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ObjectivesTo evaluate the impact of bowel resection at the time of interval cytoreductive surgery on survival.MethodsWe identified patients with advanced ovarian cancer who underwent neoadjuvant chemotherapy and interval cytoreductive surgery between 2008 and 2018 from a single-institution tumor registry. Kaplan-Meier survival analysis and Cox proportional hazards models were performed comparing patients who underwent bowel resection to those who did not.ResultsOf 158 patients, 43 (27%) underwent bowel resection. Rates of optimal (95%) and sub-optimal (5%) resection did not differ with bowel resection. Patients that required bowel resection had worse three-year survival (43% vs. 63%), even after adjusting for confounding variables of age, stage, number of neoadjuvant cycles, R0 resection, and ASA score (HR 2.27, p

BackgroundLoneliness and social isolation are significant public health problems that are being exacerbated during the coronavirus disease 2019 pandemic. Little is known about the associations between loneliness and symptom burden in oncology patients before and during the pandemic. Study purposes include determining the prevalence of loneliness in a sample of oncology patients; evaluating for differences in demographic, clinical, and symptom characteristics between lonely and nonlonely patients; and determining which demographic, clinical, and symptom characteristics were associated with membership in the lonely group.MethodsA convenience sample (n = 606) completed online surveys that evaluated the severity of loneliness, social isolation, and common symptoms (ie, anxiety, depression, fatigue, sleep disturbance, cognitive dysfunction, and pain) in oncology patients. Parametric and nonparametric tests were used to evaluate for differences in scores between the lonely and nonlonely groups. Logistic regression analysis was used to determine risk factors for membership in the loneliness group.ResultsOf the 606 patients, 53.0% were categorized in the lonely group. The lonely group reported higher levels of social isolation, as well as higher symptom severity scores for all of the symptoms evaluated. In the multivariate model, being unmarried, having higher levels of social isolation, as well as higher levels of anxiety and depressive symptoms were associated with membership in the lonely group.ConclusionsStudy findings suggest that a significant number of oncology patients are experiencing loneliness, most likely as a result of mandate social distancing and isolation procedures. The symptom burden of these patients is extremely high and warrants clinical evaluation and interventions.

Abstract Background The number of emergency department (ED) visits has significantly declined since the COVID-19 pandemic. In Taiwan, an aged society, it is unknown whether older adults are accessing emergency care during the COVID-19 epidemic. Therefore, this study aimed to investigate the impact of COVID-19 on the ED visits and triage, admission, and intensive care unit (ICU) hospitalization of the geriatric population in a COVID-19-dedicated medical center throughout various periods of the epidemic. Methods A retrospective chart review of ED medical records from April 9 to August 31, 2021 were conducted, and demographic information was obtained from the hospital’s computer database. The period was divided into pre-, early-, peak-, late-, and post-epidemic stages. For statistical analysis, one-way analysis of variance followed by multiple comparison tests (Bonferroni correction) were used. Results A statistically significant decrease in the total number of patients attending the ED was noted during the peak-, late-, and post-epidemic stages. In the post-epidemic stage, the number of older patients visiting ED was nearly to that of the pre-epidemic stage, indicating that older adults tend to seek care at the ED earlier than the general population. Throughout the entire epidemic period, there was no statistically significant reduction in the number of the triage 1& 2 patients seeking medical attention at the emergency department. In the entire duration of the epidemic, there was no observed reduction in the admission of elderly patients to our hospital or ICU through the ED. However, a statistically significant decrease was observed in the admission of the general population during the peak epidemic stage. Conclusions During the peak of COVID-19 outbreak, the number of ED visits was significantly affected. However, it is noteworthy that as the epidemic was gradually controlled, the older patients resumed their ED visits earlier that the general population as indicated by the surge in their number. Additionally, in the patient group of triage 1& 2, which represents a true emergency, the number did not show a drastic change.

Abstract Background Adherence to ethical guidelines and regulations and protecting and respecting the dignity and autonomy of participants by obtaining a valid informed consent form (ICF) prior to participation in research are crucial; The subjects did not add signatures next to the corrections made to signatures or dates on the ICF, Multiple signatures in other fields, ICF missing/missing signature, Incorrect ICF version Signed after modification, Correction tape used to correct signature, Impersonated signature, Non-research-member signature, however, ICFs are often not properly completed, which must be addressed. This study analyzed ICF signing errors and implemented measures to reduce or prevent these errors. Methods We used the plan–do–check–act (PDCA) cycle to help improve the correctness and validity of ICF signing. Results Interim and final reports from January 2016 to February 2020 including 363 ICFs were studied. The total proportion of correct ICF signatures (200, 83.3%) following the PDCA intervention was significantly higher than that before the intervention (P

Abstract Dysregulating cellular metabolism is one of the emerging cancer hallmarks. Mitochondria are essential organelles responsible for numerous physiologic processes, such as energy production, cellular metabolism, apoptosis, and calcium and redox homeostasis. Although the “Warburg effect,” in which cancer cells prefer aerobic glycolysis even under normal oxygen circumstances, was proposed a century ago, how mitochondrial dysfunction contributes to cancer progression is still unclear. This review discusses recent progress in the alterations of mitochondrial DNA (mtDNA) and mitochondrial dynamics in cancer malignant progression. Moreover, we integrate the possible regulatory mechanism of mitochondrial dysfunction–mediated mitochondrial retrograde signaling pathways, including mitochondrion-derived molecules (reactive oxygen species, calcium, oncometabolites, and mtDNA) and mitochondrial stress response pathways (mitochondrial unfolded protein response and integrated stress response) in cancer progression and provide the possible therapeutic targets. Furthermore, we discuss recent findings on the role of mitochondria in the immune regulatory function of immune cells and reveal the impact of the tumor microenvironment and metabolism remodeling on cancer immunity. Targeting the mitochondria and metabolism might improve cancer immunotherapy. These findings suggest that targeting mitochondrial retrograde signaling in cancer malignancy and modulating metabolism and mitochondria in cancer immunity might be promising treatment strategies for cancer patients and provide precise and personalized medicine against cancer.

Abstract Dendrometer bands have been proposed as an accurate method for measuring tree growth. However, the constrained observation window and the material used in them hamper long-term tree growth monitoring. This study devised a dendrometer band made from stainless steel and primarily extended the extension length of the band spring to yield ample space to monitor diameter increments long-term. A total of more than 500 individual trees, including both coniferous and broadleaf trees, were examined. We compared the dendrometer band’s long-term performance with diameter tape for 5- and 10-year measurements. The results showed that the measurements of the two methods were highly correlated (R > 0.89) in both measuring periods. Differences between the two measurements for individual trees were typically less than 5 mm, and the mean differences at a stand level were less than 2 mm. These consistent observations suggested that the dendrometer band measurements were reliable for long-term measurement. Using the dendrometer bands, we further demonstrated the annual tree growths of diameter at breast height (DBH) and basal area (BA) for ten years of measurements. The size-dependent relationships between DBH/BA growth and initial DBH were also presented. Owing to their simple installation, low cost, and reliable measurement, these dendrometer bands would be helpful in forestry and forest ecology research.

Abstract Background Taiwanese patients frequently experience severe hepatotoxicity associated with high‐dose methotrexate (HD‐MTX) treatment, which interferes with subsequent treatment. Drug–drug interactions occur when MTX is used in combination with proton pump inhibitors (PPIs), trimethoprim‐sulfamethoxazole (TMP‐SMX), or non‐steroidal anti‐inflammatory drugs (NSAIDs). In East Asia, real‐world analyses on the effects of co‐medication and other potential risk factors on the clinical course of HD‐MTX‐mediated acute hepatotoxicity in patients with osteogenic sarcoma (OGS) are limited. Methods This cohort study included patients with newly diagnosed OGS who were treated with HD‐MTX between 2009 and 2017 at Taipei Veterans General Hospital. We collected data on the clinical course of HD‐MTX‐mediated acute hepatotoxicity, co‐medications, and other potential risk factors, and analyzed the effects of these factors on the clinical course of HD‐MTX‐mediated acute hepatotoxicity. Results Almost all patients with OGS treated with HD‐MTX developed acute hepatotoxicity with elevated alanine aminotransferase (ALT) levels. Most patients with Grade 3–4 ALT elevation failed to recover to Grade 2 within 7 days. Women and children are high‐risk subgroups for HD‐MTX‐mediated elevation of ALT levels. Age is a factor that contributes to the pharmacokinetic differences of HD‐MTX. However, the concurrent use of PPIs, TMP‐SMX, or NSAIDs did not affect the elimination of MTX when administered with adequate supportive therapy. Conclusions Co‐administration of PPIs, TMP‐SMX, or NSAIDs may have limited effects on acute hepatotoxicity in well‐monitored and adequately pre‐medicated patients with OGS undergoing chemotherapy with HD‐MTX. Clinicians should pay particular attention to ALT levels when prescribing HD‐MTX to children and women.

Background: The turnover rate of nurse aides in Taiwan is high. However, the predictors of turnover behavior in the newly employed are still unclear. Objective: To examine the predictors of turnover behavior in newly employed licensed nurse aides. Methods: A longitudinal study design was used and subjects were newly employed certified nurse aides from a nurse aid training association in Taiwan. A total of five questionnaire surveys were conducted. The questionnaire was mainly used to collect information on turnover behavior, personal socioeconomic background, workplace psychosocial hazards, worker health hazards, and musculoskeletal disorders. Results: A total of 300 participants were recruited in the study. Cox regression analysis results showed that short working experience (hazard ratio [HR] = 0.21, p

Objectives The majority of female immigrants who are married in Taiwan often face a variety of stresses, which may lead to physical or mental illness. Yet few studies have validated the impact of length of residency on physical and mental health using large-scale data. This study combined five nationwide databases and explored the impact of length of residency in Taiwan on the physical and mental health of female marriage immigrants.Design This is a retrospective cohort study.Setting Taiwan.Participants A total of 168 202 female immigrants, who were registered in the national health insurance database from 2001 to 2017, were enrolled for analysis.Measure The length of residency was taken as the period from their first appearance in the national health insurance database to the end of 2017. Hypertension and diabetes were chosen as indices of physical health and depression as an index of mental health. Diagnosis standards were based on the International Classification of Disease, ninth or 10th Revision.Results The physical and mental health of the immigrants deteriorated with increasing time of residence in Taiwan. Immigrants who had resided in Taiwan for 5–10 years or ≥10 years, respectively, had a 5.8-fold (95% CI: 3.46 to 9.74) or 6.29-fold (95% CI: 4.61 to 8.59) higher adjusted risk of developing hypertension; a 3.97-fold (95% CI: 2.54 to 6.21) or 9.18-fold (95% CI: 5.48 to 15.38) higher adjusted risk of developing diabetes; and a 5.01-fold (95% CI: 3.14 to 8.01) or 12.19-fold (95% CI: 8.65 to 17.18) higher adjusted risk of developing depression than their counterparts who had lived in Taiwan for ≤5 years.Conclusion These findings suggest the time elapsed since migration can be a factor in the deterioration of both physical and mental health among female marriage immigrants in Taiwan.

Objective To demonstrate that acupuncture is beneficial for decreasing the risk of ischaemic stroke in patients with rheumatoid arthritis (RA).Design A propensity score-matched cohort study.Setting A nationwide population-based study.Participants Patients with RA diagnosed between 1 January 1997 and 31 December 2010, through the National Health Insurance Research Database in Taiwan.Interventions Patients who were administered acupuncture therapy from the initial date of RA diagnosis to 31 December 2010 were included in the acupuncture cohort. Patients who did not receive acupuncture treatment during the same time interval constituted the no-acupuncture cohort.Primary outcome measures A Cox regression model was used to adjust for age, sex, comorbidities, and types of drugs used. We compared the subhazard ratios (SHRs) of ischaemic stroke between these two cohorts through competing-risks regression models.Results After 1:1 propensity score matching, a total of 23 226 patients with newly diagnosed RA were equally subgrouped into acupuncture cohort or no-acupuncture cohort according to their use of acupuncture. The basic characteristics of these patients were similar. A lower cumulative incidence of ischaemic stroke was found in the acupuncture cohort (log-rank test, p

[This corrects the article DOI: 10.1371/journal.pone.0239703.].

Background. The COVID-19 pandemic has caused major impacts in various aspects of our life. In Malaysia, a Movement Control Order was imposed in March 2020. For almost two years, school going children and adolescents were not able to attend school physically, and their physical activity was confined within their room or house on most days. Case Description. We describe a case of a 14-year-old boy who was previously active in sports and sustained a low trauma fracture at the right neck of the femur following a prolonged period of extreme sedentary life along with poor dietary intake during the COVID-19 pandemic period. He underwent open reduction and screw fixation for the right neck femur fracture. He was thin with a low BMI (15.62 kg/m2) and a significant loss of muscle bulk in all limbs. Laboratory tests showed vitamin D deficiency (15.3 nmol/L) and the dual energy X-ray absorptiometry (DXA) showed a low Z-score for the total spine (−2.2) and total hip (−3.9). He was treated with activated vitamin D and vitamin D3 replacement. Sports physician was involved for individualized postoperative rehabilitation. Successive clinic visits showed remarkable improvements in physical fitness, sports participation, and normalization of vitamin D levels. Conclusion. A high degree of suspicion is needed to rule out secondary causes in adolescents who present with unusual fragility fractures.

We investigated the anti-EMT and antifibrotic effects of coenzyme Q0 (CoQ0), a quinone derivative from Antrodia camphorata, in TGF-β-stimulated adult retinal pigment epithelial 19 (ARPE-19) cells. Results showed that CoQ0 treatment reversed TGF-β-stimulated morphological changes from an epithelial to a fibroblastic phenotype in ARPE-19 cells. CoQ0 exhibited anti-EMT effects by impeding TGF-β-stimulated migration and invasion in ARPE-19 cells. Notably, CoQ0 triggered the epithelial marker E-cadherin and suppressed the mesenchymal marker N-cadherin expression in nonstimulated or TGF-β-stimulated ARPE-19 cells. Moreover, CoQ0 attenuated EMT and fibrotic Vimentin, MMP-9/-2, Slug, α-SMA, and VEGF expression in nonstimulated or TGF-β-stimulated ARPE-19 cells. Interestingly, CoQ0 inhibited TGF-β-induced intracellular ROS production by activating Nrf2 nuclear translocation and upregulating the HO-1, γ-GCLC, and NQO-1 enzymes in ARPE-19 cells. Moreover, Nrf2 silencing reversed TGF-β-induced ROS-mediated anti-EMT (E-cadherin/N-cadherin/Slug) and antifibrotic (α-SMA) effects in CoQ0-treated ARPE-19 cells. Therefore, CoQ0 could be utilized to treat age-related macular degeneration and proliferative vitreoretinopathy.

BackgroundEvidence-based perioperative analgesia is an important tactic for reducing patient exposure to opioids in the perioperative period and potentially preventing new persistent opioid use.Study designWe assessed the impact of a multifaceted optimal analgesia program implemented in the setting of a mature surgical pathway program at an academic medical center. Using existing multidisciplinary workgroups established for continuous process improvement in three surgical pathway areas ((colorectal, gynecology, and urologic oncology (cystectomy)), we developed an educational toolkit focused on implementation strategies for multimodal analgesia and non-pharmacologic approaches for managing pain with the goal of reducing opioid exposure in hospitalized patients. We analyzed prospectively collected data from pathway patients before dissemination of the toolkit (July 2016-June 2017; n = 869) and after (July 2017-June 2018; n = 838). We evaluated the association between program implementation and use of oral morphine equivalents (OME), average pain scores, time to first ambulation after surgery, urinary catheter duration, time to solid food after surgery, length of stay, discharge opioid prescriptions, and readmission.ResultsMultivariate regression demonstrated that the program was associated with significant decreases in intraoperative OME (14.5 ± 2.4 mEQ (milliequivalents) reduction; p < 0.0001), day before discharge OME (18 ± 6.5 mEQ reduction; p < 0.005), day of discharge OME (9.6 ± 3.28 mEQ reduction; p < 0.003), and discharge prescription OME (156 ± 22 mEq reduction; p < 0.001). Reduction in OME was associated with earlier resumption of solid food (0.58 ± 0.15 days reduction; p < 0.0002).ConclusionOur multifaceted optimal analgesia program to manage perioperative pain in the hospital was effective and further improved analgesia in the setting of a mature enhanced recovery program.

Abstract Soybean [Glycine max (L.) Merr.] is a globally important crop due to its valuable seed composition, versatile feed, food, and industrial end‐uses, and consistent genetic gain. Successful genetic gain in soybean has led to widespread adaptation and increased value for producers, processors, and consumers. Specific focus on the nutritional quality of soybean seed composition for food and feed has further elucidated genetic knowledge and bolstered breeding progress. Seed components are historical and current targets for soybean breeders seeking to improve nutritional quality of soybean. This article reviews genetic and genomic foundations for improvement of nutritionally important traits, such as protein and amino acids, oil and fatty acids, carbohydrates, and specific food‐grade considerations; discusses the application of advanced breeding technology such as CRISPR/Cas9 in creating seed composition variations; and provides future directions and breeding recommendations regarding soybean seed composition traits.

To identify the differentiating features in clinical presentation, management, and maternal/fetal outcome in complete hydatidiform mole and coexistent fetus compared with placental mesenchymal dysplasia. Between 1997 and 2015, five women with complete hydatidiform mole and coexistent fetus and four women with placental mesenchymal dysplasia were managed at the University of California San Francisco. Clinical features were analyzed and compared with previously published data. Of the five cases of complete hydatidiform mole and coexistent fetus, two had live births. β-hCG levels were > 200,000 IU/L in all cases. On imaging, a clear plane between the cystic component and the placenta favored a diagnosis of complete hydatidiform mole and coexistent fetus. None of the patients went on to develop gestational trophoblastic neoplasia (GTN), with a range of follow-up from 2 to 38 months. Combining this data with previously published work, the live birth rate in these cases was 38.8%, the rate of persistent GTN was 36.2%, and the rate of persistent GTN in patients with reported live births was 27%. Of the four cases of placental mesenchymal dysplasia, all four had live births. One patient developed HELLP syndrome and intrauterine growth restriction; the remaining three were asymptomatic. Maternal symptoms, fetal anomalies, β-hCG level, and placental growth pattern on imaging may help differentiate between complete hydatidiform mole and coexistent fetus and placental mesenchymal dysplasia. There was not an increased risk of gestational trophoblastic neoplasia in patients with complete hydatidiform mole and coexistent fetus who opted to continue with pregnancy.

ObjectiveTo evaluate correlations between rucaparib exposure and selected efficacy and safety endpoints in patients with recurrent ovarian carcinoma using pooled data from Study 10 and ARIEL2.MethodsEfficacy analyses were limited to patients with carcinomas harboring a deleterious BRCA1 or BRCA2 mutation who had received ≥2 prior lines of chemotherapy. Safety was evaluated in all patients who received ≥1 rucaparib dose. Steady-state daily area under the concentration-time curve (AUCss) and maximum concentration (Cmax,ss) for rucaparib were calculated for each patient and averaged by actual dose received over time (AUCavg,ss and Cmax,avg,ss) using a previously developed population pharmacokinetic model.ResultsRucaparib exposure was dose-proportional and not associated with baseline patient weight. In the exposure-efficacy analyses (n = 121), AUCavg,ss was positively associated with independent radiology review-assessed RECIST response in the subgroup of patients with platinum-sensitive recurrent disease (n = 75, p = 0.017). In the exposure-safety analyses (n = 393, 40 mg once daily to 840 mg twice daily [BID] starting doses), most patients received a 600 mg BID rucaparib starting dose, with 27% and 21% receiving 1 or ≥2 dose reductions, respectively. Cmax,ss was significantly correlated with grade ≥2 serum creatinine increase, grade ≥3 alanine transaminase/aspartate transaminase increase, platelet decrease, fatigue/asthenia, and maximal hemoglobin decrease (p

ARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methylation predict response to rucaparib, similar to BRCA1/BRCA2 mutations. BRCA1 methylation loss may be a major cross-resistance mechanism to platinum and PARPi. Genomic scars associated with homologous recombination deficiency are irreversible, persisting even as platinum resistance develops, and therefore are predictive of rucaparib response only in platinum-sensitive disease. The RAS, AKT, and cell cycle pathways may be additional modulators of PARPi sensitivity.

PurposeNo information is available on cancer patients' knowledge of and experiences with COVID-19. We undertook an evaluation of differences in COVID-19 symptom occurrence rates, COVID-19 testing rates, clinical care activities, knowledge of COVID-19, and use of mitigation procedures between patients who were and were not receiving active cancer treatment.MethodsPatients enrolled were > 18 years of age; had a diagnosis of cancer; and were able to complete the emailed study survey online.ResultsOf the 174 patients who participated, 27.6% (n = 48) were receiving active treatment, 13.6% were unemployed because of COVID-19, 12.2% had been tested for COVID-19, and 0.6% had been hospitalized for COVID-19. Patients who were not on active treatment reported a higher mean number of COVID-19 symptoms (3.1 (± 4.2) versus 1.9 (± 2.6)), and patients who reported a higher number of COVID-19 symptoms were more likely to be tested. Over 55% of the patients were confident that their primary care provider could diagnose COVID-19, and the majority of the patients had high levels of adherence with the use of precautionary measures (e.g., social distancing, use of face coverings).ConclusionThe high level of COVID-19 symptoms and the significant overlap of COVID-19 and cancer-related symptoms pose challenges for clinicians who are assessing and triaging oncology patients for COVID-19 testing. For patients on active treatment, clinicians face challenges with how to assess and manage symptoms that, prior to COVID-19, would be ascribed to acute toxicities associated with cancer treatments or persistent symptoms in cancer survivors.

Abstract Rescuing patients with out-of-hospital cardiac arrest (OHCA), especially those with end-stage kidney disease (ESKD), is challenging. This study hypothesizes that OHCA patients with ESKD undergoing maintenance hemodialysis have (1) higher rates of return of spontaneous circulation (ROSC) during cardio-pulmonary resuscitation (CPR) and (2) lower rates of hyperkalemia and less severe acidosis than those without ESKD. OHCA patients who received CPR between 2011 and 2020 were dichotomized into ESKD and non-ESKD groups. The association of ESKD with “any” and “sustained” ROSC were examined using logistic regression analysis. Furthermore, the effect of ESKD on hospital outcomes for OHCA patients who survived to admission was evaluated using Kaplan–Meier analysis. ESKD patients without “any” ROSC displayed lower potassium and higher pH levels than non-ESKD patients. ESKD was positively associated with “any” ROSC (adjusted-OR: 4.82, 95% CI 2.70–5.16, P

Abstract Patients with dementia are at increased risks of adverse consequences associated with motor vehicle crash injury (MVCI). However, studies of the association for patients with young-onset dementia (YOD) are limited. Therefore, we aim to investigate whether YOD was associated with adverse outcomes after hospitalization for MVCI. In this retrospective cohort study, we identified 2052 MVCI patients with YOD (aged 40–64 years) between 2006 and 2015 and included 10 260 matched MVCI patients without YOD (matching ratio: 1:5) from Taiwan’s National Health Insurance Research Database and the Taiwan Police-Reported Traffic Accident Registry. We evaluated the intensive care unit (ICU) admission, organ failure, in-hospital and 30-day mortalities, length of hospital stay, and hospital costs. Compared with participants without dementia, patients with YOD had higher rates of ICU admission (34.31% vs. 20.89%) and respiratory failure (6.04% vs. 2.94%), with a covariate-adjusted odds ratio of 1.50 (95% CI 1.33–1.70) and 1.63 (95% CI 1.24–2.13), respectively. The patients also exhibited higher in-hospital mortality (4.73% vs. 3.12%) and 30-day mortality (5.12% vs. 3.34%) than their non-YOD counterparts, but the risk ratio was not significant after adjusting for transport mode. Moreover, the log means of hospital stay and cost were higher among patients with YOD (0.09 days; 95% CI 0.04–0.14 and NT$0.17; 95% CI 0.11–0.23, respectively). This cohort study determined that YOD may be adversely associated with hospital outcomes among MVCI patients. However, the association between YOD and mortality risk may depend on transport mode.

ObjectivesThis study aimed to report the proportion of women with a new diagnosis of cervical cancer recommended for curative hysterectomy as well as associated factors. We also report recommended treatments by stage and patterns of treatment initiation.DesignThis was an observational cohort study. Inperson surveys were followed by a phone call.SettingParticipants were recruited at the two public tertiary care referral hospitals in Kampala, Uganda.ParticipantsAdult women with a new diagnosis of cervical cancer were eligible: 332 were invited to participate, 268 met the criteria and enrolled, and 255 completed both surveys.Primary and secondary outcomes measuresThe primary outcome of interest was surgical candidacy; a secondary outcome was treatment initiation. Descriptive and multivariate statistical analyses examined the associations between predictors and outcomes. Sensitivity analyses were performed to examine outcomes in subgroups, including stage and availability of radiation.ResultsAmong 268 participants, 76% were diagnosed at an advanced stage (IIB-IVB). In total, 12% were recommended for hysterectomy. In adjusted analysis, living within 15 km of Kampala (OR 3.10, 95% CI 1.20 to 8.03) and prior screening (OR 2.89, 95% CI 1.22 to 6.83) were significantly associated with surgical candidacy. Radiotherapy availability was not significantly associated with treatment recommendations for early-stage disease (IA-IIA), but was associated with recommended treatment modality (chemoradiation vs primary chemotherapy) for locally advanced stage (IIB-IIIB). Most (67%) had started treatment. No demographic or health factor, treatment recommendation, or radiation availability was associated with treatment initiation. Among those recommended for hysterectomy, 55% underwent surgery. Among those who had initiated treatment, 82% started the modality that was recommended.ConclusionWomen presented to public referral centres in Kampala with mostly advanced-stage cervical cancer and few were recommended for surgery. Most were able to initiate treatment. Lack of access to radiation did not significantly increase the proportion of early-stage cancers recommended for hysterectomy.

Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome (ARDS), are characterized by uncontrolled inflammatory responses, neutrophil activation and infiltration, damage to the alveolar capillary membrane, and diffuse alveolar injury. Neutrophil extracellular traps (NETs), formed by activated neutrophils, contribute significantly to various inflammatory disorders and can lead to tissue damage and organ dysfunction. Corilagin, a compound found in Phyllanthus urinaria, possesses antioxidative and anti-inflammatory properties. In this study, we investigated the protective effects and underlying mechanisms of corilagin in hydrochloric acid (HCl)/lipopolysaccharide (LPS)-induced lung injury. Mice received intraperitoneal administration of corilagin (2.5, 5, or 10 mg/kg) or an equal volume of saline 30 min after intratracheal HCl/LPS administration. After 20 h, lung tissues were collected for analysis. Corilagin treatment significantly mitigated lung injury, as evidenced by reduced inflammatory cell infiltration, decreased production of proinflammatory cytokines, and alleviated oxidative stress. Furthermore, corilagin treatment suppressed neutrophil elastase expression, reduced NET formation, and inhibited the expression of ERK, p38, AKT, STAT3, and NOX2. Our findings suggest that corilagin inhibits NET formation and protects against HCl/LPS-induced ALI in mice by modulating the STAT3 and NOX2 signaling pathways.

Adrenal insufficiency encompasses a group of congenital and acquired disorders that lead to inadequate steroid production by the adrenal glands, mainly glucocorticoids, mineralocorticoids and androgens. These may be associated with other hormone deficiencies. Adrenal insufficiency may be primary, affecting the adrenal gland’s ability to produce cortisol directly; secondary, affecting the pituitary gland’s ability to produce adrenocorticotrophic hormone (ACTH); or tertiary, affecting corticotrophin-releasing hormone (CRH) production at the level of the hypothalamus. Congenital causes of adrenal insufficiency include the subtypes of Congenital Adrenal Hyperplasia, Adrenal Hypoplasia, genetic causes of Isolated ACTH deficiency or Combined Pituitary Hormone Deficiencies, usually caused by mutations in essential transcription factors. The most commonly inherited primary cause of adrenal insufficiency is Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency; with the classical form affecting 1 in 10,000 to 15,000 cases per year. Acquired causes of adrenal insufficiency can be subtyped into autoimmune (Addison’s Disease), traumatic (including haemorrhage or infarction), infective (e.g. Tuberculosis), infiltrative (e.g. neuroblastoma) and iatrogenic. Iatrogenic acquired causes include the use of prolonged exogenous steroids and post-surgical causes, such as the excision of a hypothalamic-pituitary tumour or adrenalectomy. Clinical features of adrenal insufficiency vary with age and with aetiology. They are often non-specific and may sometimes become apparent only in times of illness. Features range from those related to hypoglycaemia such as drowsiness, collapse, jitteriness, hypothermia and seizures. Features may also include signs of hypotension such as significant electrolyte imbalances and shock. Recognition of hypoglycaemia as a symptom of adrenal insufficiency is important to prevent treatable causes of sudden deaths. Cortisol has a key role in glucose homeostasis, particularly in the counter-regulatory mechanisms to prevent hypoglycaemia in times of biological stress. Affected neonates particularly appear susceptible to the compromise of these counter-regulatory mechanisms but it is recognised that affected older children and adults remain at risk of hypoglycaemia. In this review, we summarise the pathogenesis of hypoglycaemia in the context of adrenal insufficiency. We further explore the clinical features of hypoglycaemia based on different age groups and the burden of the disease, focusing on hypoglycaemic-related events in the various aetiologies of adrenal insufficiency. Finally, we sum up strategies from published literature for improved recognition and early prevention of hypoglycaemia in adrenal insufficiency, such as the use of continuous glucose monitoring or modifying glucocorticoid replacement.

BackgroundThe risk of mortality is relatively high among patients who visit the emergency department (ED), and stratifying patients at high risk can help improve medical care. This study aimed to create a machine-learning model that utilizes the standard 12-lead ECG to forecast acute mortality risk in ED patients.MethodsThe database included patients who visited the EDs and underwent standard 12-lead ECG between October 2007 and December 2017. A convolutional neural network (CNN) ECG model was developed to classify survival and mortality using 12-lead ECG tracings acquired from 345,593 ED patients. For machine learning model development, the patients were randomly divided into training, validation and testing datasets. The performance of the mortality risk prediction in this model was evaluated for various causes of death.ResultsPatients who visited the ED and underwent one or more ECG examinations experienced a high incidence of 30-day mortality [18,734 (5.42%)]. The developed CNN model demonstrated high accuracy in predicting acute mortality (hazard ratio 8.50, 95% confidence interval 8.20–8.80) with areas under the receiver operating characteristic (ROC) curve of 0.84 for the 30-day mortality risk prediction models. This CNN model also demonstrated good performance in predicting one-year mortality (hazard ratio 3.34, 95% confidence interval 3.30–3.39). This model exhibited good predictive performance for 30-day mortality not only for cardiovascular diseases but also across various diseases.ConclusionsThe machine learning-based ECG model utilizing CNN screens the risks for 30-day mortality. This model can complement traditional early warning scoring indexes as a useful screening tool for mortality prediction.

Pain within the trigeminal system, particularly dental pain, is poorly understood. This study aimed to determine whether single or multiple dental pulp injuries induce persistent pain, its association with trigeminal central nociceptive pathways and whether electroacupuncture (EA) provides prolonged analgesic and neuroprotective effects in a persistent dental pain model. Models of single dental pulp injury (SDPI) and multiple dental pulp injuries (MDPI) were used to induce trigeminal neuropathic pain. The signs of dental pain-related behavior were assessed using the mechanical head withdrawal threshold (HWT). Immunofluorescence and western blot protocols were used to monitor astrocyte activation, changes in apoptosis-related proteins, and GABAergic interneuron plasticity. SDPI mice exhibited an initial marked decrease in HWT from days one to 14, followed by progressive recovery from days 21 to 42. From days 49 to 70, the HWT increased and returned to the control values. In contrast, MDPI mice showed a persistent decrease in HWT from days one to 70. MDPI increased glial fibrillary acidic protein (GFAP) and decreased glutamine synthetase (GS) and glutamate transporter-1 (GLT1) expression in the Vi/Vc transition zone of the brainstem on day 70, whereas no changes in astrocytic markers were observed on day 70 after SDPI. Increased expression of cleaved cysteine-aspartic protease-3 (cleaved caspase-3) and Bcl-2-associated X protein (Bax), along with decreased B-cell lymphoma/leukemia 2 (Bcl-2), were observed at day 70 after MDPI but not after SDPI. The downregulation of glutamic acid decarboxylase (GAD65) expression was observed on day 70 only after MDPI. The effects of MDPI-induced lower HWT from days one to 70 were attenuated by 12 sessions of EA treatment (days one to 21 after MDPI). Changes in astrocytic GFAP, GS, and GLT-1, along with cleaved caspase-3, Bax, Bcl-2, and GAD65 expression observed 70 days after MDPI, were reversed by EA treatment. The results suggest that persistent dental pain in mice was induced by MDPI but not by SDPI. This effect was associated with trigeminal GABAergic interneuron plasticity along with morphological and functional changes in astrocytes. EA exerts prolonged analgesic and neuroprotective effects that might be associated with the modulation of neuron-glia crosstalk mechanisms.

Objectives: Inpatients with COVID-19 may experience high levels of anxiety and depressive symptoms during the pandemic. No prior study has examined these symptoms with COVID-19 inpatients in Taiwan. Using data from a tertiary hospital in Northern Taiwan, we investigated anxiety and depressive symptoms and the associated sociodemographic or clinical characteristics in these patients. Methods: Data of anxiety and depressive symptoms by the Hospital Anxiety and Depression Scale (HADS) as well as the sociodemographic and clinical correlates were retrospectively retrieved and analyzed for COVID-19 patients admitted to Far Eastern Memorial Hospital from June 4 to June 28, 2021. Results: In total, 152 patients with COVID-19 were included. Among all the COVID-19 inpatients, 9.9 % (n = 15) had an HADS anxiety score of ≥8 and 7.2 % (n = 11) had an HADS depression score of ≥8. COVID-19 inpatients with HADS anxiety score ≥8 or HADS depression score ≥8 were found to have a longer length of hospital stay compared to the respective comparison group. The female patients, patients aged >55 years, and patients hospitalized for >15 days had significantly higher anxiety scores than did the corresponding comparison groups. Conclusion: COVID-19 inpatients with either anxiety or depression were associated with longer length of hospital stay. Age, sex, and hospitalization length were found to be associated with anxiety symptoms in inpatients with COVID-19. Future studies are warranted to elucidate differential mechanisms potentially related to anxiety and depressive symptoms in patients with COVID-19.

Previous studies indicated that laser acupuncture (LA) may effectively treat various medical conditions. However, brain responses associated with LA intervention have not been fully investigated. This study is focused on the effect of LA with different energy density (ED) in brain using resting-state functional magnetic resonance imaging (fMRI). We hypothesized that different ED would elicit various brain responses. We enrolled healthy adults participants and selected bilateral PC6 (Neiguan) as the intervention points. LA was applied, respectively, with ED of 0, 7.96, or 23.87 J/cm2. Two 500-s resting-state fMRI scans were acquired before and after intervention, respectively. The functional connectivity (FC) was calculated between autonomic nerve system-regulation associated brainstem structures and other brain regions. Compared to other dosages, the FC between rostral ventrolateral medulla and orbitofrontal cortex has more enhanced; the FC between caudal ventrolateral medulla, nucleus of the solitary tract/nucleus ambiguus, and dorsal motor nucleus of the vagus and somatosensory area has more weakened when ED was 23.87 J/cm2. Different dosages of LA have demonstrated varied regions of FC changes between regions of interest and other brain areas, which indicated that variations in EDs might influence the clinical efficacy and subsequent impacts through distinct neural pathways within the brain.

ObjectiveThis study aimed to recognize the gaps in dental education by studying the current level of geriatric oral health training of recent graduated dentists who have been admitted into an Advanced Education in General Dentistry (AEGD) program.MethodsThe AEGD program was developed along with the Age-Friendly 4Ms model to enhance current dental education. We adopted the Rapid Cycle Quality Improvement model to test the effectiveness of the training for AEGD residents from 2019 to 2022. A total of 18 residents participated (6 residents each year). A 5-question survey was administered before and after the rotation and Wilcoxon signed-rank with Fisher Exact tests were conducted to compare pre- and post- rotation results.ResultsAll 18 residents have completed pre- and post-program surveys. They self-reported minimal to no training in preparation to provide care to older adults with multiple chronic conditions. After the rotation, residents’ confidence in treating older adults was significantly increased (p = 0.011). Meanwhile, residents gained knowledge to apply the 4Ms framework (what matters, medication, mentation, and mobility) to their practices (p = 0.015) and provide age-friendly care for older adults.ConclusionThe study identified and addressed the missing link in dental education to gerontological and geriatrics education. More clinical rotations and didactic training to equip residents with competences of providing geriatric oral health are strongly recommended.