Randomized trial of oral versus enteral feeding for patients with postoperative pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Whether continued oral feeding may have a negative impact on healing of postoperative pancreatic fistula (POPF) is unclear. The aim was to test the hypothesis that oral feeding is non-inferior to enteral feeding in closure of POPF after pancreatoduodenectomy, and to clarify the effects of oral feeding on the duration and grade of POPF. METHODS: This multicentre, non-inferiority randomized trial of oral or enteral feeding of patients with POPF after pancreatoduodenectomy recruited patients between August 2013 and September 2016. The primary efficacy outcome was the 30-day fistula closure rate. The prespecified non-inferiority margin was 15 per cent. Other efficacy outcomes included grade of fistula, and hospital stay and costs. RESULTS: A total of 114 patients were included, and received oral (57) or enteral (57) feeding. The two groups were balanced in baseline characteristics and no patient was lost to follow-up. In intention-to-treat analysis, oral feeding was non-inferior to enteral feeding in terms of 30-day fistula closure rate (88 versus 89 per cent respectively; difference -1·8 per cent, lower limit of 95 per cent c.i. -14·4 per cent; P = 0·020 for non-inferiority). Compared with enteral feeding, oral feeding significantly reduced hospital costs and duration of stay. No significant differences were noted in the number of patients whose POPF evolved into grade B/C, or other outcomes. CONCLUSION: Oral feeding in patients with POPF after pancreatoduodenectomy did not increase the duration or grade of POPF, and was associated with reduced duration of stay and hospital costs. Registration number: NCT01755260 (http://www.clinicaltrials.gov).

Horizontal root fractures in posterior teeth without dental trauma: tooth/root distribution and clinical characteristics.

AIM: To describe the clinical characteristics and radiographic findings of horizontal root fractures (HRF) in posterior teeth without a history of dental trauma. METHODOLOGY: A total 24 patients and 31 HRF cases in 28 posterior teeth were collected from 2006 to 2015. Clinical examinations and radiographic imaging were evaluated. Value of confidence intervals of the proportions was calculated for data presentation. RESULTS: The number of males (54%) was similar to females (46%). The patients were predominantly between 50 and 70 years of age (75%). Most HRF cases were found in nonendodontically treated teeth (79%), without crown and bridge restorations (82%), and maxillary molars (54%). Many roots of maxillary molars had developed HRF, and the probability was nearly equal. Fractured teeth usually presented with periodontal and apical bone loss, and most patients (92%) were diagnosed with full mouth chronic periodontitis. Tooth wear was another common clinical feature amongst these patients. CONCLUSIONS: HRF in posterior teeth without dental trauma occurred mainly in patients aged between 50 and 70, in nonendodontically treated teeth, teeth with attrition but without crown and bridge restorations, maxillary molars and with periodontal and periapical bony destruction. Periodontal condition, occlusal wear and patients' age at diagnosis were the possible related factors. HRF in posterior teeth without dental trauma is a diagnostic challenge and even misdiagnosed. A thorough clinical examination, radiographic analysis and recognition of the clinical characteristics are helpful in the early diagnosis and treatment of HRF.

Association between psoriasis and asthma: a population-based retrospective cohort analysis.

BACKGROUND: Both psoriasis and asthma are chronic immune-mediated inflammatory diseases. OBJECTIVES: To evaluate the risk of developing asthma in patients with psoriasis compared with controls. METHODS: This cohort study was conducted using data from the Taiwan National Health Insurance Research Database. Patients with psoriasis (n = 10,288) and matched comparison patients without psoriasis (n = 41,152) were evaluated. A Cox proportional hazard regression analysis was used to determine the risk of asthma in patients with and without psoriasis. RESULTS: The risk of asthma was 1·38-fold higher [95% confidence interval (CI) 1·23-1·54] in the cohort with psoriasis than in the reference cohort, after adjusting for age, sex and comorbidities. The incidence of asthma in men and women with psoriasis exhibited nonsignificant differences. Among all patients aged > 50 years, psoriasis was associated with a higher risk of asthma compared with not having psoriasis [adjusted hazard ratio (HR) 1·49; 95% CI 1·18-1·88 (in patients aged 50-64 years); adjusted HR 1·63; 95% CI 1·34-1·99 (in patients aged > 65 years)]. CONCLUSIONS: Our results indicate that patients with psoriasis are associated with a increased risk of developing asthma.

The association between chronic obstructive pulmonary disease and dementia: a population-based retrospective cohort study.

BACKGROUND AND PURPOSE: Chronic obstructive pulmonary disease (COPD) is frequently associated with various comorbidities. However, the proportion of COPD patients with dementia has not been adequately examined. This retrospective cohort study investigated the association between COPD and dementia by using a nationwide population-based database in Taiwan. METHODS: Data were retrieved from the Taiwanese National Health Insurance Research Database and analyzed using multivariate Cox proportional hazards regression models to assess the effects of COPD on the risk of dementia after adjusting for demographic characteristics and comorbidities. RESULTS: The COPD cohort exhibited a higher prevalence of diabetes, hypertension, coronary artery disease, head injury and depression at baseline than did the non-COPD cohort (P < 0.0001). After adjusting for covariates, the COPD patients exhibited a 1.27-fold higher risk of developing dementia (hazard ratio 1.27, 95% confidence interval 1.20-1.36). The incidence rate was higher in patients with frequent acute exacerbations than in the non-COPD patients regardless of whether a hospital admission or emergency room visit was required (hazard ratio 196.8 vs. 41.7, 95% confidence intervals 145.9-265.5 and 22.3-78.0). CONCLUSION: This study shows that COPD is associated with a subsequent higher risk of dementia after adjusting for comorbidities. Specifically, the association between COPD and dementia is greater in patients with more frequent acute exacerbation events of COPD.

Research trends of Janus Kinase inhibitors: a bibliometric and visualized study from 2012 to 2023.

OBJECTIVE: Janus Kinase (JAK) inhibitors have been extensively evaluated for their potential in the management of various diseases. Despite previous research on this topic, there is a lack of bibliometric analysis that summarizes research trends on JAK inhibitors. This study aims to provide a comprehensive overview of the top 100 most frequently cited studies on JAK inhibitors over the last ten years. MATERIALS AND METHODS: The Web of Science database was used to screen and extract relevant studies on JAK inhibitors. The top 100 studies most cited within the JAK inhibitor-related research were identified and evaluated, and various data such as the year of publication, study focus and keywords, author information, and number of citations were extracted and analyzed for further examination. RESULTS: In the top 100 most cited studies of JAK inhibitors, more than 70% of studies focused on the role of JAK inhibitors in disease treatments, with 42% of these studies focused on using JAK inhibitors as treatment for autoimmune diseases and 19 of them focused on the treatment of neoplasms. Time trend analysis revealed that the keywords "tofacitinib", "atopic dermatitis", and "rheumatoid arthritis" were widely mentioned in 2016, while new trends emerged in 2018, with "ruxolitinib" and "baricitinib" being more commonly mentioned. CONCLUSIONS: The top 100 most frequently cited studies on JAK inhibitors focused primarily on the safety and efficacy of these inhibitors in the management of various diseases, particularly inflammatory diseases and neoplasms. The results can serve as a valuable reference for rheumatologists and immunologists interested in the development of JAK inhibitors and expanding future research fields.

An unusual presentation of catatonia in a patient with schizoaffective disorder.

Catatonia is currently a diagnosis that is made clinically; however, due to the varied clinical presentations of catatonia, underdiagnosis is common. We describe an unusual presentation of catatonia in a female patient with schizoaffective disorder. She was successfully treated, albeit with a significant delay. Among an extensive series of laboratory tests and treatment trials, serum levels of D-dimer were elevated during the illness and relieved with recovery.

Neuroendoscopic management of intraventricular germinoma at the foramen of Monro: case report and review of the literature.

BACKGROUND: Intraventricular tumors account for approximately 3% of adult brain tumors and 16% of childhood and adolescent brain tumors. Half of the intraventricular tumors in adults and one quarter of those in children are found in the lateral ventricles. Ependymoma, astrocytoma, oligodendroglioma, choroid plexus papilloma, meningioma and subependymal giant cell astrocytoma are the common tumors encountered at this particular site. A germinoma at this site is rare. Microsurgery of intraventricular tumors can be challenging and is performed with potential functional and cognitive complications. CASE REPORT: A 25-year-old female harboring an intraventricular tumor at the foramen of Monro with resultant obstructive hydrocephalus underwent a right intraventricular endoscopic resection of the tumor by means of frameless neuronavigation guidance and temporary external ventricular drainage. Histology showed the tumor to be a germinoma. The post-operative imaging showed that there was some residual tumor tissue in the fornix. Concerned with possibility of cerebrospinal fluid seeding, we administered postoperative adjuvant craniospinal irradiation. The patient was discharged with a Glascow outcome scale score of 5 and at last the 6-month follow-up there was no evidence of recurrence. CONCLUSION: This report suggests that in selected cases endoscopic resection of an intraventricular tumor under frameless neuronavigation guidance is feasible and safe. The target can be precisely located and procedure-related adverse events can be minimized.

Ca2+ movement and cytotoxicity induced by the pyrethroid pesticide bifenthrin in human prostate cancer cells.

Bifenthrin, a commonly used pyrethroid pesticide, evokes various toxicological effects in different models. However, the effect of bifenthrin on cytosolic-free Ca2+ level ([Ca2+]i) and cytotoxicity in human prostate cancer cells is unclear. This study examined whether bifenthrin altered Ca2+ homeostasis and cell viability in PC3 human prostate cancer cells. [Ca2+]i in suspended cells were measured using the fluorescent Ca2+-sensitive dye fura-2. Cell viability was examined by 4-[3-[4-lodophenyl]-2-4(4-nitrophenyl)-2H-5-tetrazolio-1,3-benzene disulfonate] water soluble tetrazolium-1 assay. Bifenthrin (100-400 µM) concentration-dependently induced [Ca2+]i rises. Ca2+ removal reduced the signal by approximately 30%. In Ca2+-free medium, treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) abolished bifenthrin-evoked [Ca2+]i rises. Conversely, treatment with bifenthrin abolished BHQ-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) with U73122 significantly inhibited bifenthrin-induced [Ca2+]i rises. Mn2+ has been shown to enter cells through similar mechanisms as Ca2+ but quenches fura-2 fluorescence at all excitation wavelengths. Bifenthrin (400 µM)-induced Mn2+ influx implicates that Ca2+ entry occurred. Bifenthrin-induced Ca2+ entry was inhibited by 30% by protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate) and inhibitor (GF109203X) and three inhibitors of store-operated Ca2+ channels: nifedipine, econazole, and SKF96365. Bifenthrin at 175-275 µM decreased cell viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetra acetic acid-acetoxymethyl ester. Together, in PC3 cells, bifenthrin-induced [Ca2+]i rises by evoking PLC-dependent Ca2+ release from the endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. Bifenthrin also caused Ca2+-independent cell death.

12-O-tetradecanoylphorbol-13-acetate-induced apoptosis in LNCaP cells is mediated through ceramide synthase.

Protein kinase C (PKC) activation is often antiapoptotic, although in a few cell types PKC initiates apoptosis by an unknown mechanism. Recent investigations showed that activation of PKC alpha by 12-O-tetradecanoylphorbol 13-acetate (TPA) induced apoptosis in LNCaP prostate cancer cells. The present studies examine the mechanism of this effect and show that de novo ceramide generation through the enzyme ceramide synthase is required. TPA induced rapid ceramide generation, which was detectable by 1 h and increased linearly for 12 h. TPA-induced apoptosis was measurable by 12 h and was progressive for 48 h. Investigations into the mechanism of TPA-induced ceramide generation revealed that acid and neutral sphingomyelinase activities were not enhanced. However, TPA induced an increase in ceramide synthase activity that persisted for at least 16 h. Treatment with fumonisin B1, a specific natural inhibitor of ceramide synthase, abrogated both ceramide production and TPA-induced apoptosis. Ceramide analogues bypassed fumonisin B1 inhibition to initiate apoptosis directly. Thus, ceramide appears to be a necessary signal for TPA-induced apoptosis in LNCaP cells. This represents the first description of a pathway by which PKC may signal apoptosis.

Reversal of radiation resistance in LNCaP cells by targeting apoptosis through ceramide synthase.

Cell lines derived from human prostate cancer are regarded as relatively resistant to both radiation-induced clonogenic death and apoptosis. Here we attempted to modulate the response of LNCaP prostate cancer cells to radiation therapy (XRT) by pretreatment with 12-O-tetradecanoylphorbol acetate (TPA), a known apoptogenic agent in LNCaP cells. Using plateau-phase cultures, we investigated the response of these cells to XRT, TPA, and a combination of XRT and TPA. LNCaP irradiation did not result in ceramide generation or apoptosis. However, pretreatment with TPA enabled XRT to generate ceramide via activation of the enzyme ceramide synthase and signal apoptosis. Apoptosis was abrogated by the competitive inhibitor of ceramide synthase, fumonisin B1. Furthermore, when transplanted orthotopically into the prostate of nude mice, LNCaP cells produced tumors that recapitulated the responses of LNCaP cells in vitro. XRT or TPA failed to signal apoptosis in LNCaP tumors, whereas a combination of the two resulted in substantial (20-25%) apoptosis within 24 h. There was an additional benefit associated with this regimen because TPA pretreatment protected the adjacent rectum from radiation-induced apoptosis. This represents the first description of signaling-based therapy designed to overcome one form of radiation resistance expressed preferentially in LNCaP human prostate cancer cells.

Cubic three-dimensional hybrid silica solids for nuclear hyperpolarization.

Hyperpolarization of metabolites by dissolution dynamic nuclear polarization (D-DNP) for MRI applications often requires fast and efficient removal of the radicals (polarizing agents). Ordered mesoporous SBA-15 silica materials containing homogeneously dispersed radicals, referred to as HYperPolarizing SOlids (HYPSOs), enable high polarization - P(1H) = 50% at 1.2 K - and straightforward separation of the polarizing HYPSO material from the hyperpolarized solution by filtration. However, the one-dimensional tubular pores of SBA-15 type materials are not ideal for nuclear spin diffusion, which may limit efficient polarization. Here, we develop a generation of hyperpolarizing solids based on a SBA-16 structure with a network of pores interconnected in three dimensions, which allows a significant increase of polarization, i.e. P(1H) = 63% at 1.2 K. This result illustrates how one can improve materials by combining a control of the incorporation of radicals with a better design of the porous network structures.

Deoxyribonuclease II purified from the isolated lysosomes of porcine spleen and from porcine liver homogenates. Comparison with deoxyribonuclease II purified from porcine spleen homogenates.

Porcine spleen DNase II (EC 3.1.22.1), one of the best-characterized DNases II, is subcellularly located in lysosomes because the enzyme is co-sedimented with two of the lysosomal marker enzymes, cathepsin D and acid phosphatase. The physicochemical properties, including the subunit structure, sensitivity to iodoacetate inactivation, native molecular weight and chromatographic behavior, of the DNase II purified from the isolated lysosomes of porcine spleen are indistinguishable from those of the same enzyme purified from the whole porcine spleen homogenate. DNase II can also be extracted from porcine liver with 0.05 M H2SO4 or 0.1 M NaCl and purified from either extract by a series of column chromatographies. The purified liver DNase II from either extract has the same subunit structure (alpha-chain, Mr 35,000 and beta-chain, Mr 10,000) as the purified DNase II of porcine spleen. The two liver extracts as well as the extracts of spleen and gastric mucosa contain DNase II with very similar properties on Sephadex G-100 gel filtration, on acid polyacrylamide gel electrophoresis under non-denaturing conditions, and on isoelectric focusing. The data strongly suggest that, for the same species of animal, the DNase II activities in various tissues are associated with protein molecules of identical structure.

Enantiomeric inhibitors of cholesterol esterase and acetylcholinesterase.

Enantiomers of N-methyl-N,alpha-methylbenzylbutyramide (1), 1-butyl-3-methyl-3'-alpha-methylbenzylurea (2), 1,2,3, 4-tetrahydro-1-naphthyl-N-butylcarbamate (3), 1,1'-bi-2-naphthyl-2, 2'-di-N-butylcarbamate (4), 1, 1'-bi-2-naphthyl-2-ol-2'-N-butylcarbamate (5), and 1, 1'-bi-2-naphthyl-2-butyrate-2'-N-butylcarbamate (6) are inhibitors of porcine pancreatic cholesterol esterase-catalyzed hydrolysis of 4-nitrophenyl butyrate and of electric eel acetylcholinesterase-catalyzed hydrolysis of acetylthiocholine in the presence of 5,5'-dithiobis-2-nitrobenzoate. For competitive inhibitors, values of the inhibition constant (Ki) and the enantiomeric ratio (Ecomp.) are investigated. For active site-directed irreversible inhibitors, values of the inhibition constant (Ki), the carbamylation constant (k2), the bimolecular rate constant (ki), and the enantiomeric ratio (E) are investigated. Toward both enzymes, compounds 1 are poor competitive inhibitors (Ki=102-104 microM) but have good enantioselectivities (Ecomp.=10-50, the preference for R). R-2 and S-2 are competitive inhibitors of acetylcholinesterase with Ki=26 and 80 microM, respectively (the preference for R) but are active site-directed irreversible inhibitors of cholesterol esterase with ki=4 and 16 M-1 sec-1, respectively (the preference for S). For those competitive inhibitions, both leaving group hydrophilic and hydrophobic binding sites of cholesterol esterase or both anionic substrate binding site and peripheral anionic binding site of acetylcholinesterase bind to N,N-methyl-alpha-methylbenzyl disubstituted amide parts of these inhibitors and the enzyme does not catalyze the hydrolysis of these inhibitors. The opposite stereopreference (S) for the inhibition of cholesterol esterase by compounds 2 may be due to the fact that N, N-methyl-alpha-methylbenzyl disubstituted amide parts of these inhibitors bind to the alkyl chain binding site of the enzyme. Compounds 3-6 are active site-directed irreversible inhibitors of cholesterol esterase (ki=1-13000 M-1 s-1) and peripheral anionic binding site-directed irreversible inhibitors of acetylcholinesterase (ki=1.7-1300 M-1 s-1). Compounds 3 have low enantioselectivities (E=1.3-1.4) for both enzymes. The stereopreference for atropisomers 4 and 6 is S-form toward both enzymes (E=2-30) and is identical to that of cholesterol esterase-catalyzed hydrolysis of 1,1'-bi-2-naphthyl-2,2'-diacylate. This stereopreference (S) may be due to the fact that the butyryl group or one of two butylcarbamate groups of S-atropisomers binds more effectively to the leaving group hydrophobic binding site of cholesterol esterase or the peripheral anionic binding site of acetylcholinesterase than that of R-atropisomers. The opposite stereopreference (R) for atropisomers 5 toward both enzymes may be due to a favorable interaction between the hydroxyl group of the inhibitors and the leaving group hydrophilic binding site of cholesterol esterase or the peripheral anionic binding site of acetylcholinesterase.

The association between chronic obstructive pulmonary disease and Parkinson's disease: a nationwide population-based retrospective cohort study.

OBJECTIVE: Previous research has shown that patients with chronic obstructive pulmonary disease (COPD) tend to have a higher risk for cognitive impairment and dementia, a neurodegenerative disorder. The goal of this study was to examine what relationship, if any, exists between COPD and Parkinson's disease (PD), which is also a neurodegenerative disorder. METHOD: Our study analyzed medical data from the population of Taiwan from 1998 to 2008, with a follow-up period extending to the end of 2010. We identified patients with COPD by the Taiwan National Health Insurance Research Database (NHIRD). We selected a comparison cohort from the general population that was random frequency-matched by age (in 5-year increments), sex and index year, and further analyzed the risk of PD using Cox's regression model, including sex, age and comorbidities. RESULTS: The study enrolled 20 728 COPD patients (71.1% male, mean age = 68.2 years) and 41 147 controls. The risk of developing PD was 1.37 times greater in patients with COPD compared with patients without COPD after adjusting for age, sex and comorbidities. A significantly increased risk of PD was also found in patients with COPD who had any comorbidity other than diabetes. CONCLUSION: This nationwide retrospective cohort study demonstrates that PD risk is significantly increased in patients with COPD compared with those of the general population.

Chronic obstructive pulmonary disease and allied conditions is a strong independent risk factor for osteoporosis and pathologic fractures: a population-based cohort study.

BACKGROUND: Chronic obstructive pulmonary disease and allied conditions (COPD) is frequently associated with various comorbidities. This study examined the association between osteoporosis and pathologic fractures in a sample of patients with COPD. METHODS: In this cohort study, claims data from the National Health Insurance Research Database of Taiwan were used to evaluate the risk between COPD and osteoporosis. Using data from the Longitudinal Health Insurance Database 2000, we conducted a retrospective cohort study by investigating patients aged 20 years and older who were newly diagnosed with COPD and comparing them with controls without COPD during 2000-2010. In addition, we used univariable and multivariable Cox proportional hazards regression models to measure the association between COPD and the risk of osteoporosis. RESULTS: Our results revealed that COPD was significantly associated with a high risk of osteoporosis, regardless of whether the patients with COPD were corticosteroid users and irrespective of age and sex. After adjustment for covariates, the COPD patients exhibited a 1.54-fold higher risk of developing osteoporosis (hazard ratio 1.54, 95% confidence interval 1.44-1.64). COPD was a stronger risk factor for osteoporosis in men. Moreover, patients with severe COPD had a higher risk of osteoporosis or pathologic fractures. CONCLUSION: This study revealed that COPD, which shares the characteristics of inflammatory diseases, is associated with a higher risk of osteoporosis after adjustment for comorbidities.

Providing instrumental social support is more beneficial to reduce mortality risk among the elderly with low educational level in Taiwan: a 12-year follow-up national longitudinal study.

BACKGROUND: To evaluate whether the effects of providing or receiving social support are more beneficial to reduce mortality risk among the elderly with different educational levels. METHODS: In this long-term prospective cohort study, data were retrieved from the Taiwan Longitudinal Study on Aging. This study was initiated from 1996 until 2007. The complete data from 1492 males and 1177 females aged ≥67 years were retrieved. Participants received financial, instrumental, and emotional support, and they actively provided instrumental and emotional support to others and involved in social engagement. Education attainment was divided into two levels: high and low. The low education level included illiterate and elementary school. The high education level included junior high school to senior high school and above college. Cox regression analysis was used to examine the association between providing or receiving social support on mortality with different educational levels. RESULTS: The average age of the participants in 1996 was 73.0 (IQR=8.0) years, and the median survival following years (1996-2007) of participants was 10.3 (IQR=6.7) years. Most participants were low educational level including illiterate (39.3%) and elementary school (41.2%). Participants with high educational level tend to be younger and more male significantly. On the contrary, participants with low educational level tend to have significant more poor income, more depression, more cognition impairment, more with IADL and ADL disability than high educational level. Most participants received instrumental support from others (95.5%) and also provided emotional support to others (97.7%). Providing instrumental support can reduce 17% of mortality risk among the elderly with a low level of education after adjusting several covariates [Hazard ratio (HR) = 0.83; 95% confidence interval (CI) = 0.70-0.99; p = 0.036]. CONCLUSIONS: Providing instrumental social support to others confer benefits to the giver and prolong life expectancy among the elderly with low educational levels.