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In slices taken from rats pretreated with phencyclidine, the attenuation of evoked dopamine release by baclofen was abolished, but the attenuation by muscimol was unaffected. Since phencyclidine pretreatment was followed by drug-free washout period of at least a week, the drug was not present during recording. Therefore, disruption of GABA-B modulation of dopamine is due to long-term functional changes resulting from the treatment, rather than transient changes due to the drug's presence at test. This enduring dysregulation of GABA-B modulation of accumbal dopamine release provides a plausible mechanism through which GABA dysfunction influences accumbal dopamine leading to behavioral changes seen in schizophrenia and may provide a route for novel therapeutic strategies to treat the condition.Hereditary xerocytosis is a rare red blood cell disease related to gain-of-function mutations in the FAM38A gene, encoding PIEZO1, in 90% of cases; PIEZO1 is a broadly expressed mechano-transducer that plays a major role in many cell systems and tissues that respond to mechanical stress. In erythrocytes, PIEZO1 adapts the intracellular ionic content and cell hydration status to the mechanical constraints induced by the environment. Until recently, the pathophysiology of hereditary xerocytosis was mainly believed to be based on the "PIEZO1-Gardos channel axis" in erythrocytes, according to which PIEZO1-activating mutations induce a calcium influx that secondarily activates the Gardos channel, leading to potassium and water efflux and subsequently to red blood cell dehydration. However, recent studies have demonstrated additional roles for PIEZO1 during early erythropoiesis and reticulocyte maturation, as well as roles in other tissues and cells such as lymphatic vessels, hepatocytes, macrophages and platelets that may affect the pathophysiology of the disease. These findings, presented and discussed in this review, broaden our understanding of hereditary xerocytosis beyond that of primarily being a red blood cell disease and identify potential therapeutic targets.
The value of chromosome microarray (CMA) in the prenatal detection of significant chromosome anomalies is well-established. To guide the introduction of this technique in routine clinical practice, the Joint Committee on Genomics in Medicine developed national UK guidelines for reporting prenatal CMA in 2015.

To evaluate the UK experience of utilising prenatal CMA.

A 36-item survey was distributed to all UK clinical genetics services (n=23) in March 2019 requesting information pertaining to experience since diagnostic testing commenced and current practice (March 2018 to March 2019).

Eighteen UK genetics services currently offer prenatal CMA. Sodium acrylate datasheet A total of 14,554 tests had been performed. A pathogenic copy number variant was identified in 7.8% of tests overall, though the diagnostic rate increased to 8.4% in the final year of the survey. Variants of uncertain significance (VUS) were reported in 0.7% of tests, and 'actionable' incidental findings in 0.12%.

Diagnostic rate has improved over time, while reporting of VUS has decreased. Reviewing survey responses at a national level highlights variation in testing experience and practice, raising considerations both for future guideline development and implementation of other novel techniques including prenatal whole exome sequencing.
Diagnostic rate has improved over time, while reporting of VUS has decreased. Reviewing survey responses at a national level highlights variation in testing experience and practice, raising considerations both for future guideline development and implementation of other novel techniques including prenatal whole exome sequencing.Vancouver Island marmots (Marmota vancouverensis) have been managed in a captive-breeding program since 1997, as in situ conservation efforts were insufficient in raising the numbers of this critically endangered species. The success of captive-breeding programs centers on sustainable reproduction and survival of individuals once released into the wild. Captive-born Vancouver Island marmots released to the wild have lower survival rates than their wild-born counterparts; this difference may arise from compromised hibernation patterns or behaviors. Hibernation duration, body weight over the hibernation season, and reproductive success of captive Vancouver Island marmots were reviewed to assess the effect of these variables on each other. Data from a total of 1782 hibernations and 456 breeding attempts were compiled from 1997 to 2018. The number of winters spent in captivity, the origin of the marmot (captive-born or wild-born), the facility at which hibernation occurred, and the body weight all had a significant effect on hibernation length (all p  less then  .001). Increased weight was associated with increased hibernation length by 0.4 ± 0.1 day/kg on average (p = .0015). Captive, wild-born marmots hibernated for significantly longer than their captive-born counterparts by about 21 ± 2 days (p  less then  .001). The odds of successful breeding were significantly increased with increasing hibernation length by approximatively 20% for every 10 additional days of hibernation. This study provides information on the intrinsic relationship between body weight, reproduction, and hibernation in captive Vancouver Island marmots.
To identify major barriers to video-based telehealth use among homebound older adults.

Cross-sectional survey.

A large home-based primary care (HBPC) program in New York City (NYC) serving 873 homebound patients living in the community.

Sixteen primary care physicians.

An 11-item assessment of provider perceptions of patients' experience with and barriers to telehealth.

According to physicians in the HBPC program, more than one-third (35%) of homebound patients (mean age of 82.7; 46.6% with dementia; mean of 4 comorbidities/patient) engaged in first-time video-based telehealth encounters between April and June 2020 during the first COVID-19 surge in NYC. The majority (82%) required assistance from a family member and/or paid caregiver to complete the visit. Among patients who had not used telehealth, providers deemed 27% (n = 153) "unable to interact over video" for reasons including cognitive or sensory impairment and 14% lacked access to a caregiver to assist them with technology. Physicians were not knowledgeable of their patients' internet connectivity, ability to pay for cellular plans, or video-capable device access.
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