Characteristics of tandem repeat inheritance and sympathetic nerve involvement in GAA-FGF14 ataxia.

BACKGROUND: Intronic GAA repeat expansion ([GAA] ≥250) in FGF14 is associated with the late-onset neurodegenerative disorder, spinocerebellar ataxia 27B (SCA27B, GAA-FGF14 ataxia). We aim to determine the prevalence of the GAA repeat expansion in FGF14 in Chinese populations presenting late-onset cerebellar ataxia (LOCA) and evaluate the characteristics of tandem repeat inheritance, radiological features and sympathetic nerve involvement. METHODS: GAA-FGF14 repeat expansion was screened in an undiagnosed LOCA cohort (n = 664) and variations in repeat-length were analyzed in families of confirmed GAA-FGF14 ataxia patients. Brain magnetic resonance imaging (MRI) was used to evaluate the radiological feature in GAA-FGF14 ataxia patients. Clinical examinations and sympathetic skin response (SSR) recordings in GAA-FGF14 patients (n = 16) were used to quantify sympathetic nerve involvement. RESULTS: Two unrelated probands (2/664) were identified. Genetic screening for GAA-FGF14 repeat expansion was performed in 39 family members, 16 of whom were genetically diagnosed with GAA-FGF14 ataxia. Familial screening revealed expansion of GAA repeats in maternal transmissions, but contraction upon paternal transmission. Brain MRI showed slight to moderate cerebellar atrophy. SSR amplitude was lower in GAA-FGF14 patients in pre-symptomatic stage compared to healthy controls, and further decreased in the symptomatic stage. CONCLUSIONS: GAA-FGF14 ataxia was rare among Chinese LOCA cases. Parental gender appears to affect variability in GAA repeat number between generations. Reduced SSR amplitude is a prominent feature in GAA-FGF14 patients, even in the pre-symptomatic stage.

Ag-Catalyzed Switchable Synthesis of Site-Specifically Functionalized Pyrroles via Azafulvenium Intermediates.

Here, we present a versatile, silver-catalyzed multi-auto-tandem reaction involving enamines, alkynals, and nucleophiles, utilizing the highly reactive intermediate azafulvenium. This method allows for flexible and switchable regiodivergent reactions through either intermolecular or intramolecular nucleophilic attacks, which can be controlled by adjusting the catalytic conditions. A range of site-specific functionalized or polycyclic fused pyrrole products were efficiently produced with a high level of chemocontrol.

Parabrachial nucleus astrocytes regulate wakefulness and isoflurane anesthesia in mice.

Background: The parabrachial nucleus (PBN) is an important structure regulating the sleep-wake behavior and general anesthesia. Astrocytes in the central nervous system modulate neuronal activity and consequential behavior. However, the specific role of the parabrachial nucleus astrocytes in regulating the sleep-wake behavior and general anesthesia remains unclear. Methods: We used chemogenetic approach to activate or inhibit the activity of PBN astrocytes by injecting AAV-GFAabc1d-hM3Dq-eGFP or AAV-GFAabc1d-hM4Di-eGFP into the PBN. We investigated the effects of intraperitoneal injection of CNO or vehicle on the amount of wakefulness, NREM sleep and REM sleep in sleep-wake behavior, and on the time of loss of righting reflex, time of recovery of righting reflex, sensitivity to isoflurane, electroencephalogram (EEG) power spectrum and burst suppression ratio (BSR) in isoflurane anesthesia. Results: The activation of PBN astrocytes increased wakefulness amount for 4 h, while the inhibition of PBN astrocytes decreased total amount of wakefulness during the 3-hour post-injection period. Chemogenetic activation of PBN astrocytes decreased isoflurane sensitivity and shortened the emergence time from isoflurane-induced general anesthesia. Cortical EEG recordings revealed that PBN astrocyte activation decreased the EEG delta power and BSR during isoflurane anesthesia. Chemogenetic Inhibition of PBN astrocytes increased the EEG delta power and BSR during isoflurane anesthesia. Conclusion: PBN astrocytes are a key neural substrate regulating wakefulness and emergence from isoflurane anesthesia.

Obstetricians' perspectives on trial of labor after cesarean (TOLAC) under the two-child policy in China: a cross-sectional study.

BACKGROUND: As the birth policy has been adjusted from one-child-one-couple to universal two-child-one-couple in China, there is an increasing number of women undergoing a second pregnancy after a previous cesarean section (CS). Undertaking an elective repeat CS (ERCS) has been taken for granted and has thus become a major contributor to the increasing CS rate in China. Promoting trial of labor after CS (TOLAC) can reduce the CS rate without compromising delivery outcomes. This study aimed to investigate Chinese obstetricians' perspectives regarding TOLAC, and the factors associated with their decision-making regarding recommending TOLAC to pregnant women with a history of CS under the two-child policy. METHODS: A cross-sectional survey was carried out between May and July 2018. Binary logistic regression was used to determine the factors associated with the obstetricians' intention to recommend TOLAC to pregnant women with a history of CS. The independent variables included sociodemographic factors and perceptions regarding TOLAC (selection criteria for TOLAC, basis underlying the selection criteria for TOLAC, and perceived challenges regarding promoting TOLAC). RESULTS: A total of 426 obstetricians were surveyed, with a response rate of ≥83%. The results showed that 31.0% of the obstetricians had no intention to recommend TOLAC to pregnant women with a history of CS. Their decisions were associated with the perceived lack of confidence regarding undergoing TOLAC among pregnant women with a history of CS and their families (odds ratio [OR] = 2.31; 95% CI: 1.38-1.38); obstetricians' uncertainty about the safety of TOLAC for pregnant women with a history of CS (OR = 0.49; 95% CI: 0.27-0.96), and worries about medical lawsuits due to adverse delivery outcomes (OR = 0.14; 95% CI: 0.07-0.31). The main reported challenges regarding performing TOLAC were lack of clear guidelines for predicting or avoiding the risks associated with TOLAC (83.4%), obstetricians' uncertainty about the safety of TOLAC for women with a history of CS (81.2%), pregnant women's unwillingness to accept the risks associated with TOLAC (81.0%) or demand for ERCS (80.7%), and the perceived lack of confidence (77.5%) or understanding (69.7%) regarding undergoing TOLAC among pregnant women and their families. CONCLUSION: A proportion of Chinese obstetricians did not intend to recommend TOLAC to pregnant women with a history of CS. This phenomenon was closely associated with obstetricians' concerns about TOLAC safety and perceived attitudes of the pregnant women and their families regarding TOLAC. Effective measures are needed to help obstetricians predict and reduce the risks associated with TOLAC, clearly specify the indications for TOLAC, improve labor management, and popularize TOLAC in China. Additionally, public health education on TOLAC is necessary to improve the understanding of TOLAC among pregnant women with a history of CS and their families, and to improve their interactions with their obstetricians regarding shared decision making.

Hospice care self-efficacy among clinical medical staff working in the coronavirus disease 2019 (COVID-19) isolation wards of designated hospitals: a cross-sectional study.

BACKGROUND: The COVID-19 pandemic has caused more than 462,417 deaths worldwide. A large number of patients with severe COVID-19 face death in hospital. Hospice care is truly a philosophy of care that delivers patient-centred care to the terminally ill and their families. Hospice care could provide many benefits for patients, families, and for hospice caregivers. The aim of this study is to investigate hospice care self-efficacy and identify its predictors among Chinese clinical medical staff in COVID-19 isolation wards of designated hospitals. METHODS: A cross-sectional design was used. The Hospice Care Self-Efficacy, Self-Competence in Death Work Scale, Positive Aspects of Caregiving, and Simplified Coping Style Questionnaires were administered between February and April 2020. A total of 281 eligible medical staff responded to the questionnaires, with a response rate of ≥78.9%. RESULTS: The mean score of hospice care self-efficacy was 47.04 (SD = 7.72). Self-efficacy was predicted by self-competence in death work (B = 0.433, P < 0.001), positive aspects of caregiving (B = 0.149, P = 0.027), positive coping (B = 0.219, P < 0.001), giving hospice care to dying or dead patients before fighting against COVID-19 (B = -1.487, P = 0.023), occupational exposure while fighting against COVID-19 (B = -5.244, P = 0.004), holding respect for life and professional sentiment as motivation in fighting against COVID-19 (B = 2.372, P = 0.031), and grade of hospital employment (B = -1.426, P = 0.024). The variables co-explained 58.7% variation of hospice care self-efficacy. CONCLUSION: Clinical nurses and physicians fighting COVID-19 reported a moderate level of hospice care self-efficacy during this pandemic. Exploring the traditional Chinese philosophy of life to learn from its strengths and make up for its weaknesses and applying it to hospice care may provide a new framework for facing death and dying during the COVID-19 pandemic. Continuous hospice care education to improve self-competence in death work, taking effective measures to mobilize positive psychological resources, and providing safer practice environments to avoid occupational exposure are also essential for the improvement of the hospice care self-efficacy of clinical nurses and physicians. These measures help caregivers deal effectively with death and dying while fighting against the COVID-19 pandemic.

Basal forebrain GABAergic neurons promote arousal and predatory hunting.

Predatory hunting is an important approach for animals to obtain valuable nutrition and energy, which critically depends on heightened arousal. Yet the neural substrates underlying predatory hunting remain largely undefined. Here, we report that basal forebrain (BF) GABAergic neurons play an important role in regulating predatory hunting. Our results showed that BF GABAergic neurons were activated during the prey (cricket)-hunting and food feeding in mice. Optogenetic activation of BF GABAergic neurons evoked immediate predatory-like actions to both artificial and natural preys, significantly reducing the attack latency while increasing the attack probability and the number of killed natural prey (crickets). Similar to the effect of activating the soma of BF GABAergic neurons, photoactivation of their terminals in the ventral tegmental area (VTA) also strongly promotes predatory hunting. Moreover, photoactivation of GABAergic BF - VTA pathway significantly increases the intake of various food in mice. By synchronous recording of electroencephalogram and electromyogram, we showed that photoactivation of GABAergic BF - VTA pathway induces instant arousal and maintains long-term wakefulness. In summary, our results clearly demonstrated that the GABAergic BF is a key neural substrate for predatory hunting, and promotes this behavior through GABAergic BF - VTA pathway.

Glutamatergic lateral hypothalamus promotes defensive behaviors.

The glutamatergic lateral hypothalamus (LH) has been implicated in a variety of behaviors, such as evasion and feeding, while its role in defensive behaviors and relevant neurocircuits remains unclear. Here, we demonstrated that the glutamatergic LH is a critical structure regulating defensive behaviors. Trimethylthiazole (TMT), the odor of mice predator, significantly increased c-Fos expression in the LH. Using fiber photometry technology, we found that TMT exposure increased the activity of LH glutamatergic neurons. Selective activation of LH glutamatergic neurons with optogenetics and chemogenetics promoted a series of defense-related behaviors, including fleeing, avoidance, and hiding, while selective inhibition of LH glutamatergic neurons suppressed the avoidance provoked by TMT. Activation of both the glutamatergic LH terminals in the hypothalamic paraventricular nucleus (PVN) and the glutamatergic projection from the basolateral amygdala (BLA) to the LH elicited defensive behaviors. Finally, by combining the viral-mediated retrograde tracing with anterograde activation, we found that PVN-projecting glutamatergic neurons in the LH were activated by BLA glutamatergic inputs. Taken together, our results illustrate that the glutamatergic LH is a pivotal relay of defensive behaviors and possibly promotes these behaviors through the BLA→LH→PVN pathway.