LARS-like symptoms in the general population may suggest the significance of postoperative functional problems and emotional implications of rectal surgery

Background & Aim. Sphincter-saving rectal surgery is prone to cause changes in bowel function associated with Low Anterior Resection Syndrome (LARS). Our aim was to assess LARS-like symptoms within a population of 50-80-year old in order to understand the functional disturbances and emotional impact of LARS. Materials and methods: We used a questionnaire to evaluate LARS with the following categories of symptoms: flatulence control, anal incontinence, frequency, clustering and urgency of the stools, and the psycho-emotional impact created by the presence of these symptoms. We calculated the severity of LARS on 343 responders. Results. The average age of the responders (57.4% females) was 60 years. Overall, 48.1% of those questioned had no LARS-associated symptoms, while the rest presented either minor (39.9%) or major (12%) LARS-like symptomatology according to the assessment scale. Women have a higher relative risk (1.32) of having minor or major LARS. The frequency of stools did not correlate with the overall LARS score. The psycho-emotional impact was mostly influenced by the presence of incontinence (p=0.001) and urgency (p=0.05). Discussions. The study highlights the need to integrate the initial status of patients into the overall quantification of the effects of surgery on the quality of life. Age does not influence the prevalence of LARS, but symptoms seem more prevalent in women. The psycho-emotional impact is relevant to the general population, so explanations given during the informed consent and accurate description of potential consequences of surgical intervention increase compliance to ensure better post-operative control of the symptomatology. Conclusions. Deriving a normative LARS-like score may alter the interpretation and discussion of LARS scores for future rectal cancer patients, and it also provides a better understanding of the emotional impact of such symptoms on certain population subsets or cultural groups

The Cis-regulatory Logic of the Mammalian Photoreceptor Transcriptional Network

The photoreceptor cells of the retina are subject to a greater number of genetic diseases than any other cell type in the human body. The majority of more than 120 cloned human blindness genes are highly expressed in photoreceptors. In order to establish an integrative framework in which to understand these diseases, we have undertaken an experimental and computational analysis of the network controlled by the mammalian photoreceptor transcription factors, Crx, Nrl, and Nr2e3. Using microarray and in situ hybridization datasets we have produced a model of this network which contains over 600 genes, including numerous retinal disease loci as well as previously uncharacterized photoreceptor transcription factors. To elucidate the connectivity of this network, we devised a computational algorithm to identify the photoreceptor-specific cis-regulatory elements (CREs) mediating the interactions between these transcription factors and their target genes. In vivo validation of our computational predictions resulted in the discovery of 19 novel photoreceptor-specific CREs near retinal disease genes. Examination of these CREs permitted the definition of a simple cis-regulatory grammar rule associated with high-level expression. To test the generality of this rule, we used an expanded form of it as a selection filter to evolve photoreceptor CREs from random DNA sequences in silico. When fused to fluorescent reporters, these evolved CREs drove strong, photoreceptor-specific expression in vivo. This study represents the first systematic identification and in vivo validation of CREs in a mammalian neuronal cell type and lays the groundwork for a systems biology of photoreceptor transcriptional regulation

LARS-like symptoms in the general population may suggest the significance of postoperative functional problems and emotional implications of rectal surgery

Background & Aim. Sphincter-saving rectal surgery is prone to cause changes in bowel function associated with Low Anterior Resection Syndrome (LARS). Our aim was to assess LARS-like symptoms within a population of 50-80-year old in order to understand the functional disturbances and emotional impact of LARS. Materials and methods: We used a questionnaire to evaluate LARS with the following categories of symptoms: flatulence control, anal incontinence, frequency, clustering and urgency of the stools, and the psycho-emotional impact created by the presence of these symptoms. We calculated the severity of LARS on 343 responders. Results. The average age of the responders (57.4% females) was 60 years. Overall, 48.1% of those questioned had no LARS-associated symptoms, while the rest presented either minor (39.9%) or major (12%) LARS-like symptomatology according to the assessment scale. Women have a higher relative risk (1.32) of having minor or major LARS. The frequency of stools did not correlate with the overall LARS score. The psycho-emotional impact was mostly influenced by the presence of incontinence (p=0.001) and urgency (p=0.05). Discussions. The study highlights the need to integrate the initial status of patients into the overall quantification of the effects of surgery on the quality of life. Age does not influence the prevalence of LARS, but symptoms seem more prevalent in women. The psycho-emotional impact is relevant to the general population, so explanations given during the informed consent and accurate description of potential consequences of surgical intervention increase compliance to ensure better post-operative control of the symptomatology. Conclusions. Deriving a normative LARS-like score may alter the interpretation and discussion of LARS scores for future rectal cancer patients, and it also provides a better understanding of the emotional impact of such symptoms on certain population subsets or cultural groups

The Cis-regulatory Logic of the Mammalian Photoreceptor Transcriptional Network

The photoreceptor cells of the retina are subject to a greater number of genetic diseases than any other cell type in the human body. The majority of more than 120 cloned human blindness genes are highly expressed in photoreceptors. In order to establish an integrative framework in which to understand these diseases, we have undertaken an experimental and computational analysis of the network controlled by the mammalian photoreceptor transcription factors, Crx, Nrl, and Nr2e3. Using microarray and in situ hybridization datasets we have produced a model of this network which contains over 600 genes, including numerous retinal disease loci as well as previously uncharacterized photoreceptor transcription factors. To elucidate the connectivity of this network, we devised a computational algorithm to identify the photoreceptor-specific cis-regulatory elements (CREs) mediating the interactions between these transcription factors and their target genes. In vivo validation of our computational predictions resulted in the discovery of 19 novel photoreceptor-specific CREs near retinal disease genes. Examination of these CREs permitted the definition of a simple cis-regulatory grammar rule associated with high-level expression. To test the generality of this rule, we used an expanded form of it as a selection filter to evolve photoreceptor CREs from random DNA sequences in silico. When fused to fluorescent reporters, these evolved CREs drove strong, photoreceptor-specific expression in vivo. This study represents the first systematic identification and in vivo validation of CREs in a mammalian neuronal cell type and lays the groundwork for a systems biology of photoreceptor transcriptional regulation

Patient Satisfaction with Private Recovery Services and Importance of Physician Behavior during COVID Time

Introduction: Patient satisfaction represents an essential indicator of the quality of care in the medical recuperation sector. This study aimed to identify the degree of satisfaction in patients who benefit from medical recuperation services in one private clinic from Romania and the factors that played a part in this respect. Method: An online questionnaire was completed by 105 patients of a private clinic in the period immediately following the opening of the clinic after the quarantine period due to COVID-19. The following concepts were measured: general satisfaction with clinical recuperation services (SG), physician’s behavior (PB), the impact of interventions on the state of health (IHI), modern equipment (ME), and the intention to return to the clinic (IRC). Based on a linear regression model, the impact of PB, IHI, ME, and IRC variables on general satisfaction (SG) was established. Results: The study results confirm the data from studies carried out in different sociocultural contexts in ordinary time, where physician behavior is the most crucial factor in patients’ satisfaction. Therefore, we can say that the physiotherapist’s behavior has an essential role in determining the patients’ satisfaction both in ordinary time and in COVID-19 time. The data in this study reflect the fact that satisfaction with the services offered by a medical recuperation clinic is a predictor for using the services in the future. Still, our study reflects a moderate relationship in intensity

Patient Satisfaction with Private Recovery Services and Importance of Physician Behavior during COVID Time

Introduction: Patient satisfaction represents an essential indicator of the quality of care in the medical recuperation sector. This study aimed to identify the degree of satisfaction in patients who benefit from medical recuperation services in one private clinic from Romania and the factors that played a part in this respect. Method: An online questionnaire was completed by 105 patients of a private clinic in the period immediately following the opening of the clinic after the quarantine period due to COVID-19. The following concepts were measured: general satisfaction with clinical recuperation services (SG), physician’s behavior (PB), the impact of interventions on the state of health (IHI), modern equipment (ME), and the intention to return to the clinic (IRC). Based on a linear regression model, the impact of PB, IHI, ME, and IRC variables on general satisfaction (SG) was established. Results: The study results confirm the data from studies carried out in different sociocultural contexts in ordinary time, where physician behavior is the most crucial factor in patients’ satisfaction. Therefore, we can say that the physiotherapist’s behavior has an essential role in determining the patients’ satisfaction both in ordinary time and in COVID-19 time. The data in this study reflect the fact that satisfaction with the services offered by a medical recuperation clinic is a predictor for using the services in the future. Still, our study reflects a moderate relationship in intensity.</jats:p

Genetic deletion of BACE1 in mice affects remyelination of sciatic nerves

BACE1 is a promising therapeutic and preventive target for Alzheimer’s disease because it is essential for amyloid deposition. However, the recent demonstration of BACE1 in modulating developmental myelination in both peripheral and central nervous systems raises a concern of its effect on myelin maintenance or remyelination, and inhibition of these processes will potentially be detrimental to the BACE1 inhibitor users who are susceptible to myelination diseases such as adult peripheral nerve injury or multiple sclerosis. In this report, we investigated the role of BACE1 during peripheral nerve remyelination in wild-type (WT) and BACE1-null mice. We show here that genetic deletion of BACE1 affects sciatic nerve remyelination. The impaired remyelination appears to stem from the loss of neuregulin-1 cleavage by BACE1. To demonstrate a direct cleavage of neuregulin-1 by BACE1, we have identified a BACE1 cleavage site that turns out be highly conserved among neuregulin-1 paralogues. Moreover, we show that neuregulin-1 family member neuregulin-3 is also cleavable by BACE1. We hypothesize that the BACE1-cleaved extracellular domain of axonal neuregulin-1, perhaps neuregulin-3 as well, binds to Schwann cell ErbB receptors, which in turn regulate remyelination. Pharmacological inhibition of BACE1 should be carefully monitored to avoid alteration of signaling pathway that regulates remyelination.—Hu, X., He, W., Diaconu, C., Tang, X., Kidd, G. J., Macklin, W. B., Trapp, B. D., Yan, R. Genetic deletion of BACE1 in mice affects remyelination of sciatic nerves