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The Kir4.1 channel, an inwardly rectifying potassium ion (K+) channel, is located in the hair cells of the organ of Corti as well as the intermediate cells of the stria vascularis. The Kir4.1 channel has a crucial role in the generation of endolymphatic potential and maintenance of the resting membrane potential. However, the role and functions of the Kir4.1 channel in the progenitor remain undescribed. To observe the role of Kir4.1 in the progenitor treated with the one-shot ototoxic drugs (kanamycin and furosemide), we set the proper condition in culturing Immortomouse-derived HEI-OC1 cells to express the potassium-related channels well. And also, that was reproduced in mice experiments to show the important role of Kir4.1 in the survival of hair cells after treating the ototoxicity drugs. In our results, when kanamycin and furosemide drugs were cotreated with HEI-OC1 cells, the Kir4.1 channel did not change, but the expression levels of the NKCC1 cotransporter and KCNQ4 channel are decreased. This shows that inward and outward channels were blocked by the two drugs (kanamycin and furosemide). However, noteworthy here is that the expression level of Kir4.1 channel increased when kanamycin was treated alone. This shows that Kir4.1, an inwardly rectifying potassium channel, acts as an outward channel in place of the corresponding channel when the KCNQ4 channel, an outward channel, is blocked. These results suggest that the Kir4.1 channel has a role in maintaining K+ homeostasis in supporting cells, with K+ concentration compensator when the NKCC1 cotransporter and Kv7.4 (KCNQ4) channels are deficient. [ABSTRACT FROM AUTHOR]

Simple Summary: CTHRC1 is a protein with pro-tumoral effects that is highly expressed in tumors. We found that cancer stroma is the major source of CTHRC1 secretion in pancreatic cancer, and CTHRC1 regulates cancer extracellular matrix (ECM) remodeling by activating pancreatic stellate cells (PSCs), a main component of pancreatic cancer stroma. Our results show that CTHRC1-activated PSCs differentiated into myofibroblast-like CAFs (myCAFs). Moreover, the pro-tumoral effects manifested by CTHRC1 were more potent through PSC activation than via autocrine action. Periostin, a stroma-specific molecule, demonstrated an essential role in the CTHRC1–PSCs–cancer metastasis axis. Blocking CTHRC1 reversed PSC activation in vitro and showed significant anti-tumoral effects in animal models. However, long-term CTHRC1 treatment likely caused a shift from myCAFs into inflammatory CAFs. This study elucidates PSC activation as the central mechanism underlying the pro-tumoral effects of CTHRC1 and suggests that future studies on CTHRC1 as a potential therapeutic target for pancreatic cancer are warranted. [BACKGROUND] Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein that contributes to the progression of various cancers, including pancreatic cancer. The higher expression of CTHRC1 in tumor tissues is associated with poorer survival outcomes. However, its specific roles in tumor extracellular matrix (ECM) remodeling remain unclear. Our study aims to investigate the influences of CTHRC1 on pancreatic stellate cells (PSCs), a main source of ECM production in pancreatic cancer. [METHODS AND RESULTS] The analyses of the publicly available pancreatic cancer patient data revealed that CTHRC1 is mainly expressed in cancer stroma and highly correlated with ECM-related genes. An in vitro study showed that more than 40% of these genes can be upregulated by CTHRC1. CTHRC1 specifically activated PSC into myofibroblast-like cancer-associated fibroblasts (myCAFs), which are characterized by a significantly upregulated POSTN gene expression. Periostin (coded by the POSTN gene) has a central role in the CTHRC1–PSCs–cancer metastasis axis. Furthermore, CTHRC1 promoted pancreatic cancer cell proliferation through PSC activation to a greater extent than via direct stimulation. Proof-of-concept experiments showed that the long-term (4-week) inhibition of CTHRC1 led to significant tumor suppression and ECM reduction, and also resulted in an unexpected shift in the CAF subtype from myCAFs to inflammatory CAFs (iCAFs). [CONCLUSION] PSC activation was demonstrated to be the key molecular mechanism responsible for the tumor-promoting effects of CTHRC1, and CTHRC1 has a critical role in CAF subtype differentiation and tumor microenvironment (TME) remodeling. The inhibition of CTHRC1 as a therapeutic strategy for the treatment of pancreatic cancer warrants further investigation. [ABSTRACT FROM AUTHOR]

Collaboration among physicians and nurses is vital and has shown to lead to better patient care and improve outcomes. Our study surveyed two groups of Labor and Delivery nurses in two regionally similar community hospitals in midwestern United States: one group from a new Obstetrics and Gynecology (OB/GYN) residency program (n = 49) and another from an established (legacy) OB/GYN residency program (n = 49). The survey asked nurses from the hospital with new and legacy residency program about preparedness for working with residents, perceptions of nurse‐resident‐patient relationships, collaboration and opinions about how resident physicians impact patient safety. Most nurses from the legacy residency program showed positive perceptions of collaboration with the residency and institutional support. In the new OB/GYN residency program, nurses were generally neutral and showed skepticism about collaboration with OB/GYN resident physicians and institutional support. Nurses from both hospitals felt similarly in their comfort escalating issues to administration and in their satisfaction with interprofessional collaboration within Labor and Delivery units. Providing nurses with opportunities to learn about the role of new medical residents in their patient care setting as well as intentional collaboration between nursing and residency program administration might result in more effective collaboration between physician residents and nursing staff. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to apply the yes/no Angoff and Hofstee methods to actual Korean Medical Licensing Examination (KMLE) 2022 written examination data to estimate cut scores for the written KMLE. Methods: Fourteen panelists gathered to derive the cut score of the 86th KMLE written examination data using the yes/no Angoff method. The panel reviewed the items individually before the meeting and shared their respective understanding of the minimum-compatibility physician. The standard setting process was conducted in 5 rounds over a total of 800 minutes. In addition, 2 rounds of the Hofstee method were conducted before starting the standard setting process and after the second round of yes/no Angoff. Results: For yes/no Angoff, as each round progressed, the panel's opinion gradually converged to a cut score of 198 points, and the final passing rate was 95.1%. The Hofstee cut score was 208 points out of a maximum 320 with a passing rate of 92.1% at the first round. It scored 204 points with a passing rate of 93.3% in the second round. Conclusion: The difference between the cut scores obtained through yes/no Angoff and Hofstee methods did not exceed 2% points, and they were within the range of cut scores from previous studies. In both methods, the difference between the panelists decreased as rounds were repeated. Overall, our findings suggest the acceptability of cut scores and the possibility of independent use of both methods. [ABSTRACT FROM AUTHOR]

Background: Ledipasvir/sofosbuvir increases tenofovir plasma exposures by up to 98% with tenofovir disoproxil fumarate (TDF), and exposures are highest with boosted PIs. There are currently no data on the combined use of the newer tenofovir prodrug, tenofovir alafenamide (TAF), boosted PIs and ledipasvir/sofosbuvir.Objectives: To compare the plasma and intracellular pharmacokinetics and renal safety of TAF with ledipasvir/sofosbuvir when co-administered with boosted PIs.Methods: Persons with HIV between 18 and 70 years and on a boosted PI with TDF were eligible. The study was comprised of four phases: (1) TDF 300 mg with boosted PI; (2) TAF 25 mg with boosted PI; (3) TAF 25 mg with boosted PI and ledipasvir/sofosbuvir; and (4) TAF 25 mg with boosted PI. Pharmacokinetic sampling, urine biomarker collection [urine protein (UPCR), retinol binding protein (RBP) and β2 microglobulin (β2M) normalized to creatinine] and safety assessments occurred at the end of each phase. Plasma, PBMCs and dried blood spots were collected at each visit.Results: Ten participants were enrolled. Plasma tenofovir exposures were 76% lower and tenofovir-diphosphate (TFV-DP) concentrations in PBMCs increased 9.9-fold following the switch to TAF. Neither of these measures significantly increased with ledipasvir/sofosbuvir co-administration, nor did TAF plasma concentrations. No significant changes in estimated glomerular filtration rate or UPCR occurred, but RBP:creatinine and β2M:creatinine improved following the switch to TAF.Conclusions: Ledipasvir/sofosbuvir did not significantly increase plasma tenofovir or intracellular TFV-DP in PBMCs with TAF. These findings provide reassurance that the combination of TAF, boosted PIs and ledipasvir/sofosbuvir is safe in HIV/HCV-coinfected populations. [ABSTRACT FROM AUTHOR]

Objectives: Coronavirus Disease-19 (COVID-19) is a respiratory infection characterized by the main symptoms of pneumonia and fever. It is caused by the novel coronavirus severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), which is known to spread via respiratory droplets. We aimed to determine the rate and likelihood of SARS-CoV-2 transmission from COVID-19 patients through nonrespiratory routes. Methods: Serum, urine, and stool samples were collected from 74 hospitalized patients diagnosed with COVID-19 based on the detection of SARS-CoV-2 in respiratory samples. The SARS-CoV-2 RNA genome was extracted from each specimen and real-time reverse transcription polymerase chain reaction performed. CaCo-2 cells were inoculated with the specimens containing the SARS-COV-2 genome, and subcultured for virus isolation. After culturing, viral replication in the cell supernatant was assessed. Results: Of the samples collected from 74 COVID-19 patients, SARS-CoV-2 was detected in 15 serum, urine, or stool samples. The virus detection rate in the serum, urine, and stool samples were 2.8% (9/323), 0.8% (2/247), and 10.1% (13/129), and the mean viral load was 1,210 ± 1,861, 79 ± 30, and 3,176 ± 7,208 copy/µL, respectively. However, the SARS-CoV-2 was not isolated by the culture method from the samples that tested positive for the SARS-CoV-2 gene. Conclusion: While the virus remained detectable in the respiratory samples of COVID-19 patients for several days after hospitalization, its detection in the serum, urine, and stool samples was intermittent. Since the virus could not be isolated from the SARS-COV-2-positive samples, the risk of viral transmission via stool and urine is expected to be low. [ABSTRACT FROM AUTHOR]

Objectives: To investigate registered nurses' awareness and implementation of oral health care in patients who are hospitalized in general wards or intensive care units (ICUs) in South Korea. Methods: This research was performed as a descriptive survey of 149 nurses working in nine general hospitals with at least 100 beds in major Korean cities. Results: Approximately half (40.9%) of the survey respondents reported providing oral health care for hospitalized patients but that relevant protocols were not available at most hospitals or wards (89.5%). Nurses working in an ICU were significantly more likely to provide oral health care than those working in general wards (83.9% vs 15.1%; P < .001). Most respondents (83.2%) were aware of the importance of providing oral health care for hospitalized patients; however, the proportion considering that such care should be provided by dental hygienists was greater than that considering it should be provided by nurses (36.4% vs 26.0%; P < .001). Agreement that oral health care should be provided for hospitalized patients by dental hygienists was highest in nurses working in ICUs (53.3%; P < .001). Conclusions: According to this survey, oral healthcare provision is generally low in hospitalized patients and differs between ICUs and general wards. Most respondents considered that dental hygienists should provide oral health care for hospitalized patients. There is an opportunity for nurses and dental hygienists to work collaboratively towards development of an evidence‐based protocol for oral health care in hospitalized patients. [ABSTRACT FROM AUTHOR]

Two new polyketides, 3,11-dihydroxy-6,8-dimethyldodecanoic acid (1) and trichopyrone B (2), together with two known polyketides, sorbicillin (3) and penicillone A (4), have been isolated from the cultures broth of the fungus Penicillium decumbens. Their structures were elucidated by extensive spectroscopic analysis. All isolated compounds were evaluated for their antibacterial and cytotoxic activities. Of these, compound 3 showed antifungal activity toward Candida albicans Y0109 with a MIC value of 50 μM. Moreover, compounds 3 and 4 exhibited selective cytotoxicity against the human hepatocellular carcinoma (QGY-7703) cell line with the IC50 values of 32.5 and 22.8 μM, respectively. [ABSTRACT FROM AUTHOR]

Background/Aims: The aim of this research was to investigate muscle activation in the lower limbs and trunk during five functional exercises: forward lunge, rotational lunge, anterior direction one-legged standing exercise, posteriomedial direction one-legged standing exercise, and posteriolateral onelegged standing exercise in subjects with chronic ankle instability. Methods: Twenty-four subjects (10 males and 14 females) with chronic ankle instability participated in this study. Surface electromyography was used to measure the muscle activities of the peroneus longus, lateral head of the gastrocnemius, gluteus medius, and erector spinae. Normalised muscle activities are presented as percentage of MVIC (%MVIC). One-way repeated measures analysis of variance was used at a significance level of p<0.05. Findings: The peroneus longus and the lateral head of the gastrocnemius muscle activities significantly higher in anterior direction one-legged standing exercise than in the other exercises (forward lunge: p=0.005; rotational lunge: p=0.006; posteriomedial direction one-legged standing exercise: p=0.007; posteriolateral one-legged standing exercise: p=0.008; forward lunge, rotational lunge, posteriomedial direction one-legged standing exercise, posteriolateral one-legged standing exercise: p<0.001, respectively). The muscle activity of gluteus medius significantly lower in rotational lunge than in the other exercises (forward lunge: p=0.001, one-legged standing: p<0.001). Among the one-legged standing exercises, the muscle activity of the gluteus medius was lowest in the anterior direction onelegged standing exercise. The muscle activity of the erector spinae was significantly lower in the forward lunge and anterior direction one-legged standing exercise than in the other exercises (posteriomedial direction one-legged standing exercise and posteriolateral one-legged standing exercise: p<0.001). Conclusions: The anterior direction one-legged standing exercise, which activates the peroneus longus and the lateral head of the gastrocnemius muscle and reduces other muscles' activation proximally, would be an effective exercise to activate ankle muscles in the rehabilitation of people with chronic ankle instability. [ABSTRACT FROM AUTHOR]

BACKGROUND: Push-up plus exercise is applied to scapular winging to selectively activate serratus anterior (SA). OBJECTIVES: To compare muscle activity, muscle activity ratios, and the degrees of rotation of the thoracic and lumbar spine during a modified push-up plus exercise. METHODS: In total, 20 subjects with scapular winging participated. Subjects performed the knee push-up plus with ipsilateral leg extension (KPP-ILE) and the standard push-up plus with ipsilateral leg extension (SPP-ILE) exercises. During the SPPILE and KPP-ILE, SA, pectoralis major (PM), ipsilateral external oblique (ipsiEO), and contralateral external oblique (contEO) muscle activities, the SA/PM and ipsiEO/contEO ratios were assessed and the degree of rotation of the thoracic and lumbar spine were assessed. RESULTS: Muscle activities of SA, PM, ipsiEO, contEO, and SA/PM ratio were significantly higher during SPP-ILE than KPP-ILE. The ipsiEO/contEO ratio decreased more significantly during SPP-ILE versus KPP-ILE. Thoracic and lumbar rotation values were significantly lower in SPP-ILE. CONCLUSIONS: The SPP-ILE may be a useful exercise for subjects with scapular winging because of the increased SA/PM ratio, the diminished compensatory rotation through increased scapular stabilization muscle activity and co-contraction of the abdominal trunk-stabilizing muscles. [ABSTRACT FROM AUTHOR]

Three new minor valepotriate isomers, jatamanvaltrates Z1 (1), Z2 (2), and Z3 (3), have been isolated from the whole plants ofValeriana jatamansi(syn.Valeriana wallichii.). Their structures were elucidated by extensive spectroscopic analysis, especially 2D NMR and ESI-MS/MSn. All isolated compounds displayed moderate cytotoxicity against the lung adenocarcinoma (A549), metastatic prostate cancer (PC-3 M), colon cancer (HCT-8), and hepatoma (Bel7402) cell lines with IC50values of 2.8–8.3 μM. [ABSTRACT FROM PUBLISHER]

Mothers with a history of child sexual abuse report less warmth toward their children, but whether this association differs by child gender is unknown. We examined the association of maternal child sexual abuse and warmth across child gender, accounting for depression, post-traumatic stress disorder, and child physical abuse. We verbally administered self-report measures to a cross-sectional sample of 154 mothers with a child between 8 and 12 years old. Eighty-five mothers based warmth responses on a son, and 69 on a daughter. We conducted a hierarchical multiple regression, including child gender, maternal child sexual abuse, child physical abuse, depression, post-traumatic stress disorder, and 4 two-way interaction terms with child gender. Maternal depression predicted decreased warmth, regardless of child gender, and maternal child sexual abuse predicted decreased warmth, but only toward daughters. Given previous research suggesting that maternal warmth predicts child well-being, the current finding may represent an important avenue of intergenerational transmission of risk in girls. [ABSTRACT FROM PUBLISHER]

Three new decomposition products of valepotriates, valtrals A–C (1–3), and two known products, baldrinal and homobaldrinal, are formed during the isolation procedure of the ethanol extract of the whole plants ofValeriana jatamansi. Their structures were determined by spectroscopic methods including IR, MS, 1D, and 2D NMR experiments. Compounds1–3showed selective cytotoxicity against metastatic prostate cancer (PC-3M) and colon cancer (HCT-8) cell lines. [ABSTRACT FROM PUBLISHER]

Aim Reaction times of the hip abductor were reported to be longer in elderly women than in elderly men, and this was suggested to be related to mediolateral balance performance. The aim of the present study was to investigate the effects of age and gender on the reaction performance of ankle muscles, which have predominant roles in anterioposterior balance control. Methods A total of 40 elderly subjects and 40 young subjects (even number of men and women) carried out a series of isometric plantarflexions and dorsiflexions, as forcefully and quickly as possible, in response to auditory stimulus. Surface electromyogram at the dorsiflexor and plantarflexor were recorded, together with foot plantar force. Premotor time, motor time and total reaction time derived from the experimental data were compared between age groups and genders by two-way anova. Results Both dorsiflexor and plantarflexor showed similar reaction performance. Premotor time increased with age with no gender difference. Motor time increased with age in women and not in men, resulting in longer motor time in elderly women than in elderly men. Total reaction time was dominated by premotor time, so that it was longer in the elderly with no gender difference. Conclusion Although age-related elongation of motor time was greater in women, total reaction time was not different between the genders. This may be related to no gender difference in anterioposterior balance performance. Geriatr Gerontol Int 2014; 14: 94-99. [ABSTRACT FROM AUTHOR]

Though primo vessels are frequently found in the lymph near the abdominal aorta of rabbit by Alcian blue dye, the reproductions are still difficult to require considerable skills and technical know-how at dissected tissue of animal species. However, in the inguinal lymph node of a rabbit we found a long-type primo vascular system (LTP) dyed with Alcian blue, from an abdominal lymph vessel to an inguinal lymph node. The length of LTP was over an average length of 9.1 cm. The average diameters of the primo and the lymph vessels were about 23.9 Μm and 242 Μm, respectively. The primo vessels were not floating but adhered to lymph vessels with fascial connective tissue. These primo vessels might be a functional integration in the lymph system. [ABSTRACT FROM AUTHOR]

Background To describe the characteristics of a population with high-risk sexual behaviours and associations between sexual intercourse, high-risk sexual behaviours and socio-demographic characteristics among Chinese urban adolescents. Methods In 2005, 109 754 students in grades 10-12 and 33 653 college students were anonymously surveyed using a Chinese Youth Risk Behaviour Survey. Demographic variables and indicators of forced sex, condom use and unintended pregnancy were analysed with multiple logistic regressions. Results Of students surveyed, median age was 17.6 (range 14-24 years) and 76 233 were female (53.2%); 4.8% of high school students reported had experienced sexual intercourse; of these, 32.8% reported had forced sex; 11.3% of college students reported had experienced sexual intercourse and of these, the prevalence of forced sex, condom use and unintended pregnancy were 23.5, 49.7 and 24.2%, respectively. School type and socioeconomic status were found to be independently associated with sexual intercourse and forced sex for high school students. For college students, educational level, school type, family structure, maternal education and socioeconomic status were independently associated with high-risk sexual behaviours. Conclusion This study highlights the association between high-risk sexual behaviours and school type and socioeconomic status. These results strongly suggest the importance of providing sex education in high schools and lower socioeconomic areas. [ABSTRACT FROM AUTHOR]