Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

Disability, Home Physical Environment and Non-Fatal Injuries among Young Children in China

We compared the patterns of medically attended injuries between children with and without disabilities and explored the residential environment risks in five counties of Hubei Province in the People's Republic of China by a 1:1 matched case-control study based on the biopsychosocial model of the International Classification of Functioning, Disability and Health--ICF.1201 children aged 1-14 with disabilities and 1201 their healthy counterparts matched as having the same gender, same age, and lived in the same neighborhood were recruited in our study. Characteristics of injuries in the past 12 months were compared between children with and without disabilities. The associations among disability status, home environment factors and injuries were examined in logistic regression analysis taking into account sociodemographic factors.Children with disabilities had a significantly higher prevalence of injury than children without disabilities (10.2% vs. 4.4%; P<.001). The two groups differed significantly in terms of number of injury episodes, injury place and activity at time of injury. Falls were the leading mechanism of injury regardless of disability status. Most of the injury events happened inside the home and leisure activities were the most reported activity when injured for both groups. The univariate OR for injury was 4.46 (2.57-7.74) for the disabled children compared with the non-disabled children. Disabled children whose family raised cat/dog(s) were 76% more likely to be injured during the last 12 months (OR = 1.76; 95% CI = 1.02, 3.02), comparing with those whose family did not have any cat/dog. And for children without disabilities, those whose family had cat/dog(s) were over 3 times more likely to having injuries comparing with those whose family did not have any cat/dog.Children with disabilities had a significantly increased risk for injury. Interventions to prevent residential injury are an important public health priority in children with disabilities

Two-way communication with neural networks in vivo using focused light

Neuronal networks process information in a distributed, spatially heterogeneous manner that transcends the layout of electrodes. In contrast, directed and steerable light offers the potential to engage specific cells on demand. We present a unified framework for adapting microscopes to use light for simultaneous in vivo stimulation and recording of cells at fine spatiotemporal resolutions. We use straightforward optics to lock onto networks in vivo, to steer light to activate circuit elements and to simultaneously record from other cells. We then actualize this 'free' augmentation on both an 'open' two-photon microscope and a leading commercial one. By following this protocol, setup of the system takes a few days, and the result is a noninvasive interface to brain dynamics based on directed light, at a network resolution that was not previously possible and which will further improve with the rapid advance in development of optical reporters and effectors. This protocol is for physiologists who are competent with computers and wish to extend hardware and software to interface more fluidly with neuronal networks.National Institutes of Health (U.S.) (Postdoctoral Fellowship)Simons Foundation (Postdoctoral Fellowship)National Institutes of Health (U.S.) (Predoctoral Fellowship)National Institutes of Health (U.S.)Simons Foundatio

Post hoc immunostaining of GABAergic neuronal subtypes following in vivo two-photon calcium imaging in mouse neocortex

GABAergic neurons in the neocortex are diverse with regard to morphology, physiology, and axonal targeting pattern, indicating functional specializations within the cortical microcircuitry. Little information is available, however, about functional properties of distinct subtypes of GABAergic neurons in the intact brain. Here, we combined in vivo two-photon calcium imaging in supragranular layers of the mouse neocortex with post hoc immunohistochemistry against the three calcium-binding proteins parvalbumin, calretinin, and calbindin in order to assign subtype marker profiles to neuronal activity. Following coronal sectioning of fixed brains, we matched cells in corresponding volumes of image stacks acquired in vivo and in fixed brain slices. In GAD67-GFP mice, more than 95% of the GABAergic cells could be unambiguously matched, even in large volumes comprising more than a thousand interneurons. Triple immunostaining revealed a depth-dependent distribution of interneuron subtypes with increasing abundance of PV-positive neurons with depth. Most importantly, the triple-labeling approach was compatible with previous in vivo calcium imaging following bulk loading of Oregon Green 488 BAPTA-1, which allowed us to classify spontaneous calcium transients recorded in vivo according to the neurochemically defined GABAergic subtypes. Moreover, we demonstrate that post hoc immunostaining can also be applied to wild-type mice expressing the genetically encoded calcium indicator Yellow Cameleon 3.60 in cortical neurons. Our approach is a general and flexible method to distinguish GABAergic subtypes in cell populations previously imaged in the living animal. It should thus facilitate dissecting the functional roles of these subtypes in neural circuitry

The Gender Question and Family Entrepreneurship Research

Gender in family entrepreneurship is still exploratory and, despite an increase in family entrepreneurship research, most of the studies give little or no information role of gender in family business. Existing research on family entrepreneurship tends to focus only or primarily on men, and the women appear invisible in the studies. However, there is little evidence that of extensive research focus on the issue of family entrepreneurship with the aim of building a cohesive understanding of gender in family entrepreneurship and the interactions existing between the different dimensions and components. Consequently, this chapter examines how gender issues are addressed in family entrepreneurship research. In particular, the chapter provides a critical review of the literature around the gender question in entrepreneurship, focusing on the resource-based view, organizational studies and gender in family entrepreneurship. Based on the review, a gender-aware framework is developed depicting three key areas for understanding the gendered process in family entrepreneurship: the determinants of women’s entry into family businesses, their gendered roles and the associated outcomes. Finally, implications and future research opportunities are identified and discussed

The use of tamsulosin to prevent postoperative urinary retention in laparoscopic inguinal hernia repair: a randomized double-blind placebo-controlled study

PURPOSE: The rate of postoperative urinary retention (POUR) in laparoscopic inguinal hernia repairs is 1-22%. POUR may cause patient anxiety, discomfort, and increased hospital costs. Currently there is no standard prophylaxis for POUR. Preoperative administration of tamsulosin has been shown to decrease POUR rates in urologic studies. This study aims to evaluate the efficacy of tamsulosin on the incidence of POUR in patients undergoing totally extraperitoneal (TEP) LIHR. METHODS: A randomized, double-blinded, placebo-controlled trial was initiated and accrued patients from 2017 to 2019. A total of 169 males undergoing elective TEP LIHR were included. Patients were administered tamsulosin 2 h before surgery and followed for up to 24 h postoperatively for episodes of POUR. Analysis was performed to quantify the association between patient, surgical, and perioperative factors with POUR. RESULTS: The overall rate of POUR was 9%. There was no difference in the rate of POUR between the placebo (9.9%) and tamsulosin groups (7.9%) (p = 0.433). Univariate analysis showed a trend toward POUR in patients with history of benign prostatic hypertrophy (BPH) (p = 0.058). Previously reported risk factors of older age, total IVF, length of procedure and opioid use were not associated with increased rates of POUR. Tamsulosin reduced the time to discharge by 4 to 68 min when compared to placebo. CONCLUSIONS: This study suggests that preoperative administration of tamsulosin may not reduce the risk of POUR in males undergoing elective TEP LIHR. Further study with a larger sample size may be needed to show a statistically significant difference