Serotonin Transporter Gene Polymorphism Modulates Activity and Connectivity within an Emotional Arousal Network of Healthy Men during an Aversive Visceral Stimulus.

Background and aimsThe 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) has been linked to increased stress responsiveness and negative emotional states. During fearful face recognition individuals with the s allele of 5-HTTLPR show greater amygdala activation. We aimed to test the hypothesis that the 5-HTTLPR polymorphism differentially affects connectivity within brain networks during an aversive visceral stimulus.MethodsTwenty-three healthy male subjects were enrolled. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Subjects with the s/s genotype (n = 13) were compared to those with the l allele (genotypes l/s, l/l, n = 10). Controlled rectal distension from 0 to 40 mmHg was delivered in random order using a barostat. Radioactive H2[15-O] saline was injected at time of distension followed by positron emission tomography (PET). Changes in regional cerebral blood flow (rCBF) were analyzed using partial least squares (PLS) and structural equation modeling (SEM).ResultsDuring baseline, subjects with s/s genotype demonstrated a significantly increased negative influence of pregenual ACC (pACC) on amygdala activity compared to l-carriers. During inflation, subjects with s/s genotype demonstrated a significantly greater positive influence of hippocampus on amygdala activity compared to l-carriers.ConclusionIn male Japanese subjects, individuals with s/s genotype show alterations in the connectivity of brain regions involved in stress responsiveness and emotion regulation during aversive visceral stimuli compared to those with l carriers

Exercise hyperpnea and hypercapnic ventilatory responses in women

SummaryWe studied the relationship between exercise hyperpnea (i.e., ventilatory dynamics) at the onset of exercise and hypercapnic ventilatory response (HCVR), and their differences between the follicular (FP) and luteal (LP) phases of the menstrual cycle in six healthy females. HCVR was tested under three O2 conditions: hyperoxia (FiO2=1.0), normoxia (0.21), and hypoxia (0.12). HCVR was defined as the relationship between the end-tidal PCO2 and minute ventilation (V˙E) using the regression line of the CO2 slope and a mimetically apneic threshold of CO2. HCVR provocation and measurements were conducted using an inspired CO2 concentration of up to approximately 8mmHg higher than the end-tidal PCO2 level of basal isocapnic the end-tidal PCO2 at each menstrual both the slope and threshold in HCVR showed no statistically significant difference between LP and FP under any inspired FiO2 conditions. In the case of exercise hyperpnea during the onset of submaximal exercise, the mean response time (MRT) in V˙E dynamics showed no significant difference between LP and FP. Consequently, MRT in V˙E response was not related to the slope in HCVR. During steady-state exercise, even though the V˙E/V˙CO2 showed no significance between LP and FP, V˙E/V˙CO2 was significantly related to the slope in HCVR (r=0.59, P<0.05). Exercise ventilation (i.e., V˙E/V˙CO2) would partly be adjusted by the enhancement of the chemoreflex drive to CO2 only during the steady-state exercise

Extremely large Lamb shift in a deep-strongly coupled circuit QED system with a multimode resonator

We report experimental and theoretical results on the extremely large Lamb shift in a multimode circuit quantum electrodynamics (QED) system in the deep-strong coupling (DSC) regime, where the qubit-resonator coupling strength is comparable to or larger than the qubit and resonator frequencies. The system comprises a superconducting flux qubit (FQ) and a quarter-wavelength coplanar waveguide resonator ($\lambda/4$ CPWR) that are coupled inductively through a shared edge that contains a Josephson junction to achieve the DSC regime. Spectroscopy is performed around the frequency of the fundamental mode of the CPWR, and the spectrum is fitted by the single-mode quantum Rabi Hamiltonian to obtain the system parameters. Since the qubit is also coupled to a large number of higher modes in the resonator, the single-mode fitting does not provide the bare qubit energy but a value that incorporates the renormalization from all the other modes. We derive theoretical formulas for the Lamb shift in the multimode resonator system. As shown in previous studies, there is a cut-off frequency $\omega_{\rm{cutoff}}$ for the coupling between the FQ and the modes in the CPWR, where the coupling grows as $\sqrt{\omega_n}$ for $\omega_n/\omega_{\rm{cutoff}}\ll 1$ and decreases as $1/\sqrt{\omega_n}$ for $\omega_n/\omega_{\rm{cutoff}}\gg 1$. Here $\omega_n$ is the frequency of the $n$th mode. The cut-off effect occurs because the qubit acts as an obstacle for the current in the resonator, which suppresses the current of the modes above $\omega_{\rm{cutoff}}$ at the location of the qubit and results in a reduced coupling strength. Using our observed spectrum and theoretical formulas, we estimate that the Lamb shift from the fundamental mode is 82.3\% and the total Lamb shift from all the modes is 96.5\%.Comment: 16 pages, 4 figure

Members of a novel gene family, Gsdm, are expressed exclusively in the epithelium of the skin and gastrointestinal tract in a highly tissue-specific manner

AbstractGasdermin (Gsdm) was originally identified as a candidate causative gene for several mouse skin mutants. Several Gsdm-related genes sharing a protein domain with DFNA5, the causative gene of human nonsyndromic hearing loss, have been found in the mouse and human genomes, and this group is referred to as the DFNA5–Gasdermin domain family. However, our current comparative genomic analysis identified several novel motifs distinct from the previously reported domain in the Gsdm-related genes. We also identified three new Gsdm genes clustered on mouse chromosome 15. We named these genes collectively the Gsdm family. Extensive expression analysis revealed exclusive expression of Gsdm family genes in the epithelium of the skin and gastrointestinal tract in a highly tissue-specific manner. Further database searching revealed the presence of other related genes with a similar N-terminal motif. These results suggest that the Gsdm family and related genes have evolved divergent epithelial expression profiles

Nurses' Practical Wisdom for the Support of Dementia Patients Among Hospital Outpatients

Purpose: To establish and understand nurses' practical wisdom and interventions of support for dementia and possible dementia patients at hospital outpatient wards. Methods: A qualitative design was used to collect data through semi-structured focus group interviews. The participants were 13 female nurses working at hospital outpatient wards.Data were analyzed using the KJ Method. Results: Seven themes symbolizing the properties of the final label were extracted as follows:‘Observation of patients with focused awareness, and are continuously engaged with their patients',‘Approach to the problems of the patients, and sensitively work to understand the worries of patients based on past cases of problems',‘Looking out for simple ways patients can look after themselves, implicitly and thoroughly, making the best use of the ways that patients are familiar with and which they are able to understand',‘Preparations for scheduled consultations by developing a network to assist with problem prevention and recording episodes about problems involving the patients',‘Requests for cooperation to continue treatment by choosing intermediaries/resources appropriately as based on the importance of the medical treatment',‘Responses that do not conflict with the feelings of the family by considering the possible reluctance of accepting that a family member has dementia', and‘Attitude not to blame matters on dementia by reflecting on how the environment and care ought to be'.’ Conclusion:Nurses' practical wisdom is a type of support provided for patients in a natural manner without being noticed as special or particular by the patients

Germline multigene panel testing revealed a BRCA2 pathogenic variant in a patient with suspected Lynch syndrome

There has been a rapid advance in germline multigene panel testing by next-generation sequencing, and it is being widely used in clinical settings. A 56-year-old woman suspected of having Lynch syndrome was identified as a BRCA2 pathogenic variant carrier by multigene panel testing. The patient was diagnosed with endometrial cancer at the age of 39 years, and total laparoscopic hysterectomy and bilateral salpingectomy were performed at the age of 49 years; however, bilateral oophorectomy was not performed at that time. As she had a family history of colorectal cancer and a history of endometrial cancer, Lynch syndrome was suspected. However, germline multigene panel testing revealed a pathogenic BRCA2 variant rather than pathogenic variants in mismatch repair genes. In this case, with conventional genetic risk assessment, we were unable to determine whether the patient had a high risk of hereditary breast and ovarian cancer; thus, germline multigene panel testing may provide valuable information to improve disease management strategies for patients in clinical settings. Particularly, germline multigene panel testing may be useful for detecting hereditary tumor syndromes if a patient does not present with a typical family history of cancer

Familial pancreatic cancer with PALB2 and NBN pathogenic variants: a case report

Background Family history is one of the risk factors for pancreatic cancer. It is suggested that patients with pancreatic cancer who have a familial history harbor germline pathogenic variants of BRCA1 and/or BRCA2 (BRCA1/2), PALB2, or ATM. Recently, some germline variants of familial pancreatic cancers (FPCs), including PALB2, have been detected. Several countries, including Japan, perform screening workups and genetic analysis for pancreatic cancers. We have been carrying out active surveillance for FPC through epidemiological surveys, imaging analyses, and genetic analysis. Case presentation Here, we present the case of a female patient harboring pathogenic variants of PALB2 and NBN, with a family history of multiple pancreatic cancer in her younger brother, her aunt, and her father. Moreover, her father harbored a PALB2 pathogenic variant and her daughter harbored the same NBN pathogenic variant. Given the PALB2 and NBN variants, we designed surveillance strategies for the pancreas, breast, and ovary. Conclusions Further studies are required to develop strategies for managing FPCs to facilitate prompt diagnosis before their progression

High diving metabolic rate indicated by high-speed transit to depth in negatively buoyant long-finned pilot whales

The US Office of Naval Research and Strategic Environmental Research and Development Program (SERDP) supported the fieldwork as a part of the 3S study collaboration. This study was also supported by the program Bio-Logging Science of the University of Tokyo (UTBLS).To maximize foraging duration at depth, diving mammals are expected to use the lowest cost optimal speed during descent and ascent transit and to minimize the cost of transport by achieving neutral buoyancy. Here, we outfitted 18 deep-diving long-finned pilot whales with multi-sensor data loggers and found indications that their diving strategy is associated with higher costs than those of other deep-diving toothed whales. Theoretical models predict that optimal speed is proportional to (basal metabolic rate/drag)1/3 and therefore to body mass0.05. The transit speed of tagged animals (2.7±0.3 m s−1) was substantially higher than the optimal speed predicted from body mass (1.4–1.7 m s−1). According to the theoretical models, this choice of high transit speed, given a similar drag coefficient (median, 0.0035) to that in other cetaceans, indicated greater basal metabolic costs during diving than for other cetaceans. This could explain the comparatively short duration (8.9±1.5 min) of their deep dives (maximum depth, 444±85 m). Hydrodynamic gliding models indicated negative buoyancy of tissue body density (1038.8± 1.6 kg m–3, ±95% credible interval, CI) and similar diving gas volume (34.6±0.6 ml kg−1, ±95% CI) to those in other deep-diving toothed whales. High diving metabolic rate and costly negative buoyancy imply a ‘spend more, gain more’ strategy of long-finned pilot whales, differing from that in other deep-diving toothed whales, which limits the costs of locomotion during foraging. We also found that net buoyancy affected the optimal speed: high transit speeds gradually decreased during ascent as the whales approached neutral buoyancy owing to gas expansion.Publisher PDFPeer reviewe