Potentially preventable hospital readmissions after patients' first stroke in Taiwan.
Readmission is an important indicator of the quality of care. The purpose of this study was to explore the probabilities and predictors of 30-day and 1-year potentially preventable hospital readmission (PPR) after a patient's first stroke. We used claims data from the National Health Insurance (NHI) from 2010 to 2018. Multinomial logistic regression was used to assess the predictors of 30-day and 1-year PPR. A total of 41,921 discharged stroke patients was identified. We found that hospital readmission rates were 15.48% within 30-days and 47.25% within 1-year. The PPR and non-PPR were 9.84% (4123) and 5.65% (2367) within 30-days, and 30.65% (12,849) and 16.60% (6959) within 1-year, respectively. The factors of older patients, type of stroke, shorter length of stay, higher Charlson Comorbidity Index (CCI), higher stroke severity index (SSI), regional hospital, public and private hospital, and hospital in the lower urbanized area were associated significantly with the 30-day PPR. In addition, the factors of male, hospitalization year, and monthly income were associated significantly with 1-year PPR. The ORs of long-term PPR showed a decreasing trend since implementing the national health insurance post-acute care (PAC) program in 2014 and a dramatic drop in 2018 after the government expanded the long-term care plan-LTC 2.0 in 2017. The results showed that better discharge planning, implementing post-acute care programs and long-term care plan-LTC 2.0 may benefit the care of stroke patients and help reduce long-term readmission in Taiwan.


FIELD MEASUREMENT OF THE UNATTACHED FRACTION AND ACTIVITY CONCENTRATION RATIO OF RADON PROGENY IN TYPICAL DWELLINGS.
The unattached fraction (fp) and activity concentration ratio of radon progeny (${\boldsymbol C}_{{}{}^{\bf 218}\bf{Po}}:{\boldsymbol C}_{{}{}^{\bf 214}\bf{Pb}}:{\boldsymbol C}_{{}{}^{\bf 214}\bf{Bi}}$) are important for radon exposure dose evaluation. For getting these characteristic parameters in dwellings, a series of field measurement was carried out. For comparison, a semi-continuous measurement was carried out in an office room and outdoors. Results show that the average fp is 4.5% ± 2.2% and 3.8% ± 1.7% in city dwellings and in rural dwellings, respectively. The average activity concentration ratios are 1:0.94:0.70 for radon progeny and 1:0.07:0.06 for unattached radon progeny in city dwellings, while those in rural dwellings are 1:0.88:0.66 and 1:0.09:0.07. The average values of fp are 5.1% ± 0.9% and 5.4% ± 3.1% in the office room and in outdoors without significant difference. The average activity concentration ratios are 1:0.88:0.77 for radon progeny and 1:0.11:0.11 for unattached radon progeny in outdoors.


Chimeric bovine respiratory syncytial virus with glycoprotein gene substitutions from human respiratory syncytial virus (HRSV): effects on host range and evaluation as a live-attenuated HRSV vaccine.
We recently developed a system for the generation of infectious bovine respiratory syncytial virus (BRSV) from cDNA. Here, we report the recovery of fully viable chimeric recombinant BRSVs (rBRSVs) that carry human respiratory syncytial virus (HRSV) glycoproteins in place of their BRSV counterparts, thus combining the replication machinery of BRSV with the major antigenic determinants of HRSV. A cDNA encoding the BRSV antigenome was modified so that the complete G and F genes, including the gene start and gene end signals, were replaced by their HRSV A2 counterparts. Alternatively, the BRSV F gene alone was replaced by that of HRSV Long. Each antigenomic cDNA directed the successful recovery of recombinant virus, yielding rBRSV/A2 and rBRSV/LongF, respectively. The HRSV G and F proteins or the HRSV F in combination with BRSV G were expressed efficiently in cells infected with the appropriate chimeric virus and were efficiently incorporated into recombinant virions. Whereas BRSV and HRSV grew more efficiently in bovine and human cells, respectively, the chimeric rBRSV/A2 exhibited intermediate growth characteristics in a human cell line and grew better than either parent in a bovine line. The cytopathology induced by the chimera more closely resembled that of BRSV. BRSV was confirmed to be highly restricted for replication in the respiratory tract of chimpanzees, a host that is highly permissive for HRSV. Interestingly, the rBRSV/A2 chimeric virus was somewhat more competent than BRSV for replication in chimpanzees but remained highly restricted compared to HRSV. This showed that the substitution of the G and F glycoproteins alone was not sufficient to induce efficient replication in chimpanzees. Thus, the F and G proteins contribute to the host range restriction of BRSV but are not the major determinants of this phenotype. Although rBRSV/A2 expresses the major neutralization and protective antigens of HRSV, chimpanzees infected with this chimeric virus were not significantly protected against subsequent challenge with wild-type HRSV. This suggests that the growth restriction of rBRSV/A2 was too great to provide adequate antigen expression and that the capacity of this chimeric vaccine candidate for replication in primates will need to be increased by the importation of additional HRSV genes.


Cellular Therapeutic Approaches to Cytomegalovirus Infection Following Allogeneic Stem Cell Transplantation.
Cytomegalovirus (CMV) infection is common following allogeneic hematopoietic stem cell transplant (HSCT) and is a major cause of morbidity and increased mortality. Whilst pharmacotherapy can be effective in the prevention and treatment of CMV, these agents are often expensive, toxic and in some cases ineffective due to viral resistance mechanisms. Immunotherapeutic approaches are compelling and early clinical trials of adoptively transferred donor-derived virus-specific T (VST) cells against CMV have demonstrated efficacy. However, significant logistical challenges limit their broad application. Strategies to optimize VST manufacture and cell banking alongside scientific developments to enhance efficacy whilst minimizing toxicity are ongoing. This review will discuss the development of CMV-specific T-cell therapies, the challenges of widespread delivery of VSTs for CMV and explore how VST therapy can change outcomes in CMV infection following HSCT.


Antiobesity, Regulation of Lipid Metabolism, and Attenuation of Liver Oxidative Stress Effects of Hydroxy-α-sanshool Isolated from Zanthoxylum bungeanum on High-Fat Diet-Induced Hyperlipidemic Rats.
Zanthoxylum bungeanum is a traditional Chinese medicine (TCM) used to relieve pain, dispel dampness, stop diarrhea, and prevent itching. The aim of this study was to investigate the antiobesity and hypolipidemic effects of hydroxy-α-sanshool (HAS) isolated from Z. bungeanum on hyperlipidemic rats. Wistar rats (n = 48) were randomly divided into six groups: (1) normal diet rats (ND), (2) high-fat diet- (HFD-) treated rats, (3) HFD+fenofibrate-treated rats (HFD+FNB), (4) HFD+low dose of HAS-treated rats (HFD+LD, 9 mg/kg), (5) HFD+middle dose of HAS-treated rats (HFD+MD, 18 mg/kg), and (6) HFD+high dose of HAS-treated rats (HFD+HD, 36 mg/kg). The body weight and food intake of the rats were recorded during the treatment period. After 4 weeks of HAS treatment, abdominal adipose tissues were observed and total cholesterol (T-CHO), triglycerides (TG), high-density lipoprotein (HDL) cholesterol (HDL-C), and low-density lipoprotein (LDL) cholesterol (LDL-C) of serum and liver tissues were determined. Furthermore, histochemical examinations using oil red O and hematoxylin-eosin staining (H&E) were carried out and levels of malondialdehyde (MDA) and glutathione (GSH) and activities of superoxide dismutase (SOD) in the liver were determined. After HFD feeding, the body weight gain and food efficiency ratio of HFD rats were significantly enhanced (p < 0.05vs. ND rats) and HAS treatment (18 and 36 mg/kg) significantly decreased the body weight gain and food efficiency ratio (p < 0.05vs. HFD rats). In addition, HAS treatment could decrease the abdominal adipose tissues and liver adipocytes. Furthermore, HAS treatment significantly decreased the T-CHO, TG, and LDL-C, whereas it increased HDL-C (p < 0.05vs. HFD rats) in serum and the liver. HAS treatment increased the GSH level and SOD activity in the liver (p < 0.05vs. HFD rats), whereas it decreased the levels of MDA (p < 0.05vs. HFD rats). mRNA analyses suggested that HAS treatment increases the expression of Pparg (proliferator-activated receptor γ) and Apoe (peroxisome apolipoprotein E). Immunohistochemistry and Western blotting indicated that HAS stimulation increased the levels of PPARγ and APOE in the liver, as a stress response of the body defense system. These results revealed that HAS exerts antiobesity and hypolipidemic activities in HFD rats by reducing liver oxidative stress and thus could be considered as a potential candidate drug to cure or prevent obesity and hyperlipidemia.


The relationship between oxidative stress and preeclampsia. The serum ischemia-modified albumin levels and thiol/disulfide homeostasis.
Preeclampsia (PE) is a dangerous complication of pregnancy and still a major cause of maternal-fetal morbidity and mortality. Its etiology remains largely unknown, but researchers have suggested oxidative stress-mediated inflammation for the same. The purpose of this study is to investigate the relationship between oxidative stress and PE as well as the usability of oxidative stress indicators such as serum ischemia-modified albumin (IMA) levels and thiol/disulfide balance in the prediction of PE. The study included 47 pregnant women with PE and 57 healthy pregnant women. We measured their serum IMA, native thiol, total thiol, and disulfide levels. Additionally, we determined the optimal cutoff values via the receiver operating characteristic curve analysis. There were no differences between the two groups with respect to the maternal age, body mass index, gravida, and parity. The native and total thiol levels were found to be low when the disulfide and IMA levels were high in the patients with PE (p<0.05). When the IMA level was corrected by the albumin level (IMAR), the significant difference between the two groups disappeared. We also found that the native and total thiol concentrations were correlated with the systolic and diastolic blood pressures. The optimal cut-off values calculated for the prediction of PE were as follows: 178.45 µmol/L (with sensitivity of 72% and specificity of 83%) for native thiol, 232.55 µ mol/L (with a sensitivity of 75% and specificity of 85%) for total thiol, and 29.05 µmol/L (with sensitivity of 65% and specificity of 72%) for disulfide. The balance of thiol/disulfide may play a role in the pathogenesis of PE and could be used as a biological marker for PE.


Definition and assessment of accuracy in social stereotypes.
A perennial issue in the study of social stereotypes concerns their accuracy. Yet, there is no clear concept of the various ways in which stereotypes may be accurate or inaccurate and how one would assess their accuracy. This article is designed to rectify this situation. Three forms of stereotype inaccuracy are identified: stereotypic inaccuracy, valence inaccuracy, and dispersion inaccuracy. The implications of each form are discussed, along with how each can be assessed using a full-accuracy design. Past research that has attempted to examine stereotype accuracy is reviewed, and new data on the issue are presented. Although of perennial interest, the theoretical and methodological difficulties of assessing stereotype accuracy are substantial. The goal in this article is to alert the researcher to these difficulties and point toward their solution.


Hydrolases in vacuoles from castor bean endosperm.
Vacuoles were prepared from endosperm tissue of 4-day-old castor bean seedlings (Ricinus communis var. Hale) and purified on a stepped sucrose gradient. It was shown by assays of marker enzymes that there was only trace contamination of the final preparation by other organelles (mitochondria, glyoxysomes, nuclei, spherosomes, and plastids) and by cytoplasmic components. Hydrolytic enzymes (acid protease, carboxypeptidase, phosphodiesterase, RNAase, phytase and beta-glucosidase) were present in the isolated vacuoles in amounts indicating a primarily vacuolar localization in vivo. The vacuoles also contained storage protein and high concentrations of sucrose. The over-all results indicate that the vacuoles from castor bean endosperm are the site of hydrolysis of the constituents of the protein bodies and are a temporary storage compartment for the sucrose produced from fat and protein reserves.


Tendon healing and platelet-rich plasma therapies.
The therapeutic use of platelet-rich plasma (PRP) is an autologous biotechnology that relies on the local delivery of a wide range of growth factors and cytokines with the aim of enhancing tissue healing. Understanding both tendon healing and PRP therapies is an area of research that is critically important in developing optimal formulations and protocols to achieve the intended therapeutic effects. We summarise recent information on the mechanisms inherent to the earliest response to tendon injury. We then describe the positive effect of PRP therapies on tendon healing. Research on tendinopathy has produced several biological hypotheses based on histopathological, biochemical and clinical findings showing that cell apoptosis, angiofibroblastic features or abnormal biochemical adaptations underlie the condition. The article provides insights into early healing mechanisms and the influence of PRP therapies on inflammation, cell migration, angiogenesis and the proliferation and synthesis of extracellular matrix. The knowledge gained helps to better understand and optimize tendon therapies. The use of endogenous therapies has a positive effect on experimental tendon healing. However, several obstacles need to be addressed to optimise medical practice in this field.


Genetic risk factors in tumours of the testis: lessons from twin studies.
A threefold increase for testicular carcinoma has been reported in male dizygotic twins. In this comment we suggest the hypothesis that over-exposure to endogenously hypersecreted Follicle Stimulating Hormone (FSH) may underlie the pathogenesis. This is supported by several findings. 1) FSH hypersecretion in mothers of dizygotic twins is most likely an autosomal trait implicating the possibility of male offspring with the same hormone characteristic. 2) In testicular carcinoma higher levels of cyclin D2 are found. This is an FSH dependent stimulatory regulator of mitosis. 3) There is a marked similarity between geographical distribution in occurence of dizygotic twinning and testicular carcinoma. 4) Men undergoing surgery for testicular carcinoma have higher FSH concentrations and males with Down syndrome have higher FSH levels and are more at risk to develop testicular carcinoma. We suggest to study FSH secretion in males of familial dizygotic twins and furthermore the risk of developing testicular carcinoma in males with elevated FSH. These men with one testicle and/or with dysfunctioning Sertoli/Leydig cells.


[Musculoskeletal disorders and housework in Italy].
The housework exposes to the risk of musculoskeletal disorders, which may appear as disabling diseases, both temporary and permanent ones. To evaluate the epidemiology of the phenomenon a retrospective survey was conducted by administering a mail questionnaire to a sample of 1,000 families residing in the whole national territory. The participation rate was 31.7%. Among respondents 20.5% reported spinal pain, 65.6% of them with continuous pains (41.4% assumed pain-killer drugs). 37.0% of the interviewed persons reported to disorders in upper limbs. It was analysed the association between the presence of disorders and the frequency in making some housework duties. Washing clothes (OR=1.8; C.I. 95%: 0.6-4.5), making beds (OR=1.5; C.I. 95%: 0.2-13.1), and taking care of pets (OR=1.4; C.I. 95%: 0.6-3.4) were associated, even if not in a statistically significant way, with the presence of spinal pain. Upper limbs disorders were associated with duties naturally related to such a disorder, like washing dishes (OR=4.6; C.I. 95%: 1.3-16.5), cleaning clothes (OR=3.1; C.I. 95%: 1.3-7.0), cleaning up carpets (OR=2.3; C.I. 95%: 1.3-3.9). To assist the relatives in state of need was identified as risk factor for both the body areas (OR=2.9; C.I. 95%: 1.2-6.7 for the spine, OR=2.6; C.I. 95%: 1.3-5.2 for upper limbs), putting in evidence the physical stress attributable to the duty. The exact identification of the typology of housework which can induce musculoskeletal disorders, and the level of related risks, are essential information to devise campaigns and protocols of health education aimed at the prevention of chronic pathologies caused by the housework.


Tranexamic acid in acute upper gastrointestinal bleeding.
The effect of the antifibrinolytic substance, tranexamic acid, has been studied in 5 double-blind, randomized, placebo-controlled trials in patients with acute upper gastrointestinal bleeding. The results of these trials have varied with regard to blood transfusion requirements and the frequency of operations. All of the studies have shown lower mortality in patients treated with tranexamic acid. Thus tranexamic acid would seem to be indicated in acute upper gastrointestinal bleeding.


Family Socioecological Correlates of Lifestyle Patterns in Early Childhood: A Cross-Sectional Study from the EDEN Mother-Child Cohort.
Energy balance-related behaviors (EBRBs), i.e., diet, sedentary behavior, physical activity, and sleep, combine into lifestyle patterns, which we aim to identify in French preschoolers and analyze their family correlates within the framework of a comprehensive socioecological model. Parental questionnaires provided information about family characteristics and children's EBRBs for 978 5-year-olds of the EDEN cohort. We used principal component analysis to derive lifestyle patterns from EBRBs and hierarchical multivariable linear regressions to assess their associations with family socio-demographics, parent health/behaviors, and parent-child interactions. Analyses were stratified by sex. Of the three lifestyle patterns identified (unhealthy, healthy, and mixed), the mixed pattern differed the most between sexes. Lower parental education, suboptimal maternal diet, TV during meals, and later bedtime were associated with higher adherence to unhealthy patterns. Children cognitively stimulated at home and boys of mothers not employed adhered more to the healthy pattern. Older siblings (for girls) and higher engagement of parents in leisure-time physical activity (for boys) were related to greater adherence to mixed patterns. The identification of various correlates from multiple socioecological levels suggests that tackling the potentially synergistic effect of lifestyle patterns on health requires addressing processes relevant to the parent-child dimension and structural barriers parents may encounter.


Marked increases in cathepsin B and L activities distinguish papillary carcinoma of the thyroid from normal thyroid or thyroid with non-neoplastic disease.
Cathepsin B (CB) and cathepsin L (CL) are cysteine endopeptidases involved in the processing of thyroglobulin (Tg) in the normal thyroid. As thyroglobulin expression is frequently altered in thyroid carcinomas, we have analyzed 42 human thyroid tissues from 40 patients to study the effect of malignant transformation an the expression of these endopeptidases. Our samples included 18 cases of papillary carcinoma (of which 10 also had matched adjacent normal thyroid tissue), 6 cases of normal thyroid from autopsy patients, 1 case of follicular carcinoma, 2 cases of medullary carcinoma, 2 cases of follicular adenoma, 3 cases of Hashimoto's thyroiditis (HT) and 10 samples from 8 patients with multi-nodular goiter (MNG). Enzyme-specific activities were increased 15-fold for CB and 9-fold for CL in papillary carcinoma compared with normal adjacent thyroid tissue or normal thyroid from autopsies. CB mRNA content was also markedly increased in papillary carcinoma compared with normal thyroid, primarily due to elevated levels of the 2.2-kb CB mRNA transcript. In thyroids with nonneoplastic diseases, including MNG and HT, there was no significant increase in either CB or CL enzyme activities nor CB mRNA levels compared with normal thyroids from non-cancer cases. Immunohistochemical studies on papillary carcinomas revealed increased CB staining in papillary carcinoma cells, with prominent staining close to the basement membranes of many of the neoplastic cells. Our observations suggest that CB and CL enzyme activities are potentially useful new biochemical markers for distinguishing papillary carcinoma of the thyroid from non-neoplastic thyroid disease.


Social Media Platforms Listening Study on Atopic Dermatitis: Quantitative and Qualitative Findings.
Atopic dermatitis (AD) is a chronic, pruritic, inflammatory disease that occurs most frequently in children but also affects many adults. Social media have become key tools for finding and disseminating medical information. The aims of this study were to identify the main themes of discussion, the difficulties encountered by patients with respect to AD, the impact of the pathology on quality of life (QoL; physical, psychological, social, or financial), and to study the perception of patients regarding their treatment. A retrospective study was carried out by collecting social media posts in French language written by internet users mentioning their experience with AD, their QoL, and their treatments. Messages related to AD discomfort posted between July 1, 2010, and October 23, 2020, were extracted from French-speaking publicly available online forums. Automatic and manual extractions were implemented to create a general corpus and 2 subcorpuses depending on the level of control of the disease. A total of 33,115 messages associated with AD were included in the analysis corpus after extraction and cleaning. These messages were posted by 15,857 separate web users, most of them being women younger than 40 years. Tips to manage AD and everyday hygiene/treatments were among the most discussed topics for controlled AD subcorpus, while baby-related topics and therapeutic failure were among the most discussed topics for insufficiently controlled AD subcorpus. QoL was discussed in both subcorpuses with a higher proportion in the controlled AD subcorpus. Treatments and their perception were also discussed by web users. More than just emotional or peer support, patients with AD turn to online forums to discuss their health. Our findings show the need for an intersection between social media and health care and the importance of developing new approaches such as the Atopic Dermatitis Control Tool, which is a patient-related disease severity assessment tool focused on patients with AD.


The CASPR2 cell adhesion molecule functions as a tumor suppressor gene in glioma.
Genomic translocations have been implicated in cancer. In this study, we performed a screen for genetic translocations in gliomas based on exon-level expression profiles. We identified a translocation in the contactin-associated protein-like 2 (CASPR2) gene, encoding a cell adhesion molecule. CASPR2 mRNA was fused to an expressed sequence tag that likely is part of the nuclear receptor coactivator 1 gene. Despite high mRNA expression levels, no CASPR2 fusion protein was detected. In a set of 25 glioblastomas and 22 oligodendrogliomas, mutation analysis identified two additional samples with genetic alterations in the CASPR2 gene and all three identified genetic alterations are likely to reduce CASPR2 protein expression levels. Methylation of the CASPR2 gene was also observed in gliomas and glioma cell lines. CASPR2-overexpressing cells showed decreased proliferation rates, likely because of an increase in apoptosis. Moreover, high CASPR2 mRNA expression level is positively correlated with survival and is an independent prognostic factor. These results indicate that CASPR2 acts as a tumor suppressor gene in glioma.


[Histological classification of uveal melanoma].
Cytological classification of choroidal malignant melanomas recommended by WHO and based on the Callender classification (spindle A and B, mixed and epithelioid) is presented. Prognosis according to the histological types is discussed.


Association of Mortality-Related Risk Factors in Patients with COVID-19: A Retrospective Cohort Study.
COVID-19 is a rapidly disseminating infectious disease conferred by the World Health Organization (WHO) as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics data have been identified for patients with COVID-19, but mortality-related risk factors and a comprehensive clinical course of disease in a developing country have not been specifically defined. This retrospective, single-center cohort study involved all successive inpatients having a positive COVID-19 polymerase chain reaction (PCR), with deceased or discharged clinical outcomes from 1 January to 10 May 2021. Data were extracted from electronic medical records on demographic, clinical, radiological, and laboratory findings as well as complications faced and treatment provided during follow-up, involving serial samples for viral RNA identification, and compared between the dead and survivors. To investigate the risk factors associated with in-hospital mortality, we employed the multivariate logistic regression model. In this study, 2048 patients were involved, 1458 of whom were discharged, and 590 died in hospital. More than half of patients were identified as male with old age being the potential risk factor of mortality. Exactly 94.8% of all patients presented with fever at the time of admission. Several comorbidities were present in the study population, with the most frequent comorbidity being cardiovascular diseases (1177 of 2048) and hypertension (975 of 2048) followed by cerebrovascular disease and diabetes mellitus. Mortality rates for infected patients were observed as higher in severe patients (46.3%) compared with non-severe cases (26.1%) during a follow-up. Multivariate regression analysis showed a significant association of in-hospital mortality of patients with older age, presence of hypertension and cardiovascular diseases as underlying comorbidities, increased level of cardiac troponin I and d-dimer concentration on admission, as well as septicemia and ARDS as a complication during illness. To minimize the risk of death in COVID19 patients, as well as the risk of severe complications, urgent public health measures should be properly planned and implemented on those vulnerable populations. To detect early manifestations of clinical problems, thorough and regular follow-up is warranted.


Anticancer effect and apoptosis induction by quercetin in the human lung cancer cell line A-549.
The aim of the present study was to investigate the anticancer effect of quercetin (QC) in the human lung cancer cell line A-549 and further study the mechanism of apoptosis induction by QC. Low differentiation potential A-549 human lung cancer cells were treated with QC at different doses and for different times, and the growth inhibitory rates were detected by MTT assay. Apoptosis induced by QC in A-549 cells was observed by Annexin V/PI double staining and flow cytometric assay. The relative tumor growth ratio of the treated/control tumors (T/C) (%) was chosen to represent the tumor growth inhibition of A-549 cell nude mouse xenografts by QC. Apoptosis of the nude mouse xenografts was observed by Annexin V/PI double staining and flow cytometric assay and DNA fragmentation assay. To further determine the molecular mechanism of apoptosis induced by QC, changes in the expression of bcl-2 and bax genes were detected by RT-PCR. Following incubation with QC, the cell growth of the low differentiation potential A-549 human lung cancer cells was dramatically inhibited in a dose-dependent manner. After the cells were exposed to QC for 24, 48 and 72 h, the IC50 value was 1.02 ± 0.05, 1.41 ± 0.20 and 1.14 ± 0.19 µmol/l, respectively. Apoptosis in the A-549 cells induced by QC was noted. The apoptotic subpopulation of A-549 cells was approximately 12.96 and 24.58%, respectively, when cells were incubated with 1.2 µmol/l QC for 48 and 72 h. T/C (%) of A-549 nude mouse xenografts was 44.3, when the nude mice were treated with QC (8 mg/kg). Meanwhile, apoptosis induced by QC was observed in the A-549 nude mouse xenografts. Increased expression of the bax gene and decreased expression of the bc1-2 gene were noted using RT-PCR. Our results provide further evidence of the growth inhibition of the A-549 human lung adenocarcinoma cancer cell line by QC. This effect is associated with the induction of apoptosis in A-549 cells and the molecular mechanism may be related to the reduction in expression of the apoptosis-regulating gene bcl-2, and increase in expression of the apoptosis-regulating gene bax. These results were also confirmed in vivo.


Relationship between thyroid nodules and non-functioning adrenal incidentalomas and their association with insulin resistance.
The relationship between insulin resistance and thyroid nodules in patients with non-functional adrenal incidentalomas (AI) is not clearly understood. The aim of this study was to determine the frequency of thyroid nodules in AI patients, as well as to evaluate any possible associations with disorders of insulin resistance. Patients diagnosed with a non-functional AI were approached for inclusion in the study. Insulin resistance was evaluated using homeostasis model assessment (HOMA-IR). All participants were screened for the presence of thyroid nodule by ultrasonography, and fine needle aspiration biopsies were obtained from consenting subjects. One-hundred-thirteen patients with AI and 152 age-, BMI- and gender-matched healthy controls were enrolled. AI patients had higher waist circumference and waist/hip ratio than the control group. Metabolic syndrome, hypertension and type 2 diabetes mellitus rates were significantly higher in AI patients. HOMA-IR was similar between the groups. At least one thyroid nodule was observed in 42 (27.6%) of the controls compared to 55 (48.7%) of AI patients (p < 0.001). The mean number of thyroid nodules in AI patients was significantly higher than the control subjects (2.4 ± 0.9 versus 1.7 ± 1.0, p = 0.008). Mean nodule volume was similar between AI patients and the controls. A correlation could not be established between adrenal tumor/thyroid nodule volumes and the number of thyroid nodules, HOMA-IR, waist circumference, waist/hip ratio, BMI and thyroid function tests. A higher prevalence of thyroid nodule and a higher number of thyroid nodules were determined in patients with AI compared to healthy controls.


Features and outcomes of diffuse large B-cell lymphoma of the thyroid in a large contemporary cohort.
Among 42 133 cases of diffuse large B-cell lymphoma (DLBCL) registered at the Surveillance, Epidemiology and End Results (SEER) database between 2001 and 2009, we found 487 cases (1.2%) of thyroid DLBCL. Patients were predominantly female, older and less likely to present with advanced disease than their counterparts with DLBCL of another extranodal or nodal site. Survival was superior for patients with thyroid DLBCL, even when adjusted for patient characteristics and stage. Among the 411 patients with stage I/II disease (84%), 351 had available information regarding surgical resection and radiation and at least 4 months of follow-up. Risk of death was higher for subjects who did not receive resection or radiation (hazard ratio = 2.63, 95% confidence interval 1.43-4.85), but not affected by the omission of one of these therapeutic modalities. The use of surgery or radiation may add to systemic treatment and improve survival of patients with stages I/II thyroid DLBCL.


Programmed Adult Kidney Disease: Importance of Fetal Environment.
The Barker hypothesis strongly supported the influence of fetal environment on the development of chronic diseases in later life. Multiple experimental and human studies have identified that the deleterious effect of fetal programming commonly leads to alterations in renal development. The interplay between environmental insults and fetal genome can induce epigenetic changes and lead to alterations in the expression of renal phenotype. In this review, we have explored the renal development and its functions, while focusing on the epigenetic findings and functional aspects of the renin-angiotensin system and its components.


Absence of Lipid Oxidation during Accelerated Aging of Soybean Seeds.
When seeds of soybean were subjected to accelerated aging, the amount of total lipid which was extracted from the whole seed increased with "age," whereas the extractable phospholipid decreased slightly. This small decline primarily reflected changes in the amounts of phosphatidylcholine and phosphatidylethanolamine. The levels of unsaturated fatty acids in the whole seed and in the seed axis showed no decline during aging. Similarly, the fatty acids in a polar lipid extract from the whole seed showed little change in unsaturation. These results suggest that oxidation of seed lipids may be unrelated to the process of seed aging.


Cryoglobulinemia as an initial manifestation of underlying hematological malignancy: a rare occurrence in India.
Cryoglobulinemias rarely been reported from India even though associated conditions such as hepatitis C infection, rheumatoid arthritis and plasma cell dyscrasias, etc., are common occurrences. In many regions of the country, temperatures in winter can be conducive to the precipitation of cryoglobulins, yet epidemiology of the disease suggests that it is a common condition in the west. We encountered a 68-year-old-male patient who presented with a history of headache off and on along with hepatosplenomegaly. The rare occurrence of cryoglobulinemia in our setting can delay the diagnosis, as happened in our case, since the index of suspicion of clinicians and laboratory personnel is low. We are reporting this case because of the rarity and protean clinical manifestations of cryoglobulinemia.


An additional case of craniodigital syndrome: variable expression of the Filippi syndrome?
We report on a boy with severe growth and mental retardation, syndactyly of toes and facial anomalies. This phenotype can easily be classified in the group of craniodigital syndromes, but it is difficult to make a more clearly defined diagnosis, based on other minor anomalies, because of the presence of overlapping features. On the basis of various pathognomic features, we conclude that our patient could be an additional case of Filippi syndrome. Moreover, newly recognised features in this patient may be due to variability in phenotypic expression.


Antitranspirant associated abscisic Acid effects on the water relations and yield of transplanted bell peppers.
Greenhouse and field experiments were performed to determine if increased leaf resistance induced by exogenous application of abscisic acid (ABA) could enhance the water status of transplanted bell pepper seedlings. Seedling survival and yield were also monitored in the field experiment. When seedlings were transplanted into either wet or dry potting mix in the greenhouse, ABA increased leaf resistance and leaf water potential. In the field, plots were irrigated either immediately after, or 1 day after transplanting. Under both treatments, ABA application resulted in increased leaf resistance and water potential, but seedling survival and yield were enhanced due to ABA only in plots which were irrigated 1 day after transplanting. It is concluded that antitranspirant application can reduce transplant shock and increase yield of bell pepper.


The influence of pyridoxin in the treatment of tetanus neonatorum.
During a 2-year-period (1988-1990) 31 patients with tetanus neonatorum were recruited for this study. The patients were divided into 2 groups: The first group (15 patients) was treated with ATS injection, oral metronidazole and amoxycillin, and diazepam suppositoria. The second group (16 patients) was treated with the same regimen, as the first group plus pyridoxin injection 100 mg on the first day followed by 25 mg orally on the next days. There was no statistical difference in the two groups concerning the gestation period, sex, severity of the disease (p greater than 0.05), place of delivery (all at home) and mode of delivery delivered by traditional midwife/dukun). The mortality of the first group (without pyridoxin) was 60% and the second (with pyridoxin) 37.5% (p less than 0.05).


Creating seamless junctions independent of restriction sites in PCR cloning.
A method is described for the efficient cloning of any given DNA sequence into any desired location without the limitation of naturally occurring restriction sites. The technique employs the polymerase chain reaction (PCR) combined with the capacity of the type-IIS restriction endonuclease (ENase) Eam1104I to cut outside its recognition sequence. Primers that contain the Eam1104I recognition site (5'-CTCTTC) are used to amplify the DNA fragments being manipulated. Because the ENase is inhibited by site-specific methylation in the recognition sequence, all internal Eam1104I sites present in the DNA can be protected by performing the PCR amplification in the presence of 5-methyldeoxycytosine (m5dCTP). The primer-encoded Eam1104I sites are not affected by the modified nucleotides (nt) since the newly synthesized strand does not contain any cytosine residues in the recognition sequence. In addition, the ENase's ability to cleave several bases downstream from its recognition site allows the removal of superfluous, terminal sequences from the amplified DNA fragments, resulting in 5' overhangs that are defined by the nt present within the cleavage site. Thus, the elimination of extraneous nt and the generation of unique, non-palindromic sticky ends permits the formation of seamless junctions in a directional fashion during the subsequent ligation event.


Dual-Time-Point FDG Uptake Correlates with Prognostic Factors of Invasive Breast Cancer: Clinical Usefulness of Early Delayed Scanning.
This study investigated correlations between fluorodeoxyglucose (FDG) uptake in tumors as assessed by modified dual-time-point (mDTP) FDG positron emission tomography/computed tomography (PET/CT) in invasive breast cancer (iBC) and several prognostic parameters. Thirty-two women who underwent mastectomies for iBC were retrospectively evaluated. mDTP scanning was performed using standard FDG PET/CT (PET1), followed by early delayed acquisition (PET2) without repositioning and additional CT scanning. Using maximal standardized uptake values on PET1 (SUV1) and PET2 (SUV2) in the primary breast tumor, the percentage changes between SUV1 and SUV2 (retention index, (RI)) were calculated. Prognostic parameters (e.g., tumor size and stage; number of metastatic lymph nodes; histologic grade; expression of estrogen receptor (ER), progesterone, epidermal growth factor receptor (HER-2), and p53; and the Ki-67 labeling index (LI)) were evaluated from the surgical specimens. PET2 scans were conducted 17.7 ± 1.5 min after PET1. RI values gradually increased as the histologic grade increased (p = 0.016), and were significantly higher when ER expression was absent (p = 0.023) and Ki-67 LI was high (p < 0.001). RI values also showed a moderately positive correlation with Ki-67 LI (r = 0.629; p < 0.001). RI correlated with well-known biologic prognostic factors of iBC and mDTP scanning, which could be used as a substitute for conventional DTP PET.


Utilization of Exogenous Inorganic Carbon Species in Photosynthesis by Chlorella pyrenoidosa.
The nature of the inorganic carbon utilized during photosynthesis by Chlorella pyrenoidosa was investigated using three experimental techniques (open gas analysis system with "artificial leaf" or "aqueous" chambers and O(2) electrode system) to measure carbon assimilation. Photosynthesis was studied as a function of pH and CO(2) concentration. The CO(2) concentration was inadequate to meet the requirements of photosynthesis only when HCO(3) (-) was added at high pH. Under all other conditions, the low and constant K(m) (CO(2)), in contrast to the highly variable K(m) (HCO(3) (-)), suggested that CO(2) was the major species utilized.Higher rates of photosynthesis were observed under limiting CO(2) conditions above pH 7.5 but rates of hydration of CO(2) were not consistent with the view that the stimulation in photosynthesis was supported by HCO(3) (-). In the same pH region lower rates of photosynthesis were observed under saturating CO(2) conditions. These conflicting changes seemed not to be related to pH but to some as yet undetermined effect of bicarbonate. No support was obtained for the view that the quantum efficiency was different under conditions where CO(2) was assimilated compared to conditions where CO(2) and HCO(3) (-) could be assimilated, although at saturating CO(2), lower maximal rates of photosynthesis were observed in the latter conditions.


Co-expression of myeloid antigens in childhood acute lymphoblastic leukaemia: relationship with the stage of differentiation and clinical significance.
Co-expression of myeloid antigens on the leukaemic blast cells was evaluated in 532 children with a diagnosis of acute lymphoblastic leukaemia (ALL). Using a panel of monoclonal antibodies belonging to CD11b, CD13, CD14, CD15 and CD33 an overall incidence of 4.3% was found, with values ranging between 1.8% for CD14 and 6.1% for CD15. When the data were further dissected, a significantly higher incidence of co-expression was noted in null-ALL (15/70 cases = 21.4%), compared to cases expressing a more mature immunophenotype, i.e. common-ALL (7/394 cases = 1.7%) and T-ALL (1/68 cases = 1.4%) (P less than 0.001). In null-ALL, 9/15 patients were infants, five of whom with the t(4;11); two further children also had a t(4;11). The clinical outcome of the 23 cases which co-expressed myeloid antigens was unfavourable. Only two of the 15 null-ALL, two of the seven common-ALL and the unique case with T-ALL are in fact in persistent first remission between 19 and 93 months from diagnosis. Though the overall incidence of childhood ALL expressing myeloid antigens is low, the evidence that this co-expression may be related to an unfavourable clinical course and that it more frequently occurs in null-ALL, particularly in the first year of life, suggests that the routine assessment of myeloid antigens may allow to identify a subgroup of childhood ALL with a poor clinical outcome.


Simultaneous expression of plural forms of human cytochrome P450 at desired ratios in HepG2 cells: adenovirus-mediated tool for cytochrome P450 reconstitution.
Human hepatocyte culture is widely used to predict human drug metabolism for new drug development. The limited supply and lot-to-lot (donor-to-donor) variations in enzymatic activity, however, hamper its applicability. In the present study, we explore a new cell system with adenovirus-mediated expression of cytochrome P450s (P450s) as an alternative for hepatocytes. In this system, P450 apoprotein levels and catalytic activity increased depending on the amounts of adenoviruses infected for the individual expression of CYP3A4 or CYP2C19 in HepG2 cells. Similar results were observed in the system with co-expression of CYP3A4 and CYP2C19. When HepG2 cells were infected with adednovirus for CYP3A4 and that for CYP2C19 simultaneously at a ratio of 10:1, the ratio of their apoprotein levels was similar to that observed in human hepatocytes and the metabolic profile of diazepam in the system was almost identical to that observed in hepatocyets. These results indicate that this adenovirus-mediated system makes it possible to reproducibly prepare cells expressing multiple P450s at a desired ratio, suggesting a possible use of this system in preclinical metabolic tests for a drug candidate(s), particularly to assess the influence of inter-individual variation in P450 activity.


Risk factors related to late metastases in 1,372 melanoma patients disease free more than 10 years.
In many centers, Stage I-II melanoma patients are considered "cured" after 10 years of disease-free survival and follow-up visits are interrupted. However, melanoma may relapse also later. We retrospectively analyzed a cohort of 1,372 Stage I-II melanoma patients who were disease-free 10 years after diagnosis. The aim of this study was to characterize patients who experienced a late recurrence and to compare them to those who remained disease-free to identify possible predictive factors. Multivariate Cox proportional-hazards regression analyses were carried out to evaluate the influence of different factors on the risk of recurrence. Seventy-seven patients out of 1,372 (5.6%) relapsed, 52 in regional sites and 25 in distant ones. The majority of patients (31 out of 52) experienced late recurrence in regional lymph nodes. Brain and lung were the most common site of single distant recurrence (24% each). Patients with multiple distant metastases showed a brain and lung involvement in, respectively, 40 and 48% of cases. A Cox proportional-hazards regression model analysis showed the independent role of age under 40 years, Breslow thickness >2 mm, and Clark Level IV/V in increasing the risk of Late Recurrence. These patients should be followed-up for longer than 10 years. The pattern of recurrence suggests that melanoma cells can be dormant preferentially in lymph nodes, brain and lung. A particular attention should be reserved to these anatomic sites during the follow-up after 10 years of disease-free.


Cytogenetic analysis of radiation-induced leukemia in Trp53-deficient C3H/He mice.
C3H/He mice develop acute myeloid leukemia (AML) after whole-body irradiation, but the strain becomes highly susceptible to stem cell leukemia (SCL) when a null mutation is introduced into the Trp53 gene. To examine the etiology of SCL and the influence of chromosomal instability on leukemogenesis, 12 SCLs and two AMLs arising from Trp53-deficient C3H/He mice were investigated cytogenetically. Each SCL demonstrated cell-to-cell variation in the number and structural integrity of their chromosomes, indicating chromosomal instability. Typical deletion of chromosome 2 was observed in the two AML cases, while most SCL cells did not display this aberration. Deletions and rearrangements of chromosome 11 were noticeable in SCLs from Trp53 heterozygotes but not in AMLs. Analysis of loss of heterozygosity revealed that aberrations involving chromosome 11 in SCLs resulted in loss of the wild-type Trp53 allele. These results suggest that loss of Trp53 function triggers the tumorigenic process leading toward SCL through the induction of chromosomal instability, and that SCL and AML are distinct varieties of leukemia.


DNA fingerprinting in reptiles: Bkm hybridization patterns in Crocodilia and Chelonia.
The simple tetranucleotide repeat GATA (GACA) occurs in all eukaryotes so far studied. In many species, the arrangement of these sequences varies considerably among individuals. Thus GATA (GACA) type probes produce DNA fingerprints when hybridized with restricted DNA from different individuals within a species. Banded krait minor (Bkm) satellite DNA (related to sequences originally recovered from the W chromosome of the banded krait and consisting essentially of a series of GATA repeats) is found in a wide spectrum of vertebrates and invertebrates. We used the Bkm 2(8) clone to evaluate the occurrence of this satellite in DNA from five species of Crocodilia and six species of Chelonia, including the sea turtles Chelonia mydas and Lepidochelys kempi. Well-resolved DNA fingerprints were obtained. Among the crocodilians, fewer restriction fragments were generated and fewer of the fragments were polymorphic, than among the chelonians, consistent with the view that the crocodilians are less divergent within species. The Bkm 2(8) clone can accordingly be used to advantage in individual, familial, and population studies, and perhaps in the evaluation of taxonomic relationships in these animals. This is of potential value in endangered species such as C. mydas and L. kempi.


Occlusal contacts in maximum intercuspation in normal dentitions.
A cross-sectional study of the contacts in maximum intercuspation was undertaken using a method to identify occlusal contacts, which is indicated as satisfactory by modern research. The aims were to describe in subjects with normal dentitions and normally functioning masticatory systems: (a) the general distribution of contacts; (b) the numbers in the various classes and types of occlusal contacts; (c) the numbers of teeth without contact. A randomized sample of 18 women and 20 men was used. Classical theoretical proposals for the numbers, distribution and nature of occlusal contacts were not supported. Wide variability was evident and asymmetry of distribution on the right and left sides of individual subjects was common. Contacts with stabilizing tendencies involved the mandibular supporting cusps in 79% of occurrences. Overall, the difference in the number of contacts with stabilizing effects was not significantly different from the number with unstabilizing tendencies. Contacts with mechanically unstabilizing effects did not produce clinically discernible, unfavourable sequelae in the dentitions. Because of the sparse number of stabilizing contacts, interventions involving the occlusal surfaces should maintain or improve on the number of such contacts in maximum intercuspation.


Linearly polarized single TM mode terahertz waveguide.
We design a hollow-core terahertz (THz) waveguide guiding a single linearly polarized mode. This is achieved using a hybrid cladding, where we introduce a ring of subwavelength structures, including metal wires and air-holes. The wire-based cladding is extremely anisotropic, reflecting only transverse magnetic (TM) modes. The polarization of TM modes is further manipulated by replacing some wires with air-holes. Numerical simulations confirm the guidance of only an x-polarized TM2 mode over 0.36-0.46 THz in a wavelength-scale core (diameter of 1 mm). The propagation losses are of the order 0.25 dB/cm, with low bend losses <0.3 dB/cm at 0.4 THz for a bend radius of 5 cm.


[Effects of soil fauna on microbial community during litter decomposition of Populus simonii and Fargesia spathacea in the subalpine forest of western Sichuan, China.]
To understand the relationship between soil fauna and microorganism in the detrital food chain during litter decomposition, leaf litters of poplar (Populus simonii) and fargesia (Fargesia spathacea) in a subalpine forest of western Sichuan were taken as study objects. Phospholipid fatty acid (PLFAs) biomarker method was used to determine the effects of soil fauna on the abundance, structure and diversity of microbial community during the decomposition of leaf litter of two species from April 2016 to April 2018 with in situ control experiment. The results showed that the presence of soil fauna significantly affected the microbial PLFAs content during the decomposition of both species, reducing the PLFAs content in the first 240 days and increasing the PLFAs content in the 360 to 480 days. Soil fauna participation reduced the ratio of fungi to bacteria in the decomposition of poplar litter, and increased the ratio of gram-positive bacteria (G+) to gram-negative bacteria (G-), which had the opposite effect on the ratio of fungi/bacteria and G+/G- in the decomposition of fargesia litter. Microbial diversity and evenness maintained a high level in 120th and 480th days of the decomposition, and decreased sharply in 360th and 720th days of decomposition. Soil fauna participation significantly affected microbial diversity and evenness of poplar litter, but it had no signifi-cant effect on fargesia litter. The effects of soil fauna on the changes of litter PLFAs content were different with the decomposition days and tree species. The interaction between soil fauna and microbial community during litter decomposition in subalpine forest varied with seasons and tree species.


Association of worsening of nonalcoholic fatty liver disease with cardiometabolic function and intestinal bacterial overgrowth: A cross-sectional study.
Non-alcoholic fatty liver disease (NAFLD) has been associated with small bowel bacterial overgrowth (SIBO) and cardiometabolic dysfunction. This cross-sectional study aimed to evaluate the cardio-metabolic parameters and SIBO in patients with different degrees of hepatic fibrosis estimated by NAFLD fibrosis score (NFS). Subjects (n = 78) were allocated to three groups: Healthy control (n = 30), NAFLD with low risk of advanced fibrosis (NAFLD-LRAF, n = 17) and NAFLD with a high risk of advanced fibrosis (NAFLD-HRAF, n = 31). Anthropometrics, blood pressure, electrocardiogram and heart rate variability (HRV) were evaluated. Only the NAFLD-LRAF and NAFLD-HRAF groups were submitted to blood biochemical analysis and glucose hydrogen breath tests. The NAFLD-HRAF group had higher age and body mass index when compared to the control and NAFLD-LRAF groups. The prevalence of SIBO in the NAFLD group was 8.33%. The low frequency/high-frequency ratio (LF/HF ratio) was augmented in NAFLD-LRAF (p < 0.05) when compared with control group. NAFLD-HRAF group had a wide QRS complex (p < 0.05) and reduced LF/HF ratio (p < 0.05) compared to the control and NAFLD-LRAF groups. Serum levels of albumin and platelets were more reduced in the NAFLD-HRAF subjects (p < 0.05) than in the NAFLD-LRAF. NAFLD impairs cardiac autonomic function. Greater impairment was found in subjects with a worse degree of hepatic fibrosis estimated by NFS. Hypoalbuminemia and thrombocytopenia were higher in subjects with a worse degree of hepatic fibrosis, whereas prevalence of SIBO positive was similar between the groups.


Filicide in South Asia: Demography, risk factors, psychiatric, and legal aspects.
Background & Objective: Filicide is an act of killing a child up to the age of 18 years committed by his or her parent(s) or parental figure(s), including guardians and stepparents. There is absence of data and research regarding filicide in South Asia. The present study aimed to address the empirical lacuna in South Asia and to expand the literature in order to broaden the understanding of filicide. Method: The search was conducted in the databases of PubMed, PubMed Central, Scopus, and Google Scholar. The original articles, quantitative studies, case studies, and full-length articles were included for the present review. Publications in only the English language, which clarified that the child was killed by parent(s) in eight South Asian countries from 2000 to 2020 were included. Results: A total of 13 reports of filicide were found in the eight South Asian countries; 12 from India and 1 from Pakistan. The most common method of filicide was by administering poisonous substances and burning by parents, depression was responsible for 7 cases of filicide, schizophrenia was responsible for one case. Conclusion: The review identified that there is a scarcity of research on filicide in South Asia. Rigorous research and investment for the compilation of data on filicide are needed to reduce it in South Asia. This may further help in the protection of lives of children as well as for taking steps for rehabilitation of parents and society.


Antiaromaticity Gain Activates Tropone and Nonbenzenoid Aromatics as Normal-Electron-Demand Diels-Alder Dienes.
We propose a carbonyl umpolung strategy for activating tropone as a normal-electron-demand Diels-Alder diene. Tropone has low reactivity for Diels-Alder reactions because of its [4n+2] π-aromaticity. Conversion of the carbonyl group into a hydrazone ion (═N-NR-) reverses the polarity of the exocyclic double bond, increases the [4n] ring π-antiaromaticity, and raises the HOMO energy. Computed gas-phase activation free energies for a Diels-Alder reaction with maleimide suggest a billion-fold rate increase when the tropone C═O is replaced by ═N-NR- (R = H or SO2CH3). Other nonbenzenoid aromatics can be activated as normal-electron-demand Diels-Alder dienes in the same way.


A clinical study to assess the immunogenicity and safety of a monovalent 2009 influenza A (H1N1) vaccine in an area with low-level epidemics of pandemic influenza.
We conducted a multi-center, randomized, laboratory-blinded clinical trial in 185 healthy adults (<60 years) and 107 elders (>60 years) to examine the immunogenicity and safety of different doses of an inactivated, monovalent, non-adjuvanted, split vaccine against the 2009 pandemic influenza A (H1N1) virus. The 186 adults were assigned to three treatment groups, i.e., one 15 μg hemagglutination (HA) antigen dose, two 15 μg or 30 μg HA doses in 3 weeks apart, and the 107 elders were treated with two 15 μg or 30 μg doses in 3 weeks apart. Prior to the vaccination, 4.8% subjects had hemagglutination-inhibition (HAI) antibody titers of 1:40 or more. By day 21 post-vaccination of one dose of 15 μg HA, the seroprotective rate was 95.1% and 75.5% in subjects <60 and >65 years of age, respectively; by day 21 post the second 15 μg HA dose, the seroprotective rates were 93.2% and 73.1%, respectively. The seroprotective rates for recipients of 30 μg HA antigen by day 21 were 95.2% for subjects <60 years and 81.1% for subjects >65 years of age, that was boosted to 98.3% and 80.4%, respectively with a second dose of 30 μg HA antigen. No vaccine-related serious adverse events occurred. The data indicated a single 15 μg HA dose of the vaccine induced a protective immune response in most adults, including the elders >60 years of age, and a booster dose at the third week did not render a higher level of antibody response.


Prospective clinical evaluation of serum cardiac troponin T in dogs admitted to a veterinary teaching hospital.
The purpose of this study was to measure serum cardiac troponin T (cTnT) with a commercially available human enzyme-linked immunoassay (ELISA) test in various groups of dogs, including those undergoing doxorubicin chemotherapy. Serum samples were obtained from 6 groups of dogs: (1) normal adult dogs (n = 15); (2) dogs with asymptomatic dilated cardiomyopathy (n = 5); (3) dogs with congestive heart failure (n = 10); (4) dogs with untreated neoplasia (n = 20); (5) dogs with skeletal muscle trauma (n = 10); and (6) dogs with neoplasia receiving doxorubicin chemotherapy (n = 4). One serum sample was obtained from each of the normal dogs, those with asymptomatic cardiomyopathy, those with congestive heart failure, and those with untreated neoplasia. Serum samples were obtained serially from the dogs that were undergoing doxorubicin chemotherapy; samples were collected before doxorubicin (30 mg/m2) administration and then 1, 5, 7, and 14 days after administration throughout 6 cycles for a cumulative total dose of 180 mg/m2. All normal dogs, dogs with untreated neoplasia, and dogs with asymptomatic dilated cardiomyopathy had cTnT concentrations below the lower limits of detection for the assay used (<0.05 ng/mL). Detectable concentrations of cTnT were found in 3 dogs with congestive heart failure and in 2 dogs with skeletal muscle trauma. Detectable concentrations also were found in both dogs that had received 180 mg/m2 of doxorubicin. We conclude that dogs with congestive heart failure and those with skeletal muscle trauma and dogs with neoplasia receiving high-dose doxorubicin chemotherapy may have increased serum cTnT concentration, which may be suggestive of myocardial damage.


Sexual segregation in ungulates: a comparative test of three hypotheses.
In most social ungulate species, males are larger than females and the sexes live in separate groups outside the breeding season. It is important for our understanding of the evolution of sociality to find out why sexual segregation is so widespread not only in ungulates but also in other mammals. Sexual body size dimorphism was proposed as a central factor in the evolution of sexual segregation in ungulates. We tested three hypotheses put forward to explain sexual segregation: the predation-risk, the forage-selection, and the activity budget hypothesis. We included in our analyses ungulate species ranging from non-dimorphic to extremely dimorphic in body size. We observed oryx, zebra, bighorn sheep and ibex in the field and relied on literature data for 31 additional species. The predation-risk hypothesis predicts that females will use relatively predator-safe habitats, while males are predicted to use habitats with higher predation risk but better food quality. Out of 24 studies on different species of ungulates, females and their offspring chose poorer quality but safer habitat in only eight cases. The forage-selection hypothesis predicts that females would select habitat based on food quality, while males should prefer high forage biomass. In fact, females selected higher quality food in only six out of 18 studies where males and females segregated, in eight studies there was no difference in forage quality and in four studies males were in better quality habitat. The activity budget hypothesis predicts that with increasing dimorphism in body size males and females will increasingly differ in the time spent in different activities. Differences in activity budgets would make it difficult for males and females to stay in mixed-sex groups due to increased costs of synchrony to maintain group cohesion. The predictions of the activity budget hypothesis were confirmed in most cases (22 out of 23 studies). The heavier males were compared to females, the more time females spent foraging compared to males. The bigger the dimorphism in body mass, the more males spent time walking compared to females. Lactating females spent more time foraging than did non-lactating females or males. Whether species were mainly bulk or intermediate feeders did not affect sexual differences in time spent foraging. We conclude that sexual differences in activity budgets are most likely driving sexual segregation and that sexual differences in predation risk or forage selection are additive factors.


Biostatistics: a toolkit for exploration, validation, and interpretation of clinical data.
Biostatistics plays a key role in all phases of clinical research starting from the design to the monitoring, data collection, data analysis, and interpretation of the results. A clear understanding of the statistical framework as it relates to the study hypothesis, reported results, and interpretation is vital for the scientific integrity of the study and its acceptance in the general medical community. In this brief report, we will put in perspective the general analytical framework for exploring and validating prognostic factors using data from large databases.


Sleep complaints among elderly persons: an epidemiologic study of three communities.
The frequencies of five common sleep complaints--trouble falling asleep, waking up, awaking too early, needing to nap and not feeling rested--were assessed in over 9,000 participants aged 65 years and older in the National Institute on Aging's multicentered study entitled "Established Populations for Epidemiologic Studies of the Elderly" (EPESE). Less than 20% of the participants in each community rarely or never had any complaints, whereas over half reported at least one of these complaints as occurring most of the time. Between 23% and 34% had symptoms of insomnia, and between 7% and 15% percent rarely or never felt rested after waking up in the morning. In multivariate analyses, sleep complaints were associated with an increasing number of respiratory symptoms, physical disabilities, nonprescription medications, depressive symptoms and poorer self-perceived health. Sleep disturbances, particularly among older persons, oftentimes may be secondary to coexisting diseases. Determining the prevalence of specific sleep disorders, independent of health status, will require the development of more sophisticated and objective measures of sleep disturbances.


Adaptive hypertrophy of the digit following little finger to thumb transposition.
This is a long-term retrospective study of eight patients who had undergone little finger to thumb transposition after traumatic thumb loss in order to evaluate the presence of long-term changes in the transposed digit. The transposed little finger, contralateral (nontransposed) little finger, and contralateral thumb were compared using standardized measurements of size, comparison photographs, x-rays, and volume determination using silicone mold impressions of these digits. Significant and marked hypertrophy of the transposed digit was demonstrated in all these patients. Comparison radiographs demonstrated that this enlargement was due to hypertrophy of both soft-tissue and osseous components. This study demonstrates that the little finger transposed to the thumb position undergoes an adaptive hypertrophy to become more thumblike in appearance as well as function.


Comparison of mutagenic activities of several peroxyacyl nitrates.
Salmonella typhimurium, strain TA100 was exposed to a series of peroxyacyl nitrates including peroxyacetyl nitrate (PAN), peroxypropionyl nitrate (PPN), peroxybutyryl nitrate (PBN), peroxybenzoyl nitrate (PBzN), and chloroperoxyacetyl nitrate (CPAN). Gas-phase concentrations for the individual exposures were in the high part per billion by volume ppbv range. The dose was determined from the deposition rate and measured from the net decrease of the test compound in the exposure chamber and the exposure time. The mutagenic activity for each compound determined from the dose-response relationship gave values ranging from 250 (PBN) to 6,500 (PBzN) revertants/mumols. The mutagenic activity for CPAN could not be determined, due to an interference from chloroacetaldehyde. The difficulties of quantifying the actual gas-phase chemical dose the bacteria are exposed to in this variant of the Ames test are delineated.


A novel approach for monitoring genetically engineered microorganisms by using artificial, stable RNAs.
Further improvements in technology for efficient monitoring of genetically engineered microorganisms (GEMs) in the environment are needed. Technology for monitoring rRNA is well established but has not generally been applicable to GEMs because of the lack of unique rRNA target sequences. In the work described herein, it is demonstrated that a deletion mutant of a plasmid-borne Vibrio proteolyticus 5S rRNA gene continues to accumulate to high levels in Escherichia coli although it is no longer incorporated into 70S ribosomes. This deletion construct was subsequently modified by mutagenesis to create a unique recognition site for the restriction endonuclease BstEII, into which new sequences could be readily inserted. Finally, a novel 17-nucleotide identifier sequence from Pennisetum purpureum was embedded into the construct to create an RNA identification cassette. The artificial identifier RNA, expressed from this cassette in vivo, accumulated in E. coli to levels comparable to those of wild-type 5S rRNA without being seriously detrimental to cell survival in laboratory experiments and without entering the ribosomes. These results demonstrate that artificial, stable RNAs containing sequence segments remarkably different from those present in any known rRNA can be designed and that neither the deleted sequence segment nor ribosome incorporation is essential for accumulation of an RNA product.


Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors.
The second messenger cAMP has been implicated in the regulation of mammalian and amphibian oocyte maturation. Although a decrease in intraoocyte levels of cAMP precedes germinal vesicle breakdown (GVBD), the gonadotropin induction of ovulation and oocyte maturation is associated with major increases of cAMP in ovarian follicles. In the mammalian system, isolated oocytes undergo spontaneous maturation in vitro but this process is blocked by treatment with a phosphodiesterase (PDE) inhibitor, IBMX, which increases intraoocyte cAMP levels. In contrast, the same inhibitor, when added to cultured follicles for a brief time, increases follicle cAMP levels, followed by the induction of GVBD. To resolve the paradoxical actions of this PDE inhibitor on the maturation of isolated and follicle-enclosed oocytes, we hypothesized that meiotic maturation requires opposing fluctuations of cAMP levels in the somatic granulosa and germ cells. Such opposing fluctuations may result from selective expression and regulation of PDEs in the somatic and germ cell compartments of the follicle. To test this hypothesis, PDE activity was manipulated in different follicular cells using type-specific inhibitors. The impact of the ensuing changes in cAMP levels in the two compartments was monitored by the induction of GVBD. In isolated oocytes, spontaneous GVBD was blocked by two inhibitors of type 3 PDE (cGMP-inhibited: CGI-PDE), milrinone and cilostamide. In contrast, treatment with an inhibitor for type 4 PDE (cAMP-specific), rolipram, was ineffective. These findings suggest that the oocyte expresses type 3 but not type 4 PDE and that increases in intraoocyte cAMP suppress GVBD. This hypothesis was confirmed by in situ hybridization studies with PDE3 and PDE4 probes. PDE3B mRNA was concentrated in oocytes while PDE4D was mainly expressed in granulosa cells. In cultured follicles, LH treatment induced oocyte maturation but the gonadotropin action was blocked by inhibitors of type 3 but not the type 4 PDE inhibitors. Furthermore, treatment with the type 4, but not the type 3, PDE inhibitor mimics the action of LH and induces oocyte maturation, presumably by increasing cAMP levels in granulosa cells. Our findings indicate that PDE subtypes 4 and 3 are located in follicle somatic and germ cells, respectively. Preferential inhibition of PDE 3 in the oocyte may lead to a delay in oocyte maturation without affecting the cAMP-induced ovulatory process in the somatic cells. Conversely, selective suppression of granulosa cell cAMP-PDE may enhance the gonadotropin induction of ovulation and oocyte maturation. Thus, in addition to the well-recognized differential expression and regulation of adenylate cyclase in the somatic and germ cell compartments of the follicle, we suggest that selective regulation and expression of PDEs may be involved in the regulation of cAMP levels and control of oocyte maturation in the preovulatory mammalian follicle.


Brucella abortus Promotes a Fibrotic Phenotype in Hepatic Stellate Cells, with Concomitant Activation of the Autophagy Pathway.
The liver is frequently affected in patients with active brucellosis. The present study demonstrates that Brucella abortus infection induces the activation of the autophagic pathway in hepatic stellate cells to create a microenvironment that promotes a profibrogenic phenotype through the induction of transforming growth factor-β1 (TGF-β1), collagen deposition, and inhibition of matrix metalloproteinase-9 (MMP-9) secretion. Autophagy was revealed by upregulation of the LC3II/LC3I ratio and Beclin-1 expression as well as inhibition of p62 expression in infected cells. The above-described findings were dependent on the type IV secretion system (VirB) and the secreted BPE005 protein, which were partially corroborated using the pharmacological inhibitors wortmannin, a phosphatidyl inositol 3-kinase inhibitor, and leupeptin plus E64 (inhibitors of lysosomal proteases). Activation of the autophagic pathway in hepatic stellate cells during Brucella infection could have an important contribution to attenuating inflammatory hepatic injury by inducing fibrosis. However, with time, B. abortus infection induced Beclin-1 cleavage with concomitant cleavage of caspase-3, indicating the onset of apoptosis of LX-2 cells, as was confirmed by the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay and Hoechst staining. These results demonstrate that the cross talk of LX-2 cells and B. abortus induces autophagy and fibrosis with concomitant apoptosis of LX-2 cells, which may explain some potential mechanisms of liver damage observed in human brucellosis.


Detection of antibody responses and delayed dermal hypersensitivity with Blastomyces dermatitidis yeast and mycelial lysate antigens.
Yeast cell lysate and mycelial lysate antigens prepared from one strain (T-58) of Blastomyces dermatitidis were evaluated with respect to the detection of antibodies and delayed dermal hypersensitivity. Comparable ELISA sensitivity values were evidenced with the two antigens when assayed against serum specimens from dogs with blastomycosis, sera from non-infected dogs residing in endemic and non-endemic areas for blastomycosis and sera from rabbits that were hyperimmunized with B. dermatitidis antigens. Specificity determinations with anti-Histoplasma capsulatum rabbit sera indicated that both reagents exhibited only minimal cross-reactivity; the mycelial antigen was slightly more specific than the yeast phase reagent. Similar sensitivity and specificity results were experienced when the two antigens were used to detect delayed dermal hypersensitivity in guinea pigs previously sensitized with B. dermatitidis or H. capsulatum.


Implications of group III and IV muscle afferents for high-intensity endurance exercise performance in humans.
We investigated the influence of group III/IV muscle afferents on peripheral fatigue, central motor drive (CMD) and endurance capacity during high-intensity leg-cycling. In a double-blind, placebo-controlled design, seven males performed constant-load cycling exercise (318 ± 9 W; 80% of peak power output (W(peak))) to exhaustion under placebo conditions and with lumbar intrathecal fentanyl impairing spinal μ-opioid receptor-sensitive group III/IV muscle afferents. Peripheral fatigue was assessed via changes in pre- vs. post-exercise quadriceps force in response to supramaximal magnetic femoral nerve stimulation (ΔQ(tw,pot)). CMD was estimated via quadriceps electromyogram. To rule out a direct central effect of fentanyl, we documented unchanged resting cardioventilatory responses. Compared to placebo, significant hypoventilation during the fentanyl trial was indicated by the 9% lower V(E)/V(CO(2)), causing a 5 mmHg increase in end-tidal P(CO(2)) and a 3% lower haemoglobin saturation. Arterial pressure and heart rate averaged 8 and 10% lower, respectively, during the fentanyl trial and these differences progressively diminished towards end-exercise. Although initially similar, the percent change in CMD was 9 ± 3% higher at end-exercise with fentanyl vs. placebo (P < 0.05). Time to exhaustion was shorter (6.8 ± 0.3 min vs. 8.7 ± 0.3 min) and end-exercise ΔQ(tw,pot) was about one-third greater (-44 ± 2% vs. -34 ± 2%) following fentanyl vs. placebo. The rate of peripheral fatigue development was 67 ± 10% greater during the fentanyl trial (P < 0.01). Our findings suggest that feedback from group III/IV muscle afferents limits CMD but also minimizes locomotor muscle fatigue development by stimulating adequate ventilatory and circulatory responses to exercise. In the face of blocked group III/IV muscle afferents, CMD is less inhibited but O(2) transport compromised and locomotor muscle fatigability is exacerbated with a combined net effect of a reduced endurance performance.


Suppressors of cytokine signaling (SOCS)-1 and SOCS-3 are induced by CpG-DNA and modulate cytokine responses in APCs.
During infection, the functional status of the innate immune system is tightly regulated. Although signals resulting in activation have been well characterized, counterregulative mechanisms are poorly understood. Suppressor of cytokine signaling (SOCS) proteins have been characterized as cytokine-inducible negative regulators of Janus kinase/STAT signaling in cells of hemopoietic origin. To analyze whether SOCS proteins could also be induced by pathogen-derived stimuli, we investigated the induction of SOCS-1 and SOCS-3 after triggering of macrophage cell lines, bone marrow-derived dendritic cells, and peritoneal macrophages with CpG-DNA. In this study, we show that CpG-DNA, but not GpC-DNA, induces expression of mRNA for SOCS-1 and SOCS-3 in vitro and in vivo. SOCS mRNA expression could be blocked by chloroquine and was independent of protein synthesis. Inhibitors of the mitogen-activated protein kinase pathway triggered by CpG-DNA were able to impede induction of SOCS mRNA. CpG-DNA triggered synthesis of SOCS proteins that could be detected by Western blotting. SOCS proteins were functional because they inhibited IFN-gamma as well as IL-6- and GM-CSF-induced phosphorylation of STAT proteins. Furthermore, IFN-gamma-induced up-regulation of MHC class II molecules was also prevented. The same effects could be achieved by overexpression of SOCS-1. Hence, the results indicate a substantial cross-talk between signal pathways within cells. They provide evidence for regulative mechanisms of Janus kinase/STAT signaling after triggering Toll-like receptor signal pathways.


COVID-19 and Gender Differences in Family Medicine Scholarship.
This bibliometric analysis seeks to explore how the COVID-19 pandemic impacted submission rates to Annals of Family Medicine by gender. Women represented 46.3% of all manuscript submissions included in our study (n = 1,964/4,238), spanning from January 1, 2015 to July 15, 2020. The overall volume of submissions increased during COVID-19 in comparison to pre-pandemic months; however, this increase was not evenly distributed among men and women (122% increase vs 101% increase, respectively). In the early months of the pandemic, 244 submissions were authored by men (58.5%), and 173 submissions were authored by women (41.5%). The gap in women's submission rates is troubling, as it suggests they may be at greater risk of falling behind male colleagues during and beyond the COVID-19 pandemic.


Dietary protocatechuic acid during the progression phase exerts chemopreventive effects on chemically induced rat tongue carcinogenesis.
The modifying effects of dietary administration of protocatechuic acid (PCA) during the progression phase of tongue carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. For tumor progression we developed a new animal model, where rats initiated by 4-week treatment of 20 ppm 4-NQO in drinking water, received four cycles of 20 ppm 4-NQO to induce advanced tongue cancer (one cycle: 2 weeks of 4-NQO followed by 2 weeks of tap water), starting at 14 weeks after the initiation. In this model, metastasis of tongue cancer occurred in lungs. Starting two weeks before the cycle treatment with 4-NQO, animals were fed the 2000 ppm PCA containing diet and continued on this diet until the end of the study. At the termination of the experiment (week 32), the incidences of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue tissue, and cell proliferation activity estimated by morphometric analysis of silver-stained nucleolar organizer regions protein were compared among the groups. Feeding with PCA containing diet during the progression phase significantly decreased the occurrence of advanced tongue squamous cell carcinoma with metastasis (P<0.05) and preneoplasia (hyperplasia and dysplasia) (P<0.001). In addition, PCA exposure decreased polyamine levels in the tongue tissue (P<0.001) during progression phase. Our results suggest that dietary PCA inhibits progression of 4-NQO-induced oral carcinogenesis, and such inhibition might be related to suppression of cell proliferation by PCA.


Inactivation of the type I interferon pathway reveals long double-stranded RNA-mediated RNA interference in mammalian cells.
RNA interference (RNAi) elicited by long double-stranded (ds) or base-paired viral RNA constitutes the major mechanism of antiviral defence in plants and invertebrates. In contrast, it is controversial whether it acts in chordates. Rather, in vertebrates, viral RNAs induce a distinct defence system known as the interferon (IFN) response. Here, we tested the possibility that the IFN response masks or inhibits antiviral RNAi in mammalian cells. Consistent with that notion, we find that sequence-specific gene silencing can be triggered by long dsRNAs in differentiated mouse cells rendered deficient in components of the IFN pathway. This unveiled response is dependent on the canonical RNAi machinery and is lost upon treatment of IFN-responsive cells with type I IFN Notably, transfection with long dsRNA specifically vaccinates IFN-deficient cells against infection with viruses bearing a homologous sequence. Thus, our data reveal that RNAi constitutes an ancient antiviral strategy conserved from plants to mammals that precedes but has not been superseded by vertebrate evolution of the IFN system.


Automatic specklegram fringe analysis by using symmetry evaluation of the Theta-scanning function.
New approaches are applied to overcome the difficulty of accurate angle measurements in specklegram information processing by introducing a prism rotator for compensation and by using symmetry evaluation. Together with slit scanning and the fast Fourier transform procedure, speckle random noise has been effectively suppressed, and accurate measurements of Theta and s are achieved. The method we present makes it possible to process the specklegram information automatically. The experimental setup is described in detail. The principles and experimental curves are given.


A point mutation at the X-chromosomal proteolipid protein locus in Pelizaeus-Merzbacher disease leads to disruption of myelinogenesis.
A group of inherited neurological disorders are the X-chromosome linked dysmyelinoses, in which myelin membranes of the CNS are missing or perturbed due to a strongly reduced number of differentiated oligodendrocytes. In animal dysmyelinoses (jimpy mouse, msd-mouse, md rat, shaking pup) mutations of the main integral myelin membrane protein, proteolipid protein, have been identified. Pelizaeus-Merzbacher disease (PMD) or sudanophilic leucodystrophy is an X-linked dysmyelinosis in humans. We report here on the molecular basis of the defect of affected males of a PMD kindred. Rearrangements of the PLP gene were excluded by Southern blot hybridisation analysis and PCR amplification of overlapping domains of the PLP gene. Sequence analysis revealed one single C----T transition in exon IV, which leads to a threonine----isoleucine substitution within a hydrophobic intramembrane domain. The impact of this amino-acid exchange on the structure of PLP in the affected cis membrane domain is discussed. A space filling model of this domain suggests a tight packing of the alpha-helices of the loop which is perturbed by the amino-acid substitution in this PMD exon IV mutant. The C----T transition in exon IV abolishes a Hph I restriction site. This mutation at the recognition site for Hph I (RFLP) and allele-specific primers have been used for mutation screening the PMD kindred.


Effects of Src-kinase inhibition in cancer-induced bone pain.
Bone metastases occur frequently in advanced breast, lung, and prostate cancer, with approximately 70% of patients affected. Pain is a major symptom of bone metastases, and current treatments may be inadequate or have unacceptable side effects. The mechanisms that drive cancer-induced bone pain are not fully understood; however, it is known that there is sensitization of both peripheral bone afferents and central spinal circuits. It is well established that the N-methyl-D-aspartate receptor plays a major role in the pathophysiology of pain hypersensitivity. Inhibition of the non-receptor tyrosine kinase Src controls N-methyl-D-aspartate receptor activity and inhibiting Src reduces the hypersensitivity associated with neuropathic and inflammatory pains. As Src is also implicated in osteoclastic bone resorption, we have investigated if inhibiting Src ameliorates cancer-induced bone pain. We have tested this hypothesis using an orally bioavailable Src inhibitor (saracatinib) in a rat model of cancer-induced bone pain. Intra-tibial injection of rat mammary cancer cells (Mammary rat metastasis tumor cells -1), but not vehicle, in rats produced hindpaw hypersensitivity to thermal and mechanical stimuli that was maximal after six days and persisted for at least 13 days postinjection. Daily oral gavage with saracatinib (20 mg/kg) beginning seven days after intra-tibial injection reversed the thermal hyperalgesia but not the mechanical allodynia. The analgesic mechanisms of saracatinib appear to be due to an effect on the nervous system as immunoblotting of L2-5 spinal segments showed that mammary rat metastasis tumor cells-1 injection induced phosphorylation of the GluN1 subunit of the N-methyl-D-aspartate receptor, indicative of receptor activation, and this was reduced by saracatinib. Additionally, histology showed no anti-tumor effect of saracatinib at any dose and no significant effect on bone preservation. This is the first demonstration that Src plays a role in the development of cancer-induced bone pain and that Src inhibition represents a possible new analgesic strategy for patients with bone metastases.


Patient controlled analgesia: redefining its role in an Indian cancer hospital.
This report describes a noninterventional audit of current patient-controlled analgesia (PCA) use in an Indian cancer hospital over a 1-year period. Because there appeared to be an underutilization of PCA in the authors' hospital, they performed this audit. A major reason to start PCA was inadequate analgesia despite ongoing epidural or standard PRN analgesic regimes, especially in thoracic, major abdominal, and pelvic bone surgeries. PCA was used for an average 52.13 hours. The reason to stop the PCA in 72 patients was minimal usage due to decreased need after the second postoperative day. Multiple triggers at the same time were a common problem encountered in 21 patients. A blocked intravenous (IV) line was encountered in 12 patients. Thirty-one patients ranked their pain relief with PCA as excellent and 39 patients stated it as good. Their protocols shall be suitably amended to ensure that PCA shall be used in immediate postoperative period as a principal modality of pain relief, especially in the above-mentioned group in absence of epidural analgesia.


Comparison of the hydrolysis of the three types of natriuretic peptides by human kidney neutral endopeptidase 24.11.
The degradation of 3 human natriuretic peptides by human kidney neutral endopeptidase 24.11 has been investigated. The studies revealed that hANP-28 and hCNP-22 are the preferred substrates, whereas hBNP-32 is not. The enzyme has been known to inactivate hANP-28 from cleavage at the Cys-Phe bond at the beginning of its ring structure. Analysis of the cleavage sites of each peptide indicated that the initial cleavage site of hCNP-22 is analogous to that of hANP-28. The Cys-Phe bond of hBNP-32 was insensitive to this enzymatic cleavage. We speculate that the stability of hBNP-32 may result from the insusceptibility of its Cys-Phe bond at the beginning of the ring structure.


Synthesis of 1,4-bis[2,2-bis(4-alkoxyphenyl)vinyl]benzenes and side chain modulation of their solid-state emission.
A series of 1,4-bis[2,2-bis(4-alkoxyphenyl)vinyl]benzene molecules with aggregation-induced emission (AIE) activity were synthesized. The conformations and packing arrangements of these molecules in the solid state can be adjusted by changing the side chains, which subsequently modulates their solid-state emission. The fluorescence quantum yield of 1e with the n-C(6)H(13) side chain in the solid state could reach up to 60.3% in the solid state.


Treatment with taurine, diltiazem, and vitamin E retards the progressive visual field reduction in retinitis pigmentosa: a 3-year follow-up study.
The purpose of this study to assess the effect of the formula taurine/diltiazem/vitamin E on the progression of visual field loss in retinitis pigmentosa. A double blind, placebo controlled study in 62 patients: visual field threshold values were obtained in a Humphrey Field Analyzer from center (30 degrees) and periphery (30-60 degrees), every 4 months during 3-year follow-up. Data were analyzed by univariate regression, with slopes obtained from the best fit lines. Based on slope values, three groups of patients were identified as those showing negative, positive, or zero slope: > or = 1 to < or = +1. In controls (32 patients), at central area, the distribution in negative, zero, or positive slope was, respectively, 16 (50%), 11 (35%), and 5 (15%). In the treated group (30 patients) this distribution was 6 (20%) negative, 17 (53%) zero, and 7 (23%) positive slope. In periphery, 16 control patients were distributed as 11 (69%) negative, 4 (25%) zero, and 1 (6%) positive slope. In the treated group (17 patients), the distribution was opposite: 1 (6%) negative, 7 (41%) zero, and 9 (53%) positive slope. Nineteen patients receiving treatment up to 6 years showed similar distribution by slope values. Eight out of 9 patients switched from placebo (2 years) to treatment (2-3 years), showed improving changes in their slope values. A beneficial effect of the treatment decreasing the rate of visual field loss was observed, likely through a protective action from free radical reactions in affected photoreceptors.


Beta- and gamma-catenin expression in oral squamous cell carcinomas.
Cell-cell adhesion is mediated by cadherins (integral membrane proteins) which form a complex with catenins (cytoplasmatic proteins). Down-regulation of cadherins and more recently of catenins has frequently been detected in many types of human carcinomas, in which it has been associated to tumor progression. While E-cadherin expression has been extensively studied in many forms of human cancers, including oral SCC, less is known about the expression levels of catenins in oral SCCs. The objective of this study was to evaluate the role of these proteins in the carcinogenetic process of the oral cavity. We evaluated by immunohistochemistry beta- and gamma-catenin expression in 30 cases of intraoral squamous cell carcinomas at different degree of cellular differentiation. As already reported for E-cadherin, the beta- and gamma-catenin expression showed an inverse relationship with the degree of differentiation, being the membranous expression of both catenins homogeneously reduced in less differentiated oral squamous cell carcinomas (grade 3). More interestingly, a decreased expression of these molecules was also found at the invasive front of grade 2 and sometimes of grade 1 carcinomas, thus suggesting a more aggressive biological behavior of these cancer cells. An absent staining for both beta- and gamma-catenins could constitute a hallmark of aggressive biological behavior even in tumor still well or moderately differentiated, at least in the peripheral invading front constituted by less differentiated tumor cells.


Impact of a nurse-led intervention on quality of life in patients with chronic non-malignant pain: An open randomized controlled trial.
To determine the effect of a comprehensive nurse-led programme for patients with chronic non-malignant pain, on quality of life, level of pain, anxiety, and depression, as primary outcomes and patients' satisfaction as a secondary end point. An open-label randomized controlled trial was carried out. The experimental group received both a nurse-led intervention on healthy lifestyles, education on self-esteem, pain awareness, communication, and relaxation techniques. The control group received usual care. Quality of life, level of pain, anxiety, and depression were the main outcomes. Data were obtained at baseline, immediately after the intervention, and 6 and 9 months. The study was carried out from 2015-2017. The sample was composed of 279 patients. At 9 months, the effect size (non-parametric effect size statistic A) favoured the intervention group for SF-36 mental health score (A = 0.79; 95% CI: 0.73-0.85), anxiety (A = 0.58; 95% CI: 0.51-0.65), pain intensity (A = 0.57; 95% CI: 0.51-0.64), and depression (A = 0.58; 95% CI: 0.51-0.65). Smaller differences were found on physical scores between the intervention and the usual care group. Patients showed a high level of satisfaction with the introduced intervention. A comprehensive nurse-led programme for patients with chronic non-malignant pain has a positive impact on their quality of life, level of pain, and mental health. Studies have reported that the problem of chronic pain is not optimally controlled. A structured nurse-led programme has been tested to facilitate healthy behaviours to help patients manage their chronic pain and to provide them with the necessary tools for their self-care. This nurse-led intervention improved their mental health and decreased their level of pain.


[Automated analysis of all-night records of tracheal sound to detect sleep disordered breathing].
In sleep-disordered breathing, tracheal sounds disappear during apnea and vary cyclicly during hypopnea. We tried to detect these changes in tracheal sounds automatically with a personal computer, and we evaluated the diagnostic accuracy of this system for detecting sleep-disordered breathing. Polysomnography and tracheal sound recording were done in 33 subjects with possible sleep apnea/hypopnea syndrome. Eighteen had positive results defined as an apnea/hypopnea index greater than 15. Tracheal sounds were digitized and a personal computer was used to calculate short time power spectra (44-600 Hz) every 0.2 seconds by the fast Fourier transform. The moving averages (18 seconds) of the logarithms of the power spectra were calculated every 2 seconds. Transient falls in the moving averages of more than 12 dB were detected. Those that were lower than 5 dB above the level of background noise were classified as tracheal sound apneas. The number of falls of more than 12 dB and the number of tracheal sound apneas correlated strongly with the number of apneas plus hypopneas (r = 0.95) and with the number of apneas (r = 0.97), respectively. The sensitivity and specificity of tracheal sound analysis for the sleep apnea/hypopnea syndrome (as defined above) were 89% and 60%, respectively, when the criteria was more than 15 falls of more than 12 dB per hour. We conclude that tracheal sound analysis by this method is useful as a screening test for the sleep apnea/hypopnea syndrome.


Adenovirus-mediated gene transfection in the isolated lymphatic vessels.
The authors describe technical details of experimental protocol of gene transfection in isolated rat mesenteric lymphatic vessels (MLVs). Authors also refer to the recent publication in Microcirculation, which provides wide set of experimental evidences obtained from confocal microscopic imaging and isolated vessels functional tests, which confirmed a successful achievement of the following goals. (1) Optimization of the experimental conditions to maintain the isolated "normal" rat mesenteric vessels in culture for sufficiently long periods of time to permit effective knockdown or overexpression of selected proteins/genes. (2) Development of the effective transfection protocols for lymphatic muscle and/or endothelial cells in intact isolated rat MLVs without nonspecific impairment on lymphatic contractile function due to the transfection protocol per se.


Oblique Surface Dose Calculation in High-Energy X-ray Therapy.
During radiation therapy, incident radiation oblique to the skin surface is high and may cause severe skin damage. Understanding the dose of radiation absorbed by the skin is important for predicting skin damage due to radiation. In this study, we used a high-energy (4 MV) X-ray system and an optically stimulated luminescence dosimeter (OSLD) that was developed for personal exposure dosimetry. We determined the dose variation and angular dependence, which are the characteristics of a small OSLD required to derive the calculation formula for the oblique surface dose. The dose variation was determined using the coefficient of variation. The maximum coefficient of variation for 66 small-field OSLDs was 1.71%. The angular dependence, obtained from the dose ratio of the dosimeter in the vertical direction, had a maximum value of 1.37. We derived a new equation in which the oblique surface dose can be calculated within the error range of -7.7-5.1%.


[Analysis of early lactate clearance rate in prognosis of neural function of patients with cardiac arrest].
To explore the correlations between early lactate clearance and the prognosis of neural function of patients with cardiac arrest (CA). The total number of patients with CA and restored spontaneous circulation was 74. Their general clinical data such as gender, age, cause of CA, heart rhythm pre-CA, CA duration, resuscitation time, Apache II score, mean arterial pressure (MAP) and presence or absence of convulsion or central hyperthermia were recorded. The levels of lactate at admission and after 6 h's therapy were also collected and used for calculating the 6 h lactate clearance rate for each patient. According to the cerebral performance category, they were divided into two groups of better neural function (CPC1-2, A, n = 24) and worse neural function (CPC3-5, B, n = 50). General clinical data, lactate level and lactate clearance rate of two groups were compared to determine whether or not there was a significant difference. Logistic regression analysis was also used to select independent prognostic factors of neural function. No significant differences existed in gender, age, cause of CA, heart rhythm before CA, Apache II score, MAP, number of cases with concurrent convulsion or central hyperthermia (P > 0.05). And CA duration and save resuscitation time had significant inter-group differences (7.92 vs 11.16, 17.47 vs 23.80, P < 0.05). The lactate level at admission had no significant inter-group difference (10.7 vs 11.2, P > 0.05) while the 6 h's lactate level of group A was significantly less than that of group B (7.05 vs 5.26, P < 0.05). And the 6 h lactate clearance rate in group A was also significant higher than that in group B (48.79% vs 33.67%, P < 0.05). Logistic regression analysis revealed that 6 h lactate clearance rate and CA duratio were independent prognostic factors for neurological function in post-cardiac arrest patients. Early lactate clearance may be associated with the prognosis of neural function for CA patients.