CT psoas calculations on the prognosis prediction of emergency laparotomy: a single-center, retrospective cohort study in eastern Asian population.
Emergency laparotomy (EL) has a high mortality rate. Clinically, frail patients have a poor tolerance for EL. In recent years, sarcopenia has been used as an important indicator of frailty and has received much attention. There have been five different calculation methods of psoas for computed tomography (CT) to measure sarcopenia, but lack of assessment of these calculation methods in Eastern Asian EL patients. We conducted a 2-year retrospective cohort study of patients over 18 years of age who underwent EL in our institution. Five CT measurement values (PMI: psoas muscle index, PML3: psoas muscle to L3 vertebral body ratio, PMD: psoas muscle density, TPG: total psoas gauge, PBSA: psoas muscle to body face area ratio) were calculated to define sarcopenia. Patients with sarcopenia defined by the sex-specific lowest quartile of each measurement were compared with the rest of the cohort. The primary outcome was "ideal outcome", defined as: (1) No postoperative complications of Clavien-Dindo Grade ≥ 4; (2) No mortality within 30 days; (3) When discharged, no need for fluid resuscitation and assisted ventilation, semi-liquid diet tolerated, and able to mobilize independently. The second outcome was mortality at 30-days. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were used. Two hundred and twenty-eight patients underwent EL met the inclusion criteria, 192 (84.2%) patients had an ideal outcome after surgery; 32 (14%) patients died within 30 days. Multivariate analysis showed that, except PMD, each calculation method of psoas was independently related to clinical outcome (ideal outcome: PML3, P < 0.001; PMI, P = 0.001; PMD, P = 0.157; TPG, P = 0.006; PBSA, P < 0.001; mortality at 30-days: PML3, P < 0.001; PMI, P = 0.002; PMD, P = 0.088; TPG, P = 0.002; PBSA, P = 0.001). In ROC analysis, the prediction model containing PML3 had the largest area under the curve (AUC) value (AUC value = 0.922 and 0.920, respectively). The sarcopenia determined by CT psoas measurements is significantly related to the clinical outcome of EL. The calculation of CT psoas measurement is suitable for application in outcome prediction of EL. In the future, it is necessary to develop a scoring tool that includes sarcopenia to evaluate the risk of EL better.


An unexpected guest: Pulmonary echinococcosis diagnosed by intraoperative frozen section examination. A case report and literature review.
Echinococcosis is caused by tapeworms belonging to the Echinococcus genus. The most common site of infection is the liver although it may involve almost any organ. Symptoms of pulmonary echinococcosis vary depending on the location and structure of the cyst. While uncomplicated cysts usually appear at imaging as well-defined homogeneous lesions with fluid content and smooth walls of variable thickness, complicated lesions may have a more heterogeneous content with higher density making more difficult the distinction from malignancies or other infections. Hereby we describe the case of a 61-year-old Northern African male admitted to our tertiary center for left upper chest pain who then underwent a chest computed tomography (CT) scan which demonstrated a large hypodense lesion, with smooth and thick walls, in the upper left lobe. The following magnetic resonance confirmed the homogeneous fluid content, and the 18 F- fluorodeoxyglucose-positron emission tomography/CT demonstrated a mild uptake of the walls. According to these findings, the main differential diagnoses at imaging included bronchogenic cyst, synovial sarcoma, and pulmonary hematoma although the patient denied any recent trauma. Given the large size and clinical symptoms he underwent surgery. Intra-operative frozen section, supported by imprint cytology, excluded the presence of malignancy while suggested an echinococcal laminar exocyst. The final pathological examination confirmed the diagnosis of echinococcosis (i.e., Echinococcus Granulosus protoscolex). After surgery he was treated with albendazole and at the six-month follow-up he was in good clinical conditions. Our case highlights the importance of considering rare infections, particularly in individuals from endemic areas. Frozen tissue analyses can be a diagnostic challenge and often require ancillary tools such as imprint cytology and serial sections for more sensitive and accurate diagnosis.


Evidence of Need to Use Self-Report Measures of Psychosocial Functioning in Older Children and Adolescents with Voiding Dysfunction.
Previous reports have revealed significantly higher rates of psychosocial difficulties in children and adolescents with voiding dysfunction compared to their healthy peers. However, these findings are based solely on parental reporting and do not include self-reporting of psychosocial problems in older pediatric patients. We collected data from 200 consecutive patients 11 to 16 years old during outpatient clinic visits. Patients completed the Pediatric Symptom Checklist-Youth Report, parents completed the parental report of the same measure, and patients and parents collaboratively completed the Dysfunctional Voiding Scoring System. Of the patients 25.5% met the cutoff score for clinically significant levels of psychosocial difficulties. However, only a fourth of those patients met the cutoff on the parent and self-report measures. Additionally patient self-reports of internalizing and externalizing problems were significantly related to severity of voiding dysfunction. Screening for psychosocial problems in older children and adolescents with voiding dysfunction should include reports from the parent and the child. In our sample 37.3% of patients needing a mental health followup would have been missed if only 1 version of the measure had been administered.


Suboptimal Guideline Adherence and Biomarker Underutilization in Monitoring of Post-operative Crohn's Disease.
Crohn's disease recurrence after ileocecal resection is common. Guidelines suggest colonoscopy within 6-12 months of surgery to assess for post-operative recurrence, but use of adjunctive monitoring is not protocolized. We aimed to describe the state of monitoring in post-operative Crohn's. We conducted a retrospective study of patients with Crohn's after ileocolic resection with ≥ 1-year follow-up. Patients were stratified into high and low risk based on guidelines. Post-operative biomarker (C-reactive protein, fecal calprotectin), cross-sectional imaging, and colonoscopy use were assessed. Biomarker, radiographic, and endoscopic post-operative recurrence were defined as elevated CRP/calprotectin, active inflammation on imaging, and Rutgeerts ≥ i2b, respectively. Data were stratified by surgery year to assess changes in practice patterns over time. P-values were calculated using Wilcoxon test and Fisher exact test. Of 901 patients, 53% were female and 78% high risk. Median follow-up time was 60 m for LR and 50 m for high risk. Postoperatively, 18% low and 38% high risk had CRPs, 5% low and 10% high risk had calprotectins, and half of low and high risk had cross-sectional imaging. 29% low and 38% high risk had colonoscopy by 1 year. Compared to pre-2015, time to first radiography (584 days vs. 398 days) and colonoscopy (421 days vs. 296 days) were significantly shorter for high-risk post-2015 (P < 0.001). Probability of colonoscopy within 1 year increased over time (0.48, 2011 vs. 0.92, 2019). Post-operative colonoscopy completion by 1 year is low. The use of CRP and imaging are common, whereas calprotectin is infrequently utilized. Practice patterns are shifting toward earlier monitoring.


In vivo effects of zoledronic acid on peripheral gammadelta T lymphocytes in early breast cancer patients.
Amino-bisphosphonates are potent activators of human gammadelta T cells. The aim of our study was to evaluate the immunomodulating properties of a single-dose of zoledronic acid (ZA) on gammadelta T cells in a select group of disease-free breast cancer patients with osteopenia. Blood samples were obtained, from 23 patients, before and 7, 28, 56, 90 and 180 days after a single-dose (4 mg) of ZA and analyzed by flow cyometry. A significant decrease of the different gammadelta T cell subsets was observed: Naïve (CD3+/Vdelta2+/CD45RA+/CD27+) after 180 days (P < 0.01); Central Memory (CD3+/Vdelta2+/CD45RA-CD27+) after 28 (P < 0.05), 90 (P < 0.01) and 180 days (P < 0.01); and Effector Memory (CD3+/Vdelta2+/CD45RA-/CD27-) after 56 (P < 0.01) and 90 (P < 0.05) days. Based on the observed gammadelta T cells kinetics patients could be divided in two groups: "responders" that showed a significant decrease in total numbers of gammadelta T cells and "non-responders" that showed no significant change. However, in vitro phosphoantigen stimulation of patients cells did not show significant differences in terms of IFN-gamma response by Vdelta2 T cells. We describe for the first time a long-lasting activation of effector subsets of gammadelta T cells in disease-free breast cancer patients after a single-dose of ZA. Our results highlight the need to further investigate the clinical significance of the immunomodulating properties of N-BPs.


Linking SNPs to CAG repeat length in Huntington's disease patients.
Allele-specific silencing using small interfering RNAs targeting heterozygous single-nucleotide polymorphisms (SNPs) is a promising therapy for human trinucleotide repeat diseases such as Huntington's disease. Linking SNP identities to the two HTT alleles, normal and disease-causing, is a prerequisite for allele-specific RNA interference. Here we describe a method, SNP linkage by circularization (SLiC), to identify linkage between CAG repeat length and nucleotide identity of heterozygous SNPs using Huntington's disease patient peripheral blood samples.


Optimal dose of garlic to inhibit dimethylhydrazine-induced colon cancer.
This study was designed to investigate the optimal dose of garlic during long-term feeding and its preventive and therapeutic effects on colon cancer in rats induced by 1,2-dimethylhydrazine (DMH). A total of 240 male Sprague-Dawley rats were grouped and fed with either a basal or a garlic diet of different concentration, and some groups were subcutaneously injected with DMH 20 mg/kg once a week for 20 weeks. The incidence of colon tumor was significantly decreased in the groups fed with 2.5%, 5%, and 10% garlic diets (p < 0.001). There was no distinct difference among these concentrations (p > 0.05). Therefore the minimal optimal dose of garlic to inhibit colon cancer was 2.5%. The equivalent dose of this concentration in humans is 4.76 g/m2 body surface/day. In a therapeutic study, the tumor-inducing interval in nude mice subcutaneously injected with colon cancer cells (CC-M2) was prolonged by a 2.5% garlic diet (p < 0.01). Thus smaller tumor volume and longer survival time were found in the garlic group than in the controls (p < 0.01). However, the growth rate of tumors was not markedly inhibited by garlic. All rats finally died within 18 weeks. This study suggested that a 2.5% garlic dose may be used mainly as an inhibitor to prevent colon cancers and improve survival time.


Angioinfarction plus nephrectomy for metastatic renal cell carcinoma--an update.
We treated 100 patients with metastatic renal cell carcinoma by angioinfarction of the primary tumor followed by radical nephrectomy. Of the patients 88 also received postoperative parenteral progesterones. We achieved an over-all response rate of 28 per cent (complete regression of all metastatic lesions in 7 patients, regression greater than 50 per cent in 8 and stabilization for at least 1 year in 13). Patients with parenchymal pulmonary metastases only have the best survival rate (64 per cent at 1 year) and are most likely to benefit from angioinfarction and nephrectomy. The presence of hilar or mediastinal adenopathy, pleural effusion or nonpulmonary metastases confers a worse prognosis. These patients do not appear to survive longer with preoperative angioinfarction than if treated by nephrectomy alone. Our data demonstrate that it is critically important to stratify patients by site and volume of disease when results are reported and compared for any patient undergoing treatment for metastatic renal cell carcinoma.


Hormonal manipulation of carrageenin-induced pyresis in rats,.
The intensity of the hyperthermic response in rats promoted by subplantar injections of 1 mg of carrageenin is directly related to the irritant properties of the type of carrageenin. The overall pyretic response is more dramatic in female rats than in male rats. Subtle changes in the time-course hyperthermic profiles are seen after hormonal modifications.


Development of a machine learning-based prediction model for sepsis-associated delirium in the intensive care unit.
Septic patients in the intensive care unit (ICU) often develop sepsis-associated delirium (SAD), which is strongly associated with poor prognosis. The aim of this study is to develop a machine learning-based model for the early prediction of SAD. Patient data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and the eICU Collaborative Research Database (eICU-CRD). The MIMIC-IV data were divided into a training set and an internal validation set, while the eICU-CRD data served as an external validation set. Feature variables were selected using least absolute shrinkage and selection operator regression, and prediction models were built using logistic regression, support vector machines, decision trees, random forests, extreme gradient boosting (XGBoost), k-nearest neighbors and naive Bayes methods. The performance of the models was evaluated in the validation set. The model was also applied to a group of patients who were not assessed or could not be assessed for delirium. The MIMIC-IV and eICU-CRD databases included 14,620 and 1723 patients, respectively, with a median time to diagnosis of SAD of 24 and 30 h. Compared with Non-SAD patients, SAD patients had higher 28-days ICU mortality rates and longer ICU stays. Among the models compared, the XGBoost model had the best performance and was selected as the final model (internal validation area under the receiver operating characteristic curves (AUROC) = 0.793, external validation AUROC = 0.701). The XGBoost model outperformed other models in predicting SAD. The establishment of this predictive model allows for earlier prediction of SAD compared to traditional delirium assessments and is applicable to patients who are difficult to assess with traditional methods.


Trace metal pollution risk assessment in urban mangrove patches: Potential linkage with the spectral characteristics of chromophoric dissolved organic matter.
Mangroves are inter-tidal ecosystems with important global ecological roles. Today, mangroves around the world are at risk of fragmentation, especially in areas with rapid urbanization. Mangroves experiencing habitat fragmentation may be more intensely affected by human activities and a scenario that might have been ignored by previous studies on trace metal (TM) environmental geochemistry. Here, we investigated the typically fragmented habitats in a subtropical mangrove estuary (the Danshuei Basin in Taiwan Strait) to evaluate how human activities affect the geochemical behaviors of TMs. Ni, Sb, Zn, Cr, Cu, and Cd were the primary contaminants found in the mangrove patches. Metal sequestration from the riverine (Ni, Cr) and in-patch activity (Sb, Zn, Cu, Cd) are primary sources of TM's risk. Using the synthesized pollution risk assessment, we showed that most of the mangrove patches are under moderate pollution risk. A significant relationship between the TMs pollution indicators and the absorption coefficient at 254 nm (a254), implying that the a254 could be a potential convenient parameter in the TMs risk assessment, which might be partly explained by the bio-remediation of sulfate-reduction microorganism. This study demonstrates the ecological risks posed by TM pollution on urban mangrove patches and emphasizes the importance of a more comprehensive survey for estuarine mangrove patch environments to achieve Sustainable Development Goals.


Role of phosphoinositide 3-kinase in the autophagic death of serum-deprived PC12 cells.
The death of serum-deprived undifferentiated PC12 cells shows both autophagic and apoptotic features. Since it is still controversial whether the autophagy is instrumental in the cell death or a mere epiphenomenon, we tested the effects of inhibiting the autophagy by a variety of phosphoinositide 3-kinase inhibitors, and provided evidence that the autophagy, or a related trafficking event, is indeed instrumental in the cell death. Furthermore, by comparing the effects of PI3-K inhibition and caspase-inhibition on autophagic and apoptotic cellular events, we showed that in this case the autophagic and apoptotic mechanisms mediate cell death by parallel pathways and do not act in series.


Zinc deficiency aggravates tubulointerstitial nephropathy caused by ureteral obstruction.
Ureteral ligation causes tubulointerstitial nephropathy characterized by the tubular dilatation, the interstitial expansion, and a leukocyte infiltration into the tubulointerstitium. The present study was designed to explore whether zinc (Zn) deficiency affects the development of unilateral ureteral obstruction (UUO)-induced tubulointerstitial nephropathy. Compared to rats fed a standard diet, rats fed a Zn-deficient diet exhibited a greater influx of leukocytes into the tubulointerstitium of the cortex of the obstructed kidney 3 d following UUO. Furthermore, rats fed a Zn-deficient diet showed a slight invasion of leukocytes into the tubulointerstitium of the cortex of the contralateral nonobstructed kidney (CLK), although there was no infiltration of leukocytes into the CLK of rats fed a standard diet. These histological changes, however, were ameliorated by administration of enalapril, an angiotensin (ANG) I-converting enzyme inhibitor. Thus, it is suggested that Zn deficiency aggravates UUO-induced tubulointerstitial nephropathy via an increase in the action of ANG II.


Sound wave propagation in weakly polydisperse granular materials.
Dynamic simulations of wave propagation are performed in dense granular media with a narrow polydisperse size-distribution and a linear contact-force law. A small perturbation is created on one side of a static packing and its propagation, for both P- and S-waves, is examined. A size variation comparable to the typical contact deformation already changes sound propagation considerably. The transmission spectrum becomes discontinuous, i.e., a lower frequency band is transmitted well, while higher frequencies are not, possibly due to attenuation and scattering. This behaviour is qualitatively reproduced for (i) Hertz non-linear contacts, for (ii) frictional contacts, (iii) for a range of smaller amplitudes, or (iv) for larger systems. This proves that the observed wave propagation and dispersion behaviour is intrinsic and not just an artifact of (i) a linear model, (ii) a frictionless packing, (iii) a large amplitude non-linear wave, or (iv) a finite size effect.


Cytological features of lipoblastoma: a report of three cases.
Lipoblastoma is a rare benign neoplasm occurring mostly in children under the age of three. Accurate preoperative diagnosis is mandatory for planning the treatment. The main aim of this study is to establish the cytological features of lipoblastoma and to answer the question: "Is cytological diagnosis of lipoblastoma reliable?"Preoperative fine-needle aspiration biopsy (FNAB) and tissue sections of three children treated for lipoblastoma at the Division of Pediatrics, University Medical Center, Ljubljana, Slovenia, in the period from 1997 to 2004 were reexamined. The Giemsa- and Papanicolaou-stained FNAB smears were moderately or poorly cellular and contained lipocytes, lipoblasts, and spindle cells in various proportions. The tumor cells were in clusters and tissue fragments or as single cells. Thin branching capillaries were observed in most of the clusters and tissue fragments. In the background, abundant myxoid extracellular material and naked oval nuclei were present. In the first case, the cytological diagnosis was benign soft-tissue tumor, in the second the diagnosis was not conclusive and the last case was correctly diagnosed as lipoblastoma. In the differential diagnosis of the second case, both lipoblastoma and liposarcoma were considered cytologically as well as histologically. At 7-yr follow-up, there is no evidence of the disease.Thus, we conclude that lipoblastoma with typical cytological features could be accurately diagnosed by FNAB. However, tumors containing numerous lipoblasts could pose a diagnostic problem.


Management of a common oral lesion of the elderly.
Lichen planus of the oral cavity produces significant functional and symptomatic problems for elderly patients. Oral lesions often occur in the absence of concomitant skin lesions. Unlike cutaneous lesions, oral lesions of lichen planus may become a chronic, recurring problem that is difficult to control. The diagnostic features of lichen planus of the oral cavity are reviewed and treatment strategies presented. Periodic follow-up is recommended to monitor the disease process and to observe for the development of early squamous cell carcinoma.


Breath-hold three-dimensional true-FISP imaging of coronary arteries using asymmetric sampling.
To evaluate the feasibility of using asymmetric sampling in a three-dimensional, magnetization-prepared, segmented true-FISP (fast imaging with steady-state precession) sequence in order to reduce the sensitivity to resonance offsets, while simultaneously improving imaging speed. Asymmetric sampling reduces the repetition time, leading to reduced resonance offset effects and improved resolution in a fixed imaging time. However, it introduces additional phase terms due to blood flow, which can cause image artifacts. Computer simulations were performed to study the off-resonance and flow effects of asymmetric sampling in true-FISP. Coronary artery imaging was performed in healthy volunteers. Simulations and volunteer studies show that image artifacts due to flow-induced phase variations may be acceptable at low velocities. Volunteer studies demonstrate that relatively high-resolution coronary artery images can then be acquired within a single breath-hold with segmented three-dimensional true-FISP imaging using data asymmetry in the readout direction. Asymmetric sampling is a useful modification to true-FISP for reducing the off-resonance artifacts and improving imaging speed when the flow velocities are small.


Diet and age at menarche.
Early menarche has been associated with higher risk of breast cancer. A prospective study has been conducted in Quebec City, Canada, to evaluate the relationship of dietary intake to age at menarche. On three occasions during the schoolyear 1986-87, 2,299 pre-menarche. Incidence density ratios (IDRs) adjusted for age at entry and mothers' age at menarche were computed using proportional hazards models. IDRs for quartiles of energy, nutrient and food-group intakes were not different from the null value. In this population of well-nourished girls, diet did not influence the age at onset of menarche.


Novel expression patterns of Pax3/Pax7 in early trunk neural crest and its melanocyte and non-melanocyte lineages in amniote embryos.
Neural crest cells are considered a key vertebrate feature that is studied intensively because of their relevance to development and evolution. Here we report the expression of Pax7 in the dorsal non-neural ectoderm and in the trunk neural crest of the early chick embryo. Pax7 is expressed in the trunk neural crest migrating along the ventral and dorsolateral routes. Pax7 is first downregulated in the neural crest-derived neuronal precursors, secondly in the glial, and finally in the melanocyte precursors. Conserved developmental expression in the melanocyte lineage of both Pax3 and Pax7 was evidenced in chick and quail, but only Pax3 in mouse and rat.


Congenital third nerve palsy with amblyopia of the contralateral eye.
A child with congenital third nerve palsy using the palsied eye for fixation is presented. Apparently, amblyopia developed in the secondarily deviating eye. This is the first case report of which we are aware with such a disturbance, ie, primary ocular motor palsy in one eye and sensory amblyopia in the other.


Impairment of mitochondrial respiration in platelets and placentas: a pilot study in preeclamptic pregnancies.
Preeclampsia (PE) is a major complication of pregnancy with partially elucidated pathophysiology. Placental mitochondrial dysfunction has been increasingly studied as major pathomechanism in both early- and late-onset PE. Impairment of mitochondrial respiration in platelets has recently emerged as a peripheral biomarker that may mirror organ mitochondrial dysfunction in several acute and chronic pathologies. The present study was purported to assess mitochondrial respiratory dys/function in both platelets and placental mitochondria in PE pregnancies. To this aim, a high-resolution respirometry SUIT (Substrate-Uncoupler-Inhibitor-Titration) protocol was adapted to assess complex I (glutamate + malate)- and complex II (succinate)-supported respiration. A decrease in all respiratory parameters (basal, coupled, and maximal uncoupled respiration) in peripheral platelets was found in preeclamptic as compared to healthy pregnancies. At variance, placental mitochondria showed a dichotomous behavior in preeclampsia in relation to the fetal birth weight. PE pregnancies with fetal growth restriction were associated with decreased in coupled respiration (oxidative phosphorylation/OXPHOS capacity) and maximal uncoupled respiration (electron transfer/ET capacity). At variance, these respiratory parameters were increased for both complex I- and II-supported respiration in PE pregnancies with normal weight fetuses. Large randomized controlled clinical studies are needed in order to advance our understanding of mitochondrial adaptive vs. pathological changes in preeclampsia.


Adjusting for confounded variables: pulmonary function and smoking in a special population.
Confounded variables present an obstacle to valid inference in many environmental and occupational studies. We describe a series of procedures that we used to address this problem in a study of pulmonary function and smoking. Subjects were drawn from the Multiple Risk Factor Intervention Trial (MRFIT), a prospective study of coronary heart disease. Confounding of smoking, hypertension, and hyperlipidemia was designed into the trial and was beyond the control of our ancillary study. We used statistical techniques to detect and characterize the pattern of confounding, identify important variables affecting pulmonary function, and perform appropriate adjustments for extraneous influences (i.e., other than smoking). Among the techniques we used were factor analysis, stepwise multiple regression, and bootstrap replication. Analysis of the adjusted pulmonary function measurements showed that they were satisfactorily standardized and free of artifact. Moreover, use of the adjusted values sharpened our statistical results concerning smoking, the ultimate object of the study. We contrast the use of external and internal standards and discuss methods for detecting, ruling out, or counteracting confounding.


Fetal pulmonary artery stiffness is a strong predictor of persistent pulmonary hypertension of the newborn - An echocardiographic study.
Pulmonary artery stiffness (PAS) is a strong and independent predictor of mortality in adult patients with pulmonary hypertension (PH). But the change in PAS during perinatal period remains unknown. Here, we aimed to explore the feasibility and performance of PAS on predicting persistent pulmonary hypertension of the newborn (PPHN). 1325 fetuses underwent a dedicated echocardiography screening for fetal heart defects during second trimester, third-trimester and neonatal period with the measurement of acceleration time (PAAT) and maximal frequency shift (MFS) of pulmonary artery flow. PAS (MFS/PAAT ratio) was calculated. Six fetuses were diagnosed as PPHN. Compared with the normal fetuses, those with PH had greater values of PAS during each period of time (second trimester, 52.6(46.2-54.5) vs. 32.4(28.0-39.4) kHz/s, p = 0.0003; third trimester, 52.9(46.1-55.3) vs. 29.7(27.3-33.3) kHz/s, p = 0.0002; neonatal period, 127.4(85.2-150.8) vs. 26.6(22.7-35.0) kHz/s, p < 0.0001). There was a statistically significant correlation between PAS and mean pulmonary artery pressure (p < 0.05) but no correlation between PAS and gestational age (p > 0.05) whether in normal fetuses or not. The area under receiver operating characteristic curve (AUC) of 0.97 for PAS during third trimester was superior to that for PAS during second trimester (AUC, 0.94) in predicting PPHN. The optimal cutoff value of PAS during third trimester was 37.40 KHz/s, with a sensitivity of 100%, a specificity of 91%, and an accuracy of 92%. There was a significant difference in PAS between normal fetuses and those with PH. PAS has a power performance on predicting PPHN.


A randomized single-blind trial of split-dose PEG-electrolyte solution without dietary restriction compared with whole dose PEG-electrolyte solution with dietary restriction for colonoscopy preparation.
Colonoscopy preparation regimens are poorly tolerated, requiring the use of a large volume of an unpalatable solution and diet restriction for adequate cleansing. The aim of this study was to compare the efficacy of two regimens of bowel preparation before colonoscopy: a whole dose of polyethylene glycol electrolyte solution (PEG-E), with diet restriction vs. a split dose with no diet restriction. A total of 141 patients (ages 20-84 years, 81 men) were randomly assigned to receive either 4 L PEG-E, along with a liquid diet the day before colonoscopy (Group A) or 2 L PEG-E with a regular diet the day before colonoscopy followed by another 2 L PEG-E on the day of the procedure (Group B). The quality of the preparation was graded by the endoscopist (poor to excellent), who was blinded to the type of preparation. Tolerability of the assigned preparation and adverse effects were recorded by an independent investigator by using a questionnaire administered before colonoscopy. Intra- and interobserver variability was studied by using randomly chosen videotapes of colonoscopies performed as part of the study. There were 73 patients in Group A and 68 patients in Group B. The quality of the preparation was significantly better in Group B ( p = 0.011). The tolerability of the preparation regimen was not different overall between study groups in terms of side effects (except for bloating, which was more frequent in Group B, p = 0.039) or willingness to repeat the preparation. There was a nonsignificant trend toward improved adherence to the assigned preparation in favor of Group B ( p = 0.062). Inter- and intraobserver variability analysis showed good to excellent correlation among endoscopists. Colonic preparation with split-dose PEG-E and no dietary restriction provides better quality colon cleansing than whole-dose preparation, with no significant impact on patient tolerability and side effects.


Bacterial adherence to urethral catheters.
Closed sterile catheter drainage has markedly reduced the incidence of nosocomial urinary tract infections. Infections that occur during closed drainage must ascend by colonizing the catheter or urethra. Our study compared adherence by different bacterial species to different catheter surfaces. We found no bacteria adhering to the hydrophilic catheter surface. Of the gram-negative bacteria Proteus mirabilis showed the greatest adherence to the other catheters and it, like most bacteria, showed the most marked adherence to the red rubber catheter.


How diverse is heterochromatin in the Caesalpinia group? Cytogenomic characterization of Erythrostemon hughesii Gagnon & G.P. Lewis (Leguminosae: Caesalpinioideae).
Cytogenomic characterization of Erythrostemon hughesii reveals a heterogeneity of repeats in its subtelomeric heterochromatin. Comparative analyses with other Caesalpinia group species reveal a significant reduction in the abundance of Ty3-gypsy/Chromovirus Tekay retrotransposons during its evolution. In numerically stable karyotypes, repetitive DNA variability is one of the main causes of genome and chromosome variation and evolution. Species from the Caesalpinia group (Leguminosae) are karyotypically characterized by 2n = 24, with small chromosomes and highly variable CMA+ heterochromatin banding patterns that correlate with environmental variables. Erythrostemon hughesii differs from other species of the group examined to date for having subtelomeric CMA+ bands; this contrasts with most species in the group which have proximal bands. Here we analyse the repeatome of E. hughesii using genome skimming and chromosomal mapping approaches to characterize the identity of the most abundant repetitive elements and their physical location. The repetitive fraction of E. hughesii comprises 28.73% of the genome. The most abundant elements were retrotransposons (RT) with long terminal repeats (LTR-RT; 9.76%) and satellite DNAs (7.83%). Within the LTR-RTs, the most abundant lineages were: Ty1/copia-Ale (1%), Ty3/gypsy CRM (0.88%) and Ty3/gypsy Athila (0.75%). Using fluorescent in situ hybridization four satellite DNAs and several LTR-RT elements were shown to be present in most subtelomeric CMA+ bands. These results highlight how the repeatome in E. hughesii, a species from Oaxaca state in Mexico, is clearly distinct from Northeast Brazilian species of the Caesalpinia group, mainly due to its high diversity of repeats in its subtelomeric heterochromatic bands and low amount of LTR-RT Ty3/gypsy-Tekay elements. Comparative sequence analysis of Tekay elements from different species is congruent with a clade-specific origin of this LTR-RT after the divergence of the Caesalpinia group. We hypothesize that repeat-rich heterochromatin may play a role in leading to faster genomic divergence between individuals, increasing speciation and diversification.


Therapy with granulocyte colony-stimulating factor in systemic lupus erythematosus may be associated with severe flares.
Recombinant human granulocyte colony-stimulating factor (G-CSF) has been used for treatment of febrile neutropenia in systemic lupus erythematosus (SLE) and other systemic rheumatic diseases. We describe 2 patients with SLE with disease flares with irreversible loss of renal function in association with G-CSF therapy. Eighteen patients with SLE treated with G-CSF for neutropenia have been reported, of whom 4 developed mild disease flares or cutaneous vasculitis. Our experience suggests that G-CSF therapy should be used with considerable caution in patients with SLE.


cGMP-dependent protein kinase decreases calcium sensitivity of skinned cardiac fibers.
Chemically skinned (Lubrol WX) cardiac muscle fibers produce half-maximum isometric tension at pCa 6.18 (pH 6.7) in presence of MgATP (10 mM). After addition of cGMP (5 microM) and cGMP-dependent protein kinase (0.1 microM), the pCa required for half-maximum activation is 5.96, while maximum tension is not affected. Similar shifts in the tension/pCa-relationship have been observed after incubation of skinned cardiac muscle fibers with cAMP of catalytic subunit of the cAMP-dependent protein kinase. The shift in the Ca2+-sensitivity is associated with an increased incorporation of radioactivity into a Mr 28000 band (presumably troponin-I) and a Mr 145000 band.


Diagnostic value of serum and tissue eosinophil in diagnosis of asthma among patients with chronic rhinosinusitis.
Chronic rhinosinusitis (CRS) is one of the most common chronic inflammatory diseases of sinonasal mucosa. Asthma among CRS patients is often underdiagnosed which makes the management of CRS more challenging. Therefore, using serum and tissue eosinophil as an indicator and predictor of asthma in CRS patients is vital for further preventing recurrent and increasing the effectiveness of treatment for CRS. To determine the association and diagnostic ability of serum and tissue eosinophils in the diagnosis of asthma among CRS patients. A cross-sectional study was conducted involving 24 CRS patients with asthma and without asthma, respectively, from the Otorhinolaryngology clinic of two tertiary hospitals located on the East Coast of Peninsular Malaysia. Serum and tissue eosinophils (obtained from nasal polyp) levels between both groups were compared. Association between serum and tissue eosinophils with asthma was evaluated using logistic regression analysis, adjusting for important sociodemographic characteristics. The diagnostic ability of serum and tissue eosinophil was then evaluated by assessing the receiver operating characteristic curve. A total of 48 CRS patients with a mean [SD] age of 47.50 [14.99] years were included. Patients with asthma had significantly higher serum [0.48 vs 0.35 × 109/L] and tissue eosinophil [100 vs 8.5 per HPF] levels. Tissue eosinophils were found to be an independent predictor of asthma with adjusted OR 1.05, p < 0.001, after adjusting for age and serum eosinophils. The area under the receiver operating characteristic curve for serum eosinophil was 69.0%. At optimal cut-off value (0.375 × 109/L), the sensitivity and specificity for serum eosinophil was 75.0% and 70.8%. The area under the receiver operating characteristic curve for tissue eosinophil was 93.4%. At the optimal cut-off value (58.0 per HPF), the sensitivity and specificity for tissue eosinophils were 79.2% and 91.7%, respectively. This study indicates a significantly higher level of serum and tissue eosinophils in CRS with asthma. However, there was no correlation between serum and tissue eosinophils in both group. Based on this study, the CRS patient needs to be screened for asthma if the level of serum eosinophil is > 0.375 × 109/L and tissue eosinophil > 58 per HPF.


Connection between El Niño-Southern Oscillation events and river nitrate concentrations in a Mediterranean river.
The causes of interannual nitrate variability in rivers remain uncertain, but extreme climatic events have been suggested as drivers of large nitrate inputs to rivers. Based on a 24-year data set (1983-2006), we suggest that El Niño-Southern Oscillation (ENSO) can affect nitrate behavior in a seasonal extra-tropical stream, the Llobregat (NE Iberian Peninsula), located thousands of kilometers away from the ENSO oscillating system via atmospheric teleconnections. Two commonly used indices, the Southern Oscillation Index (SOI) and the self-calibrating-Palmer Drought Severity Index (scPDSI) showed highly significant correlations with nitrate concentrations, which recurrently increased during La Niña phases, coinciding with severe droughts.


Enhancing Diabetes Self-management and Education: A Critical Analysis of ChatGPT's Role.
ChatGPT, an advanced natural language processing model, holds significant promise in diabetes self-management and education. ChatGPT excels in providing personalized educational experiences by tailoring information to meet individual patient needs and preferences. It aids patients in developing self-management skills and strategies, fostering proactive disease management. Additionally, ChatGPT addresses healthcare access disparities by enabling patients to access educational resources irrespective of their geographic location or physical limitations. However, it is important to acknowledge and address the deficiencies of ChatGPT, such as its limited medical expertise, contextual understanding, and emotional support capabilities. Strategies for optimizing ChatGPT include regular training and updating, integration of healthcare professionals' expertise, improvement in contextual comprehension, and enhancing emotional support. By addressing these limitations and striking a balance between the benefits and limitations, ChatGPT can play a significant role in empowering patients to better understand and manage diabetes. Further research and development are needed to refine ChatGPT's capabilities and address ethical considerations, but its integration in patient education holds the potential to transform healthcare delivery and create a more informed and engaged patient population.


[Normal pregnancy after a Budd-Chiari syndrome treated by shunting: apropos of a case, review of the literature].
A patient who had a meso-atrial by-pass for a Budd-Chiari syndrome a year before conception carried her pregnancy to term. The authors have reviewed the literature. When they had studied the literature the authors took into account cirrhoses of the liver and portal hypertension in association with pregnancy. They concluded that a patient who had had a Budd-Chiari syndrome, particularly when she had also had a porto-caval shunt, was not in principle unable to have a pregnancy.


EPA and DHA levels in whole blood decrease more rapidly when stored at -20 °C as compared with room temperature, 4 and -75 °C.
High-throughput n-3 fatty acid profiling is enabled by collection techniques such as venous whole blood and fingertip prick (FTP) sampling, but the resulting increased sample numbers increases storage demand. Highly unsaturated fatty acids (HUFA) in erythrocytes are susceptible to oxidation, but this tendency is poorly characterized in venous and FTP whole blood. Presently, whole blood samples with low and high n-3 content collected with ethylenediaminetetraacetic acid were stored on chromatography paper with and without BHT pre-treatment for up to 180 days at different temperatures (room, 4, -20, -75 °C). Whole blood prepared with heparin and BHT and stored in cryovials was also examined. Eicosapentaenoic acid (EPA, 20:5n-3) + docosahexaenoic acid (DHA, 22:6n-3) is relatively stable when stored at -75 °C under various conditions but rapidly decreases in whole blood when stored at -20 °C. At -20 °C, BHT + heparin prepared whole blood can prevent decreases in cryovials up to 180 days but BHT only slows the decreases on chromatography paper. Surprisingly, whole blood stored at 4 °C and room temperature was less susceptible to decreases in EPA + DHA as compared with -20 °C storage. Assessments of n-3 blood biomarkers indicate the % n-3 HUFA in total HUFA was more stable as compared with the sum of the relative % of EPA + DHA. In conclusion, FTP and venous whole blood for fatty acid analysis should be stored at -75 °C whenever possible. In the absence of -75 °C storage conditions, BHT should be added and 4 °C or room temperature appear to be better alternatives to -20 °C.


Serologic and clinical features of patients with discoid lupus erythematosus: relationship of antibodies to single-stranded deoxyribonucleic acid and of other antinuclear antibody subsets to clinical manifestations.
Serologic and clinical data were obtained from forty patients with discoid lupus erythematosus in 1982. Clinical disease was characterized by quality, extent, severity, activity, photosensitivity, and systemic manifestations. The patient's sera were examined for the presence of antinuclear, anti-Ro and anti-La, anti-ribonucleoprotein and anti-Sm, anti-single-stranded deoxyribonucleic acid (ssDNA), and antinative DNA antibodies. In late 1984, thirty-three patients had follow-up clinical examinations. On the initial evaluation the patients with positive antinuclear antibody (ANA) findings were clinically characterized by a significantly higher incidence of photosensitivity and arthritis, an elevated erythrocyte sedimentation rate, and cutaneous lesions of subacute cutaneous lupus erythematosus. The activity and extent of disease in 1982 did not correlate with the presence of ANA. Elevated levels of ssDNA antibodies were present in seven of the forty patients (significantly greater than control subjects; (p less than 0.005) and correlated with widespread, active discoid lupus erythematosus, an elevated erythrocyte sedimentation rate, and a slightly greater risk of systemic lupus erythematosus in 1982. At the 2-year follow-up examination, thirteen of the seventeen patients with a positive ANA had active clinical cutaneous disease, and ten of the sixteen patients with negative ANA findings had continued activity (not statistically significant). However, all seven patients with elevated ssDNA antibody levels had continued activity, and disease progression had occurred in three. Thus the presence of ssDNA seems to correlate strongly with active, progressive lupus erythematosus. The presence of antibody abnormalities in patients with discoid lupus erythematosus correlates with clinical disease and provides more support for the theory linking discoid lupus erythematosus to systemic lupus erythematosus as part of a continuum.


Use of a novel self-assembling hemostatic gel as a complementary therapeutic tool for endoscopic sphincterotomy-related bleeding.
PuraStat is a novel self-assembling peptide hydrogel developed as a hemostatic agent for endoscopic and surgical procedures which can be applied to bleeding from various lesions of the gastrointestinal tract. Yamamoto and colleagues present a video showing the actual endoscopic hemostasis using PuraStat for endoscopic sphincterotomy-related bleeding.


Proprotein convertase subtilisin/kexin type 9 inhibition in cardiovascular disease: current status and future perspectives.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) targets the degradation of low-density lipoprotein (LDL) receptors; it has been proved that its inhibition improves cardiovascular outcomes in patients with established atherosclerotic cardiovascular disease (ASCVD). Herein, we review the current status of PCSK9 inhibitors in clinical practice and the future scope of PCSK9 inhibition. The results of two recent large clinical trials reveal that two PCSK9 monoclonal antibodies evolocumab and alirocumab reduce the risk of a cardiovascular event on top of background statin therapy in patients with stable ASCVD and those with recent acute coronary syndrome, respectively. However, there are several ongoing concerns regarding the efficacy in reducing mortality, cost-effectiveness, and long-term safety of extremely low LDL cholesterol levels with PCSK9 inhibition. The results of ongoing cardiovascular outcomes trials with PCSK9 monoclonal antibodies for primary prevention and with small interfering RNA to PCSK9 for secondary prevention may help to shape the use of this new therapeutic class.


Combination treatment with irritant and recombinant interleukin 2 in the peritoneal cavity for evoking effective anti-tumor activity: generation of lymphokine-activated killer cells and tumor-specific killer cells.
Meth A sarcoma, growing in the subcutaneous tissue of syngeneic BALB/c mice, regressed completely after an intraperitoneal (ip) injection of proteose peptone (PP) (on day 6) followed by 2 ip administrations (on days 7 and 8) of human recombinant interleukin-2 (IL-2, 25 micrograms/day), whereas one such treatment alone had little effect on the tumor growth. While this combination treatment was effective in anti-asialo GM1 antibody-treated mice, no such effect was noted in T cell-depleted ATXFL (thymectomized, irradiated and fetal liver cell-reconstituted) mice. These results show that T cells are mainly responsible for this antitumor effect. Treatment with a combination of PP and IL-2, but not with either PP or IL-2 alone, resulted in a marked increase in the T cell population in the peritoneal cavity after the treatment. At an early stage after the combination treatment, both peritoneal exudate cells (PEC) and spleen cells exhibited killing activity with a promiscuous specificity. However, at a later stage, 7 days after the treatment, Meth A-specific killer activity was observed in both PEC and the spleen. Meth A rechallenge was rejected by the mice in which the tumor had regressed, but the antigenically different Meth 1 was accepted by them. A similar result was obtained in Winn's neutralization test. These results suggest that this combination treatment, which is effective in the generation of lymphokine-activated killer cells in the peritoneal cavity, finally resulted in the induction of tumor-specific killer cells in the periphery. These results clearly show the anti-tumor efficacy of combination treatment with PP and rIL-2.


Interplay of cannabinoid 2 (CB2) receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration.
Remote neuronal degeneration and death/injury, which often occur in regions remote but functionally connected to the primary lesion site, may play a pivotal role in extending neuronal damage/dysfunction following traumatic brain injury, stroke, or peripheral nerve injury, as well as in chronic neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis. Even though the precise mechanisms of remote neuronal injury are poorly understood and no efficacious treatment options are available, it involves glial activation, inflammation, oxidative/nitrative stress, and apoptotic cell death. The newly discovered endocannabinoid signaling system consisting of endocannabinoids (endogenous bioactive lipid mediators), their synthetic and metabolizing enzymes, and their primary G protein-coupled cannabinoid 1 and 2 (CB(1) and CB(2)) receptors has been implicated in the regulation of numerous physiological and pathological processes/functions, including those associated with neurodegeneration. Using a well-characterized rodent model of remote neuronal degeneration, Oddi et al. (J Mol Med 2012, in press, DOI 10.1007/s00109-012-0884-1 ) have demonstrated that targeting CB(2) cannabinoid receptors may represent a promising novel approach to attenuate this pathological process. This editorial discusses the clinical significance of these interesting observations and the mechanisms of the possible interplay of CB(2) receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration.


IAEA Coordinated Research Project: updated decay data library for actinides.
Recommended nuclear decay data for specific actinides are important in fuel-cycle studies for thermal and fast reactors and inventory studies for safeguards. Therefore, a programme of work was initiated in 2005 to improve the actinide decay data library of the International Atomic Energy Agency through the efforts of a Coordinated Research Project (CRP). The proposed contents of the new database are described, including the agreement to include additional actinides and a significant number of natural decay chain radionuclides. This work is on-going, and is estimated for completion in 2009/10.


Osteoid osteoma of the upper extremity. A diagnostic challenge.
Osteoid osteomas are benign tumors that may commonly mimic other entities in the upper extremity. The purpose of this study is to describe the clinical and imaging features of osteoid osteomas involving the upper extremity, highlight the difficulties in the diagnosis in the various areas and propose a diagnostic workup. Fourty-eight patients with histologically confirmed osteoid osteoma of the upper extremity treated at the authors' department from 1985 to 2000 were retrospectively reviewed. Data pertinent on the patients' history, lesion location, clinical and imaging characteristics as well as any unique features of individual patients were collected. There were 29 males and 19 females with a mean age of 28 years (range 20-42). The average duration of symptoms before definite diagnosis was 18 months (range 2-62). Pain was the presenting symptom in 46 of 48 patients, whereas swelling was the main complaint in 2 of the patients. Mean pre-operative visual analogue pain scale (VAS), was 8.8 ranging from 5.1 to 9.3. Eight lesions were located in the humerus, 4 in the ulna and 7 in the radius. In the carpal bones, 4 were located in the scaphoid, 4 in the capitate and 5 in the hamate. Seven lesions were located at the metacarpals and 9 lesions at the phalanges (5 proximal, no middle and 4 distal phalangeal lesions). Radiographs alone were sufficient to establish the diagnosis of osteoid osteoma in 32 cases. Bone scans identified a "hot spot" in 16 patients without previous radiographic evidence of a lesion and furthermore, computed tomography was performed in 32 patients to assist in the intraosseous localization of the lesion, and in the pre-operative planning. All patients underwent operative excision of the lesion and the diagnosis was confirmed by histology. Mean follow-up was 28 months (range 25-42). Fourty-three patients had an uneventful recovery. Mean post-operative VAS value was 1.8 ranging from 0 to 3. Osteoid osteoma of the upper extremity often mimics other etiologies and the complex anatomy of the upper extremity, as well as the tendency of patients to relate their symptoms to trauma are factors that easily lead to misdiagnosis or delay in the diagnosis. A high index of suspicion is essential and the diagnosis is based on an accurate clinical assessment and careful selection of imaging studies.


Prehospital care by EMTs and EMT-Is in a rural setting: prolongation of scene times by ALS procedures.
Because the initiation of IV lines by emergency medical technicians-Intermediates (EMT-Is) appeared to delay the patient's transport to the hospital, we undertook a retrospective study of 370 patients to compare prehospital care rendered by EMTs (EMT-A equivalent) and EMT-Is in a rural setting. Our study was limited to acute medical conditions in which protocols called for IV lines (124 patients with chest pain, 122 with acute respiratory distress, 99 with seizures, and only 25 with cardiac arrest) (the cardiac arrest cases were too few for statistical significance). We found that the difference in scene times for EMTs and EMT-Is not attempting IV lines was 6.1 and 6.9 minutes, respectively. The average scene time of EMT-Is attempting an IV line was 19.6 minutes (P less than .001) compared with EMT times, or times for EMT-Is not attempting an IV line. One hundred twenty-eight of 370 patients received IV medication within ten minutes of arrival in the emergency department, and ten of these patients had their IV lines initiated successfully in the field. Thirty-nine percent of patients with ED IV lines received IV medication within ten minutes of arrival, while only 21% of patients with a field IV line received medication in this period (P less than .05). We conclude that initiating a field IV line in this specific patient population significantly increased scene time and did not improve the chances of these patients receiving IV medication within ten minutes of arrival in the emergency department.


Vacuum-assisted vaginal delivery and levator ani avulsion in primiparous women.
We compared the incidence and type of levator ani avulsion diagnosed by translabial ultrasound evaluation in primiparous women six months after vacuum-assisted or spontaneous vaginal delivery. This retrospective observational study was performed between January 2011 and December 2013. Primiparous women six months after vacuum-assisted vaginal delivery and after spontaneous vaginal delivery underwent translabial ultrasound evaluation. The distance between the urethra and fibers of the musculus levator ani puborectalis (levator-urethra gap) was measured. A levator-urethra gap >25 mm was considered a musculus levator ani avulsion. In total, 184 women participated in the study. Among them, 92 had vacuum extraction and 92 had uncomplicated spontaneous delivery. A longer levator-urethra gap on both sides of the pubic bone was found in women after vacuum-assisted vaginal delivery (p < 0.0001 for both sides). Musculus levator ani avulsion was identified in 20 women (unilateral in 16 cases and bilateral in four cases). No difference in an incidence of musculus levator ani avulsion was identified in women after vacuum-assisted vaginal delivery [11/92 (12%)] compared to spontaneous delivery [9/92 (10%); p = 0.81]. Vacuum-assisted vaginal delivery in primiparous women is associated with a longer levator-urethra gap but not with a higher frequency of avulsion of the musculus levator ani.


The Oryctes virus: its detection, identification, and implementation in biological control of the coconut palm rhinoceros beetle, Oryctes rhinoceros (Coleoptera: Scarabaeidae).
In view of the increasing and devastating damage by rhinoceros beetle (Oryctes rhinoceros) to coconut palms in the middle of last century, many efforts were made to find an efficient natural control factor against this pest, which could not be controlled by pesticides. The basic procedures of these monitoring programmes are outlined together with the final detection of a virus disease in oil palm estates in Malaysia in 1963. In extensive laboratory studies, the virus was isolated and identified as the first non-occluded, rod-shaped insect virus, morphologically resembling the baculoviruses. Infection experiments clarified the pathology, histopathology, and virulence of the virus and demonstrated that the virus was extremely virulent to larvae after peroral application. These findings encouraged the first pilot release of virus in 1967 in coconut plantations of Western Samoa where breeding sites were contaminated with virus. Surprisingly, the virus became established in the Samoan rhinoceros beetle populations and spread autonomously throughout the Western Samoan islands. As a consequence, there was a drastic decline of the beetle populations followed by a conspicuous recovery of the badly damaged coconut stands. This unexpected phenomenon could only be explained after it was shown that the adult beetle itself is a very active virus vector and thus was responsible for the efficient autodissemination of the virus. The functioning of the beetle as a 'flying virus factory' is due to the unique cytopathic process developing in the midgut after peroral virus infection. Pathological details of this process are presented. Because of the long-term persistence of the virus in the populations, rhinoceros beetle control is maintained. Incorporation of virus into integrated control measures and successful virus releases in many other countries are recorded.


On the validation of magnetic resonance velocimetry in single-phase turbulent pipe flows.
A nuclear magnetic resonance imaging technique is used to measure velocity distributions in turbulent pipe flows up to Re=24580. While turbulent intensity is usually determined from signal attenuation, we deduce turbulent intensity from velocity distribution with no need to suppose a gaussian distribution for velocity fluctuations. Skewness and flatness measurements are also presented in this paper. Comparison with DNS show good agreement and we show that NMR data is sufficently accurate to provide turbulent viscosity profile. The low field system used in this study allow the suppression of susceptibility artifacts and thus open its use for studying two-phase flows. We postulate that the method used here could be applied to two-phase flows and would thus provide valuable information on turbulent viscosity models.


The knowledge of our knowledge.
This classic article was published in the first volume and issue of Philosophical Constructs for the Chiropractic Profession. In this paper, Dr. McAndrews reviews the use of the term "philosophy" in chiropractic and urges the chiropractic profession to consider the use and misuse of this term. Reprinted with permission from McAndrews JF. The Knowledge of Our Knowledge. Philosophical Constructs for the Chiropractic Profession. 1991;1:14-17.


A Predictive Biophysical Model of the Combined Action of Radiation Therapy and Immunotherapy of Cancer.
Immunotherapy with checkpoint inhibitors has an enormous potential in therapy of metastatic cancers. Immunotherapy is generally combined with local treatments, such as radiation therapy. The time schedule of drug-radiation combination is largely based on empirical observations, and a comprehensive predictive model would be needed to optimize treatments. We present a biophysical model predicting the combined interaction and apply it to describe preclinical experimental data. The model considers the dependences of primary and distal tumor masses, immune cell kinetics targeting tumor cells, and signals causing immune cell replenishment after radiation mechanistic interpretation of the low frequency of abscopal responses. It is benchmarked against 16 experiments with synthetic tumors in murine models. The model predicts that immune response is stronger for checkpoint inhibitor administration at the time of irradiation or shortly after. The model discriminates correctly between tumor remission and continued growth in all considered experimental cases, including radiation and checkpoint delivery alone or in combination. It identifies a radiation dose window maximizing immune response and avoiding on one side the understimulation of the immune system and radiation-induced depletion of the immune cell pool on the other. Consequently, abscopal effects can be established in certain circumstances only. The model allows a quantitative mechanistic interpretation of the interaction of radiation with checkpoint blockers and will be helpful for optimizing clinical trials.


Effects of pentobarbital and ketamine on brain injury-induced anti-ischemic activity.
Survival rates following incomplete brain ischemia induced during pentobarbital anesthesia were significantly higher in mice with a minor brain injury, inflicted one week before, than in those given a sham operation. Improvement of the survival rates in mice with brain injury, however, became insignificant when brain ischemia was imposed during ketamine anesthesia, suggesting that the actions of certain factors or protective mechanisms against brain ischemia, developed by brain injury, are antagonized by ketamine and/or potentiated by barbiturate anesthesia.


Impact of colonialism on Māori and Aboriginal healthcare access: a discussion paper.
Historical socio-political processes have produced gross inequity of health resource for Aboriginal Australians and New Zealand Māori. This paper argues that socio-political factors resulting from the entrenchment of colonialism have produced significant personal and structural barriers to the utilisation of healthcare services and directly impact the health status of these two vulnerable groups. Discussion Paper. Understanding the actual barriers preventing the utilisation of healthcare facilities, as perceived by Indigenous people, is essential in reducing the gross disparity between Indigenous and non-Indigenous morbidity and mortality in Australia and New Zealand.


Design considerations of a randomized clinical trial on a cognitive behavioural intervention using communication and information technologies for managing chronic low back pain.
Psychological treatments have been successful in treating chronic low back pain (CLBP). However, the effect sizes are still modest and there is room for improvement. A way to progress is by enhancing treatment adherence and self-management using information and communication technologies (ICTs). Therefore, the objective of this study was to design a trial investigating the short- and long-term efficacy of cognitive behavioural treatment (CBT) for CLBP using or not ICTs. A secondary objective of this trial will be to evaluate the influence of relevant variables on treatment response. Possible barriers in the implementation of CBT with and without ICT will also be investigated. A randomised controlled trial with 180 CLBP patients recruited from specialised care will be conducted. Participants will be randomly assigned to three conditions: Control group (CG), CBT, and CBT supported by ICTs (CBT + ICT). Participants belonging to the three conditions will receive a conventional rehabilitation program (back school). The CBT group program will last six sessions. The CBT + ICT group will use the internet and SMS to practice the therapeutic strategies between sessions and in the follow-ups at their homes. Primary outcome variables will be self-reported disability and pain intensity. Assessment will be carried out by blinded assessors in five moments: pre-treatment, post-treatment and 3-, 6-, and 12-month follow-ups. The influence of catastrophizing, fear-avoidance beliefs, anxiety and depression in response to treatment in the primary outcomes will also be analysed. This study will show data of the possible benefits of using ICTs in the improvement of CBT for treating CLBP. ClinicalTrials.gov, NCT01802671.


Symptomatic intraocular inflammation in multiple sclerosis.
The aim of this study was to determine the type and outcome of uveitis in patients with multiple sclerosis. A retrospective study of 16 patients attending the uveitis clinic who had a clinically definite diagnosis of multiple sclerosis and symptomatic intraocular inflammation. The type of uveitis and complications present as well as the outcome of therapeutic intervention, either medical or surgical, was determined. Chronic, bilateral anterior uveitis was present in six patients. Secondary cataracts requiring surgery occurred in 10 eyes, and trabeculectomy was done on five eyes for secondary glaucoma. Symptomatic vitritis (visual blurring and/or visually significant floaters) occurred in eight patients and was bilateral in four. Occlusive peripheral retinal vasculitis with subsequent areas of ischaemia and neovascularization requiring panretinal laser photocoagulation developed in eight eyes, five of which also required vitrectomy. Other posterior segment complications included macular oedema (four) and epiretinal membrane involving the macula (two). Five patients required systemic steroids for control of posterior uveitis. The median visual improvement following cataract surgery or vitrectomy was 3 Snellen lines to a median visual acuity of 6/18. A wide range of clinical patterns of uveitis, which may be both symptomatic and sight-threatening, occur in patients with multiple sclerosis. In addition, the complications of uveitis may cause significant visual morbidity, much of which is amenable to appropriate surgical intervention. It is important that these potentially remediable conditions are recognized and treated to ensure that patients with multiple sclerosis retain optimum visual function.


Relative canalicular tear flow as assessed by dacryoscintigraphy.
Studies evaluating the relative importance of the upper and lower canaliculi in tear drainage have been many and varied, and at times the application of the data to clinical situations is difficult. In order to evaluate the relative tear flow in the upper and lower canaliculi and to quantitatively evaluate the different tear flow rates by a physiologic method, we have studied 11 patients using partial canalicular obstructions and dacryoscintigraphy. The authors found no statistical difference in tear flow between the upper and lower canalicular systems. This information has clinical application when deciding whether to repair an isolated canalicular injury.


Saturable adenosine 5'-triphosphate-independent binding of [3H]-ouabain to brain and cardiac tissue in vitro.
1. Several investigators have proposed that membrane Na+, K+-adenosine 5'-triphosphatase (Na+, K+-ATPase) is a mechanism for the transmembrane transport of cardiac glycosides, rather than the receptor for pharmacological actions of these agents. This implies that the glycosides bind to an intracellular constituent (receptor) other than Na+, K+-ATPase. 2. In search for such a receptor site, saturable ATP-independent [3H]-ouabain binding was studied in rat brain and dog and guinea-pig heart homogenates. The binding of the glucoside to this site results in a relatively unstable complex which is stabilized by K+ to a lesser extent than is the complex formed with the ATP-dependent binding to Na+, K+-ATPase. 3. The ATP-independent ouabain binding sites are more abundant in rat brain tissue than in cardiac tissue, and have a lower ouabain affinity compared to the binding sites on Na+, K+-ATPase. 4. These results do not support the contention that there are intracellular inotropic receptors for digitalis.


Inhibition of the CXCL12/CXCR4 axis prevents periurethral collagen accumulation and lower urinary tract dysfunction in vivo.
Several studies show that prostatic fibrosis is associated with male lower urinary tract dysfunction (LUTD). Development of fibrosis is typically attributed to signaling through the transforming growth factor β (TGF-β) pathway, but our laboratory has demonstrated that in vitro treatment of human prostatic fibroblasts with the C-X-C motif chemokine ligand 12 (CXCL12) chemokine stimulates myofibroblast phenoconversion and that CXCL12 has the capacity to activate profibrotic pathways in these cells in a TGF-β-independent manner. We have previously reported that feeding mice high-fat diet (HFD) results in obesity, type II diabetes, increased prostatic fibrosis, and urinary voiding dysfunction. The purpose of this study was to test the hypothesis that in vivo blockade of the CXCL12/CXCR4 axis would inhibit the development of fibrosis-mediated LUTD in HFD-fed mice. Two-month-old male senescence-accelerated mouse prone-6 mice were fed either a HFD or low-fat diet (LFD) for 8 months. Half of each dietary group were given constant access to normal water or water that contained the C-X-C chemokine receptor type 4 (CXCR4; CXCL12 receptor) antagonist CXCR4AIII. At the conclusion of the study, mice were weighed, subjected to oral glucose tolerance testing and cystometry, and lower urinary tract tissues collected and assessed for collagen content. HFD-fed mice became significantly obese, insulin resistant, and hyperglycemic, consistent with acquisition of metabolic syndrome, compared with LFD-fed mice. Anesthetized cystometry demonstrated that HFD-fed mice experienced significantly longer intercontractile intervals and greater functional bladder capacity than LFD-fed mice. Immunohistochemistry demonstrated high levels of CXCR4 and CXCR7 staining in mouse prostate epithelial and stromal cells. Picrosirius red staining indicated significantly greater periurethral collagen deposition in the prostates of HFD than LFD-fed mice. Treatment with the CXCR4 antagonist CXCR4AIII did not affect acquisition of metabolic syndrome but did reduce both urinary voiding dysfunction and periurethral prostate collagen accumulation. This is the first study to report that obesity-induced lower urinary tract fibrosis and voiding dysfunction can be repressed by antagonizing the activity of the CXCR4 chemokine receptor in vivo. These data suggest that targeting the CXCL12/CXCR4 signaling pathway may be a clinical option for the prevention or treatment of human male LUTD.


Fifteen Years After Katrina: Paving the Way for Health Care Transformation.
Following the devastation of the Greater New Orleans, Louisiana, region by Hurricane Katrina, 25 nonprofit health care organizations in partnership with public and private stakeholders worked to build a community-based primary care and behavioral health network. The work was made possible in large part by a $100 million federal award, the Primary Care Access Stabilization Grant, which paved the way for innovative and sustained public health and health care transformation across the Greater New Orleans area and the state of Louisiana.


A computer-aided treatment planning technique for universal wedges.
Some modern accelerators provide only one wedge built into the head of the treatment machine. A continuous range of wedge angles can be generated using wedged and unwedged beams in different proportions. However, this may pose difficulty in treatment planning since the planners will have to work with twice as many beams to achieve a desirable dose distribution. We have developed a simple algorithm to solve the treatment planning problem involving wedged and open beam combinations. The algorithm is based on the assumption that the user has some knowledge of the dose distribution to be optimized. Some properties of the distributions are then used to set up the system of equations for optimization. Unlike other optimization techniques, it does not require specification of dose value to every interest point selected, and it allows each specified dose value to vary within a clinically acceptable range. Examples are given to illustrate the application of the algorithm for some standard treatment plans.


Short chain carboxylic acids production and dynamicity of microbial communities from co-digestion of swine manure and corn silage.
Short chain carboxylic acids (SCCAs) have attracted much attention due to their wide application and benefit of high economy. This study investigated the influence of organic load rates (OLRs) on short-chain carboxylic acids (SCCAs) production and microbial communities for co-digestion of swine manure (SM) and corn silage (CS) during four different OLRs stages in a semi-continuous mode. The results showed that relatively stable SCCAs concentration of 10.5-13.6 g COD/L and SCCAs yield of 0.42 mg COD/mg VS was achieved at OLR of 3.0 g VS/L·d. The maximum concentration of 19.1 g COD/L was achieved at 3.5 g VS/L·d. Volatile fatty acids (VFAs) (include acetic, n-butyric and caproic acids) accounted for approximately 80% of SCCAs. Hydrolysis bacteria (HB) including Clostridium, Terriporobacter, Intestinibacter, and Turiibacter decreased with the increase of OLR, while acidogenic bacteria (AB) including Acetobacter, Lactobacillus, Aeriscardovia, and Pseudomonas increased, resulting in insufficient degradation of CS.


Blood pressure is elevated in normotensive pregnant women with intrauterine growth restriction.
To assess the relationship between blood pressure pattern and intrauterine growth restriction in normotensive pregnant women. Twenty-four-hour ambulatory blood pressure was consecutively performed between 32 and 34 weeks in 139 normotensive, non-proteinuric, primigravidae with intrauterine growth restriction (IUGR) and in 140 primigravidae, matched for age and gestation, who were and remained normotensive throughout pregnancy and whose fetuses had regular fetal growth, who served as controls. Although all measures were within the normotensive range, blood pressure of mothers with IUGR were significantly higher than controls. Twenty-four-hour mean, daytime, and nighttime systolic were 119.9+/-11.9, 122.6+/-11.7, 114.4+/-13.3 mmHg, in women with IUGR and 108.0+/-7.4, 109.2+/-7.3, 102.1+/-8.5 mmHg, in controls. Twenty-four-hour diastolic average, daytime, and nighttime diastolic (mean+/-S.D.) 78.1+/-9.3, 69.2+/-10.6, 67.2+/-9.0 mmHg, in women with IUGR and 64.1+/-5.7, 66.0+/-5.7, 58.2+/-6.3 mmHg, in normal pregnant women. All differences p<0.0001. Pregnant women with idiopathic IUGR have blood pressure higher than normal. Although within clinic normotensive range, slightly higher levels of blood pressure can alter uterine and placental perfusion and determine fetal growth restriction.


Typing of intermediate filaments in malignant fibrous pleural tumors.
We report two cases of a malignant fibrous pleural tumor, one of the localized type and one of the diffuse type. In both cases, typing of intermediate filaments by immunofluorescence microscopy showed that the tumor cells were positive for vimentin and negative for (cyto)keratin and desmin. This result supports the concept that malignant fibrous pleural tumors do not arise from the (cyto)keratin-positive pleural mesothelium but from the submesothelial fibrous tissue. Thus, instead of the usual term "malignant fibrous mesothelioma", the term "malignant submesothelial fibrosarcoma" should be preferred.


Markers of Disease Severity in Patients with Spanish Influenza in the Japanese Armed Forces, 1919-1920.
We examined preserved medical charts of 470 Spanish influenza patients (8 with fatal cases) hospitalized at former army hospitals in Japan during 1919-1920. The following factors were associated with longer periods of hospitalization: adventitious discontinuous lung sounds, maximum respiration rate, continuation of high fever after hospital admission, and diphasic fever.


Heparanase expression is a prognostic indicator for postoperative survival in pancreatic adenocarcinoma.
Pancreatic ductal adenocarcinoma has a median survival of less than 6 months from diagnosis. This is due to the difficulty in early diagnosis, the aggressive biological behaviour of the tumour and a lack of effective therapies for advanced disease. Mammalian heparanase is a heparan-sulphate proteoglycan cleaving enzyme. It helps to degrade the extracellular matrix and basement membranes and is involved in angiogenesis. Degradation of extracellular matrix and basement membranes as well as angiogenesis are key conditions for tumour cell spreading. Therefore, we have analysed the expression of heparanase in human pancreatic cancer tissue and cell lines. Heparanase is expressed in cell lines derived from primary tumours as well as from metastatic sites. By immunohistochemical analysis, it is preferentially expressed at the invading edge of a tumour at both metastatic and primary tumour sites. There is a trend towards heparanase expression in metastasising tumours as compared to locally growing tumours. Postoperative survival correlates inversely with heparanase expression of the tumour reflected by a median survival of 34 and 17 month for heparanase negative and positive tumours, respectively. Our results suggest, that heparanase promotes cancer cell invasion in pancreatic carcinoma and could be used as a prognostic indicator for postoperative survival of patients.


Selective inhibition of cyclooxygenase-2 expression by 15-deoxy-Delta(12,14)(12,14)-prostaglandin J(2) in activated human astrocytes, but not in human brain macrophages.
Overexpression of the inducible cyclooxygenase (COX-2) and inducible NO synthase (iNOS) in activated brain macrophages (microglia) and astrocytes appears central to many neuroinflammatory conditions. 15-Deoxy-Delta(12,14)-PGJ(2) (15d-PGJ(2)) is a ligand for the peroxisome proliferator-activated receptor (PPAR)gamma. It has been proposed as an inhibitor of microglial activation, based on the study of iNOS down-regulation in rodent microglia. Because iNOS induction after cytokine activation remains controversial in human microglia, we examined the effect of 15d-PGJ(2) and other PPAR agonists on human microglia and astrocytes, using COX-2 induction as an index of activation. We found that PPAR alpha ligands (clofibrate and WY14643) enhanced IL-1 beta-induced COX-2 expression in human astrocytes and microglia, while inhibiting IL-1 beta plus IFN-gamma induction of iNOS in astrocytes. This is the first description of an inhibition of iNOS uncoupled from that of COX-2. 15d-PGJ(2) suppressed COX-2 induction in human astrocytes. It prevented NF-kappa B binding to the COX-2 promoter through a new pathway that is the repression of NF-kappa Bp50 induction by IL-1 beta. In contrast, 15d-PGJ(2) increased c-Jun and c-Fos DNA-binding activity in astrocytes, which may result in the activation of other inflammatory pathways. In human microglia, no effect of 15d-PGJ(2) on COX-2 and NF-kappa Bp65/p50 induction was observed. However, the entry of 15d-PGJ(2) occurred in microglia because STAT-1 and c-Jun expression was modulated. Our data suggest the existence of novel pathways mediated by 15d-PGJ(2) in human astrocytes. They also demonstrate that, unlike astrocytes and peripheral macrophages or rodent brain macrophages, human microglia are not subject to the anti-inflammatory effect of 15d-PGJ(2) in terms of COX-2 inhibition.


From Atomic Guideline-Based Recommendations to Complete Therapeutic Care Plans: A Knowledge-Based Approach Applied to Breast Cancer Management.
How textual clinical practice guidelines are written may have an impact on how they are formalized and on the kind of recommendations issued by the clinical decision support systems (CDSSs) that implement them. Breast cancer guidelines are mostly centered on the description of the different recommended therapeutic modalities, represented as atomic recommendations, but seldom provide comprehensive plans that drive care delivery. The objective of this work is to implement a knowledge-based approach to develop a care plan builder (CPB) that works on atomic recommendations to build patient-centered care plans as sequences of chronologically ordered therapeutic steps. The CPB uses the atomic recommendations issued by the guideline-based decision support system (GL-DSS) of the DESIREE project. The domain knowledge is represented as the list of all care plans that apply to breast cancer patients. Scenarios are introduced to locate the patient on these theoretical care plans. The CPB has been evaluated on a sample of 99 solved clinical cases leading to an overall performance of 89,8%.


Clinical evaluation of a two-incision fistula technique for the treatment of oral ranulas.
Oral ranulas are caused by extravasation of mucus from the sublingual glands, and the preferred treatment varies. We have developed a two-incision fistula operation for their treatment, and in this clinical study we have evaluated the efficacy and safety of this approach. Twelve patients with oral ranulas confirmed by fine needle aspiration cytology were enrolled and gave their consent to be treated by our new technique. The clinical outcomes and complications were evaluated during a period that ranged from 8-24 months. Nine ranulas became smaller and gradually disappeared, and there were no complications or injury to Wharton's duct. Three ranulas recurred, but disappeared after a second operation. The two-incision fistula operation can be effective and safe as an initial treatment for oral ranulas, and the method may become the preferred management for retention cysts.


Combined Surgery Versus Phacoemulsification Alone for Patients with Primary Angle‑Closure Glaucoma: A meta-analysis.
The purpose of this meta-analysis is to systematically compare the efficacy and safety between combined surgery (phacoemulsification combined with trabeculectomy) and phacoemulsification for primary angle‑closure glaucoma (PACG) patients. This work was done through the data searched from the PubMed, EMBASE and the Cochrane Library. The Cochrane Handbook was also used to evaluate the quality of the included studies. In addition, this meta-analysis was performed using Revman 5.4 software. A total of seven randomized controlled trials (RCTs) were included. Compared with phacoemulsification alone, combined surgery resulted in significant reduction in the IOP (MD = -1.45, 95%CI, -2.38 to -0.51, p = .002). And more reduction in number of glaucoma medications was shown in the combined surgery group (MD, -0.59; 95%CI, -1.01 to -0.17; p = .006). For the improvement of the best corrected visual acuity (BCVA), there was no statistical differences between two groups (MD, 0.05; 95%CI, -0.01 to 0.11; p = .08). In subgroup analysis, the BCVA improved more significantly for medically controlled PACG patients in the phacoemulsification alone group (MD, 0.09; 95%CI, 0.01 to 0.07; p = .02). Compared with the phacoemulsification alone group, more complications were shown in the combined surgery group (RR, 0.22; 95%CI, 0.09 to 0.56; p = .001). For lowering IOP, combined surgery was superior to phacoemulsification alone for PACG patients. Meanwhile, combined surgery generated more complications. For medically controlled PACG patients, phacoemulsification alone is more conducive to the improvement of BCVA.


Gliosarcoma developing in close relationship to an abscess cavity injected with thorotrast.
A case of an unusual tumor developing at the site of an abscess is reported. The tumor presented 21 years after burr hole drainage of the abscess and instillation of the contrast medium thorotrast. The bizarre nature of the tumor and its immediate proximity to the thorotrast lead the authors to believe that the tumor was caused by the contrast medium.


Synthesis of antimalarial amide analogues based on the plant serrulatane diterpenoid 3,7,8-trihydroxyserrulat-14-en-19-oic acid.
A plant-derived natural product scaffold, 3,7,8-trihydroxyserrulat-14-en-19-oic acid (1) was isolated in high yield from the aerial parts of the endemic Australian desert plant Eremophila microtheca. This scaffold (1) was subsequently used in the generation of a series of new amide analogues via a one-pot mixed anhydride amidation using pivaloyl chloride. The structures of all analogues were characterized using MS, NMR, and UV data. The major serrulatane natural products (1-3), isolated from the plant extract, and all amide analogues (6-15) together with several pivaloylated derivatives of 3,7,8-trihydroxyserrulat-14-en-19-oic acid (16-18) were evaluated for their antimalarial activity against 3D7 (chloroquine sensitive) and Dd2 (chloroquine resistant) Plasmodium falciparum strains, and preliminary cytotoxicity data were also acquired using the human embryonic kidney cell line HEK293. The natural product scaffold (1) did not display any antimalarial activity at 10µM. Replacing the carboxylic acid of 1 with various amides resulted in moderate activity against the P. falciparum 3D7 strain with IC50 values ranging from 1.25 to 5.65µM.


Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy.
To conduct systematic epidemiologic, neuro-ophthalmologic, psychophysical, and mitochondrial DNA (mtDNA) genetic examinations on a newly identified pedigree with Leber hereditary optic neuropathy (LHON). Observational population cohort study. A prospective investigation of an entire Brazilian LHON family. A field investigation by an international team conducted in a remote part of Brazil. We evaluated 265 (both eyes) of the 328 living family members of this LHON pedigree. Only members of this pedigree were studied. Those entering the pedigree as spouses were used as controls. We conducted epidemiologic interviews emphasizing possible environmental risk factors, comprehensive neuro-ophthalmologic examinations, psychophysical tests, Humphrey visual field studies, fundus photography, and blood testing for mitochondrial genetic analysis. We reconstructed a seven-generation maternal lineage descended from a common ancestor dating to the 1870s. All maternally related family members were invariably homoplasmic 11778 with a haplogroup J mtDNA, 33 being affected, of which 22 are still living. With each subsequent generation, there was a progressive decrease of penetrance, and only males were affected in the last two generations. A significant exposure (greater than 95% confidence intervals) to a variety of environmental risk factors characterized the affected individuals, with smoking as the most common (P <.01). Both affected and carriers (95% confidence intervals) presented with a significantly lower incidence of hypertension and high cholesterol compared with the control group (P <.05). Almost 95% of a 328-living-member pedigree with LHON 11778/J haplogroup was comprehensively studied. Our initial results indicate the strong influence of environmental risk factors. The remarkably reduced incidence of cardiovascular risk in the maternal lineage is discussed. Further genetic analysis may reveal a role for the nuclear genome.


Study on the changes of LHR, FSHR and AR with the development of testis cells in Hu sheep.
The process of testis development in mammals is accompanied by the proliferation and maturation of Sertoli, Leydig and germ cells. Spermatogenesis depends on hormone regulation, which must bind to a receptor to exert its biological effects. The changes in Hu sheep testis cell composition and FSHR, LHR and AR expression during different developmental stages are unclear (newborn, puberty and adulthood). To address this, using single-cell RNA sequencing, we analyzed testis cell composition and hormone receptor expression changes during three important developmental stages of Hu sheep. We observed significant changes in the composition of somatic and germ cells in different Hu sheep testis developmental stages. Furthermore, we analyzed the FSHR, LHR and AR distribution and expression changes at three important periods and verified them by qRT-PCR and immunofluorescence. Our results suggest that after birth, the proportion of germ cells increased gradually, peaking in adulthood; the proportion of Sertoli cells decreased gradually, reaching the lowest in adulthood; and the proportion of Leydig cells increased and then decreased, reaching the lowest in adulthood. In addition, FSHR, LHR and AR are mainly located in Sertoli, Leydig and germ cells. LHR and FSHR expression decreased with increasing age, while AR expression increased and then decreased with increasing age.


Transaortic fine-needle aspiration of centrally located lung cancer under endoscopic ultrasound guidance: the final frontier.
We describe endoscopic ultrasound guided fine-needle aspiration of a mass adjacent to the descending thoracic aorta, which was performed without complication.


Detection of early squamous metaplasia in bladder biopsies of spinal cord injury patients by immunostaining for cytokeratin 14.
A prospective, immunohistochemical study of bladder biopsies taken from spinal cord injury (SCI) patients. To investigate whether cytokeratin 14 immunostaining may be useful to detect early squamous metaplasia in bladder biopsies from patients with SCI. Southport, United Kingdom. Biopsy of bladder mucosa was taken from adults with SCI, while they underwent an elective therapeutic procedure in the urinary tract. A total of, 54 biopsies, which showed transitional epithelium only with no evidence of squamous metaplasia on routine H&E staining, formed the study group. In all, 22 biopsies, which showed squamous metaplasia on routine H&E staining, acted as controls. All biopsies were benign with no evidence of dysplasia or malignancy. Immunohistochemical staining for cytokeratin 14 was performed on all biopsies in a single batch, using a standard avidin-biotin complex method. All control biopsies showed positive immunostaining for cytokeratin 14 in basal and parabasal cells in areas of squamous metaplasia. Of the 54 biopsies, which showed only transitional epithelium on H&E staining, immunohistochemistry for cytokeratin 14 showed no staining in 47 biopsies. The remaining seven biopsies showed positive immunostaining for cytokeratin 14 in the epithelium, in individual cells or clusters of basal cells, revealing unexpected early squamous metaplasia in these biopsies. Immunostaining for cytokeratin 14 identifies an early phenotypic switch from transitional to squamous epithelium in bladder mucosa. Cytokeratin 14 staining is sufficiently sensitive to identify early squamous metaplasia, which is not yet evident on examination of routine H&E stained sections. This early identification may be of use in alerting physicians to change bladder management regimens to prevent predisposition to recurrent urinary infection and progression of squamous metaplasia. A cost/benefit analysis should be performed to assess the feasibility of routine cytokeratin 14 immunostaining of bladder biopsies from SCI patients.


Diagnosis of genital herpes by polymerase chain reaction amplification.
A new polymerase chain reaction (PCR) method employing type-specific primers and probes was applied to 114 clinical specimens obtained from 58 female patients with genital lesions or who had a history of genital herpes. Ten and 15 specimens, respectively, were positive for herpes simplex virus (HSV)-1 and HSV-2 by cell culture. All of 10 culture-confirmed HSV-1 cases and 11 of 15 (73%) culture-confirmed HSV-2 cases were identified by PCR. Although there were several cases with discrepancy between cell culture and PCR for HSV-2, the results suggest that this PCR procedure could be applied to clinical specimens from the female genital tract.


Controllable broadband multicolour single-mode polarized laser in a dye-assembled homoepitaxial MOF microcrystal.
Multicolour single-mode polarized microlasers with visible to near-infrared output have very important applications in photonic integration and multimodal biochemical sensing/imaging but are very difficult to realize. Here, we demonstrate a single crystal with multiple segments based on the host-guest metal-organic framework ZJU-68 hierarchically hybridized with different dye molecules generating controllable single-mode green, red, and near-infrared lasing, with the lasing mode mechanism revealed by computational simulation. The segmented and oriented assembly of different dye molecules within the ZJU-68 microcrystal causes it to act as a shortened resonator, enabling us to achieve dynamically controllable multicolour single-mode lasing with a low three-colour-lasing threshold of ~1.72 mJ/cm2 (approximately seven times lower than that of state-of-the-art designed heterostructure alloys, as reported by Fan F et al. (Nat. Nanotechnol. 10:796-803, 2015) considering the single pulse energy density) and degree of polarization >99.9%. Furthermore, the resulting three-colour single-mode lasing possesses the largest wavelength coverage of ~186 nm (ranging from ~534 to ~720 nm) ever reported. These findings may open a new route to the exploitation of multicolour single-mode micro/nanolasers constructed by MOF engineering for photonic and biochemical applications.


Treatment of mice with the anticoccidial drug Toltrazuril does not interfere with the development of a specific cellular intestinal immune response to Eimeria falciformis.
Immunity against Eimeria-infections is highly specific and it depends on cell-mediated effector mechanisms. Infections of BALB/c mice with 1,000 sporulated oocysts of Eimeria falciformis led to protection against challenge infections. Treatment with the anti-coccidium Toltrazuril, during primary infection, terminated the ongoing disease and did not interfere with the establishment of protective immunity against challenge infections. Mesenteric lymph node cells of infected, treated as well as non-treated and challenged BALB/c mice, showed a similar proliferation upon stimulation with parasite antigen. In contrast, neither cells of the Peyer's patches, intraepithelial lymphocytes, nor spleen cells responded to stimulation with parasite antigens. Cells from all compartments and of all investigated groups proliferated and released the cytokines IFN-gamma and IL-4 in response to the mitogen Concanavalin A. The number of cells releasing IFN-gamma or IL-4 was not dependent on the status of infection or previous treatment with Toltrazuril. The serum IgG response against total sporozoite antigens of individual mice showed that in addition, a systemic humoral response developed in infected mice, independent of a previous drug treatment, although the specific IgG antibody concentration was higher in non-treated mice. Thus, Toltrazuril does not impair the parasite specific intestinal cellular and systemic antibody response and does not prevent the development of protection against challenge infection.


Differential susceptibility of peripheral nerves of the hen to triorthocresyl phosphate and to trauma.
The nerve fibres of largest diameter and of greatest length are considered to be the most vulnerable to triorthocresyl phosphate (TOCP). In this study, the differential vulnerability of the particular sciatic nerve branches was determined in the course of TOCP neuropathy and of Wallerian degeneration. The branch innervating the lateral gastrocnemius muscle, made up predominantly of large-diameter fibres, proved most susceptible to TOCP. By contrast, after proximal sciatic-nerve transection, degeneration commenced in the lateral nerve of the third digit, containing long nerve fibres of small diameter.


Physiologically-induced changes in proopiomelanocortin mRNA levels in the pituitary gland of the amphibian Xenopus laevis.
In the pars intermedia of the pituitary gland of the amphibian Xenopus laevis the level of mRNA encoding proopiomelanocortin (POMC), the precursor protein for alpha-melanophore-stimulating hormone (alpha-MSH), is shown to be dependent on physiological parameters. POMC mRNA levels in the pars intermedia of black-background-adapted Xenopus are much higher than those of white-adapted animals. These physiological changes in POMC mRNA levels are tissue-specific because they were not found in the pars distalis of the pituitary gland. Background transfer experiments revealed that modulation of POMC gene activity is much slower than changes in the secretion of alpha-MSH.


Temperature and irradiance and the total daily photosynthetic production of the crown of a Pinus radiata tree.
Carbon dioxide exchange rates were recorded for different ages and positions of foliage and parts of the main stem of a 7-m tall Pinus radiata D. Don tree growing in a large, artificially lit, controlled-environment room. Irradiance levels were varied from dark to approximately full sunlight, and air temperatures from 10° to 35°C in 5°C steps. Leaf temperatures within the cuvettes used for CO2 exchange measurements, however, were up to 5°C higher than the room air temperature set but this varied with position in the tree crown, the shaded lower crown being at approximately room temperature. A balance sheet was prepared to show the photosynthetic gains and respiratory losses of different parts of the crown over 24 h at each air temperature and at irradiances of 400, 270, and 135 W m-2 during the 8-h photosynthetic period. The greatest daily photosynthetic gain was at 10° C, although this temperature is considered sub-optimal for growth. At temperatures greater than 25° C, even at the greatest irradiance level for 8 h, total respiration was greater than photosynthesis.