Attenuation of spontaneous, nocturnal growth hormone secretion in children with hypothyroidism and its correlation with plasma insulin-like growth factor I concentrations.
To define further the alterations in growth hormone (GH) secretion that occur in childhood hypothyroidism, we quantified spontaneous nocturnal secretion in seven patients with primary hypothyroidism. We examined the relationship between plasma insulin-like growth factor I (IGF-I) and GH secretory profile in each patient before and during therapy with L-thyroxine. In contrast to the results of previous studies that used pharmacologic tests of GH release, spontaneous GH secretion was consistently attenuated in the hypothyroid state. Mean nocturnal GH levels were reduced by 58% (1.48 +/- 0.38 ng/ml, mean +/- SEM) in comparison with values obtained during L-thyroxine therapy (3.54 +/- 0.71 ng/ml, p less than 0.01). Coincident with the reduced levels of GH, plasma IGF-I concentrations were lower in patients before therapy (0.46 +/- 0.20 U/ml) compared with concentrations during therapy (1.50 +/- 0.34 U/ml, p less than 0.01). In treated, euthyroid patients, GH and IGF-I levels were equivalent to those of normal children. The excellent correlation (r = 0.77) between plasma IGF-I and mean nocturnal GH concentrations indicates that reduced plasma IGF-I levels in hypothyroidism probably result from suppressed GH secretion.


Nuclear positioning.
The nucleus is the largest organelle and is commonly depicted in the center of the cell. Yet during cell division, migration, and differentiation, it frequently moves to an asymmetric position aligned with cell function. We consider the toolbox of proteins that move and anchor the nucleus within the cell and how forces generated by the cytoskeleton are coupled to the nucleus to move it. The significance of proper nuclear positioning is underscored by numerous diseases resulting from genetic alterations in the toolbox proteins. Finally, we discuss how nuclear position may influence cellular organization and signaling pathways.


Percutaneous reconstruction of patellar tendon using semitendinosus tendon in chronic patellar tendon injury--case series and outcome.
Chronic patellar tendon injuries are rare. Patients with these debilitating injuries present with extension lag and quadriceps atrophy. Diagnosis is usually made on a clinical background. Various methods of reconstruction of torn patellar tendon have been described and the ideal method of treatment is a matter of debate. We retrospectively reviewed the medical records of nine patients with chronic patellar tendon injury that came to us between June 2006 and July 2012. In all patients, the patellar tendon was reconstructed percutaneously using semitendinosus tendon. Picrusting of quadriceps was required in two patients to pull the patella down. Average follow-up was 4.5 years. At final follow-up Lysholm score, Siwek and Rao grading were good to excellent in all patients, and at 12 months, all patients showed quadriceps strength 80% or more of opposite quadriceps. Percutaneous reconstruction of the patellar tendon in chronic patellar tendon injury using semitendinosus tendon gives excellent result. Picrusting of quadriceps along with lateral release may be required to pull the patella down. Level IV.


Follicular Lymphoma Diagnostic Caveats and Updates.
Follicular lymphoma is a common small B-cell lymphoma, likely to be encountered by any practicing pathologist, regardless of specialty. Although the features of typical follicular lymphoma are well known and in most instances easily identifiable, there are lesser-appreciated morphologic appearances that can raise alternative diagnostic possibilities. The limited tissue available in core needle biopsies can make it additionally challenging to thoroughly evaluate those features in the context of architecture. Furthermore, ancillary testing including immunohistochemistry and molecular/genetic analysis do not always show classic findings and may pose additional challenges to interpretation. To review the morphologic features of follicular lymphoma with a discussion of morphologic variants and mimics; to discuss pitfalls of ancillary testing and provide the practicing pathologist with an appropriate context for interpretation of immunohistochemical and molecular/genetic studies when follicular lymphoma is part of the differential diagnosis; and to propose diagnostic strategies when there is limited tissue for evaluation. We used examples of follicular lymphoma from our institution as well as a review of the literature, with a focus on the diagnostic aspects that are broadly relevant to a general pathology practice. Follicular lymphoma can occasionally present with atypical morphologic, immunohistochemical, or molecular/genetic features. In particular, those findings can be difficult to interpret in the setting of a limited tissue sample. Awareness of those possibilities will help guide the pathologist to a more accurate and precise diagnosis.


Measurement of carotid pulse wave velocity using ultrafast ultrasound imaging in hypertensive patients.
The study aimed to assess the utility of ultrafast ultrasound imaging for evaluation of carotid pulse wave velocity (PWV) in newly diagnosed hypertension patients. This prospective non-randomized study enrolled 90 hypertensive patients in our hospital from September to December 2013 as a hypertension group. An age- and sex-matched cohort of 50 healthy adults in our hospital from September to December 2013 was also included in the study as a control group. Carotid PWV at the beginning and at the end of systole (PWV-BS and PWV-ES, respectively) and intima-media thickness (IMT) were measured by ultrafast ultrasound imaging technology. The associations of PWV-BS, PWV-ES, and IMT with hypertension stage were evaluated by Spearman correlation analysis. PWV-BS and PWV-ES in the hypertension group were significantly elevated compared with those in control group. Different hypertension stages significantly differed in PWV-BS and PWV-ES. PWV-BS and PWV-ES appeared to increase with the hypertension stage. Moreover, IMT, PWV-BS, and PWV-ES were positively correlated with the hypertension stage in hypertensive patients. Ultrafast ultrasound imaging was a valid and convenient method for the measurement of carotid PWV in hypertensive patients. Ultrafast ultrasound imaging might be recommended as a promising alternative method for early detection of arterial abnormality in clinical practice.


Effect of a single dose of polychlorinated biphenyls on hepatic cell proliferation and the DNA binding activity of NF-kappaB and AP-1 in rats.
Polychlorinated biphenyls (PCBs) are environmental pollutants that, because of their persistence and biomagnification, raise concerns about the health consequences of long-term exposure. PCB mixtures induce hepatocellular carcinomas in rodents, but the mechanism of their promoting activity is not clear. Previous studies have shown that oxidative stress occurs after PCB administration, with the induction of lipid peroxidation and oxidative DNA damage, which may contribute to their promoting activity. In this study, we examined whether the oxidative stress-sensitive transcription factors NF-kappaB or AP-1 were activated by PCBs in the liver. Male Sprague-Dawley rats were injected i.p. with corn oil, 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153, 30, 150, or 300 micromol/kg), 3,3',4,4'-tetrachlorobiphenyl (PCB-77, 30, 150, or 300 micromol/kg), or both PCBs (each 30 or 150 micromol/kg). Rats were euthanized 2, 6, or 24 h, or 2, 6, and 10 d after the PCB injection. Electrophoretic mobility shift assays (EMSAs) were performed to determine NF-kappaB and AP-1 DNA binding activities. The highest NF-kappaB DNA binding activity was observed in rats receiving higher doses of PCB-153 (150 and 300 micromol/kg), with peak activation occurring 2 d after injection. AP-1 activation was not detected at any timepoint. Hepatocyte proliferation, as measured by the labeling index, was increased only in groups receiving the highest dose of PCB-153 or the combination of two PCBs (150 micromol/kg each) at day 2, and not by any other PCB treatment at any timepoint. These results show that PCB-153, but not PCB-77, can induce hepatocyte proliferation and hepatic NF-kappaB activation after a single dose.


How to assess physical work-ability with Functional Capacity Evaluation methods in a more specific and efficient way?
The objective of this paper is to propose a three-step procedure that can be used in the selection of functional tests from any full Functional Capacity Evaluation (FCE) method in order to assess efficiently physical work-ability in workers with musculoskeletal complaints (MSC) and related functional limitations. Recently, some authors have considered the selection of functional tests specific to particular jobs from within a full FCE method. In the present study, based on existing literature and on their own expertise on FCE methods, the authors develop in an analogous manner a conceptual framework for selecting functional tests specific to particular MSCs from within a full FCE method. The first step is to establish the worker's medical condition and to assign it to one or more defined MSC categories (upper extremity, back, lower extremity). The second step is to identify activities that are restricted by the medical condition (e.g., lifting and bending for MSC of the back). The third and final step is to select functional tests from a full FCE tests battery to permit measurement of the restricted activities identified in Step 2, striving to avoid redundancy by selecting a limited number of tests for each activity under investigation. The proposed three-step procedure is a new approach to enhance the efficiency and practicality of FCEs.


Identifying optimal clinical trial candidates for locoregionally advanced nasopharyngeal carcinoma: Analysis of 9468 real-world cases and validation by two phase 3 multicentre, randomised controlled trial.
This study aims to identify the optimal high-risk candidates for clinical trials in locoregionally advanced nasopharyngeal carcinoma (NPC). Non-metastatic NPC patients (n = 9,468) were included. Recursive partitioning analyses (RPA) were performed to generate risk stratification. Receiver operating characteristics curve was used to determine the cut-off value of pre-treatment Epstein-Barr virus (EBV) DNA for progression-free survival (PFS). Individual-level data from two clinical trials were used for validation. Anatomic stratification based on T and N category (eighth edition TNM, TNM-8) classified the N2-3 or T4 as an anatomic high-risk group with 5-year PFS of 69% (95% confidence interval: 68-71%). Prognostic stratification identified patients with pre-treatment EBV DNA ≥4000 copies/mL as a prognostic high-risk group with 5-year PFS of 69% (67-70%). The c-index was significantly higher for anatomic stratification (0.621, p < 0.001) and prognostic stratification (0.585, p < 0.001) compared with existing TNM-8 stage groups (0.562). The validation cohorts based on clinical trials data showed greater PFS benefit than the results of the original trials [Hazard ratio: NCT01245959, 0.64 vs. 0.67; NCT01872962, 0.42 vs. 0.52]. Moreover, detectable post-treatment EBV DNA indicated a high risk of progression with 5-year PFS of 38.7% and was the most adverse independent factor for all endpoints. N2-3 or T4 NPC patients were ideal candidates for multicenter clinical trials in locoregionally advanced NPC. Patients with detectable post-treatment EBV DNA are suitable candidates for adjuvant trials.


Two new triterpenoid saponins from Caragana microphylla seeds.
Two new triterpenoid saponins, caraganins A and B (1 and 2), structurally characterized by a 22-oxo group, were isolated from the seeds of Caragana microphylla Lam., together with their n-butyl esters as artifacts (1a and 2a). Their structures and configurations were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. Compounds 1a and 2a exhibited potent antibacterial activity against Staphylococcus aureus and Bacillus subtilis with minimum inhibitory concentration values ranging from 3.125 to 6.25 μg/ml.


Pediatric Anterior Cruciate Ligament Reconstruction.
The increasing incidence of anterior cruciate ligament injuries in skeletally immature children demands careful attention by orthopedic surgeons. Assessing skeletal age is essential to selecting the appropriate reconstruction technique. Males with a bone age of 15 years or older and females of 13 years and older are ideal candidates for a transphyseal anterior cruciate ligament reconstruction because there is minimal risk of growth disturbance. Children with substantial growth remaining (skeletal age males ≤12 years and females ≤10 years) seem to be at risk for more significant growth disturbance, so we generally recommend physeal-sparing techniques for these younger patients.


Influence of region of interest size and ultrasound lesion size on the performance of 2D shear wave elastography (SWE) in solid breast masses.
To evaluate the influence of the region of interest (ROI) size and lesion diameter on the diagnostic performance of 2D shear wave elastography (SWE) of solid breast lesions. A study group of 206 consecutive patients (age range 21-92 years) with 210 solid breast lesions (70 benign, 140 malignant) who underwent core biopsy or surgical excision was evaluated. Lesions were divided into small (diameter <15 mm, n=112) and large lesions (diameter ≥15 mm, n=98). An ROI with a diameter of 1, 2, and 3 mm was positioned over the stiffest part of the lesion. The maximum elasticity (Emax), mean elasticity (Emean) and standard deviation (SD) for each ROI size were compared to the pathological outcome. Statistical analysis was undertaken using the chi-square test and receiver operating characteristic (ROC) analysis. The ROI size used has a significant impact on the performance of Emean and SD but not on Emax. Youden's indices show a correlation with the ROI size and lesion size: generally, the benign/malignant threshold is lower with increasing ROI size but higher with increasing lesion size. No single SWE parameter has superior performance. Lesion size and ROI size influence diagnostic performance.


[Phenotypical antibiotic resistances of bacteriological isolates originating from pet, zoo and falconry birds].
The prevalence of resistant bacteria in pet birds, zoo birds and falconry birds is still largely unknown. Therefore, antibiograms of rapidly-growing aerobic bacteria obtained from these birds were retrospectively evaluated. Between 2007 and 2016 a total of 1036 antibiograms were evaluated. The bacteria isolates originated from 811 birds of 20 zoological orders (mostly Psittaciformes [61.8 %] and Passeriformes [14.5 %] and from alive patients or pathological examinations. The birds were primarily kept in Southern Germany. Phenotypic in vitro sensitivity of bacterial isolates to various antibiotics was determined using a standardized agar diffusion test. The most frequently examined bacteria species were Escherichia coli (n = 386 isolates), Staphylococcus (S.). aureus (n = 150), Enterobacter cloacae (n = 122), Klebsiella pneumoniae (n = 86) and Pseudomonas aeruginosa (n = 64). Resistance to at least one antibiotic agent was detected in 53.1 % of the E. coli isolates, most commonly to doxycycline (50.3 %) and ampicillin (46.1 %), as well as in 95.9 % of Enterococcus faecalis isolates and 78.0 % of Staphylococcus aureus isolates. Multidrug resistance to 3 or more antibiotic groups was frequent in S. aureus (37.3 % of isolates). Resistance rates were higher in isolates from pet birds and captive birds of prey than in isolates from zoo birds.Resistant isolates were more common in Psittaciformes than in Passeriformes. An increasing resistance rate for fluoroquinolones in E. coli (a minimum of 0 % in 2005 and a maximum of 27.3 % in 2011) and decreasing resistance rates for tetracyclines in S. aureus (a maximum of 38.2 % in 2007 and lowest values of 0 % in 2014 and 2015) were observed over the examined period. The detected resistance rates of bacteria in pet birds, zoo birds and falconry birds must be considered as being problematic. They indicate the importance of microbial sensitivity testing for a conscientious therapy of pet birds, zoo birds and falconry birds. Critical treatment situations may arise from infections with S. aureus.


Assessment of the effect of a single oral dose of telithromycin on sotalol-induced qt interval prolongation in healthy women.
Telithromycin belongs to ketolides, a new class of macrolide antibiotics. Macrolides are known to have the potential to prolong QT interval duration. Previous studies have shown that telithromycin did not induce significant QT interval prolongation in healthy subjects compared with placebo. The main objective of this study was to demonstrate the absence of amplification of QT interval prolongation induced by sotalol, when telithromycin and sotalol were co-administered. The secondary objective was to correlate the QT interval changes induced by the study drugs to plasma concentrations during the elimination phase. Twenty-four women received sotalol (160 mg) together with placebo or telithromycin (800 mg) in a two-period, double-blind, randomized study. Electrocardiograms were recorded at rest. Comparison of maximal corrected QT interval (QTc(max)) with sotalol in the presence or absence of telithromycin was performed. The relation between sotalol concentration and QTc was studied using linear regression. Mean difference (95% CI) between QTc(max) with sotalol-placebo and QTc(max) with sotalol-telithromycin was -15.5 ms (-27.7 to -3.2 ms). QTc(max) interval prolongation was lower (P < 0.05) with sotalol-telithromycin than with sotalol-placebo, in relation to decreased sotalol plasma concentrations. Regression analysis showed that the relationship between sotalol plasma concentration and QTc interval duration was not modified by telithromycin co-administration. Our results do not support a potential synergistic effect on QT interval prolongation between sotalol and telithromycin. The decrease of mean QTc interval in subjects taking telithromycin and sotalol may be explained by a decrease of sotalol concentration.


A pilot study of leukocytapheresis efficacy with 1.5 liter blood processing volume in patients with ulcerative colitis.
Standard leukocytapheresis (LCAP) protocols recommend the processing of a 3 L blood volume. In this study, we evaluated the clinical effects of LCAP with 1.5 L of blood processing (1.5L-LCAP) in patients with active ulcerative colitis (UC). Ten patients with moderate to severe UC were enrolled. Their clinical and endoscopic responses, the kinetics of the peripheral blood counts and cytokine responses were evaluated. Clinical and endoscopic effects were assessed using the clinical activity index described by Rachmilewitz, and by Matts' endoscopic classification, respectively. The 1.5L-LCAP induced clinical remission in 8 out of 10 patients (80%). Endoscopic improvement was noted in 6 out of 7 patients (85.7%). Prednisolone (PSL) was used in 8 patients; the PSL dose could be reduced in 6 patients, and weaning was possible in one patient. Adverse effects were not observed during 1.5L-LCAP therapy. During the 1.5L-LCAP session, the leukocyte count reached the minimum at 1.0 L of blood processing, but promptly increased after completion of the session, and reached a maximum after 30 min. Interleukin (IL)-1beta-induced IL-8 and IL-6 secretion by peripheral blood mononuclear cells were both significantly reduced by 1.5L-LCAP therapy. 1.5L-LCAP was clinically effective for active UC patients. Cellular responses induced by 1.5L-LCAP were similar to those induced by a standard LCAP session.


Measuring substance abuse program treatment orientations: the Drug and Alcohol Program Treatment Inventory.
Assessment of therapeutic orientation is a significant problem in substance abuse program evaluation. This study reports the initial results of a new approach to measuring treatment orientation through a self-report survey that focuses on distinctive features of substance abuse treatment orientations. The Drug and Alcohol Program Treatment Inventory (DAPTI) assesses treatment goals and activities specific to eight orientations: AA/12 Step, Therapeutic Community, Cognitive-Behavioral, Insight/Psychodynamic, Rehabilitation, Dual Diagnosis, Medical and Marital/Family Systems. We present findings from a nationwide assessment of 327 Veterans Administration (VA) Substance Abuse treatment programs that demonstrate promising subscale internal consistency, discriminant validity, and concurrent validity. In addition, the DAPTI distinguishes between programs with independently verified orientations and between inpatient, extended care, outpatient, and methadone maintenance programs. The DAPTI may be helpful in systematically assessing differences in treatment orientations between different types of programs, such as inpatient, community residential, and outpatient care.


Cervicofacial actinomycosis in a patient treated for tonsillar carcinoma.
A 50-year-old patient who underwent locoregional radiotherapy and surgery for a tonsillar carcinoma, developed osteomyelitis with Actinomyces israelii with fistulization in the treated area, during chemotherapy treatment. This rare complication is discussed.


Extracellular production of a thermostable Cellvibrio endolytic β-agarase in Escherichia coli for agarose liquefaction.
Four GH16 family β-agarases (GH16A, GH16B, GH16C, and GH16D), originated from an agarolytic bacterium Cellvibrio sp. KY-GH-1, were expressed in an Escherichia coli system and their activities were compared. Only GH16B (597 amino acids, 63.8 kDa), with N-terminal 22-amino acid signal sequence, was secreted into the culture supernatant and demonstrated a robust endolytic agarose hydrolyzing activity for producing neoagarotetraose (NA4) and neoagarohexaose (NA6) as end products. The optimal temperature and pH for the enzyme activity were 50 °C and 7.0, respectively. The enzyme was stable up to 50 °C and over a pH range of 5.0-8.0. The kinetic parameters, including Km, Vmax, kcat, and kcat/Km, of GH16B β-agarases for agarose were 14.40 mg/mL, 542.0 U/mg, 576.3 s-1, and 4.80 × 106 s-1 M-1, respectively. The addition of 1 mM MnCl2 and 15 mM tris(2-carboxyethyl)phosphine enhanced the enzymatic activity. When agarose or neoagaro-oligosaccharides were used as substrates, the end products of enzymatic catalysis were NA4 and NA6, whereas agaropentaose was produced along with NA4 and NA6 when agaro-oligosaccharides were used as substrates. Treatment of 9%[w/v] melted agarose with the enzyme (1.6 µg/mL) under continuous magnetic stirring at 50 °C for 14 h resulted in efficient agarose liquefaction into NA4 and NA6. Purification of NA4 and NA6 from the enzymatic hydrolysate (9%[w/v] agarose, 20 mL) via Sephadex G-15 column chromatography yielded ~ 650 mg NA4/~ 900 mg NA6 (i.e., ~ 85.3% of the theoretical maximum yield). These findings suggest that the recombinant thermostable GH16B β-agarase is useful for agarose liquefaction to produce NA4 and NA6.


Color density spectral array of bilateral bispectral index system: Electroencephalographic correlate in comatose patients with nonconvulsive status epilepticus.
to describe the characteristics of the color density spectral array (CDSA) of bilateral bispectral index (b-BIS) monitoring system in patients with comatose nonconvulsive status epilepticus (NCSE). We hypothesized that CDSA could be helpful for monitoring NCSE in critically subjects if continuous EEG (cEEG) is not available. we retrospectively analyzed comatose patients admitted to our neurological intensive care unit (NICU) from 2011 to 2014 with a diagnosis of definitive NCSE that underwent b-BIS monitoring for at least 24h to guide anesthetic sedation. Clinical, electroencephalography and neuroimaging findings were analyzed. Moreover, all parameters from the b-BIS data including the CDSA were reviewed during periods of NCSE (NCSE pattern) and profound sedation (sedation pattern). 15 NCSE patients were included. The delay from the diagnosis of NCSE to the onset of b-BIS monitoring was 8 (0.5-31)h and total time of b-BIS monitoring 7.8±6.5 days. CDSA during NCSE pattern was characterized by continuous or intermittent red and dark red tones, spectral edge frequency (SEF) in the delta-theta range, with or without asymmetry and BIS number trend with significant variability. In contrast, CDSA during sedation revealed predominance of orange, yellow, green and occasionally blue tones, SEF in the alpha-beta range, absence of asymmetry and stability of BIS number. b-BIS monitoring system and, in particular, CDSA used by nonexpert NICU personnel may be helpful to follow-up episodes of NCSE, to detect recurrences of nonconvulsive seizures (NCSzs), and to monitor profound anesthetic therapy in comatose patients when cEEG is not available.


Use of medications or devices for erectile dysfunction among long-term prostate cancer treatment survivors: potential influence of sexual motivation and/or indifference.
To evaluate the potential association between sexual motivation and patterns of erectile dysfunction (ED) therapy among a large cohort of localized prostate cancer treatment survivors. The use of medications and devices to improve erections and sexual health-related quality of life (HRQOL) were evaluated using a mailed Expanded Prostate Cancer Index Composite survey administered to 896 men 4 to 8 years after brachytherapy, three-dimensional conformal external beam radiotherapy (3D-CRT), or radical prostatectomy and 112 control men. The responding participants (73% of those surveyed) were classified by prostate cancer treatment, sexual motivation, and ED therapy use. Bivariate and multivariate analyses were used to identify the factors associated with ED therapy use and sexual HRQOL outcome. The quality of erections unassisted by medications or devices was not different among the treatment groups. Prostate cancer survivors used medications or devices for ED more commonly than did the control men (30% versus 13%; P <0.01). One half of the prostate cancer survivors with ED reported indifference regarding their ED (small to no sexual bother despite absent or poor unassisted erections). Conversely, among men who were bothered by poor erections, 48% of the brachytherapy, 61% of the 3D-CRT, and 23% of radical prostatectomy subjects had never tried commonly available medications or devices to improve their erections (P <0.01). The current use of at least one erection aid was an independent determinant of more favorable sexual HRQOL (P <0.01). Many men who are bothered by posttreatment ED reported never having tried medications or devices to improve their erections. The lack of ED therapy was more prevalent among patients with erectile concerns after brachytherapy or 3D-CRT than after radical prostatectomy, suggesting possible opportunities for improving sexual HRQOL among long-term survivors.


Discovery biomarker to optimize obeticholic acid treatment for non-alcoholic fatty liver disease.
The response rate to obeticholic acid (OCA), a potential therapeutic agent for non-alcoholic fatty liver disease, is limited. This study demonstrated that upregulation of the alternative bile acid synthesis pathway increases the OCA treatment response rate. The hepatic transcriptome and bile acid metabolite profile analyses revealed that the alternative bile acid synthesis pathway (Cyp7b1 and muricholic acid) in the OCA-responder group were upregulated compared with those in the OCA-non-responder group. Intestinal microbiome analysis also revealed that the abundances of Bacteroidaceae, Parabacteroides, and Bacteroides, which were positively correlated with the alternative bile acid synthesis pathway, were higher in the OCA-responder group than in the non-responder group. Pre-study hepatic mRNA levels of Cyp8b1 (classic pathway) were downregulated in the OCA-responder group. The OCA response rate increased up to 80% in cases with a hepatic Cyp7b1/Cyp8b1 ratio ≥ 5.0. Therefore, the OCA therapeutic response can be evaluated based on the Cyp7b1/Cyp8b1 ratio or the alternative/classic bile acid synthesis pathway activity.


National Health Interview Surveys for health care policy.
Eleven National Health Interview Surveys (NHIS), from nine countries are reviewed to describe their objectives, topics and methods. The NHIS-data are evaluated in terms of their validity and reliability as well as their usefulness for health care policy decisions. With some modifications in design and methods, NHISs have potential for collecting recent and policy-relevant data. Suggestions are offered to improve the usefulness of NHIS-data for health care policy.


Overcoming Near-Cognate Suppression in a Release Factor 1-Deficient Host with an Improved Nitro-Tyrosine tRNA Synthetase.
Genetic code expansion (GCE) technologies incorporate non-canonical amino acids (ncAAs) into proteins at amber stop codons. To avoid unwanted truncated protein and improve ncAA-protein yields, genomically recoded strains of Escherichia coli lacking Release Factor 1 (RF1) are becoming increasingly popular expression hosts for GCE applications. In the absence of RF1, however, endogenous near-cognate amber suppressing tRNAs can lead to contaminating protein forms with natural amino acids in place of the ncAA. Here, we show that a second-generation amino-acyl tRNA synthetase (aaRS)/tRNACUA pair for site-specific incorporation of 3-nitro-tyrosine could not outcompete near-cognate suppression in an RF1-deficient expression host and therefore could not produce homogenously nitrated protein. To resolve this, we used Rosetta to target positions in the nitroTyr aaRS active site for improved substrate binding, and then constructed of a small library of variants to subject to standard selection protocols. The top selected variant had an ~2-fold greater efficiency, and remarkably, this relatively small improvement enabled homogeneous incorporation of nitroTyr in an RF1-deficient expression host and thus eliminates truncation issues associated with typical RF1-containing expression hosts. Structural and biochemical data suggest the aaRS efficiency improvement is based on higher affinity substrate binding. Taken together, the modest improvement in aaRS efficiency provides a large practical impact and expands our ability to study the role protein nitration plays in disease development through producing homogenous, truncation-free nitroTyr-containing protein. This work establishes Rosetta-guided design and incremental aaRS improvement as a viable and accessible path to improve GCE systems challenged by truncation and/or near-cognate suppression issues.


High-dose thiotepa, etoposide and carboplatin as conditioning regimen for autologous stem cell transplantation in patients with high-risk Hodgkin's lymphoma.
Autologous stem cell transplantation (ASCT) generally provides good results in Hodgkin's lymphoma (HL). We studied a high-dose chemotherapy regimen based on thiotepa, etoposide and carboplatin (TECA). Fifty-eight patients with advanced HL were treated with thiotepa, etoposide and carboplatin for transplant induction. The overall response rate was 79·3% (39 CR: 67·2%; and 7 PR: 12·1%); 12 patients (20·1%) were non-responders. The 5-year overall survival rate was 77·6%; five initially responder patients relapsed within the first 5 years of follow-up and underwent salvage therapy. The TECA conditioning regimen for ASCT in HL results in a good anti-HL effect, positive response to treatment and high 5-year overall survival rate. It was also well tolerated and did not induce excessive toxicity, suggesting that TECA may be a very useful conditioning regimen for HL.


Association between the rate of low-birth weight newborns and the incidence of end-stage renal disease in 47 prefectures in Japan.
An ecological study is a useful epidemiologic tool for public health surveillance and establishment of a new hypothesis. Here, we used an ecological study to analyze the association between birth weight and end-stage renal disease (ESRD). We performed ecological regression analysis by using data obtained from the national database of Japan. The data include regional incidence of ESRD beginning maintenance dialysis therapy, regional rate of low-birth weight (LBW) newborn babies of all newborn babies, the average birth weight of newborns, the body mass index (BMI) score, the prevalence of diabetes mellitus, and the amount of payment for drugs, in the 47 prefectures of Japan. The mean regional rates of LBW newborn babies from 1999 to 2008 statistically correlated with the mean incidences of ESRD during the same time periods in each prefecture. The correlation coefficients between the yearly rate of LBW newborns and the yearly incidence of ESRD in each prefecture became higher after statistically considering the effects of the cost per resident for prescriptions of angiotensin II receptor blocker and angiotensin converting enzyme inhibitor. Furthermore, the final model predicting the regional incidence of ESRD by a stepwise multiple regression analysis consisted of the average BMI score and the rate of LBW newborns in each prefecture. Although this study cannot explain the reason for this unexpected correlation between the regional rate of LBW babies and the regional incidence of ESRD at the same time points, the statistically significant correlations shown in this study should be taken into consideration.


Gene expression is stable in a complete CIB1 knockout keratinocyte model.
Epidermodysplasia verruciformis (EV) is a genodermatosis characterized by the inability of keratinocytes to control cutaneous β-HPV infection and a high risk for non-melanoma skin cancer (NMSC). Bi-allelic loss of function variants in TMC6, TMC8, and CIB1 predispose to EV. The correlation between these proteins and β-HPV infection is unclear. Its elucidation will advance the understanding of HPV control in human keratinocytes and development of NMSC. We generated a cell culture model by CRISPR/Cas9-mediated deletion of CIB1 to study the function of CIB1 in keratinocytes. Nine CIB1 knockout and nine mock control clones were generated originating from a human keratinocyte line. We observed small changes in gene expression as a result of CIB1 knockout, which is consistent with the clearly defined phenotype of EV patients. This suggests that the function of human CIB1 in keratinocytes is limited and involves the restriction of β-HPV. The presented model is useful to investigate CIB1 interaction with β-HPV in future studies.


Imaging of chronic posttraumatic osteomyelitis.
Posttraumatic osteomyelitis is frequently characterized by chronicity and recurrent activation of infection. The diagnosis is usually made on the basis of clinical, laboratory, and imaging examinations. The conventional radiograph is the basic imaging study that provides important information about skeletal deformity, bone quality, identification of metallic implants, and consolidation of the former fracture site. Other imaging techniques are required to determine the grade of activity, to define the extent of infection and to delineate small sequestra, intraosseus fistula and abscesses. A variety of more sophisticated modalities, such as modern cross-sectional imaging and radionuclide studies, are available, and the decision to choose the most suitable method can be very difficult. This review gives an overview of definition, epidemiology, and pathophysiology of chronic posttraumatic osteomyelitis and discusses the value of currently used imaging modalities.


Severe Kawasaki heart disease treated with an internal mammary artery graft in pediatric patients. A first successful report.
Two Japanese boys, 6 and 10 years old, required operation for severe Kawasaki heart disease. Both had multiple coronary arterial aneurysms and stenoses, and one had mitral regurgitation as well. The operations consisted of anastomosis between the left internal mammary artery and the left anterior descending artery and insertion of an autologous saphenous vein between the aorta and the posterior descending artery in both patients. The mitral valve was replaced in the one with mitral regurgitation. Angina pectoris has been completely relieved as confirmed by postoperative angiocardiography. Late results of coronary bypass grafting with the saphenous vein in pediatric patients with Kawasaki disease have been less than satisfactory because of the high occlusion rate of the graft. The internal mammary artery may be superior, at least theoretically, to the saphenous vein graft because it is a "living graft" with a high possibility of growing and with less susceptibility to degeneration. This is the first report of successful operation utilizing an internal mammary artery graft in coronary bypass for Kawasaki disease.


Relationship of multiple metals mixture and osteoporosis in older Chinese women: An aging and longevity study.
Osteoporosis has become a major health problem in older women. Previous studies have linked individual metals exposure with osteoporosis, but combined effects remain inconclusive. We aimed to explore the individual and combined association between multiple metals mixture and osteoporosis risk in older Chinese women. A total of 2297 older women (aged ≥60) from the Hongshuihe region of Guangxi, southern China included. We measured 22 blood metal levels through inductively coupled plasma mass spectrometry. And osteoporosis was defined as a T score ≤ -2.5. The least absolute shrinkage and selection operator (LASSO) penalized regression, and Bayesian kernel machine regression (BKMR) models were performed to explore the association between blood metals and osteoporosis risk. Of 2297 older women, there were 829 osteoporosis and 1468 non-osteoporosis participants. The median age was 71 and 68 years old in the osteoporosis and the non-osteoporosis group, respectively. In the single-metal model, rubidium and vanadium were negatively associated with osteoporosis (P for trend = 0.02 and 0.002, respectively), and lead presented the reverse trend (P for trend = 0.01). The LASSO penalized regression model selected nine metals (calcium, cadmium, cobalt, lead, magnesium, rubidium, strontium, vanadium and zinc), which were included in the subsequent analysis. And the multiple-metal model presented a consistent trend with the single-metal model using the selected metals. Furthermore, we performed BKMR to explore the combined effect, and found an overall negative effect between metals mixture and osteoporosis risk when all the metals were fixed at 50th, and rubidium and vanadium were the main contributors. In addition, blood Rb and V were significantly negatively related to OP risk with other metals at different levels (25th, 50th and 75th percentiles). The study suggests metal mixture exposure and osteoporosis risk in older Chinese women, and further studies need to be conducted.


Membrane protein production in Escherichia coli cell-free lysates.
Cell-free protein production has become a core technology in the rapidly spreading field of synthetic biology. In particular the synthesis of membrane proteins, highly problematic proteins in conventional cellular production systems, is an ideal application for cell-free expression. A large variety of artificial as well as natural environments for the optimal co-translational folding and stabilization of membrane proteins can rationally be designed. The high success rate of cell-free membrane protein production allows to focus on individually selected targets and to modulate their functional and structural properties with appropriate supplements. The efficiency and robustness of lysates from Escherichia coli strains allow a wide diversity of applications and we summarize current strategies for the successful production of high quality membrane protein samples.


Identification of the lantibiotic nisin Q, a new natural nisin variant produced by Lactococcus lactis 61-14 isolated from a river in Japan.
Lactococcus lactis 61-14 isolated from river water produced a bacteriocin active against a wide range of Gram-positive bacteria. N-terminal amino acid sequencing, mass spectral analysis of the purified bacteriocin, and genetic analysis using nisin-specific primers showed that the bacteriocin was a new natural nisin variant, termed nisin Q. Nisin Q and nisin A differ in four amino acids in the mature peptide and two in the leader sequence.


Unveiling the potential of nanobubbles in water: Impacts on tomato's early growth and soil properties.
Nanobubbles (NBs) in water have been proven to improve plant growth and seed germination, potentially reducing both water and fertilizer consumption. To unravel the promotion mechanism of NBs on plant growth, this study investigated the characteristics of NBs in tap water and their impacts on tomato's early growth, soil chemical properties, enzymatic activity and electrochemical properties of plant roots. Oxygen NBs (ONBs) were found to increase the seed germination by 10 % and plant growth by 30 %-50 % (e.g., stem and diameter), whereas nitrogen NBs (NNBs) only had a significant promotion (7 %-34 %) on plant height. Additionally, compared to control group, irrigation with ONBs increased the peroxidase activities by 500 %-1000 % in tomato leaves, which may increase the expression of genes for peroxidase and promote cell proliferation and plant growth. Moreover, electrical impedance spectroscopy (EIS) revealed that the ONBs could reduce the interfacial impedance due to the increased active surface area and electrical conductivity of root.


Clastogenicity of atrazine assessed with the Allium cepa test.
Atrazine is classified as a restricted use pesticide and it is currently included in an international revision program for re-evaluating the human and ecological (non-human populations) health risks associated with its release into the environment. The present study was undertaken to add new data on the genotoxic potential of atrazine using the Allium cepa chromosome aberration test. The test concentrations were based on the Maximum Contaminant Levels in water intended for human consumption set by European and US regulations. Atrazine produced a concentration-related increase in the number of total somatic chromosome aberrations, although this increase was statistically significant (p<0.05) only at the highest test concentration (5 microg/L). Analysis of the categories of structural chromosome damage indicated that breaks were the predominant lesion induced; the percent of cells per bulb with breaks also increased in a concentration-related manner, and the increase was statistically significant at the two highest test concentrations (1 and 5 microg/L) (p<0.05). The Allium cepa plant assay detected the clastogenicity of atrazine at concentrations that are likely to be encountered in water, a common site of atrazine contamination.


Haplotyping-Assisted Diploid Assembly and Variant Detection with Linked Reads.
Phasing is essential for determining the origins of each set of alleles in the whole-genome sequencing data of individuals. As such, it provides essential information for the causes of hereditary diseases and the sources of individual variability. Recent technical breakthroughs in linked-read (referred to as co-barcoding in other chapters of the book) and long-read sequencing and downstream analysis have brought the goal of accurate and complete phasing within reach. Here we review recent progress related to the assembly and phasing of personal genomes based on linked-reads and related applications. Motivated by current limitations in generating high-quality diploid assemblies and detecting variants, a new suite of software tools, Aquila, was developed to fully take advantage of linked-read sequencing technology. The overarching goal of Aquila is to exploit the strengths of linked-read technology including long-range connectivity and inherent phasing of variants for reference-assisted local de novo assembly at the whole-genome scale. The diploid nature of the assemblies facilitates detection and phasing of genetic variation, including single nucleotide variations (SNVs), small insertions and deletions (indels), and structural variants (SVs). An extension of Aquila, Aquila_stLFR, focuses on another newly developed linked-reads sequencing technology, single-tube long-fragment read (stLFR). AquilaSV, a region-based diploid assembly approach, is used to characterize structural variants and can achieve diploid assembly in one target region at a time. Lastly, we introduce HAPDeNovo, a program that exploits phasing information from linked-read sequencing to improve detection of de novo mutations. Use of these tools is expected to harness the advantages of linked-reads technology, improve phasing, and advance variant discovery.


Pattern of Altered Plasma Elemental Phosphorus, Calcium, Zinc, and Iron in Alzheimer's Disease.
Metal/mineral dyshomeostasis has been implicated in the development of Alzheimer's disease (AD). The aim of the study was to investigate the difference in absolute and percentage levels of plasma phosphorus, calcium, iron, zinc, copper, selenium in cognitively normal (CN) and AD subjects. Total reflection X-ray fluorescence (TXRF) spectroscopy was used to detect plasma metals/minerals in CN and AD subjects (n = 44 per group). TXRF detected significantly increased plasma levels of phosphorus (p = 1.33 × 10-12) and calcium (p = 0.025) in AD compared to CN subjects, with higher phosphorus/calcium (p = 2.55 × 10-14) ratio in the former. Percentage concentrations calculated for phosphorus, calcium, iron, zinc, copper, selenium by dividing the concentration of each element by the total concentration of these elements and multiplying by 100%, demonstrated phosphorus was higher in AD compared to CN subjects, while calcium, iron, zinc, copper and selenium were lower in AD subjects, with area under the curves as high as 0.937 (p = 6 × 10-5) computed from receiver operating curves. With exclusion of high levels of phosphorus and calcium from percentage calculations, iron levels remained low in AD whereas zinc was higher in AD, and copper and selenium levels were similar. We demonstrate altered distribution of elements in the plasma of AD subjects with high interdependencies between elemental levels and propose the potential of TXRF measurements for disease monitoring.


Comparison of clinical features of arrhythmogenic right ventricular cardiomyopathy in men versus women.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease characterized by myocardial necrosis followed by fibrous-fatty replacement. The pathologic process constitutes the basis for ventricular arrhythmias due to re-entrant circuits. Even if this genetic disease is transmitted in the majority of cases with autosomal dominant trait, in all reported series ARVC is prevalent in men. In this study we investigate the impact that gender may have on clinical presentation in a large series of patients with ARVC. A total of 171 consecutive patients (mean 29 +/- 12 years, range 13 to 65) affected by ARVC were examined with family and personal history, 12-lead electrocardiogram (ECG), 24-hour ECG, signal-averaged ECG, and echocardiogram. Moreover, electrophysiological study and ventricular angiography were performed in selected cases. In the 171 subjects, 71% were men and 29% women (p = 0.02). No gender differences were found considering the age at the time of diagnosis and of study enrolment and the prevalence of index cases and family members. The genders differed in prevalence of abnormal ECG (69% vs 52%, p = 0.036) and presence of late potentials (60% vs 40%, p = 0.01). Moreover, men had larger right ventricular dimensions and practiced competitive sports more frequently (26% vs 14%, p <0.001). Nonetheless, gender was not associated with a high incidence of life-threatening ventricular arrhythmias or with a poor outcome. In conclusion, our data show that diagnosis of ARVC is less common in female patients, who present a higher prevalence of mild forms. Nonetheless, the degree of electrical instability does not differ significantly between genders in affected subjects. Even if ARVC remains mainly a male disease, gender does not have a role in patients' outcome. The cause of the under-representation of women is not clear, even if potentially important factors such as sexual hormones and physical activity could play a role.


Compartmentalized activities of HMGCS1 control cervical cancer radiosensitivity.
The underlying mechanisms by which cellular metabolism affects cervical cancer cell radiosensitivity remain poorly understood. Here, we found that loss of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 (HMGCS1), a key enzyme catalyzing the conversion of acetoacetyl-CoA to HMG-CoA in the cholesterol biosynthesis pathway, sensitizes the cervical cancer cells to radiation. We observed a compartmentalized cellular distribution of HMGCS1 in nuclei, cytosol, and mitochondria of cervical cancer cells and found that cytosolic HMGCS1 and mitochondrial HMGCS1 contribute together to the regulation of radiosensitivity. Mechanistically, we show that cytosolic HMGCS1 regulates radiosensitivity via manipulating the cholesterol metabolism, while mitochondrial HMGCS1 controls mitochondrial gene expression, thereby sustaining the mitochondrial function of cervical cancer cells. Together, our study identifies HMGCS1 as a novel regulator of radiosensitivty in cervical cancer cells, providing a molecular link between altered cholesterol metabolism, mitochondrial respiration, and radiosensitivity. Thus, targeting HMGCS1 may improve the therapeutic outcome of cervical cancer radiotherapy.


Injectable PLGA porous beads cellularized by hAFSCs for cellular cardiomyoplasty.
Cellular cardiomyoplasty has been limited by poor graft retention after cell transplantation. To ensure good retention of the engrafted cells, a microfluidic device was used to fabricate spherical porous beads of poly(D,L-lactic-co-glycolic acid) as a platform for cell delivery. The beads thus obtained had a relatively uniform size, a highly porous structure, and a favorably interconnected interior architecture, to facilitate the transportation of oxygen and nutrients. These porous beads were loaded with human amniotic fluid stem cells (hAFSCs) to generate cellularized microscaffolds. Live/dead assay demonstrated that most of the cells in the porous constructs were viable. The hAFSCs that were grown in beads formed a complex three-dimensional organization with well-preserved extracellular matrices (ECM) according to their porous structure. Retention of the administered beads was clearly identified at the site of engraftment following an experimentally induced myocardial infarction in a rat model. The results of echocardiography, magnetic resonance imaging, and histological analyses suggest that the transplantation of hAFSC beads into an infarcted heart could effectively maintain its gross morphology, prevent successive ventricular expansion, and thereby improve the post-infarcted cardiac function. Immunofluorescent staining revealed that the microenvironment that was provided by the infarcted myocardium might offer cues for the induction of the engrafted hAFSCs into angiogenic and cardiomyogenic lineages. Our results demonstrate that the cellularized beads with endogenously secreted ECM were of sufficient physical size to be entrapped in the interstitial tissues following transplantation, thereby benefiting the infarcted heart.


Chromogenic substrates in haemostasis.
Advances in knowledge of the structure-function relationships of the proteins involved in haemostatic pathways, have made it possible to synthesize small peptides which mimic the active site of many of the serine proteases concerned. Attachment to the cleavage site of such synthetic peptides, of a detector molecule such as para-nitroaniline which, when released, produces a coloured compound has enabled many of the enzyme reactions of haemostasis, and most of the co-factors and naturally-occurring inhibitors, to be individually and sensitively quantitated. Chromogenic substrate assays are very specific and overcome the criticism levelled at many conventional assays that, being based on the speed of formation or the rate of destruction of a fibrin clot, they frequently involve enzymatic reactions in addition to that being examined. Moreover, chromogenic substrate assays are generally simple and quick to perform and are readily automated. They are thus economical of manpower and, more importantly from the point of view of patient care, they permit the rapidly-changing status of those with acute derangements of haemostasis to be monitored more frequently and comprehensively than is possible using some conventional assays. Chromogenic substrate assays have some limitations, however. Since they mimic only a small portion of the natural substrate, they may not be sensitive to structural defects elsewhere in the molecule, and may thus not totally reflect biological activity. Though technically simple to perform, the defined incubation times and temperatures must be rigidly adhered to if reliable results are to be obtained.(ABSTRACT TRUNCATED AT 250 WORDS)


Postoperative complications in the Tube Versus Trabeculectomy (TVT) study during five years of follow-up.
To describe postoperative complications encountered in the Tube Versus Trabeculectomy (TVT) Study during 5 years of follow-up. Multicenter randomized clinical trial. Seventeen clinical centers. Patients 18 to 85 years of age who had previous trabeculectomy and/or cataract extraction with intraocular lens implantation and uncontrolled glaucoma with intraocular pressure (IOP) ≥18 mm Hg and ≤40 mm Hg on maximum tolerated medical therapy. Tube shunt (350-mm(2) Baerveldt glaucoma implant) or trabeculectomy with mitomycin C (MMC 0.4 mg/mL for 4 minutes). Surgical complications, reoperations for complications, visual acuity, and cataract progression. Early postoperative complications occurred in 22 patients (21%) in the tube group and 39 patients (37%) in the trabeculectomy group (P = .012). Late postoperative complications developed in 36 patients (34%) in the tube group and 38 patients (36%) in the trabeculectomy group during 5 years of follow-up (P = .81). The rate of reoperation for complications was 22% in the tube group and 18% in the trabeculectomy group (P = .29). Cataract extraction was performed in 13 phakic eyes (54%) in the tube group and 9 phakic eyes (43%) in the trabeculectomy group (P = .43). A large number of surgical complications were observed in the TVT Study, but most were transient and self-limited. The incidence of early postoperative complications was higher following trabeculectomy with MMC than tube shunt surgery. The rates of late postoperative complications, reoperation for complications, and cataract extraction were similar with both surgical procedures after 5 years of follow-up.


Microbiological investigation of retrodiscal tissues from patients with advanced internal derangement of the temporomandibular joint.
The aim of this study was to investigate the presence of bacteria in samples of retrodiscal tissues taken from patients suffering from advanced internal derangement of the temporomandibular joint (TMJ). 12 fresh retrodiscal tissue samples were taken from 12 consecutive patients who underwent unilateral TMJ discectomy for advanced TMJ internal derangement (Wilkes stage IV). The retrodiscal tissue samples were stained and cultured for the presence of micro-organisms in microbiology laboratories. No evidence of bacteria or other micro-organisms was found in any of the tissue specimens procured from the TMJ. This study failed to identify the presence of bacteria or other micro-organisms in fresh retrodiscal tissue specimens of the TMJ in patients with advanced TMJ internal derangement.


The use of eHealth to promote physical activity in thoracic malignancies survivors: A systematic review and meta-analysis.
Survival rates for many forms of thoracic malignancies have improved over the past few decades, however, many survivors are coping with the side effects of cancer treatment for longer. Physical activity (PA) has been proposed as a therapeutic strategy to combat the effects of treatment in cancer survivors and eHealth could be a good way to encourage patients to practice it. To explore the effects of eHealth in the promotion of PA among thoracic malignancies. Suitable articles were searched using PubMed, Web of Science and Scopus databases using a combination of medical subject headings. In total, 4781 articles were identified, of which ten met eligibility criteria. Different eHealth interventions were described in these studies: mobile application (app) (n = 3), website (n = 2), email (n = 2), web and mobile application (n = 1), telephone counseling (n = 1) and online sheet (n = 1). All studies reported improvements in PA, with 8/10 studies reporting statistically significant changes. Our results show that eHealth programs are useful to promote PA in malignancy thoracic survivors, compared to no intervention, conventional treatment or a dietary approach. Moreover, the meta-analysis also revealed eHealth is a good way to improve the level of PA in thoracic malignancies survivors.


Emulating tightly bound electrons in crystalline solids using mechanical waves.
Solid state physics deals with systems composed of atoms with strongly bound electrons. The tunneling probability of each electron is determined by interactions that typically extend to neighboring sites, as their corresponding wave amplitudes decay rapidly away from an isolated atomic core. This kind of description is essential in condensed-matter physics, and it rules the electronic transport properties of metals, insulators and many other solid-state systems. The corresponding phenomenology is well captured by tight-binding models, where the electronic band structure emerges from atomic orbitals of isolated atoms plus their coupling to neighboring sites in a crystal. In this work, a mechanical system that emulates dynamically a quantum tightly bound electron is built. This is done by connecting mechanical resonators via locally periodic aluminum bars acting as couplers. When the frequency of a particular resonator lies within the frequency gap of a coupler, the vibrational wave amplitude imitates a bound electron orbital. The localization of the wave at the resonator site and its exponential decay along the coupler are experimentally verified. The quantum dynamical tight-binding model and frequency measurements in mechanical structures show an excellent agreement. Some applications in atomic and condensed matter physics are suggested.


Evolution of low-copy number and major satellite DNA sequences coexisting in two Pimelia species-groups (Coleoptera).
Satellite DNA sequence evolution has been studied in several insect species from the genus Pimelia (Tenebrionidae, Coleoptera). Low-copy number homologs of the previously characterized major satellite DNA from P. monticola (PMON) have been cloned and sequenced from six congeneric species belonging to two species groups: Ibero-Balearic and Moroccan. Sequence analysis of a sample of low-copy number repeats revealed two subfamilies, differing on average 17.5% due to randomly spread single point mutations. Each subfamily is specific for a group of taxa in congruence with their biogeography. Within each group, there is no significant species-specific clustering of the sequences. These results suggest that the two satellite subfamilies arose after the split of an ancestral lineage into the North African and Ibero-Balearic Pimelia species-groups, but before their subsequent radiation. Rate heterogeneity tests suggest that PMON sequences have evolved faster in the lineage leading to the Moroccan group. Comparison of sequence divergences between minor PMON and the previously characterized major PIM357 satellite obtained from the same taxa, points to similar evolutionary dynamics. Both sequences are evolving in parallel accumulating mutations in a gradual manner irrespectively of significant differences in abundance. These data show that copy number of the sequence families does not necessarily affect the sequence change dynamics of satellite repeats.


The relationship between tumour necrosis, tumour proliferation, local and systemic inflammation, microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma.
There is increasing evidence that the local and systemic inflammatory responses are associated with survival in oesophageal cancer. The aim of this study was to examine the relationship between tumour necrosis, tumour proliferation, local and systemic inflammation and microvessel density and survival in patients undergoing potentially curative resection of oesophageal adenocarcinoma. The interrelationship between tumour necrosis, tumour proliferation, local inflammatory response (Klintrup-Makinen criteria, intra-tumoural CD8+ lymphocyte and macrophage infiltration), systemic inflammatory response (modified Glasgow Prognostic score (mGPS)), and microvessel density was examined in 121 patients undergoing potentially curative resection for oesophageal adenocarcinoma (including type I and II tumours of the gastro-oesophageal junction). Tumour necrosis was not significantly associated with any tumour measure other than the degree of differentiation. On multivariate analysis, only age (HR 1.93, 95% CI 1.23-3.04, P=0.004), mGPS (HR 2.91, 95% CI 1.51-5.62, P=0.001), positive to total lymph node ratio (HR 2.38, 95% CI 1.60-3.52, P<0.001) and macrophage infiltration (HR 1.49, 95% CI 1.02-2.18, P=0.041) were independently associated with cancer-specific survival in oesophageal adenocarcinoma. Intra-tumoural macrophages were associated with tumour proliferation (P<0.001) and CD8+ lymphocytes infiltration (P<0.01). The results of this study suggest that tumour necrosis does not link local and systemic inflammatory responses and is not significantly associated with survival. In contrast, tumour macrophage infiltration appears to have a central role in the proliferative activity and the coordination of the inflammatory cell infiltrate and is independently associated with poorer survival in patients with oesophageal adenocarcinoma.


MicroRNAs as components of systemic signaling pathways in Drosophila melanogaster.
MicroRNAs (miRNAs) ensure progression through development by synchronizing cell fate transitions in response to environmental cues. These cues are mediated at least in part by steroid hormones. Emerging evidence indicates that miRNAs are also components of additional systemic signaling pathways, including insulin, stress, immune, and circadian pathways. Thus, the roles that miRNAs play during development are reflected in their post-developmental functions, where they similarly function to coordinate cell behavior in response to environmental cues. In this review, we summarize current work highlighting the role of miRNAs in systemic signaling pathways in Drosophila melanogaster as a way of synthesizing the underlying roles of miRNAs in both animal developmental transitions and adult physiology.


Causal effects of opioids on postpartum depression: a bidirectional, two-sample Mendelian randomization study.
Postpartum depression is the most common psychiatric disorder in pregnant women during the postpartum period and requires early detection and treatment. Previous studies have found that opioids use affects depression and anxiety disorders. Although it has long been suspected that opioids may contribute to the development of postpartum depression, observational studies are susceptible to confounding factors and reverse causality, making it difficult to determine the direction of these associations. To examine the causal associations between opioids and non-opioid analgesics with postpartum depression, we utilized large-scale genome-wide association study (GWAS) genetic pooled data from two major databases: opioids, salicylate analgesic, non-steroidal anti-inflammatory drugs (NSAIDs), and aniline analgesics GWAS data from the United Kingdom Biobank database. GWAS data for postpartum depression were obtained from the FinnGen database. The causal analysis methods used random-effects inverse variance weighting (IVW), and complementary sensitivity analyses using weighted median, MR-Egger method, and MR-PRESSO test. In the IVW analysis, Mendelian randomization (MR) analysis showed that opioids increased the risk of postpartum depression (OR, 1.169; 95% CI, 1.050-1.303; p = 0.005). Bidirectional analysis showed a significant causal relationship between genetically predicted postpartum depression and increased risk of opioids and non-opioid analgesics use (opioids OR, 1.118; 95% CI, 1.039-1.203; p = 0.002; NSAIDs OR, 1.071; 95% CI, 1.022-1.121; p = 0.004; salicylates OR, 1.085; 95% CI, 1.026-1.146; p = 0.004; and anilides OR, 1.064; 95% CI, 1.018-1.112; p = 0.006). There was no significant heterogeneity or any significant horizontal pleiotropy bias in the sensitivity analysis. Our study suggests a potential causal relationship between opioids use and the risk of postpartum depression. Additionally, postpartum depression is associated with an increased risk of opioids and non-opioid analgesics use. These findings may provide new insights into prevention and intervention strategies for opioids abuse and postpartum depression.


Mechanism of the cardiovascular activity of dibenzoxazepine in cats.
Small i.v. doses of dibenzoxazepine (DBO) (50--400 microgram/kg) given to anesthetized cats resulted in dose related increases in heart rate (up to 70 beats/min) and blood pressure (up to 80 mm Hg). The pressor response was blocked by pretreatment of the animals with phentolamine; pretreatment for 3 days with 6-hydroxdopamine; with mecamylamine and spinal transection between C1 and C2 but not by propranolol or adrenalectomy. The increase in heart rate was blocked by pretreatment with propranolol, 6-hydroxydopamine, mecamylamine and spinal transection whereas adrenalectomy only affected the response slightly. DBO produced only negative effects on the isolated rabbit heart. Bioassay of arterial blood showed an increased level of circulating catecholamines corresponding to the cardiovascular stimulation. DBO had no tyramine-like activity on the isolated rabbit aortic strip but slightly potentiated the contraction induced by noradrenaline. These findings strongly suggest that the cardiovascular effects resulted from central stimulation of the sympathetic nervous system. A minor part of the observed sympathomimetic effects may also be the result of the ability of DBO to potentiate the effects of noradrenaline perhaps by blocking catecholamine uptake.


Prevention of gastric mucosal lesions following aortic cross-clamping.
Stress ulceration is frequently encountered after cardiovascular surgery. In this study of 32 male baboons, severe gastric ischaemia was used to produce gastric stress lesions. The occurrence of these lesions was reduced by allopurinol (P = 0.03) and completely prevented by the combination of allopurinol with superoxide dismutase (P = 0.004). A shorter ischaemic period also reduced the number of lesions (P = 0.02). Concurrent with the stress lesion formation, there was a fall in mucosal glutathione and oxidized glutathione levels (P less than 0.05).


Early continence after ileal neobladder: objective data from inpatient rehabilitation.
To evaluate early continence of patients who underwent inpatient rehabilitation after radical cystectomy (RC) and orthotopic bladder substitution (ONB). We conducted a retrospective analysis on the data of 283 patients who underwent a three weeks inpatient rehabilitation after RC and ONB for bladder cancer between January 2016 and July 2017. All patients were treated with a special multimodal continence therapy. The continence status was evaluated by measuring urine loss by a 24-h pad test and urine volume on uroflowmetry at the beginning (T1) and at the end (T2) of inpatient rehabilitation. Multivariate linear regression analysis was performed to identify independent predictors of urine loss. Median patient age was 63 years. NS was documented for 142 patients (50.2%). Median urine loss decreased significantly (p < 0.001) in the 24-h pad test, from 442 gm at T1 (median 29 days after surgery) to 88 gm at T2 (median 50 days after surgery). Urine volume increased significantly (p < 0.001) from a median of 78 ml at T1 to a median of 157 ml at T2. Age (p = 0.002), diabetes (p = 0.031), obesity (p = 0.003), and nerve sparing (p = 0.011) were identified as independent predictors for urine loss at the end of inpatient rehabilitation. Continence improved significantly during the three weeks of inpatient rehabilitation. Younger age, the absence of diabetes or obesity, and NS resulted in better continence in the early postoperative period after ONB.


The effects of task complexity on brake response time before and after primary right total knee arthroplasty.
To study the effects of an increase in task complexity on brake response time (BRT) in patients undergoing total knee arthroplasty (TKA). A prospective repeated-measures design was used. The measurements took place 1 day before and 10 and 30 days after surgery. Clinic. The data of patients (N=21) who were admitted for primary total arthroplasty of the right knee were pooled for analysis. On each measurement day patients performed 5 practice and 10 test trials for 2 tasks (1 simple, 1 complex) in a car simulator. Task complexity was increased by adding a second movement to the first task performed. BRT, reaction time (RT), and movement time were assessed. An increase in task complexity increased BRT, RT, and movement time at all measurement times. Right TKA increased BRT by increasing movement time. Thirty days after surgery BRT was no longer increased compared with preoperative values in both tasks. Task complexity consistently increased BRT and its components. The effects of task complexity remained constant throughout the 3 measurements. After right TKA, we suggest patients should be advised to wait 30 days after surgery before resuming driving.


Normal tissue complication probability of acute eyelids erythema following radiotherapy of head and neck cancers and skull-base tumors.
Radiation therapy is broadly used as one of the main treatment methods for patients with head and neck cancers and skull base tumors. However, it can lead to normal tissue complications. Therefore, this study aimed to model normal tissue complication probability (NTCP) of eyelid skin erythema after radiation therapy. The dataset of 45 patients with head and neck and skull base tumors was prospectively collected from their dose-volume histograms (DVHs). Grade 1 + eyelid skin erythema based on the Common Terminology Criteria for Adverse Events (CTCAE 4.0) was evaluated as the endpoint after a three-month follow-up. The Lyman-Kutcher-Burman (LKB) radiobiological model was developed based on generalized equivalent uniform dose (gEUD). Model parameters were calculated by maximum likelihood estimation. Model performance was evaluated by ROC-AUC, Brier score and Hosmer-Lemeshow test. After three months of follow-up, 13.33% of patients experienced eyelids skin erythema grade 1 or more. The parameters of the LKB model were: TD50 = 30 Gy, m = 0.14, and n = 0.10. The model showed good predictive performance with ROC-AUC = 0.80 (CI:0.66-0.94) and a Brier score of 0.20. In this study, NTCP of eyelid skin erythema was modeled based on the LKB radiobiological model with good predictive performance.


The Wnt/frizzled/GSK-3 beta pathway: a novel therapeutic target for cardiac hypertrophy.
An excessive hypertrophic response of the heart to an increased workload is a leading cause of heart failure. At present, cardiac hypertrophy is treated with inhibitors of the renin-angiotensin system or with beta-adrenoceptor antagonists. These current therapeutic strategies inhibit prohypertrophic signaling pathways, but this therapy is inadequate in a substantial number of patients. However, the hypertrophic response of the heart is the net result of activation of prohypertrophic and antihypertrophic pathways. Glycogen synthase kinase-3 beta (GSK-3 beta) has a powerful antihypertrophic effect, but is inhibited by growth factors and hypertrophic stimuli through phosphorylation at the Ser9 residue of GSK-3 beta. Activation of the Wnt/frizzled pathway also results in inactivation of GSK-3 beta through sequestration of the kinase rather than phosphorylation at Ser9. In this Opinion article we will review the current evidence for the involvement of Wnt/frizzled signaling and the activation of GSK-3 beta in the regulation of cardiac hypertrophy, and subsequently discuss the potential of this pathway to serve as a novel therapeutic approach for cardiac hypertrophy.


Factors affecting the risk of developing lower back musculoskeletal disorders (MSDs) in experienced and inexperienced rodworkers.
Injury and dropout rates during rodwork training appear to reflect difficulties encountered by apprentices adapting to increased physical demands of tying on slab, one of the rodworking tasks with the highest injury risk. Because experience influences work strategies, and consequently the risk of developing musculoskeletal disorders (MSDs), this study aimed to identify differences in work practices associated with tying rebar on slab, potentially relevant to back MSD development, in experienced and inexperienced rodworkers. Fourteen male rodworkers were recruited from either experienced (>2 years experience post apprenticeship), or inexperienced (<6 months experience) groups. Both tied an area with rebar laid on the ground. Trunk flexion/extension angles were measured. L4/L5 moments were estimated from T9 Erector Spinae EMG. Experienced workers were found to spend longer periods of time in trunk flexed postures, with lower peak L4/L5 moments. Our findings revealed practices associated with each group might have different implications on back health.


Applications of combined DNA microarray and chromosome sorting technologies.
The sequencing of the human genome has led to the availability of an extensive mapped clone resource that is ideal for the construction of DNA microarrays. These genomic clone microarrays have largely been used for comparative genomic hybridisation studies of tumours to enable accurate measurement of copy number changes (array-CGH) at increased resolution. We have utilised these microarrays as the target for chromosome painting and reverse chromosome painting to provide a similar improvement in analysis resolution for these studies in a process we have termed array painting. In array painting, chromosomes are flow sorted, fluorescently labelled and hybridised to the microarray. The complete composition and the breakpoints of aberrant chromosomes can be analysed at high resolution in this way with a considerable reduction in time, effort and cytogenetic expertise required for conventional analysis using fluorescence in situ hybridisation. In a similar way, the resolution of cross-species chromosome painting can be improved and we present preliminary observations of the organisation of homologous DNA blocks between the white cheeked gibbon chromosome 14 and human chromosomes 2 and 17.


Broadband inhomogeneous lens with conical radiation pattern.
This manuscript presents a lens antenna with simultaneous broadside and conical beams. The lens is designed for the Ku band using the ray inserting method. The proposed conical radiation pattern is broadband due to good matching with the source and surroundings. The simulation is conducted using the CST microwave studio solver. Instead of complex antenna shapes used in other works, a simple circular patch ring and RF connector are used as the lens feed to generate broadside and omnidirectional conical patterns, respectively. To validate the performance of the designed lens and its two-port feed antenna, the lens structure is realized and fabricated using the 3D printing method. Polyethylene terephthalate glycol (PETG) plastic material is utilized for constructing the lens in this work. The electromagnetic characteristics of PETG in the Ku band are accurately measured. The results of simulations and experiments demonstrate the good performance of the designed lens over a wide frequency bandwidth. The advantage of this designed structure over other works is its high gain and broad bandwidth.


Squamous cell carcinoma of the lip: is there a role for adjuvant radiotherapy in improving local control following incomplete or inadequate excision?
The treatment of squamous cell carcinoma of the lip with surgery is usually curative but incomplete/inadequate excision may be associated with recurrence and poor outcome. There is no consensus in the literature on the definition of an adequate excision margin. Patients treated for squamous cell carcinoma of the lip at Westmead Hospital, Sydney, between 1980 and 2000 were eligible for inclusion. Polytomous logistic regression analysis was undertaken to assess for predictors of recurrence. Recurrence-free and overall survival were calculated using Kaplan-Meier survival curves. A total of 130 patients was identified. Median age at diagnosis was 64 years (23-97 years). Most lesions (90%) were located on the lower lip in 96 (74%) male patients. Median follow-up duration was 54 months (0-189 months). Most patients -presented with T1 lesions (75%). Initial treatment was surgery (39%), radiotherapy (48%) or both (13%). Twenty-seven per cent of excised lesions had a close (< or =2 mm) or positive margin. A total of 40 patients (31%) had recurrence (18% lymph nodes, 11% lip and 2% both). In the surgery group recurrence was significantly more likely with close or positive margins (P = 0.05). The 2 year -recurrence-free survival was 82% and 54% for radiotherapy and surgery, respectively (P < 0.001). The 2 year overall survival was similar (90% radiotherapy vs 100% surgery; P = 0.58). Incomplete or inadequate excision of some lip cancers results in local recurrence. If re-excision is not feasible -surgeons should consider the role of adjuvant radiotherapy in improving local control.


A case report of fibular aplasia, tibial campomelia, and oligosyndactyly (FATCO) syndrome associated with Klinefelter syndrome and review of the literature.
Limb development is a complex regulated development phenomenon involving multiple genes. Fibular Aplasia, Tibial Campomelia and Oligosyndactyly (FATCO) syndrome (MIM#246570) is a syndrome of unknown genetic basis and inheritance with variable expressivity and penetrance. Its counterpart, Fuhrmann syndrome or Femoral-Fibularaplasia-Campomelia and Oligosyndactyly are a result of defect in the WNT7a gene located on the 3p25. Former is proposed to be a development dysplasia of defective dorso-ventral polarity assignment and distal limb development. Ectrodactyly and fibular a/hypoplasia (EFA, MIM# 113310) share the full phenotypic spectrum of FATCO syndrome, whether they are allelic disorders or represent two variable presentations in the spectrum of the same disorder is not an established fact. We report here one Indian patient with findings of FATCO syndrome with associated Klinefelter syndrome. This is the first such report which is likely to be a co-incidental finding and has implications for genetic counseling. Therapeutic, Level IV.


Testosterone metabolism in the medial basal hypothalamus of the starved male rat.
The conversion of testosterone to estradiol by aromatase and to dihydrotestosterone by 5 alpha-reductase was measured in the medial basal hypothalamus of starved and control male rats. Activities of both enzymes were significantly reduced in starved animals. Aromatase activity was 18.2 +/- 2.3 versus 29.8 +/- 5.7 fmol E2/mg protein/90 min (mean +/- SEM, P less than 0.02) and 5 alpha-reductase was 4.95 +/- 0.35 versus 5.96 +/- 0.30 pmol DHT/mg protein/90 min (P less than 0.02) for starved and control animals respectively. The results indicate that hypothalamic metabolism of testosterone is decreased during starvation. Therefore the increased sensitivity of the T-LH feedback described earlier in starved rats [4] cannot be explained by changes in central testosterone metabolism.


MACULAR HOLE-RELATED RETINAL DETACHMENT COMPLICATING AUTOSOMAL RECESSIVE BESTROPHINOPATHY: CLINICAL FEATURES, MULTIMODAL IMAGING, AND SURGICAL OUTCOME.
To report a case of full-thickness macular-hole related retinal detachment in a patient with autosomal recessive bestrophinopathy. A 3-year-old boy presented for squint assessment. In the examination, there were typical features of autosomal recessive bestrophinopathy in the left eye and a macular hole-related retinal detachment in his right eye. Color fundus photography, autofluorescence, fundus fluorescence angiography, and spectral-domain optical coherence tomography were recorded. Optical coherence tomography of the right eye showed a full-thickness macular hole retinal detachment. The retina showed retinoschisis affecting the inner and outer nuclear layer at the fovea and parafoveal region. Also, hyperreflective dots were seen at the hole and on the inner retinal surface. The left eye showed subretinal fluid with stalactite-like extensions into the subretinal space, and hyperreflective material seen above the retinal pigment epithelium. Fundus autofluorescence showed hyperautofluorescence at the fovea of the right eye and punctate hyperautofluorescent spots in the mid-periphery of the left eye. After pars plana vitrectomy and temporal internal limiting membrane flap, the hole was closed and all the schitic cavities collapsed at the sixth-week follow-up visit. A full-thickness macular hole-related retinal detachment can develop in autosomal recessive bestrophinopathy in the pediatric age group. Pars plana vitrectomy with temporal internal limiting membrane flap may be helpful for successful surgical repair.


Feasibility and preliminary outcomes of fetoscopic laser photocoagulation for monochorionic twin gestation with selective intrauterine growth restriction accompanied by severe oligohydramnios.
This study aimed to clarify the feasibility and perinatal outcomes of fetoscopic laser photocoagulation (FLP) for monochorionic twin gestation with selective intrauterine growth restriction (sIUGR) accompanied by both abnormal umbilical artery Doppler waveforms and isolated severe oligohydramnios of the sIUGR twin. In this prospective clinical trial, which included 10 cases with absent or reversed end-diastolic flow in the umbilical artery and severe oligohydramnios of the sIUGR twin, the main outcomes investigated were the feasibility of FLP and the rate of severe FLP-related maternal complications. The survival rate and incidence of neurological abnormalities of the twins at 28 days of age were also evaluated. FLP was completed for all cases without major intraoperative maternal complications, although one case experienced threatened preterm labor requiring intensive treatment after the procedure. Three sIUGR and 10 larger twins were alive without neurological abnormalities at 28 days of age, while intrauterine fetal death occurred in the remaining seven sIUGR twins. FLP for monochorionic twins with sIUGR, especially when accompanied by abnormal Doppler and severe oligohydramnios of the sIUGR twin, appears to be feasible and potentially beneficial for the larger twin, as well as for some sIUGR twins.


Identification and in vitro and in vivo validation of the key role of GSDME in pyroptosis-related genes signature in hepatocellular carcinoma.
We used pyroptosis-related genes to establish a risk-score model for prognostic prediction of liver hepatocellular carcinoma (LIHC) patients. A total of 52 pyroptosis-associated genes were identified. Then, data for 374 LIHC patients and 50 normal individuals were acquired from the TCGA database. Through gene expression analyses, differentially expressed genes (DEGs) were determined. The 13 pyroptosis-related genes (PRGs) confirmed as potential prognostic factors through univariate Cox regression analysis were entered into Lasso and multivariate Cox regression to build a PRGs prognostic signature, containing four PRGs (BAK1, GSDME, NLRP6, and NOD2) determined as independent prognostic factors. mRNA levels were evaluated by qRT-PCR, while overall survival (OS) rates were assessed by the Kaplan-Meier method. Enrichment analyses were done to establish the mechanisms associated with differential survival status of LIHC patients from a tumor immunology perspective. Additionally, a risk score determined by the prognostic model could divide LIHC patients into low- and high-risk groups using median risk score as cut-off. A prognostic nomogram, derived from the prognostic model and integrating clinical characteristics of patients, was constructed. The prognostic function of the model was also validated using GEO, ICGC cohorts, and online databases Kaplan-Meier Plotter. Small interfering RNA-mediated knockdown of GSDME, as well as lentivirus-mediated GSDME knockdown, were performed to validate that knockdown of GSDME markedly suppressed growth of HCC cells both in vivo and in vitro. Collectively, our study demonstrated a PRGs prognostic signature that had great clinical value in prognosis assessment.


In vitro cytodifferentiation of perinatal rat islet cells within a tridimensional matrix of collagen.
Cell suspensions prepared by collagenase digestion of pancreases obtained from rat fetuses (21.5 d old) and newborns (2.5 d old) were mixed with a collagen solution and inoculated on a collagen base layer. At the onset of the culture, most acinar cells became necrotic, whereas other epithelial cells proliferated. Most of the cell clusters arranged themselves into simple polarized structures composed of epithelial cells forming hollow spheres, and from these budded neoformed endocrine islets. Scarce fibroblasts were located close to these structures. Immunocytochemical localization of insulin and glucagon, as well as ultrastructural characteristics of the cell types revealed an intrainsular distribution similar to the in vivo localization. Tridimensional matrix of collagen offers, to perinatal pancreatic cells in culture, an environment close to the in vivo conditions: cells reorganize themselves in tissuelike structures and cell interactions concerned in the cytodifferentiation of pancreatic islets occur. This system allows for the study of undifferentiated epithelial cells--the presumed stem cells--differentiating and differentiated endocrine cells in the same preparation.


A review on COVID-19 transmission, epidemiological features, prevention and vaccination.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections and millions of deaths over past two years. Currently, many countries have still not been able to take the pandemic under control. In this review, we systematically summarized what we have done to mitigate the COVID-19 pandemic, from the perspectives of virus transmission, public health control measures, to the development and vaccination of COVID-19 vaccines. As a virus most likely coming from bats, the SARS-CoV-2 may transmit among people via airborne, faecal-oral, vertical or foodborne routes. Our meta-analysis suggested that the R0 of COVID-19 was 2.9 (95% CI: 2.7-3.1), and the estimates in Africa and Europe could be higher. The median Rt could decrease by 23-96% following the nonpharmacological interventions, including lockdown, isolation, social distance, and face mask, etc. Comprehensive intervention and lockdown were the most effective measures to control the pandemic. According to the pooled R0 in our meta-analysis, there should be at least 93.3% (95% CI: 89.9-96.2%) people being vaccinated around the world. Limited amount of vaccines and the inequity issues in vaccine allocation call for more international cooperation to achieve the anti-epidemic goals and vaccination fairness.


Endoluminal instillation of bisacodyl in patients with severe (slow transit type) constipation is useful to test residual colonic propulsive activity.
Chronic constipation is a frequent symptom among the general population, and a minority of cases do not respond to any therapeutic measures, except surgery. The purpose of this study was to test the residual colonic motor propulsive activity with a pharmacologic stimulus in a series of patients referred for severe constipation. Twenty-five chronically constipated patients, slow transit type, age range 16-71 years, unresponsive to conventional medical treatment and referred for functional evaluation, entered the study. Colonic manometry by means of an endoscopically positioned probe was carried out in all patients. Following a basal recording period, a placebo solution followed by 10 mg bisacodyl solution was infused into the colon through the more proximal recording port. After bisacodyl infusion, about 90% of patients showed a motor response characterized by the appearance (within on average 13 +/- 3 min) of one or more high-amplitude propagated contractions, the manometric equivalent of mass movements, and about 75% of these were followed (mean 18.5 +/- 4 min) by defecation. Physiological and pharmacological testing of colonic motor activity may be important in severely constipated patients, especially in those labeled as 'intractable', in whom more in depth investigation planning may encourage further therapeutic efforts.


[Studies on the growth, chemical components and physiological characteristics of F1 generation of Dendrobium huoshanense].
Through a comparison between F1 and its' parents on the growth, chemical components and physiology, this study aims to find the possibility of selecting new dendrobium hybrids with high yield and good quality. To determinate the growth, chemical components, photosynthesis, hormones and isoenzyme in the plants. Photosynthetic area, content of chlorophyll, net photosynthesis and yield of F1 generation are higher than those of the parents; chla/b rate is lower; growth is almost the same as in Dendrobium moniliforme; content of chemical components are the same as in D. huoshanense. F1 is approaching of advantages of parents. Physiological characters, yield and quality of F1 are greatly improved by hybridization.


Inflammatory modulation and outer membrane vesicles (OMV) production associated to Bacteroides fragilis response to subinhibitory concentrations of metronidazole during experimental infection.
An experimental infection based on a tissue cage model was reproduced to evaluate the interference subinhibitory concentration (SIC) of metronidazole in Bacteroides fragilis OMV production patterns and immunological and histological characteristics of the host facing the experimental challenge. A tissue cage model was reproduced for B. fragilis experimental challenge in three Wistar rats groups: negative control group (NC) without bacterial inoculation; positive control group (PC) infected with parental strain; and experimental group (EG) infected with the parental strain and treated with metronidazole SIC. Tissue cage sections and histological preparations were evaluated under optical and transmission electron microscope. Observations included OMV identification and count and cellular envelope evaluation. Transcriptional analyses were performed to evaluate cytokines expression levels. Total counts of leukocytes and neutrophils were higher for EG, and slight increase in PC group. It was observed an exacerbated inflammatory infiltrate after 8 days on infection. The expression of TNF-α was increased during the experiments, along with IL-1α and IL-6. MCP-1 levels were suppressed in almost every evaluated time-point. The IL-10 was exacerbated in EG group. A massive production and release of OMV and cell wall thickening were observed especially the EG group. Despite literature data suggest positive association between OMV and antimicrobial stress for Gram negatives, no correlations are made for B. fragilis and drug-response during experimental model of infection. Results corroborate observations in which OMV may be involved in bacterial pathogenicity once the phenomenon was observed along histological evidence of exacerbated inflammation and cytokines modulation.


Quantitative hydro-geophysical analysis of a complex structural karst aquifer in Eastern Saudi Arabia.
The Umm er Radhuma (UER) Formation is a major karst aquifer in Saudi Arabia. This study investigated the hydraulic and petrophysical characteristics of the folded UER carbonate aquifer using integrated hydrological and geophysical logging datasets to understand its complex hydraulic setting as well as detect possible water flow. Petrophysical analysis showed that the UER aquifer has three zones with different lithologic and hydraulic properties. The upper zone attains the best properties with average values of 20%, >100 mD, 3.30 × 10-5-1.34 × 10-3 m/s, and 1.49 × 10-3-6.04 × 10-2 m2/s, with respect to effective porosity, permeability, hydraulic conductivity and transmissivity. The gamma-ray logs indicate a good fracture system near the upper zone of the UER Formation. Pumping test measurements of transmissivity, hydraulic conductivity and storage coefficients were matched with those from geophysical logs and found to be within the expected range for confined and leaky aquifers. Hydrogeological properties were mapped to detect possible groundwater flow in relation to the dominant structure. The underground water of the folded UER aquifer was forced along meandering flow patterns from W-E to SW-NE through the anticlinal axes. The integrated approach can be further used to enhance local aquifer models and improve strategies for identifying the most productive zones in similar aquifer systems.


Femoral revision total hip arthroplasty using a long-stem femoral component. Clinical and radiographic analysis.
Proximal femoral bone stock deficiencies exist during many femoral revision arthroplasties, thus providing inadequate support and fixation for conventional-length cemented femoral components. The authors analyzed the long-term clinical and roentgenographic results of 165 hips requiring femoral revision arthroplasty with a long-stem femoral prosthesis. Intraoperative complications occurred in 23% of hips, with femoral perforations in 16% and femoral fractures in 5%. Of 110 hips with at least 5 years of follow-up study (average, 6.7 years), functional ratings were graded excellent in 34%, good in 36%, fair in 17%, and poor in 13%. Failures occurred in 17 hips (12%) and were attributed to aseptic loosening (11 hips), femoral component fracture (2), femoral shaft fracture (1), and sepsis (3). Symptomatic trochanteric separations occurred in 16% of hips. Rerevision or resection arthroplasty was required in 7 hips (5%) and recommended for another 10 hips (7%). Cemented long-stem femoral components (versus cemented conventional-length stems) decrease the extent and progression of femoral lucencies, thereby lowering the incidence of mechanical failures and improving long-term functional results in cemented femoral revision arthroplasty.


Speech perception by budgerigars (Melopsittacus undulatus): the voiced-voiceless distinction.
Discrimination of synthetic speech sounds from the bilabial, alveolar, and velar voice onset time (VOT) series was studied in 5 budgerigars. The birds were trained, using operant conditioning procedures, to detect changes in a repeating background of sound consisting of a synthetic speech token. Response latencies for detection were measured and were used to construct similarity matrices. Multidimensional scaling procedures were then used to produce spatial maps of these speech sounds, in which perceptual similarity was represented by spatial proximity. The results of these experiments suggest that budgerigars discriminate among synthetic speech sounds from these three VOT continua, especially between those from the bilabial and alveolar series, in a categorical fashion.


Fetal sex alters maternal anti-Mullerian hormone during pregnancy in cattle.
Anti-Mullerian hormone (AMH) is expressed by both male and female fetuses during mammalian development, with males expressing AMH earlier and at significantly higher concentration. The aim of the current study was to explore the potential impact of pregnancy and fetal sex on maternal AMH and to determine if plasma (Pl) AMH or placenta intercotyledonary membrane and cotyledonary AMH receptor 2 (AMHR2) mRNA expression differ in pregnant cows carrying male vs. female fetuses. AMH levels in blood were measured using a bovine optimized ELISA kit. Cows pregnant with a male fetus were observed to have a significantly greater difference in Pl AMH between day 35 and 135 of gestation. Average fetal AMH level between 54 and 220days of gestation was also observed to be significantly higher in male vs. female fetuses. Intercotyledonary membranes and cotyledons were found to express AMHR2 between days 38 and 80 of gestation at similar levels in both fetal sexes. These findings support the hypothesis that fetal sex alters maternal Pl AMH during pregnancy in cattle.