The Perplexity Surrounding Chiari Malformations - Are We Any Wiser Now?
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ABSTRACT:
SUBMITTER: Hiremath SB
PROVIDER: S-EPMC7658834 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveInherited variants predisposing patients to type 1 or 1.5 Chiari malformation (CM) have been hypothesized but have proven difficult to confirm. The authors used a unique high-risk pedigree population resource and approach to identify rare candidate variants that likely predispose individuals to CM and protein structure prediction tools to identify pathogenicity mechanisms.MethodsBy using the Utah Population Database, the authors identified pedigrees with significantly increased numbers of members with CM diagnosis. From a separate DNA biorepository of 451 samples from CM patients and families, 32 CM patients belonging to 1 or more of 24 high-risk Chiari pedigrees were identified. Two high-risk pedigrees had 3 CM-affected relatives, and 22 pedigrees had 2 CM-affected relatives. To identify rare candidate predisposition gene variants, whole-exome sequence data from these 32 CM patients belonging to 24 CM-affected related pairs from high-risk pedigrees were analyzed. The I-TASSER package for protein structure prediction was used to predict the structures of both the wild-type and mutant proteins found here.ResultsSequence analysis of the 24 affected relative pairs identified 38 rare candidate Chiari predisposition gene variants that were shared by at least 1 CM-affected pair from a high-risk pedigree. The authors found a candidate variant in HOXC4 that was shared by 2 CM-affected patients in 2 independent pedigrees. All 4 of these CM cases, 2 in each pedigree, exhibited a specific craniocervical bony phenotype defined by a clivoaxial angle less than 125°. The protein structure prediction results suggested that the mutation considered here may reduce the binding affinity of HOXC4 to DNA.ConclusionsAnalysis of unique and powerful Utah genetic resources allowed identification of 38 strong candidate CM predisposition gene variants. These variants should be pursued in independent populations. One of the candidates, a rare HOXC4 variant, was identified in 2 high-risk CM pedigrees, with this variant possibly predisposing patients to a Chiari phenotype with craniocervical kyphosis.
| S-EPMC10193467 | biostudies-literature
Project description:BackgroundCavalier King Charles Spaniels (CKCS) suffer pain associated with Chiari-like malformation and syringomyelia (CMSM). People suffer from a similar condition and describe numerous sensory abnormalities. Sensory changes have not been quantified in affected CKCS.ObjectivesTo use quantitative sensory testing (QST) to quantify thermal and mechanical thresholds in CKCS and to compare QST in dogs with and without syringomyelia (SM).AnimalsForty-four CKCS.MethodsProspective study. Dogs underwent neurological examinations and craniocervical magnetic resonance imaging (MRI). Thermal testing was performed over the humerus and thorax (n = 32); mechanical testing was performed on the paw and neck (n = 44). Latencies, thresholds, and response rates were compared with presence and severity of SM on MRI, presence of pain reported by the owner and pain identified on examination.ResultsThirty dogs had SM, 30 were painful on examination, 29 were owner-reported symptomatic. Thermal and mechanical variables were not significantly different based on presence or severity of SM. Dogs with pain on examination had decreased mechanical thresholds on the paw (0.38 kg, SD = 0.18) and neck (2.05 kg, SD = 0.74) compared to thresholds of dogs without pain on examination on the paw (0.60 kg, SD = 0.30) and neck (2.72 kg, SD = 0.57; P = .021).Conclusions and clinical importanceMechanical and thermal sensitivity does not appear to be related to the presence of SM, but mechanical sensitivity appears to be related to the presence of pain and clinical signs. Mechanical testing may be useful for assessing sensory abnormalities during clinical trials.
| S-EPMC6272044 | biostudies-literature
Project description:Zhu-Tokita-Tachenouchi-Kim syndrome (ZTTK) is a recently recognized malformation syndrome presenting with craniofacial dysmorphism, developmental delay/intellectual disability, seizures, anomalies involving brain white matter, and other body-organs. In humans, the disorder is linked to the loss-of-function variants in the SON gene (MIM# 617140). Herewith, a new case of this syndrome is reported in a 2-year-old Caucasian child who presented the classical clinical features of the ZTTK syndrome in association with hydrocephalus and Chiari malformations type 1 an anomaly previously unreported. Exome analysis showed a de novo heterozygous variant in SON gene. Literature review of similar cases is reported.
| S-EPMC9755635 | biostudies-literature
Project description:Despite the clear need, progress toward a vaccine for congenital cytomegalovirus (CMV) has been slow. However, recent events have provided new interest, and several vaccine candidates are either in clinical trials or the trials are close to starting. In this issue of Clinical and Vaccine Immunology, Schleiss and colleagues show that a nonreplicating lymphocytic choriomeningitis virus (rLCMV)-vectored vaccine expressing CMV glycoprotein B (gB) and/or pp65 induces B and T cells and improves pup survival in a guinea pig model of congenital CMV infection (Clin Vaccine Immunol 24:e00300-16, 2017, https://doi.org/10.1128/CVI.00300-16). The combination vaccine appeared to be the most effective.
| S-EPMC5216425 | biostudies-literature
Project description:Initial evidence suggests that cultural differences have consequences for wise reasoning (perspective taking, consideration of change and alternatives, intellectual humility, search for compromise, and adopting an outsider's vantage point), with more reports of wise reasoning about interpersonal conflicts among Japanese (as compared to American) young and middle-aged adults. Similarly, we found that people from the rice-farming area of southern China also exhibited greater wise reasoning when they encountered conflicts with a friend or in the workplace than those from the wheat-farming area of northern China (N = 487, 25 provinces). The relationship between rice farming and wise reasoning was mediated by loyalty/nepotism. This research advances study of the relationship between wisdom and culture. It also provides evidence for the influence of social-ecological factors on wisdom and culture.
| S-EPMC7040192 | biostudies-literature
Project description:Nearly two decades ago, pathologic examination results suggested that acoustic factors, such as mid-frequency active naval military sonar (MFAS) could be the cause of acute decompression-like sickness in stranded beaked whales. Acute systemic gas embolism in these whales was reported together with enigmatic cystic liver lesions (CLL), characterized by intrahepatic encapsulated gas-filled cysts, tentatively interpreted as "gas-bubble" lesions in various other cetacean species. Here we provide a pathologic reinterpretation of CLL in odontocetes. Among 1,200 cetaceans necropsied, CLL were only observed in four striped dolphins (Stenella coeruleoalba), with a low prevalence (2%, N = 179). Together, our data strongly suggest that CLL are the result of the combination of a pre-existing or concomitant hepatic vascular disorder superimposed and exacerbated by gas bubbles, and clearly differ from acute systemic gas embolism in stranded beaked whales that is linked to MFAS. Budd-Chiari-like syndrome in dolphins is hypothesized based on the present pathologic findings. Nonetheless, further researched is warranted to determine precise etiopathogenesis(es) and contributing factors for CLL in cetaceans.
| S-EPMC9314369 | biostudies-literature
Project description:For almost half a century, inotropes have been administered to preterm infants with the ultimate goal of increasing their blood pressure. A number of trials, the majority of which focused on dopamine administration, have demonstrated increased blood pressure following inotrope administration in preterm infants and have led to continued use of inotropes in our neonatal units. We have also seen an increase in the number of potential agents available to the clinician. However, we now know that hypotension is a much broader concept than blood pressure alone, and our aim should instead be focused on improving end organ perfusion, specifically cerebral perfusion. Only a limited number of studies have incorporated the organ-relevant hemodynamic changes and long-term outcomes when assessing inotropic effects in neonates, the majority of which are observational studies or have a small sample size. In addition, important considerations, including the developing/maturing adrenergic receptors, polymorphisms of these receptors, and other differences in the pharmacokinetics and pharmacodynamics of preterm infants, are only recently being recognized. Certainly, there remains huge variation in practice. The lack of well-conducted randomized controlled trials addressing these relevant outcomes, along with the difficulty executing such RCTs, leaves us with more questions than answers. This review provides an overview of the various inotropic agents currently being used in the care of preterm infants, with a particular focus on their organ/cerebral hemodynamic effects both during and after transition.
| S-EPMC5898425 | biostudies-literature
Project description:Averaging independent numerical judgments can be more accurate than the average individual judgment. This "wisdom of crowds" effect has been shown with large, diverse samples, but the layperson wishing to take advantage of this may only have access to the opinions of a small, more demographically homogeneous "convenience sample." How wise are homogeneous crowds relative to diverse crowds? In simulations and survey studies, we demonstrate three necessary conditions under which small socially diverse crowds can outperform socially homogeneous crowds: Social identity must predict judgment, the effect of social identity on judgment must be at least moderate in size, and the average estimates of the social groups in question must "bracket" the truth being judged. Seven survey studies suggest that these conditions are rarely met in real judgment tasks. Comparisons between the performances of diverse and homogeneous crowds further confirm that social diversity can make crowds wiser but typically by a very small margin.
| S-EPMC5834705 | biostudies-literature
Project description:BackgroundImpaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial.Methods/design602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140-199 mg/dl). In addition, IGT subjects were required to have FPG = 95-125 mg/dl and at least one other high risk characteristic. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA1C, lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2-3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated.Primary endpoint is conversion of IGT to T2DM based upon FPG >or= 126 or 2-hour PG >or= 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance.ConclusionACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM.Trial registrationclinical trials.gov identifier: NCT00220961.
| S-EPMC2725044 | biostudies-literature
Project description:OBJECTIVE:Women experience a variety of changes at midlife that may affect sexual function. Qualitative research approaches can allow a deeper understanding of women's experiences. We conducted 20 individual interviews and three focus groups among sexually active women aged 45 to 60 years (total n?=?39) to explore how sexual function changes during midlife. METHODS:Interviews and focus groups were conducted by a trained facilitator using a semistructured guide. All data were audio-recorded and transcribed. Two investigators used a subsample of data to iteratively develop a codebook. The primary investigator coded all data. A second investigator coded a randomly selected 25% of interviews. Codes regarding changes in sexual function were examined and key themes emerged. RESULTS:The mean age was 52, and most women were peri- or postmenopausal. Fifty-four per cent of women were white, 36% black, and 10% of another race. Participants discussed positive and negative changes in sexual function. The most common negative changes were decreased frequency of sex, low libido, vaginal dryness, and anorgasmia. Participants attributed negative changes to menopause, partner issues, and stress. Most participants responded to negative changes with adaptation, including changing sexual behavior and prioritizing different aspects of sex. Participants also reported positive changes, attributed to higher self-confidence, increased self-knowledge, and better communication skills with aging. CONCLUSIONS:In this qualitative study, women described experiencing both positive and negative changes in sexual function during midlife. When negative changes occurred, women often adapted behaviorally and psychologically. Providers should recognize that each woman's experience is unique and nuanced, and they should provide tailored care regarding sexual function at midlife.
| S-EPMC5821528 | biostudies-literature