On the Association Between Demographic Structural Change and the Effectiveness of Nurse Staffing Policy for Inpatient Care: Evidence from Taiwan.

Purpose: This study investigates the influence of demographic changes on the effectiveness of hospital nurse staffing policy, measured by the cumulative response of inpatient care quality to adjustments in hospital nurse staffing levels in Taiwan. Methods: The research design utilized in this study aligns with the observational time-series methodology, and a total of 99 monthly time-series observations were collected from multiple databases administered by the Taiwan government over the period from January 2015 to March 2023. Specifically, the time-varying parameter vector autoregressive and autoregressive distributed lag models were employed to investigate the association between age distribution and nurse staffing policy effectiveness. Results: The time-varying impulse responses of the unplanned 14-day readmission rate after discharge to changes in nurse staffing levels indicate a positive association between patient-to-nurse ratios and unplanned 14-day readmission rates across various types of hospitals. Nevertheless, the effectiveness of hospitals' nurse staffing policy is observed to diminish with population aging, particularly evident in medical centers and regional hospitals. Conclusion: Policymakers should establish lower mandated patient-to-nurse ratios, grounded in practical nurse workforce planning, to address the needs of an aging society and enhance inpatient care quality through improved nurse staffing in hospitals.

Unveiling a novel entry gate: Insect foregut as an alternative infection route for fungal entomopathogens.

Insects and their natural microbial pathogens are intertwined in constant arms races, with pathogens continually seeking entry into susceptible hosts through distinct routes. Entomopathogenic fungi are primarily believed to infect host insects through external cuticle penetration. Here, we report a new variety, Beauveria bassiana var. majus (Bbm), that can infect insects through the previously unrecognized foregut. Dual routes of infection significantly accelerate insect mortality. The pH-responsive transcription factor PacC in Bbm exhibits rapid upregulation and efficient proteolytic processing via PalC for alkaline adaptation in the foregut. Expression of PalC is regulated by the adjacent downstream gene Aia. Compared to non-enteropathogenic strains such as ARSEF252, Aia in Bbm lacks a 249-bp fragment, resulting in its enhanced alkaline-induced expression. This induction promotes PalC upregulation and facilitates PacC activation. Expressing the active form of BbmPacC in ARSEF252 enables intestinal infection. This study uncovers the pH-responsive Aia-PalC-PacC cascade enhancing fungal alkaline tolerance for intestinal infection, laying the foundation for developing a new generation of fungal insecticides to control destructive insect pests.

False Liver Metastasis by Positron Emission Tomography/Computed Tomography Scan after Chemoradiotherapy for Esophageal Cancer-Potential Overstaged Pitfalls of Treatment.

In patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy (nCRT), subsequent restaging with F-18-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) can reveal the presence of interval metastases, such as liver metastases, in approximately 10% of cases. Nevertheless, it is not uncommon in clinical practice to observe focal FDG uptake in the liver that is not associated with liver metastases but rather with radiation-induced liver injury (RILI), which can result in the overstaging of the disease. Liver radiation damage is also a concern during distal esophageal cancer radiotherapy due to its proximity to the left liver lobe, typically included in the radiation field. Post-CRT, if FDG activity appears in the left or caudate liver lobes, a thorough investigation is needed to confirm or rule out distant metastases. The increased FDG uptake in liver lobes post-CRT often presents a diagnostic dilemma. Distinguishing between radiation-induced liver disease and metastasis is vital for appropriate patient management, necessitating a combination of imaging techniques and an understanding of the factors influencing the radiation response. Diagnosis involves identifying new foci of hepatic FDG avidity on PET/CT scans. Geographic regions of hypoattenuation on CT and well-demarcated regions with specific enhancement patterns on contrast-enhanced CT scans and MRI are characteristic of radiation-induced liver disease (RILD). Lack of mass effect on all three modalities (CT, MRI, PET) indicates RILD. Resolution of abnormalities on subsequent examinations also helps in diagnosing RILD. Moreover, it can also help to rule out occult metastases, thereby excluding those patients from further surgery who will not benefit from esophagectomy with curative intent.

Dachshund Homolog 1: Unveiling Its Potential Role in Megakaryopoiesis and Bacillus anthracis Lethal Toxin-Induced Thrombocytopenia.

Lethal toxin (LT) is the critical virulence factor of Bacillus anthracis, the causative agent of anthrax. One common symptom observed in patients with anthrax is thrombocytopenia, which has also been observed in mice injected with LT. Our previous study demonstrated that LT induces thrombocytopenia by suppressing megakaryopoiesis, but the precise molecular mechanisms behind this phenomenon remain unknown. In this study, we utilized 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced megakaryocytic differentiation in human erythroleukemia (HEL) cells to identify genes involved in LT-induced megakaryocytic suppression. Through cDNA microarray analysis, we identified Dachshund homolog 1 (DACH1) as a gene that was upregulated upon TPA treatment but downregulated in the presence of TPA and LT, purified from the culture supernatants of B. anthracis. To investigate the function of DACH1 in megakaryocytic differentiation, we employed short hairpin RNA technology to knock down DACH1 expression in HEL cells and assessed its effect on differentiation. Our data revealed that the knockdown of DACH1 expression suppressed megakaryocytic differentiation, particularly in polyploidization. We demonstrated that one mechanism by which B. anthracis LT induces suppression of polyploidization in HEL cells is through the cleavage of MEK1/2. This cleavage results in the downregulation of the ERK signaling pathway, thereby suppressing DACH1 gene expression and inhibiting polyploidization. Additionally, we found that known megakaryopoiesis-related genes, such as FOSB, ZFP36L1, RUNX1, FLI1, AHR, and GFI1B genes may be positively regulated by DACH1. Furthermore, we observed an upregulation of DACH1 during in vitro differentiation of CD34-megakaryocytes and downregulation of DACH1 in patients with thrombocytopenia. In summary, our findings shed light on one of the molecular mechanisms behind LT-induced thrombocytopenia and unveil a previously unknown role for DACH1 in megakaryopoiesis.

The association between smoking cessation and lifestyle/genetic variant rs6265 among the adult population in Taiwan.

Recent studies showed significant associations between socio-demographic, lifestyle factors, polymorphic variant rs6265, and smoking cessation behaviours. We examined rs6265 TT, TC and CC genotypes and their association with socio-demographic and other variables, including mental health status, drinking, exercise, and smoking behaviour among Taiwanese adults. Data on rs6265 were retrieved from the Taiwan Biobank, which contained genetic data collected between 2008 to 2019 from 20,584 participants (aged 30-70 years). Participants who smoked for more than 6 months prior to enrolment were categorized as smokers. If they had smoked and later quit for more than 6 months, they were classified as former smokers. Information regarding drinking, exercise, depression, and bipolar disorder were obtained through questionnaires and were categorized as either as affirmative (yes) or negative (no) responses. In contrast to previous studies, we found that the association between the polymorphism rs6265 and smoking behaviour was not significant (P-value = 0.8753). Males with lower education levels, young persons, and alcohol drinkers showed significant smoking behaviours (P-value < .0001). This population-based study indicates that rs6265 has no significant correlations with smoking cessation behaviour among adults in Taiwan.

A modified procedure of T-tube maneuver to treat tracheal total obstruction involving ablative bronchoscopy sparing open surgical intervention.

Objectives: The study objectives were to test an innovative T-tube procedure involving ablative bronchoscopy for the treatment of total airway occlusion and to orchestrate a safe and nontraumatic maneuver to treat intricate subglottic stenosis amenable for substituting the conventional surgical intervention. Methods: This was an uncontrolled single-center cohort study on 1254 patients from January 2001 to June 2021. Patients underwent the modified T-tube procedure treatment for tracheal stenosis. Only 42 patients were included in the study because they had full records for subglottic total occlusion sitting tracheostomy. The ablative bronchoscopy, aided by a fixed suspending laryngoscope, was applied to retunnel their total airway occlusion. T-tube revision and removal were conducted under general anesthesia with laryngeal mask airway aid during follow-up. Results: The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. The 42 patients included in the study had a mean age of 52.29 years (range, 9-84 years) with 22 men (52.38%). Their mean length of hospital stay was 13.67 days (range, 2-45 days). Their mean operation time was 73 minutes (range, 43-256 minutes). Their mean length of the tracheal stenosis was 2.8 cm (range, 0.8-6.3 cm). Outcomes were good in 29 patients (69.05%), satisfactory in 10 patients (23.81%), and considered failures in 3 patients (7.14%). A total of 16 patients (38.10%) underwent decannulation, and 3 patients (7.14%) were shifted to a Shiley tracheostomy. All 42 patients had a median follow-up of 6.2 years (range, 1.5-16.3 years). Conclusions: The modified T-tube procedure, which offered both resilience and versatility, improved the conventional technique in treating those patients experiencing total tracheal stenosis and who were unqualified for conventional open surgery.

The ASH1-PEX16 regulatory pathway controls peroxisome biogenesis for appressorium-mediated insect infection by a fungal pathogen.

Entomopathogenic fungi infect insects by penetrating through the cuticle into the host body. To breach the host cuticle, some fungal pathogens produce specialized infection cells called appressoria, which develop enormous turgor pressure to allow cuticle penetration. However, regulatory mechanisms underlying appressorium turgor generation are poorly understood. Here, we show that the histone lysine methyltransferase ASH1 in the insecticidal fungus Metarhizium robertsii, which is strongly induced during infection of the mosquito cuticle, regulates appressorium turgor generation and cuticle penetration by activating the peroxin gene Mrpex16 via H3K36 dimethylation. MrPEX16 is required for the biogenesis of peroxisomes that participate in lipid catabolism and further promotes the hydrolysis of triacylglycerols stored in lipid droplets to produce glycerol for turgor generation, facilitating appressorium-mediated insect infection. Together, the ASH1-PEX16 pathway plays a pivotal role in regulating peroxisome biogenesis to promote lipolysis for appressorium turgor generation, providing insights into the molecular mechanisms underlying fungal pathogenesis.

Regulatory Roles of Histone Modifications in Filamentous Fungal Pathogens.

Filamentous fungal pathogens have evolved diverse strategies to infect a variety of hosts including plants and insects. The dynamic infection process requires rapid and fine-tuning regulation of fungal gene expression programs in response to the changing host environment and defenses. Therefore, transcriptional reprogramming of fungal pathogens is critical for fungal development and pathogenicity. Histone post-translational modification, one of the main mechanisms of epigenetic regulation, has been shown to play an important role in the regulation of gene expressions, and is involved in, e.g., fungal development, infection-related morphogenesis, environmental stress responses, biosynthesis of secondary metabolites, and pathogenicity. This review highlights recent findings and insights into regulatory mechanisms of histone methylation and acetylation in fungal development and pathogenicity, as well as their roles in modulating pathogenic fungi-host interactions.

The Effect of a Tele-Health Intervention Program on Home-Dwelling Persons with Dementia or MCI and on Their Primary Caregivers during the Stay-at-Home-Order Period in the COVID-19 Pandemic Outbreak: Evidence from Taiwan.

BACKGROUND: The Taiwanese government implemented a stay-at-home order that restricted all community-based health promotion activities for the elderly by shutting down all community care centers from May 2021 to August 2021 to control the spread of COVID-19. Community-based dementia care centers were barely able to provide dementia care services during that period. METHODS: The data used in this study were collected from a community-based dementia care center that was able to continue their dementia care services through a Tele-Health intervention program. The difference-in-differences methodology was applied to evaluate the effects of the Tele-Health intervention program on home-dwelling persons with dementia or mild cognitive impairment and on their primary caregivers during the COVID-19 pandemic. RESULTS: The Tele-Health intervention program significantly increased the well-being of the participants and their primary caregivers, but the negative correlations between the Tele-Health intervention program and family functioning were also found to be significant. CONCLUSIONS: The significant substitution (negative) effects between the Tele-Health intervention program and family functioning raises the concern that promotion of the Tele-Health intervention program comes at the potential cost of a loss of family functioning. Policymakers should be cautious when considering the Tele-Health intervention program in response to pandemics and demographic transitions.

Robotic or transanal total mesorectal excision (TaTME) approach for rectal cancer, how about both? Feasibility and outcomes from a single institution.

Laparoscopic surgery for rectal cancer is technically challenging. Robotic and transanal TME (TaTME) are both novel approaches developed to provide better visualization and dissection. We aim to combine both approaches in a hybrid procedure and evaluate the feasibility as well as patient and oncological outcomes in this study. A review of a prospectively maintained database of patients who underwent a hybrid abdominal robotic approach with TaTME for rectal cancer between January 2016 and October 2018 was undertaken. Patient demographics, tumor characteristics and surgical outcomes were recorded and analyzed. A total of 69 patients (43 males, 26 females) received this hybrid approach. Their median age was 58 years (range 35-87) with a mean BMI of 24.3 kg/m2 (range 16.4-44.2). Median distance from anal verge was 5 cm (range 2-9). The patients had a median hospital length of stay of 7 days (range 5-28). Complication rate was 17.4% (12 patients) with 3 patients (4.3%) requiring a reoperation. TME quality was optimal with all of them either complete (81.2%) or almost complete (18.8%). 65 patients (94.2%) had an R0 resection with 4 patients (5.8%) with involved circumferential resection margins (≤ 1 mm). The median number of lymph nodes harvested was 20 (range 6-37). After a median follow-up of 27.7 months (range 7-42), local recurrence was identified in 2 patients (4%). Three patients (5.2%) had distant recurrence at the 3-year mark. Hybrid robotic abdominal dissection with transanal TME for rectal cancer appears to be feasible with comparable surgical outcomes to other traditional approaches.

Feasibility of in situ chondrogenesis for the entire umbilical cord in preliminary preparation for tracheal graft.

BACKGROUND: There remains a scarcity of both autografts and allografts for tracheal transplantation after long-segmental resection. Subsequently, tissue engineering has become a promising alternative for tracheal transplantation, which requires successful in vitro chondrogenesis. METHODS: To optimize the protocol for in situ chondrogenesis using the pig-derived whole Umbilical Cord (UC) as the starting material, it must be performed without using the UC-multipotent stromal cell (MSCs) isolation procedure. Nevertheless, chondrogenic induction is performed under a variety of conditions; with or without TGF-ß1 at different concentrations, and also in combination with either a rotatory or hollow organ bioreactor. The engineered explant sections were analyzed using various histochemical and immunohistochemical stains to assess the expression of chondrocyte markers. Cell viability was determined through use of the APO-BrdU TUNEL assay kit. RESULTS: The results showed that culture conditions induced heterogeneous chondrogenesis in various compartments of the UC. Moreover, explants cultured with 10 ng/ml TGF-ß1 under hypoxic (1% O2) in combination with a bioreactor, significantly enhanced the expression of aggrecan and type II collagen, but were lacking in the production of Glycosaminoglycans (GAGs), as evidenced by alcian blue staining. We speculated that whole segment UCs allowed for the differentiation into premature chondrocytes in our tissue-engineered environments. CONCLUSION: This study has provided exciting preliminary evidence showing that a stem cell-rich UC wrapped around an anatomical tracheal scaffold and implanted in vivo can induce nodes of new cartilage growth into a structurally functional tissue for the repairing of long-segmental tracheal stenosis.

Empyema thoracis complicated by anaemia as caused by occult bonelet aspiration.

A 62-year-old man was referred to our medical centre with productive cough and high fever over the span of one week, as well as the affiliated symptoms of chronic cough and dizziness for more than six months. Computed tomography (CT) of the thorax was performed and analysed revealing lobulated empyema with thick pleura and two foreign body (FB) retentions in the right lower lobe bronchus. The patient proceeded to thoracoscopic decortications and finalized through retrieval of two dark black stained bonelets with ignored aspiration. After surgery, the patient recovered uneventfully and was discharged in stable condition.

De novo cartilage growth after implantation of a 3-D-printed tracheal graft in a porcine model.

BACKGROUND: Experiments were conducted on the assumption that vivid chondrogenesis would be boosted in vivo following previously preliminary chondrogenesis in a mesenchymal stem cell (MSC)-rich entire umbilical cord (UC) in vitro. METHODS: Virtual 3-D tracheal grafts were generated by using a profile obtained by scanning the native trachea of the listed porcine. Although the ultimate goal was the acquisition of a living specimen beyond a 3-week survival period, the empirical results did not meet our criteria until the 10th experiment, ending with the sacrifice of the animal. The categories retrospectively evolved from post-transplant modification due to porcine death using 4 different methods of implantation in chronological order. For each group, we collected details on graft construction, clinical outcomes, and results from both gross and histology examinations. RESULTS: Three animals died due to tracheal complications: one died from graft crush, and two died secondary to erosion of the larger graft into the great vessels. It appeared that the remaining 7 died of tracheal stenosis from granulation tissue. Ectopic de novo growth of neocartilage was found in three porcine subjects. In the nearby tissues, we detected neocartilage near the anastomosis containing interim vesicles of the vascular canals (VCs), perichondrial papillae (PPs) and preresorptive layers (PRLs), which were investigated during the infancy of cartilage development and were first unveiled in the tracheal cartilage. CONCLUSIONS: 3-D-printed anatomically precise grafts could not provide successful transplantation with stent-sparing anastomosis; nonetheless, de novo cartilage regeneration in situ appears to be promising for tracheal graft adaptability. Further graft refinement and strategies for managing granulated tissues are still needed to improve graft outcomes.

Phantom simulation of liver metastasis on a positron emission tomography with computed tomography scan after neoadjuvant chemoradiotherapy for distal esophageal cancer: a case report.

BACKGROUND: Neoadjuvant chemoradiotherapy is currently the gold standard treatment for esophageal cancer prior to surgery. This radiation therapy will sometimes lead to liver damage parallel to esophageal lesions, which mimics liver metastasis visualized by 18F-fluorodeoxyglucose positron emission tomography with computed tomography. In this report, we publish virtual radiation-induced liver damage images obtained during surgery, along with the coherent pathology, in order to confirm the false-positive result through an optimally decisive radiological examination. CASE PRESENTATION: We report a case of a Asian male patient with distal esophageal cancer who had undergone neoadjuvant chemoradiotherapy (5000 cGy). Subsequently, a new lesion was discovered during a positron emission tomography with computed tomography scan 6 weeks later, near the left caudate lobe of the liver during tumor restaging. To exclude the possibility of liver metastasis, serial imaging was conducted, which included liver sonography, computed tomography, and magnetic resonance imaging for a more intimate probe. The patient's condition was verified as being liver inflammation change, as seen by the liver magnetic resonance imaging presentation. Thoracoscopic esophagectomy was performed with cervical esophagogastrostomy via the retrosternal route, along with a feeding jejunostomy. The procedure was performed smoothly, with an intraoperative liver biopsy also being conducted 2 weeks later, after positron emission tomography with computed tomography restaging. The pathology report revealed esophageal cancer in the form of poorly differentiated squamous cell carcinoma, pT3N1M0. The liver biopsy revealed obvious inflammation change after radiation therapy, which elucidated sinusoidal congestion with the attenuated hepatic cords and filled with erythrocytes. There was no evidence of liver metastasis. The patient recovered uneventfully and was discharged with his oral intake performing smoothly, and a stable condition was observed during 12 months of outpatient department follow-up. CONCLUSIONS: New foci of increased 18F-fluorodeoxyglucose avidity are commonly seen in the caudate and left hepatic lobes of the liver during neoadjuvant chemoradiation for distal esophageal cancer, and these findings generally reflect radiation-induced liver disease rather than metastatic disease. Awareness of the pitfalls of a high 18F-fluorodeoxyglucose uptake in radiation-induced liver injury is crucial in order to avoid misinterpretation and overstaging. Except for the location of 18F-fluorodeoxyglucose uptake, the shape of the lesion, and an maximum standardized uptake value (> 10/h), a convincing liver magnetic resonance imaging scan or even a liver biopsy can provide accurate information for distinguishing radiotherapy-induced liver injury from liver metastasis.