Estrogen and Progestogen Correlates of the Structure of Female Copulation Calls in Semi-Free-Ranging Barbary Macaques (Macaca sylvanus)

Females of many Old World primates produce conspicuous vocalizations in combination with copulations. Indirect evidence exists that in Barbary macaques (Macaca sylvanus), the structure of these copulation calls is related to changes in reproductive hormone levels. However, the structure of these calls does not vary significantly around the timing of ovulation when estrogen and progestogen levels show marked changes. We here aimed to clarify this paradox by investigating how the steroid hormones estrogen and progesterone are related to changes in the acoustic structure of copulation calls. We collected data on semi-free-ranging Barbary macaques in Gibraltar and at La Forêt des Singes in Rocamadour, France. We determined estrogen and progestogen concentrations from fecal samples and combined them with a fine-grained structural analysis of female copulation calls (N = 775 calls of 11 females). Our analysis indicates a time lag of 3 d between changes in fecal hormone levels, adjusted for the excretion lag time, and in the acoustic structure of copulation calls. Specifically, we found that estrogen increased the duration and frequency of the calls, whereas progestogen had an antagonistic effect. Importantly, however, variation in acoustic variables did not track short-term changes such as the peak in estrogen occurring around the timing of ovulation. Taken together, our results help to explain why female Barbary macaque copulation calls are related to changes in hormone levels but fail to indicate the fertile phase

PolyQ Repeat Expansions in ATXN2 Associated with ALS Are CAA Interrupted Repeats

Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ) repeats of 27–33 in ATAXIN-2 (ATXN2), encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs) rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1–3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT), while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC). Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2

The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Abstract: Transformative technologies are enabling the construction of three-dimensional maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) intends to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, consortia, and the biomedical research community at large towards the shared vision of a comprehensive, accessible three-dimensional molecular and cellular atlas of the human body, in health and under various disease conditions

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Intrauterine device embedded in omentum of postpartum patient with a markedly retroverted uterus: a case report

Abstract Background The intrauterine device is a popular form of long-acting reversible contraception. Although generally safe, one of the most serious complications of intrauterine device use is uterine perforation. Risk factors for perforation include position of the uterus, force exerted during intrauterine device insertion, postpartum period, and breastfeeding. This case is important and needs to be reported because it highlights the need to assess risk factors for uterine perforation. It adds to the medical literature because it examines the relationship between position of the uterus and the location of uterine perforation. This case report is unusual in that it describes the mechanism and specific location of uterine perforation in relation to the position of the uterus. Case presentation We present a case of an intrauterine device found in the omentum of a 30-year-old white postpartum woman with a significantly retroverted uterus after the intrauterine device threads were not visualized on speculum examination during a 6-week placement check. The intrauterine device was located and removed via laparoscopy without complication. Conclusions This case report will be of interest to women’s health practitioners because it illustrates the importance of identifying patients with risk factors for uterine perforation, examining the relationship between uterine position and location of perforation. This is especially significant because the true incidence of perforation may be higher than the numbers reported in the literature. There is no specific diagnostic code for uterine perforation and it is unlikely that retrospective studies can accurately identify all cases

Differences in the clinical profile and outcomes of typical and atypical takotsubo syndrome: data from the international takotsubo registry

IMPORTANCE: Apical ballooning is broadly recognized as the classic form of takotsubo syndrome (TTS). Atypical subtypes of TTS also exist, which constitute about 20% of all cases. To date, clinical profile and course of atypical TTS types have rarely been studied. OBJECTIVE: To characterize the clinical profile and outcomes of typical vs atypical types of TTS in a large patient cohort. DESIGN, SETTING, AND PARTICIPANTS: Records of 1750 patients from the International Takotsubo Registry, comprising 26 participating cardiovascular centers in 9 different countries, were reviewed and data on clinical profile and outcomes collected from January 1, 2011, to December 31, 2014. MAIN OUTCOMES AND MEASURES: Clinical characteristics and in-hospital as well as long-term outcomes were assessed. RESULTS: Of 1750 patients diagnosed with TTS between 1998 and 2014, a total of 1430 (81.7%) presented with apical TTS (defined as typical TTS) and 320 (18.3%) with midventricular, basal, or focal TTS (all defined as atypical TTS). Patients with atypical TTS were younger than those with typical TTS (mean [SD], 62.5 [13.3] vs 67.3 [12.9] years; P < .001). Brain natriuretic peptide levels on admission were lower (median factor increase of the upper limit of normal, 4.18 vs 6.59; P = .02) and left ventricular ejection fraction was higher (mean [SD], 43.4% [10.7%] vs 40.6% [12.0%]; P < .001) in patients with atypical than those with typical forms of TTS. ST-segment depression was more prevalent in patients with atypical TTS (31 of 286 [10.8%] vs 90 of 1292 [7.0%]; P = .03), while ST-segment elevation was found more frequently in patients with typical TTS (593 of 1292 [45.9%] vs 97 of 286 [33.9%]; P < .001). Patients with atypical TTS more often had neurologic disorders than those with typical TTS (81 of 274 [29.6%] vs 286 of 1251 [22.9%]; P = .02). While in-hospital mortality was comparable between patients with atypical and typical TTS (10 of 320 [3.1%] vs 62 of 1430 [4.3%]; P = .32), the atypical forms showed a favorable outcome at 1 year (P = .01). However, after adjustment for confounders, only left ventricular ejection fraction less than 45%, atrial fibrillation, and neurologic disease, but not the type of TTS, were independent predictors. After 1 year, patients with both types of TTS showed a similar prognosis at long-term follow-up. CONCLUSIONS AND RELEVANCE: Atypical TTS has different characteristics than typical TTS, including younger age of onset, more frequent ST-segment depression, higher prevalence of neurologic diseases, less pronounced reduction in left ventricular ejection fraction, and lower brain natriuretic peptide values on admission. Outcomes are comparable between patients with both types after adjustment for confounders, suggesting that both should be equally monitored

Modulation of SR Ca2+ release by the triadin-to-calsequestrin ratio in ventricular myocytes

Calsequestrin (CSQ) is a Ca2+storage protein that interacts with triadin (TRN), the ryanodine receptor (RyR), and junctin (JUN) to form a macromolecular tetrameric Ca2+signaling complex in the cardiac junctional sarcoplasmic reticulum (SR). Heart-specific overexpression of CSQ in transgenic mice (TGCSQ) was associated with heart failure, attenuation of SR Ca2+release, and downregulation of associated junctional SR proteins, e.g., TRN. Hence, we tested whether co-overexpression of CSQ and TRN in mouse hearts (TGCxT) could be beneficial for impaired intracellular Ca2+signaling and contractile function. Indeed, the depressed intracellular Ca2+concentration ([Ca]i) peak amplitude in TGCSQwas normalized by co-overexpression in TGCxTmyocytes. This effect was associated with changes in the expression of cardiac Ca2+regulatory proteins. For example, the protein level of the L-type Ca2+channel Cav1.2 was higher in TGCxTcompared with TGCSQ. Sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a) expression was reduced in TGCxTcompared with TGCSQ, whereas JUN expression and [3H]ryanodine binding were lower in both TGCxTand TGCSQcompared with wild-type hearts. As a result of these expressional changes, the SR Ca2+load was higher in both TGCxTand TGCSQmyocytes. In contrast to the improved cellular Ca2+, transient co-overexpression of CSQ and TRN resulted in a reduced survival rate, an increased cardiac fibrosis, and a decreased basal contractility in catheterized mice, working heart preparations, and isolated myocytes. Echocardiographic and hemodynamic measurements revealed a depressed cardiac performance after isoproterenol application in TGCxTcompared with TGCSQ. Our results suggest that co-overexpression of CSQ and TRN led to a normalization of the SR Ca2+release compared with TGCSQmice but a depressed contractile function and survival rate probably due to cardiac fibrosis, a lower SERCA2a expression, and a blunted response to β-adrenergic stimulation. Thus the TRN-to-CSQ ratio is a critical modulator of the SR Ca2+signaling.</jats:p

Variations in outcomes of hemodialysis vascular access by race/ethnicity in the elderly

OBJECTIVE: Prevalence of end stage renal disease, modality of treatment and type of hemodialysis vascular access utilized varies widely by race/ethnicity in the United States, but outcomes of hemodialysis vascular access by race/ethnicity are poorly described. The objective of this study is to evaluate variations in outcomes of hemodialysis vascular access in the elderly by race/ethnicity. METHODS: Medicare Outpatient, Inpatient and Carrier files were queried from 2006-2011 for beneficiaries that were age ≥66 and dialysis dependent at time of index fistula/graft creation, qualified for Medicare by age only and were continuously enrolled in Medicare twelve months before and after index fistula/graft creation. Primary outcome measures were early vascular access failure and 12-month failure-free survival, specifically, the variation in the difference between fistula and graft in non-White versus White race/ethnicity groups.. RESULTS: Fistulas comprised a smaller proportion of index procedures performed in Blacks (65.9%, P<.001) and Asians (71.4%, P<.001), compared to Whites (78.0%) with no difference in Hispanics (78.7%, P=.59). Incidence of early failure after graft versus fistula was: Whites, 34.9% versus 43.5% (P<.001), Blacks, 32.9% versus 49.1% (P<.001), Asians, 30.8% versus 40.5% (P=.014) and Hispanics 35.2% versus 43.2% (P=.005). The difference in early failure after fistula versus graft in Blacks was significantly larger than the difference in Whites (P<.001). 12-month failure-free survival after index graft versus fistula was: Whites, 41.9% versus 38.9% (P=.008), Blacks 48.5% versus 37.3% (P<.001), Asians 51.6% versus 45.2% (P=.98) and Hispanics 51.9% versus 42.2% (P<.001). The difference in 12-month failure-free survival after graft versus fistula in Blacks and in Hispanics was larger than the difference in Whites (P<.001 and P=.02, respectively). CONCLUSIONS: Outcomes of fistulas versus grafts in the elderly vary significantly by race/ethnicity. The decreased risk of early failure after graft versus fistula creation is larger in Blacks compared to Whites. The higher failure-free survival at 12 months after graft versus fistula creation is larger in Blacks compared to Whites and trends toward being larger in Hispanics compared to Whites