonfatal cardiac arrests) were not included. A random-effects model was used to pool study estimates calculating the overall incidence rates (IR) for each time-era, geographic region, and age group. We analyzed 2 periods (before vs after 2000, following clinical implementation of ICD in HCM). Following 2000, 5-year intervals were used to demonstrate the temporal change in SCD rates. RESULTS: A total of 98 studies (N = 70,510 patients and 431,407 patient-years) met our inclusion criteria. The overall rate of HCM SCD was 0.43%/y (95% CI: 0.37-0.50%/y; I2 = 75%; SCD events: 1,938; person-years of follow-up: 408,715), with young patients (<18 years of age) demonstrating a >2-fold-risk for sudden death vs adult patients 18-60 years of age (IR: 1.09%; 95% CI: 0.69%-1.73% vs IR: 0.43%; 95% CI: 0.37%-0.50%) (P value for subgroup differences <0.01). Contemporary SCD rates from 2015 to present were 0.32%/y and significantly lower compared with 2000 or earlier (IR: 0.32%; 95% CI: 0.20%-0.52% vs IR: 0.73%; 95% CI: 0.53%-1.02%, respectively). Reported SCD rates for HCM were lowest in North America (IR: 0.28%; 95% CI: 0.18%-0.43%,) and highest in Asia (IR: 0.67%; 95% CI: 0.54%-0.84%). CONCLUSIONS: Contemporary HCM-related SCD rates are low (0.32%/y) representing a 2-fold decrease compared with prior treatment eras. Young HCM patients are at the highest risk. The maturation of SCD risk stratification strategies and the application of primary prevention ICD to HCM are likely responsible for the notable decline over time in SCD events. In addition, worldwide geographic disparities in SCD rates were evident, underscoring the need to increase access to SCD prevention treatment for all HCM patients.

Importance of newer cardiac magnetic resonance-based risk markers for sudden death prevention in hypertrophic cardiomyopathy: An international multicenter study.

BACKGROUND: The sudden death (SD) risk stratification algorithm in hypertrophic cardiomyopathy (HCM) has evolved, underscored recently by novel cardiac magnetic resonance (CMR)-based risk markers (left ventricular apical aneurysm, extensive late gadolinium enhancement, and end-stage disease with systolic dysfunction) incorporated into the 2020 American Heart Association (AHA)/American College of Cardiology (ACC) HCM guidelines. OBJECTIVE: The purpose of this study was to assess the specific impact of newer, predominantly CMR-based risk markers in a large multicenter HCM population that underwent primary prevention implantable cardioverter-defibrillator (ICD) implants. METHODS: Longitudinal study of 1149 consecutive HCM patients from 6 North American and European HCM centers prospectively judged to be at high SD risk based on ≥1 AHA/ACC individual risk markers and prophylactically implanted with an ICD was performed. European Society of Cardiology (ESC) risk score was retrospectively analyzed with respect to the known clinical outcome. RESULTS: Of 1149 patients with an ICD, 162 (14%) experienced device therapy terminating ventricular tachycardia/ventricular fibrillation 4.6 ± 4.2 years after implant. CMR-based markers solely or in combination led to ICD implantation in 49 of the 162 patients (30%) experiencing device therapy. Particularly low ESC scores (<4%/5 years) would have excluded an ESC ICD recommendation for 67 patients who nevertheless experienced appropriate ICD therapy, including 26 with the CMR-based risk markers not part of the ESC formula. CONCLUSION: Identification and incorporation of novel guideline-supported CMR-based risk markers enhance selection of HCM patients for SD prevention with ICDs. Absence of CMR-based markers from the ESC risk score accounts, in part, for it not identifying many HCM patients with SD events. These data support inclusion of CMR as a routine part of HCM patient evaluation and risk stratification.

Reduction in Ventricular Tachyarrhythmia Burden in Patients Enrolled in the RAID Trial.

BACKGROUND: The RAID (Ranolazine Implantable Cardioverter-Defibrillator) randomized placebo-controlled trial showed that ranolazine treatment was associated with reduction in recurrent ventricular tachycardia (VT) requiring appropriate implantable cardioverter-defibrillator (ICD) therapy. OBJECTIVES: This study aimed to identify groups of patients in whom ranolazine treatment would result in the highest reduction of ventricular tachyarrhythmia (VTA) burden. METHODS: Andersen-Gill analyses were performed to identify variables associated with risk for VTA burden among 1,012 patients enrolled in RAID. The primary endpoint was VTA burden defined as VTA episodes requiring appropriate treatment. RESULTS: Multivariate analysis identified 7 factors associated with increased VTA burden: history of VTA, age ≥65 years, New York Heart Association functional class ≥III, QRS complex (≥130 ms), low ejection fraction (<30%), atrial fibrillation (AF), and concomitant antiarrhythmic drug (AAD) therapy. The effect of ranolazine on VTA burden was seen among patients without concomitant AAD therapy (HR [HR]: 0.68; 95% CI: 0.55-0.84; P < 0.001), whereas no effect was seen among those who are concomitantly treated with other AADs (HR: 1.33; 95% CI: 0.90-1.96; P = 0.16); P = 0.003 for interaction. In patients with cardiac resynchronization therapy (CRT) ICDs, ranolazine treatment was associated with a 36% risk reduction for VTA recurrence (HR: 0.64; 95% CI: 0.47-0.86; P < 0.001), whereas among patients with ICDs without CRT no significant effect was noted (HR: 0.94; 95% CI: 0.74-1.18; P = 0.57); P = 0.047 for interaction. CONCLUSIONS: In patients with high risk for VTA, ranolazine is effective in reducing VTA burden, with significantly greater effect in CRT-treated patients, those without AF, and those not treated with concomitant AADs. In patients already on AADs or those with AF, the addition of ranolazine did not affect VTA burden. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).

PACAP, an autocrine/paracrine regulator of gonadotrophs.

Hypothalamic-hypophysiotropic peptides are the proximate regulators of pituitary cells, but they cannot fully account for the complex functioning of these cells. Accordingly, awareness is growing that an array of peptides produced in the pituitary exert paracrine/autocrine functions. One such peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), was originally identified as a hypothalamic activator of cAMP production in pituitary cells. Gonadotrophs and folliculostellate cells are the main source of pituitary PACAP, and each pituitary cell type expresses a PACAP receptor. PACAP increases alpha-subunit (Cga) and Lhb mRNAs, and it stimulates the transcription of follistatin (Fst) that, in turn, restrains activin signaling to repress Fshb and gonadotropin-releasing hormone-receptor (Gnrhr) expression as well as other activin-responsive genes. The PACAP (Adcyap1) promoter is activated by cAMP, and pituitary cells may communicate by a feed-forward, cAMP-dependent mechanism to maintain a high level of PACAP in the fetal pituitary. At birth, pituitary PACAP declines and pituitary follistatin levels decrease, which together with increased gonadotropin-releasing hormone secretion allow Gnrhr and Fshb to increase and facilitate activation of the newborn gonads. Changes in Adcyap1 expression levels in the adult pituitary may contribute to the selective rise in follicle-stimulating hormone (FSH) from age 20-30 days to the midcycle surge and to the secondary increase in FSH that occurs before estrus. These results provide further support for the notion that PACAP is a key player in reproduction through its actions as a pituitary autocrine/paracrine hormone.

Effects of cross-language voice training on speech perception: whose familiar voices are more intelligible?

Previous research has shown that familiarity with a talker's voice can improve linguistic processing (herein, "Familiar Talker Advantage"), but this benefit is constrained by the context in which the talker's voice is familiar. The current study examined how familiarity affects intelligibility by manipulating the type of talker information available to listeners. One group of listeners learned to identify bilingual talkers' voices from English words, where they learned language-specific talker information. A second group of listeners learned the same talkers from German words, and thus only learned language-independent talker information. After voice training, both groups of listeners completed a word recognition task with English words produced by both familiar and unfamiliar talkers. Results revealed that English-trained listeners perceived more phonemes correct for familiar than unfamiliar talkers, while German-trained listeners did not show improved intelligibility for familiar talkers. The absence of a processing advantage in speech intelligibility for the German-trained listeners demonstrates limitations on the Familiar Talker Advantage, which crucially depends on the language context in which the talkers' voices were learned; knowledge of how a talker produces linguistically relevant contrasts in a particular language is necessary to increase speech intelligibility for words produced by familiar talkers.

Endocrine Dysfunction in Patients With Myotonic Dystrophy.

Myotonic dystrophy is a dominantly inherited multisystem disorder that results from increased CTG repeats in the 3' region of the myotonic dystrophy protein kinase gene (DMPK). The mutant DMPK mRNA remains in the nucleus and sequesters RNA-binding proteins, including regulators of mRNA splicing. Myotonic dystrophy is characterized by a highly variable phenotype that includes muscle weakness and myotonia, and the disorder may affect the function of many endocrine glands. DMPK mRNA is expressed in muscle, testis, liver, pituitary, thyroid, and bone; the mutated form leads to disruption of meiosis and an increase in fetal insulin receptor-A relative to adult insulin receptor-B, resulting in adult primary testicular failure and insulin resistance predisposing to diabetes, respectively. Patients with myotonic dystrophy are also at increased risk for hyperlipidemia, nonalcoholic fatty liver disease, erectile dysfunction, benign and malignant thyroid nodules, bone fractures, miscarriage, preterm delivery, and failed labor during delivery. Circulating parathyroid hormone and adrenocorticotropic hormone levels may be elevated, but the mechanisms for these associations are unclear. This review summarizes what is known about endocrine dysfunction in individuals with myotonic dystrophy.

Utility and safety of axillo-subclavian venous imaging with carbon dioxide (CO) prior to chronic lead system revisions.

BACKGROUND: Prior to attempting placement of one or more electrodes to revise existing rhythm control devices, patency of the central veins should be documented, in view of a high incidence of significant chronic occlusions. Since iodinated contrast venography may be contraindicated in select situations, imaging of the axillo-subclavian venous system with gaseous carbon dioxide (CO(2)) was evaluated prospectively in 23 consecutive individuals who were considered for revision of previously implanted pacemaker or automatic cardioverter defibrillator lead systems. METHODS: Approximately 20 mL of CO(2) were manually infused via CO(2) primed injection tubing into a vein at or above the level of the antecubital fossa ipsilateral to the side of prior lead placements. Digital subtraction imaging over the axillo-subclavian region, lower neck, and mediastinum was performed. Formal interpretation was obtained from one of three interventional radiologists and at least one electrophysiologist. RESULTS: Significant venous occlusions were identified in five (22%) patients. Vascular access utilized for the subsequent 18 revisions performed included the imaged patent ipsilateral vein in 14 patients and the contralateral, right-sided subclavian venous system in three patients. One patient required epicardial left ventricular lead placement. There were no complications from venography. CONCLUSIONS: Axillo-subclavian venography with gaseous CO(2) in patients undergoing pacemaker or implantable cardioverter defibrillator lead revisions is feasible and safe when use of iodinated dye is contraindicated. This technique should be employed in patients with azotemia, dye contrast allergies, or significant inflammation in the vicinity of the intravenous line insertion.

SHBG and total testosterone levels in men with adult onset hypogonadism: what are we overlooking?

BACKGROUND: Adult onset male hypogonadism (AOH) is a common clinical condition whose diagnosis and management are controversial, and is often characterized by a low level of SHBG, but our understanding of why testosterone levels are low when SHBG is low is incomplete. METHODS: This retrospective chart review was performed to compare the relationship between SHBG and testosterone in the plasma of men presenting for evaluation of AOH with a cohort of men treated chronically with transdermal testosterone. RESULTS: The level of SHBG was < 30 nmol/L in 73% of men who presented for evaluation of AOH, and was inversely proportional to BMI in both the untreated and the testosterone-treated men. As in previous populations, the level of SHBG was highly positively correlated (r = 0.71, p < 0.01) with the total testosterone level in untreated men presenting for evaluation of AOH, but no relationship was found between the level of SHBG and total testosterone among men who were being treated with a transdermal testosterone preparation. CONCLUSIONS: These findings further support the idea that SHBG regulates testicular negative feedback either directly or by modulating the entry of testosterone or estradiol into cells in the hypothalamus and/or pituitary to control gonadotropin synthesis and secretion which explains in part the low testosterone levels in men with AOH. TRIAL REGISTRATION: Not applicable.