Class II, division 1 treatment with Fränkel and Edgewise appliances--a comparative study of mandibular growth and facial esthetics.
A statistical comparison of treatment changes in twenty patients treated with a Fränkel appliance and twenty treated with the Edgewise mechanism. Both groups showed similar improvements, with no significant differences in mandibular growth.


Desmoplastic infantile astrocytoma with multiple intracranial and intraspinal localizations at presentation.
Desmoplastic infantile gliomas (DIG) are rare tumors that occur in infants aged between 1 and 24 months. The tumor in general has a favorable prognosis after surgical resection. There are no treatment algorithms, however, for patients with multiple intracranial and intraspinal presentations. In an 11-month-old girl with a history of nystagmus, magnetic resonance imaging (MRI) demonstrated contrast-enhancing lesions in the suprasellar region, the cerebellar vermis, and the spinal axis. The tumor in the cerebellar vermis was removed via a suboccipital midline approach. The histological examination revealed a desmoplastic infantile astrocytoma (DIA) WHO grade I. Postoperatively, it was decided to adopt a wait-and-see strategy. Further development, up to 16 months after surgery, was unremarkable. Follow-up MRI showed no recurrence of the posterior fossa tumor, mild progress of the suprasellar tumor, and significant regression of the spinal tumors. DIA is a rare mostly benign brain tumor found in infants. The final diagnosis always relies on histology. Surgical resection is the recommended therapy for symptomatic tumors; however, more experience is needed to develop treatment recommendations for multiple-site tumors.


The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2016 Update on Research.
The Society of Thoracic Surgeons Adult Cardiac Database (ACSD) is an international voluntary effort that is the foundation of our specialty's efforts in clinical performance assessment and quality improvement. Containing nearly 6,000,000 patient records, the ACSD is a robust resource for clinical research. Seven major original publications and four review articles were generated from the ACSD in 2015. The risk-adjusted outcome analyses and quality measures reported in these studies have made substantial contributions to inform daily clinical practice. This report summarizes the ACSD-based research efforts published in 2015.


Cell lineage analysis of Schwann cells in the PNS determined by shiverer-normal mouse chimeras.
The myelin of the peripheral nervous system from the shiverer mutant mice is characterized by the absence of myelin basic protein, while the other myelin protein components are present at normal levels. Myelin lamella formation is normal in the shiverer mutant. Therefore, by using antiserum against myelin basic protein, we can distinguish the shiverer from the wild-type control myelin immunohistochemically. To study the cell lineage of Schwann cells, chimeras produced by the aggregation of eight-cell embryos from wild-type mice and shiverer mice have been used. Using myelin basic protein as a marker, it was observed that Schwann cells in the sciatic nerve existed as patches of cells with like-genotype. The patches occurred in a linear array along the axons with some intermingling of Schwann cells. Complete randomization by intermingling of Schwann cells was not observed and clones of Schwann cells may persist as contiguous groups throughout peripheral nerve development.


Nasopharyngeal carcinoma: result of treatment with cis-diamminedichloroplatinum II, 5 fluorouracil, and radiation therapy.
Combined CT (CDDP + 5FU) and RT were given to 28 patients with NPC during July 1982-May 1985. Two, 1, 4, and 21 were in Stages I-IV (AJC), respectively. None had distant metastasis. Four did not complete the planned treatment, and one each had more or fewer CT courses than planned. The median duration of follow-up of surviving patients was 29 months (19-52,x 31.1). Objective response (CR + PR) at the primary lesion was 27/28 (96.4%), whereas CR was 23/28 (82%). CR + PR and CR of the regional nodes were 21/22 (95.5%) and 18/22 (82%) respectively. Remaining node in the 2 patients, who did not prematurely die were pathologically negative. Response at N site should therefore be 100% CR. Only patients with T3 (1/5) and T4 (3/13) lesions had residual disease at the T site after initial treatment. Salvage therapy was able to induce CR in all asymptomatic PR patients. There were 4 relapses, 2 at T, and 1 each at T + N and T + M sites. All M disease occurred in patients with huge and/or low cervical lymphadenopathy. Five patients died, one of an unrelated disease, and one each of T, M, T + N, and T + M diseases. The remaining 23 patients were still alive, and all except 3 were free of disease. Side effects, mainly from RT, were clinically acceptable. One had transient cervical myelitis. Myelosuppression was mild and of short duration. Activity of CT was seen at both T, and N sites after the upfront CT. Compared to our previous experience using RT alone, the result of this study suggested a positive role of CT in this disease. However, future prospective randomized trials are required to better define its role.


Supraspinal FMRFamide antagonizes morphine-induced horizontal, but not vertical, locomotor activity.
Morphine and the molluscan neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide) were administered to mice alone or in combination intracerebroventricularly (ICV) and the effect on locomotor activity was measured. Morphine given alone (0.5 micrograms) significantly increased horizontal locomotor activity compared to vehicle-treated controls. FMRFamide at low doses (0.01-10 micrograms) had no effect of its own, but blocked the morphine-induced increase in horizontal locomotor activity. Unlike the opiate antagonist naloxone (1.0 micrograms), FMRFamide (up to 10 micrograms) had no effect on morphine-induced decrease in vertical activity. These data further support a role for FMRFamide as a modulator of opiate action, but comparison to naloxone suggests that FMRFamide might not act as a pure competitive antagonist of this opiate effect.


[Providing studies quality for pesticides risk evaluation in their use according to proper laboratory practice rules].
The article covers experience of proper laboratory practice in hygienic studies examining air and workers' skin for assessment of exposure levels of pesticides in natural conditions of agricultural production.


Comparison of immediate versus day to day variability of ventricular tachycardia induction by programmed stimulation.
The use of programmed stimulation to assess long-term oral antiarrhythmic drug efficacy for ventricular tachycardia is complicated by the fact that mode of ventricular tachycardia induction varies from day to day in the absence of drug therapy. The purpose of this prospective study was to assess whether mode of ventricular tachycardia induction is more reproducible within one study than from day to day. Thirty-nine consecutive patients with documented sustained ventricular tachyarrhythmias secondary to coronary artery disease underwent three inductions of ventricular tachycardia at 15 min intervals in the absence of drug therapy. A stimulation protocol in which the only major variable was the number of extrastimuli required for tachycardia induction was used. Subsequent day to day variability in mode of tachycardia induction was also assessed in the same patients at two further drug-free inductions at intervals of 5 +/- 2 days. The number of extrastimuli required for tachycardia induction was significantly more reproducible at the immediate repeat studies than from day to day (69% of patients versus 31%, p less than 0.01). From these data, probability tables were derived that show the likelihood that changes in inducibility at subsequent tachycardia inductions are due to chance. The QRS configuration of induced ventricular tachycardia was also more reproducible at the immediate studies (64% versus 26%, p less than 0.01). Basic electrophysiologic and stimulation variables differed over a significantly wider range from day to day than at the immediate studies.(ABSTRACT TRUNCATED AT 250 WORDS)


Antimicrobial resistance of 914 beta-hemolytic streptococci isolated from pharyngeal swabs in Spain: results of a 1-year (1996-1997) multicenter surveillance study. The Spanish Surveillance Group for Respiratory Pathogens.
A nationwide susceptibility surveillance study of beta-hemolytic streptococcal isolates from pharyngeal swabs obtained in 11 Spanish hospitals between May 1996 and April 1997 against 12 antibiotics was carried out. Of the isolates 86% (786 of 914 isolates) were group A and 8.4% (77 of 914 isolates) were group C. No resistance was found to beta-lactam antibiotics, but significant differences (P < 0.001) with respect to lack of susceptibility to macrolides were found between groups (27% for group A and 12% for group C) and between seasons (13.2% in summer and 31.7% in winter). Most of these isolates displayed the M phenotype (low-level resistance to erythromycin and susceptibility to clindamycin).


Rurality and differences in pharmacy characteristics and community factors associated with provision of naloxone in the pharmacy.
Pharmacies are the most accessible healthcare settings across urban, suburban, and rural areas of the United States and, thus a key venue in the overdose risk environment. Pharmacy dispensing of naloxone is part of the public health response to the opioid overdose crisis, yet little is known about the pharmacy- and community-level characteristics with which naloxone provision is associated. We conducted a longitudinal analysis of pharmacy-level quarterly naloxone dispensed from one large US community pharmacy chain from the 1st quarter of 2013 to the 2nd quarter of 2017, examining associations between naloxone provision and pharmacy-level characteristics and community factors in two US states, Rhode Island and Massachusetts. Rurality was defined using the rural urban commuting area (RUCA) scale scores, calculated based on US 2010 Census variables. Pharmacy-level characteristics (e.g., 24 h store, average daily volumes of total prescriptions, nonprescription syringe sales, buprenorphine prescriptions) derived from the pharmacy chain; community factors (e.g., RUCA score, ZIP-code level age, race distributions, and median household income) were obtained from the decennial census files. The linear mixed effects methods modeled dispensing history and the number of naloxone doses dispensed through binomial and negative binomial distributions respectively, accounting for trend and covariates. Adjusted analyses of dispensing data from 449 pharmacies in two states indicated that more rural pharmacies (i.e., stores in areas with higher RUCA scores), pharmacies with higher volumes of all prescriptions and of buprenorphine, that sell more nonprescription syringes, that have drive-throughs and longer weekend hours, and that are located in communities with younger age distributions were associated with increased likelihood of ever dispensing naloxone and a greater number of naloxone doses dispensed (all p<.05). Pharmacies are a key evolving element in the overdose risk environment, striving to develop reputations as sources of wellness, prevention, and harm reduction supplies, like naloxone. Pharmacy naloxone dispensing may be an especially effective strategy to alter the overdose risk environment in rural communities.


Genetic resistance and specificity in sister taxa of Daphnia: insights from the range of host susceptibilities.
Host genetic diversity can affect various aspects of host-parasite interactions, including individual-level effects on parasite infectivity, production of transmission stages and virulence, as well as population-level effects that reduce disease spread and prevalence, and buffer against widespread epidemics. However, a key aspect of this diversity, the genetic variation in host susceptibility, has often been neglected in interpreting empirical data and in theoretical studies. Daphnia similis naturally coexists with its competitor Daphnia magna and is more resistant to the endoparasitic microsporidium Hamiltosporidium tvaerminnensis, as suggested by a previous survey of waterbodies, which detected this parasite in D. magna, but not in D. similis. However, under laboratory conditions D. similis was sometimes found to be susceptible. We therefore asked if there is genetic variation for disease trait expression, and if the genetic variation in disease traits in D. similis is different from that of D. magna. We exposed ten clones of D. similis and ten clones of D. magna to three isolates of H. tvaerminnensis, and measured infection rates, parasite-induced host mortality and parasite spore production. The two Daphnia species differ in the range and variation of their susceptibilities. The parasite produced on average two-fold more spores when growing in D. magna clones than in D. similis clones. We confirm that D. similis is indeed much more resistant than D. magna and suggest that this could create a dilution effect in habitats where both species coexist.


Granulocyte activation by a cell surface complex of Staphylococcus saprophyticus: a receptor-mediated phenomenon.
High molecular weight cell surface complex (CSC) from Staphylococcus saprophyticus strain S 1 could be shown to be a potent stimulator of human polymorphonuclear leukocyte (PMN) chemiluminescence whereas human monocytes were not activated. Heating of the CSC (100 degrees C for 5 min) as well as protease treatment significantly (p less than 0.001) inhibited the PMN activating process suggesting that the protein part of the molecule mediates its biological activity. Data on the biochemical character of the CSC are given. Preincubation of PMNs with CSC inhibited another chemiluminescence response to this substance and to homologous opsonized S. saprophyticus, respectively. However, restimulation with formylmethionyl peptides (fMLP) or non-opsonized staphylococci suggested that the PMN function is a receptor-mediated phenomenon. These data were substantiated since fMLP activated PMNs could be evidently re-stimulated with CSC but not with analogue peptides. Evaluation of the bactericidal capacity of human PMNs yielded comparable results.


Disposable urea biosensor based on nanoporous ZnO film fabricated from omissible polymeric substrate.
In the present study, a facile and simple fabrication method of a semiconductor based urea biosensor was reported via three steps: (i) producing a ZnO-PVA composite film by means of a polymer assisted electrodeposition of zinc oxide (ZnO) on the F-doped SnO2 conducting glass (FTO) using water soluble polyvinyl alcohol (PVA), (ii) obtaining a nanoporous ZnO film by PVA omission via a subsequent post-treatment by annealing of the ZnO-PVA film, and (iii) preparation of a FTO/ZnO/Urs biosensor by exploiting a nanoporous ZnO film as an efficient and excellent platform area for electrostatic immobilization of urease enzyme (Urs) which was forced by the difference in their isoelectric point (IEP). The characterization techniques focused on the analysis of the ZnO-PVA film surfaces before and after annealing, which had a prominent effect on the porosity of the prepared ZnO film. The surface characterization of the nanostructured ZnO film by a field emission-scanning electron microscopy (FE-SEM), exhibited a film surface area as an effective bio-sensing matrix for enzyme immobilization. The structural characterization and monitoring of the biosensor fabrication was performed using UV-Vis, Fourier Transform Infrared (FT-IR), Raman Spectroscopy, Thermogravimetric Analysis (TGA), Cyclic Voltammetry (CV), and Electrochemical Impedance Spectroscopy (EIS) techniques. The impedimetric results of the FTO/ZnO/Urs biosensor showed a high sensitivity for urea detection within 8.0-110.0mg dL(-1) with the limit of detection as 5.0mg dL(-1).


WITHDRAWN: Subsegmental Thrombus in COVID-19 Pneumonia: Immuno-Thrombosis or Pulmonary Embolism? Data Analysis of Hospitalized Patients with Coronavirus Disease.
This article has been withdrawn at the request of the author(s). The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.


Novel immunogenic baculovirus expressed virus-like particles of foot-and-mouth disease (FMD) virus protect guinea pigs against challenge.
Vaccination is a well accepted strategy for control of foot-and-mouth disease (FMD) in endemic countries. Currently, chemically inactivated virus antigens are used for preparation of FMD vaccine. To develop a non-infectious and safe recombinant vaccine, we expressed structural polypeptide of FMDV (O/IND/R2/75) using baculovirus expression system. We show that inclusion of mutated viral 3C protease in frame with the polypeptide (P1-2A), enhanced the yield of structural proteins. The structural proteins retained antigenicity and assembled into empty virus-like particles (VLPs). Immunization of guinea pigs with purified fractions of the VLPs resulted in humoral and cell mediated immune response by 4 weeks. The VLPs elicited comparable humoral immune response and relatively higher cell mediated immune response, when compared to conventional vaccine in guinea pigs. Further, up to 70% of the VLP immunized guinea pigs were protected against challenge with homologous guinea pig adapted virus. Our results highlight the application of recombinant FMDV VLPs in FMD vaccination.


Endometrial intraepithelial neoplasia with secretory differentiation: diagnostic features and underlying mechanisms.
Endometrial intraepithelial neoplasia (EIN) with secretory differentiation and ordinary EIN occurring in a secretory context are rare but recognized findings. We determined how often secretory differentiation in EIN was associated with evidence of circulating progestins in the background endometrium, and studied clinical characteristics and clinical outcomes of affected patients. We selected 41 patients with secretory differentiation in either the EIN itself (n=31) and/or background endometrium (n=38). Most (90%, 28/31) secretory EINs were associated with circulating progestins. Rare exceptions were observed, suggesting that secretory EIN may occur as a hormone-independent phenomenon. Circulating progestins are not sufficient, however, to induce EIN secretory differentiation, as 26% (10/38) of EIN within a secretory background were of the ordinary (non-secretory) type. EIN patients with secretory endometrium in the background are younger (averaging 45 years) than the aggregate group of all patients with EIN (53 years in previously published studies) and are often premenopausal with a cyclical source of endogenous progestins. Involution of EIN during follow-up was more frequent (81%, 17/21) for those with a secretory background at the time of initial EIN diagnosis compared with historical averages (25%, 36/142). These results suggest a potential role for endogenous progesterone, as well as therapeutic progestins, in modulating EIN outcomes.


Development of the swimbladder in the European eel ( Anguilla anguilla).
The swimbladder of the adult eel, Anguilla anguilla, with its bipolar countercurrent system, the rete mirabile, is a widely used model for swimbladder function, but very little is known about the development of this swimbladder. Our histological studies on the developing swimbladder revealed that during metamorphosis the swimbladder becomes present as a dorsal outgrowth of the esophagus. It is filled with surfactant, and gas was not detected in the swimbladder. In the young glass-eel, the epithelial (gas gland) cells of the swimbladder are columnar, but do not yet have the typical basolateral labyrinth established in adult animals. Few blood vessels are found in the swimbladder tissue, and the submucosa is present as a thick layer of connective tissue, giving a large diffusion distance between blood vessel and swimbladder lumen. Within the next 2 or 3 months of development, gas gland cells develop their typical basolateral labyrinth, and the thickness of the submucosa is significantly reduced, resulting in a short diffusion distance between blood vessels and the swimbladder lumen. The first filling of the swimbladder with gas is observed while the gas gland cells are still in a poorly differentiated status and it appears unlikely that these cells can accomplish their typical role in gas deposition. The presence of small gas bubbles in the swimbladder as well as in the ductus pneumaticus at the time of initial swimbladder inflation suggests that the swimbladder is filled by air gulping or possibly by taking up gas bubbles from the water.


IgM in a human neuropathy related to paraproteinemia binds to a carbohydrate determinant in the myelin-associated glycoprotein and to a ganglioside.
The IgM in three patients with paraproteinemia and peripheral neuropathy was shown to bind to human myelin-associated glycoprotein (MAG) that had been purified to homogeneity by gel filtration on Sepharose CL-6B. The antigenic determinant reacting with the IgM from all three patients was in the carbohydrate part of the MAG molecule. In addition, the IgM from the same three patients bound to a single ganglioside of human sciatic nerve. The results indicate that the IgM paraproteins in these patients react with a carbohydrate determinant that is shared between MAG and a peripheral nerve ganglioside.


Family Systems Cultural and Resilience Dimensions to Consider in Nutrition Interventions: Exploring Preschoolers' Eating and Physical Activity Routines During COVID-19.
To describe the weight-related family functioning of racial minority families with low income using family systems theory as an interpretive framework. Primarily a qualitative study with interviews plus; descriptive demographics, anthropometrics, a family functioning measure, and food insecurity screening. Telephone interviews with families of preschool-aged children in an urban setting. Primary caregivers of preschool-aged children. Cultural impacts on family systems. Interviews were audio-recorded, transcribed verbatim, and loaded into NVivo 12 for thematic analysis. Descriptive statistics. The 23 participants were mothers and 2 maternal grandmothers. Seventy-four percent were African American, most children were normal weight (n = 15, 65%), mean family function scores were high, and more than half the families were at risk for food insecurity (n = 13, 56%). Acculturation and intergenerational eating-related cultural dimensions were discerned as the overarching themes influencing family cohesion. Family cohesion appeared to have helped the families adapt to the impact of coronavirus disease 2019. Cultural dimensions such as acculturation and intergenerational influences appeared to be associated with social cohesion and family functioning around weight-related behaviors for these families. These findings add cultural and family resilience dimensions to family systems theory in nutrition interventions.


Differences in length of stay in Veterans Health Administration and other United States hospitals: is the gap closing?
Compare risk-adjusted length of stay (LOS) in VA and other United States (non-VA) hospitals and determine if relative differences in LOS have changed in recent years. Retrospective cohort study. Patients with ten common medical diagnoses admitted to all VA hospitals and to non-VA hospitals included in the National Hospital Discharge Survey (NHDS) during 1996 through 1999. Comparable data elements were obtained from VA administrative databases and the NHDS. LOS was adjusted for age, gender, marital status, and comorbidity. Comorbidity was assessed using a validated methodology that considers 30 conditions. Unadjusted mean LOS was longer in VA than non-VA patient for all 4 years, in aggregate (7.1 vs. 4.9 days, respectively; P < 0.001), and for each year individually. However, the difference in mean LOS in VA and non-VA patients declined from 2.9 days in 1996 to 1.6 days in 1999. LOS in VA patients remained longer (P < 0.001) in linear regression analyses, adjusting for demographics and comorbidity. However, the difference in LOS declined from 28.5% (95% CI, 28.1%-29.0%) in 1996 to 17.0% (95% CI, 16.6%-17.4%) in 1999. These results were similar in analyses of individual geographic regions. Risk-adjusted LOS was longer in VA hospitals than in other United States hospitals. However, differences in LOS narrowed between 1996 and 1999. These findings suggest that changes in the organization and delivery of VA health care in the mid-1990s may be closing the gap between the VA and other healthcare systems in hospital utilization.


The impact of lipoprotein apheresis in patients with refractory angina and raised lipoprotein(a): Objectives and methods of a randomised controlled trial.
It is well established that Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor and predictor of major adverse cardiovascular events. Lipoprotein apheresis is currently the most effective approved treatment available, with minimal effect conferred by conventional lipid lowering agents. A growing body of evidence suggests that aggressively lowering raised Lp(a) may improve cardiovascular and clinical outcomes, although more prospective research is required in this field. Angina which is refractory to conventional medical therapy and revascularisation is extremely challenging to manage. There is a significant unmet need to establish therapeutic options. Our goal is to determine the impact of lipoprotein apheresis on clinical parameters and symptoms of patients with refractory angina secondary to advanced coronary disease and raised Lp(a). Determining whether we should aggressively lower Lp(a) in such patients remains a very important question, which could potentially impact on the management of a large population. We will also gain insight into how this treatment works and the mechanisms via which Lp(a) increases cardiovascular risk. We are currently conducting a prospective, randomised controlled crossover study of patients with refractory angina and raised Lp(a), randomised to undergoing three months of weekly lipoprotein apheresis or sham apheresis. Patients will then crossover to the opposite study arm after a 1 month wash-out phase. We will assess myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, oxidised LDL and their antibodies, exercise capacity, angina and quality of life at the beginning and end of treatment, to determine the net true treatment effect on the above parameters. This is a novel area of research, as previous studies have not assessed the role of lipoprotein apheresis in patients with refractory angina and raised Lp(a) in a prospective randomised controlled manner.


Morphologically aggressive appearance of a human papilloma virus (HPV)-related conjunctival papilloma that was clinically suspicious for malignancy - A case report.
Conjunctival squamous papilloma is a benign tumor that might be linked to Human papillomavirus (HPV) infection. The most common appearance is a pedunculated fleshy mass. We are reporting a unique of HPV-related conjunctival papilloma that was excised with the suspicious of malignancy. A 35-year-old Saudi male who has been investigated for a suspicious pancreatic lesion and presented with a concurrent right eye conjunctival yellowish cystic mass. The mass was excised for diagnostic purpose to rule out malignancy in view of the history, the clinical appearance of the lesion, and the adjacent conjunctival severe congestion. The histopathological examination concluded a viral-related conjunctival papilloma. There was no evidence of recurrence of the lesion 2 years postoperatively. The common clinical appearance of a benign conjunctival papilloma is usually described as fleshy pedunculated mass with irregular grayish red surface. Such a lesion might be related to several etiologies, one of which is HPV. The mass in our case was highly vascularized and cystic with yellowish areas, which raised the suspicion of a malignant lesion. The histopathological findings, however, confirmed the benign nature of the lesion and supported the viral etiology by HPV. HPV-related conjunctival papilloma may have various morphological appearances. Histopathological examination is the key for final diagnosis of such types of lesions.


Antibiotic resistance bacteria and antibiotic resistance genes survived from the extremely acidity posing a risk on intestinal bacteria in an in vitro digestion model by horizontal gene transfer.
Antibiotic resistance bacteria (ARB) and antibiotic resistance genes (ARGs) are emerging contaminants posing risk to human health. To investigate the pathogenic ARBs and the horizontal gene transfer (HGT) via both extracellular ARGs (eARGs) and intracellular ARGs (iARGs), an in vitro digestion simulation system was established to monitoring the ARB and ARGs passing through the artificial digestive tract. The results showed that ARB was mostly affected by the acidity of the gastric fluid with about 99% ARB (total population of 2.45 × 109-2.54 × 109) killed at pH 2.0 and severe damage of bacterial cell membrane. However, more than 80% ARB (total population of 2.71 × 109-3.90 × 109) survived the challenge when the pH of the gastric fluid was 3.0 and above. Most ARB died from the high acidity, but its ARGs, intI1 and 16 S rRNA could be detected. The eARGs (accounting for 0.03-24.56% of total genes) were less than iARGs obviously. The eARGs showed greater HGT potential than that of iARGs, suggesting that transformation occurred more easily than conjugation. The transferring potential followed: tet (100%) > sul (75%) > bla (58%), related to the high correlation of intI1 with tetA and sul2 (p < 0.01). Moreover, gastric juice of pH 1.0 could decrease the transfer frequency of ARGs by 2-3 order of magnitude compared to the control, but still posing potential risks to human health. Under the treatment of digestive fluid, ARGs showed high gene horizontal transfer potential, suggesting that food-borne ARBs pose a great risk of horizontal transfer of ARGs to intestinal bacteria.


Characterization of a macroporous polyvinyl alcohol scaffold for the repair of focal articular cartilage defects.
Focal cartilage defects reduce the ability of articular cartilage to resist mechanical loading and provide lubrication during joint motion. The limitations in current surgical treatments have motivated the use of biocompatible scaffolds as a future treatment option. Here we describe a second generation macroporous, polyvinyl alcohol (PVA) scaffold with independently tunable morphological and mechanical properties. The compressive moduli of the PVA scaffold increased with increasing polymer concentration and applied compressive strain, with values in the range for human articular cartilage (HA > 1000 kPa, EY > 500 kPa). Scaffolds also possessed strain-dependent permeability and Poisson's ratio. The interconnected macroporous network was found to facilitate chondrocyte seeding and proliferation through the scaffold over one week in culture. Overall, these promising characteristics demonstrate the potential of this macroporous scaffold for future studies in focal cartilage defect repair.


Skeletal muscle stiffness and pain following eccentric exercise of the elbow flexors.
Stiffness and pain occurring after eccentric exercise have been studied in human elbow flexor muscles. Increased muscle stiffness and flexion deformities of the elbow developed immediately after the exercise and were greatest 1-4 days later. Muscle tenderness and pain experienced during elbow extension developed more slowly but were both maximal at the same time as the muscle stiffness. EMG recordings at times when there was pain and flexion deformity showed the biceps to be electrically silent. This demonstrates that the pain was not due to sustained electrical activity in the muscle and the flexion was a consequence of shortening of non-contractile elements, presumably the connective tissue. It is suggested that some response to damaged connective tissue may cause increased mechanical sensitivity of muscle receptors which, in turn, gives rise to pain when the muscle is stretched or pressed.


Rupture of the larynx in a newborn.
Lesions of the laryngotrachea due to repeated intubation trauma after birth are reported. A macrosomic neonate was born at term after uneventful pregnancy. On the basis of diminished uterine contractions and arrest of descent, the head was delivered by using obstetric forceps. No intubation was attempted after birth. Ten hours later, the infant developed acute life-threatening respiratory distress and subcutaneous emphysema. Intubation was impossible. Open surgical exploration of the neck revealed a rupture of the cricothyroid ligament within the larynx. The defect was closed immediately, and after artificial ventilation for 7 days, the infant was extubated. One year later, the child is developing satisfactorily, without stridor or hoarseness. In macrosomic neonates after traumatic delivery, a laryngotracheal lesion should be considered when respiratory distress syndrome combined with subcutaneous emphysema occurs.


Response to "Impact of a Required, Longitudinal Scholarly Project in Medical School: a Content Analysis of Medical Students' Reflections".
We present a letter to the editor in response to the article by Nikiforova et al. "Impact of A Required, Longitudinal Scholarly Project in Medical School: a Content Analysis of Medical Students' Reflections". We discuss our experiences of undertaking a similar module in our medical school and examine the authors' use of feedback in their analysis. We also present our views on the importance of feedback and the aspects that we feel maximise students experiencing with undertaking a longitudinal research project.


Inter-examiner and intra-examiner reliability of optical coherence tomography angiography in vascular density measurement of retinal and choriocapillaris plexuses in healthy children aged 6-15 years.
This study aimed to test the inter-examiner and intra-examiner reliability of macular vascular density (VD) measurement of retinal and choriocapillaris plexuses in healthy children using optical coherence tomography angiography (OCTA). Ninety-two school children were prospectively recruited. Macular OCTA images (6 × 6 mm2) were obtained thrice by two examiners using the RTVue-XR Avanti OCT system. The coefficient of variation (COV), intraclass correlation coefficient (ICC), and Bland-Altman plots were used to evaluate the repeatability and reproducibility. Ninety participants aged 6-15 years were enrolled; two participants were excluded because of low-quality images. In the retina, the reproducibility and repeatability of VD became poorer from superficial to deep retinal capillary plexus (superficial: COV = 4.61-11.11%; intermediate: COV = 7.73-14.15%; deep: COV = 14.60-32.28%). For both reproducibility and repeatability, the ICC ranged from moderate to high (superficial plexus: ICC = 0.570-0.976; intermediate plexus: ICC = 0.720-0.968; deep plexus: ICC = 0.628-0.954). In the choroid, the inter-examiner reproducibility and intra-examiner repeatability of the VD measurement of choriocapillaris were excellent in the macula, fovea, parafovea, and perifovea (COV = 1.00-6.10%; ICC = 0.856-0.950). The parameters of the foveal avascular zone (FAZ) also showed significant reproducibility and repeatability (COV = 0.01-0.21%; ICC = 0.743-0.994). The VD measurements of the choriocapillaris and FAZ parameters using OCTA showed excellent inter-examiner and intra-examiner reliability in school children. The reproducibility and repeatability of the VD of three retinal capillary plexuses depended on the depth of the retinal capillary plexus.


Hyperspectral imaging-based classification of rice leaf blast severity over multiple growth stages.
Rice blast, which is prevalent worldwide, represents a serious threat to harvested crop yield and quality. Hyperspectral imaging, an emerging technology used in plant disease research, is a stable, repeatable method for disease grading. Current methods for assessing disease severity have mostly focused on individual growth stages rather than multiple ones. In this study, the spectral reflectance ratio (SRR) of whole leaves were calculated, the sensitive wave bands were selected using the successive projections algorithm (SPA) and the support vector machine (SVM) models were constructed to assess rice leaf blast severity over multiple growth stages. The average accuracy, micro F1 values, and macro F1 values of the full-spectrum-based SVM model were respectively 94.75%, 0.869, and 0.883 in 2019; 92.92%, 0.823, and 0.808 in 2021; and 88.09%, 0.702, and 0.757 under the 2019-2021 combined model. The SRR-SVM model could be used to evaluate rice leaf blast disease during multiple growth stages and had good generalizability. The proposed SRR data analysis method is able to eliminate differences among individuals to some extent, thus allowing for its application to assess rice leaf blast severity over multiple growth stages. Our approach, which can supplement single-stage disease-degree classification, provides a possible direction for future research on the assessment of plant disease severity during multiple growth stages.


Medulloblastoma in an adult suggestive of external granule cells as its origin: a histological and immunohistochemical study.
We describe a rare case of medulloblastoma in an adult woman with histological findings suggesting an origin for this neoplasm in the external granular layer or its remnants. The patient presented with cerebellar dysfunction, and neuroimaging revealed a right cerebellar mass lesion. Pathological examination of the operative specimen revealed a medulloblastoma with occasional areas of neuronal or glial differentiation. Zic protein was also detected immunohistochemically in the tumor cells. The tumor cells were mainly distributed in the subarachnoid space and extended to the cerebellar parenchyma through the perivascular space to form tumor nodules. A suggestive finding, as concerns the origin of this neoplasm, was that the tumor cells were also spread evenly along the subpial zone of the molecular layer, reminiscent of the cellular architecture of the fetal external granular layer.


Influence of P-glycoprotein expression on in vitro cytotoxicity and in vivo antitumour activity of the novel pyrrolobenzodiazepine dimer SJG-136.
SJG-136 is a novel pyrrolobenzodiazepine dimer analogue that acts as a minor-groove interstrand DNA cross-linking agent. The present study investigated the impact of ABCB1 (mdr-1) expression on the activity of SJG-136 using both in vitro and in vivo systems. SJG-136 was highly potent in the colon cancer cell lines HCT-116, HT-29 and SW620 (IC50 0.1-0.3 nM). However, HCT-8 and HCT-15 cells expressing significant levels of mdr-1 were less sensitive (IC50 2.3 and 3.7 nM, respectively) using a SRB assay. The cytotoxicity was increased in HCT-15 and A2780(AD) in presence of 5 microg/ml verapamil. Mdr-1 mRNA expression was determined by qRT-PCR and correlated to SJG-136 IC50s (r2=0.86, P=0.0001). Isogenic 3T3 cells expressing mdr-1 cDNA (3T3 pHamdr-1) were less sensitive to SJG-136 than the parental 3T3 cells (IC50 208 and 6.3 nM, respectively). Finally, SJG-136 (120 microg/kg/d dx5) was highly active against A2780 xenografts (SGD=275) but not A2780(AD) xenografts (SGD=67).


The biology of steroid hormones and endocrine treatment of breast cancer.
Recognition of the role of oestrogens in the stimulation of breast tumour growth has led to the development of several therapies based on endocrine intervention. Endocrine agents are currently used as a treatment for steroid receptor-positive breast cancer and more recently as a preventative measure in high-risk populations. Accurate quantification of resulting steroid hormonal profiles is essential to the understanding of the biological action and efficacy of these agents. In premenopausal women GnRH agonists suppress ovarian oestrogen synthesis and reduce oestradiol to close to postmenopausal levels. GnRH agonists used in combination with an aromatase inhibitor suppress levels even further. In contrast, tamoxifen can lead to markedly enhanced levels. In postmenopausal women aromatase inhibitors can achieve an almost complete inhibition of the aromatase enzyme.


Role of delta-opioid receptor subtypes in anxiety-related behaviors in the elevated plus-maze in rats.
Recent studies have shown that endogenous opioid systems are associated with the regulation of emotional responses. In particular, it has been reported that delta-opioid receptors act naturally to inhibit stress and anxiety. The present study was designed to examine the possible involvement of opioid delta-receptor subtypes in the anxiety-related behavior in the elevated-plus-maze test. Six-week-old male Lewis rats were used. The total numbers of visits to the closed and open arms and the cumulative time spent and visits in the open arms were determined. Plasma corticosterone levels were measured by enzyme immunoassay. Naltrindole (NTI), a delta-opioid receptor antagonist (3 mg/kg s.c.), induced a significant decrease in the percentages of time spent and visits in the open arms. Naltriben (NTB), a delta2-opioid receptor antagonist (3 mg/kg s.c.), but not 7-benzylidenenaltrexone, a delta1-opioid receptor antagonist, produced similar anxiety-related behaviors in the elevated plus-maze. These effects of NTI and NTB were antagonized by pretreatment with (+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC80), a delta-opioid receptor agonist. Furthermore, after exposure to the elevated plus-maze, the maximal increase in the plasma corticosterone level in NTI-treated rats was clearly higher than that in vehicle-treated rats. However, when NTI and SNC80 were coadministered, higher levels of plasma corticosterone were not seen after exposure to the elevated plus-maze. These results suggest that endogenous delta2-opioid-receptor-mediated systems are involved in the regulation of anxiety-related behaviors and might play a physiologically important role in the regulation of adrenocortical activity.


Fetal arrhythmias: Diagnosis and management.
This article reviews important features for improving the diagnosis and management of fetal arrhythmias. The normal fetal heart rate ranges between 110 and 160 beats per minute. A fetal heart rate is considered abnormal if the heart rate is beyond the normal ranges or the rhythm is irregular. The rate, duration, and origin of the rhythm and degree of irregularity usually determine the potential for hemodynamic consequences. Most of the fetal rhythm disturbances are the result of premature atrial contractions (PACs) and are of little clinical significance. Other arrhythmias include tachyarrhythmias (heart rate in excess of 160 beats/min) such as atrioventricular (AV) reentry tachycardia, atrial flutter, and ventricular tachycardia, and bradyarrhythmias (heart rate <110 beats/min) such as sinus node dysfunction, complete heart block (CHB) and long QT syndrome (which is associated with sinus bradycardia and pseudo-heart block).


Design of a bioaugmented multistage biofilter for accelerated municipal wastewater treatment and deactivation of pathogenic microorganisms.
Biological treatment of municipal wastewater for reuse in irrigation is highly required, especially with the current global financial and water shortage crises. Bioaugmentation is a simple and cost-effective technology which could be a useful tool in alleviating this challenge. Thus, this study aimed to enhance the biological treatment of municipal wastewater using a bioaugmented substance supplemented in a three-stages bio-filter consisting of a sedimentation step followed by gravel biofiltration and then sand biofiltration at a laboratory scale. Also, a toxicity assay, the antimicrobial effect of the bioaugmented substance against pathogenic microorganisms, and identification of the synergistic effect of the bacterial consortium involved in the bioaugmented substance were studied. The bioaugmented substance was nontoxic and had an antimicrobial effect against the tested potentially pathogenic microorganisms (Escherichia coli, Pseudomonas aeruginosa, Listeria monocytogenes, Staphylococcus aureus, and Candida albicans). The minimum effective concentration of the bioaugmented substance for organic, inorganic and microbial pollutants removal from high strength wastewater was 2.5 ppm with a contact time of 6-8 h. The removal efficiencies of H2S, COD, BOD5, total solids (TS), total dissolved solids, total suspended solids, ammonia, nitrate, phosphorus, and oil and grease reached 85, 93.4, 83.5, 37, 49.2, 93.4, 100, 55.7, 76.6 and 76.6%, respectively in the treated effluent after sand biofiltration. The physicochemical parameters of the treated wastewater effluent were below the Egyptian recommended limits (Law 84/1984) for use in irrigation. However, COD and BOD values were 90.33 and 38.46 mgO2/L, respectively, and were still above the regulations (COD ≤60 and BOD ≤20). The high fecal coliforms count in the wastewater influent (8.4 × 108 MPN-index/100 mL) were 95.1% removed after the sedimentation stage, and 99.99% removal was achieved after gravel and sand biofiltration. Thus, this study successfully designed a bioaugmented multistage biofiltration system for the effective removal of pollutants from wastewater, especially in resource-limited areas.


Effect of light adaptation on electrical responses of the retinas of four species of bats.
The levels of light adaptation at which the retinas of 4 species of microchiropteran bats became unable to generate electroretinograms were progressively ordered. The order correlated well with light preferences based on activity patterns of the 4 species. These results suggest that the ability of the retina to function in ambient light may govern some natural behaviors of these bats.


Screening for unhealthy diet and exercise habits: The electronic health record and a healthier population.
The US spends more money than any other country in the world on health care but does not have the best health outcomes. Most healthcare dollars are spent on treatment of preventable chronic conditions including heart disease, hypertension, diabetes, hypertension, and obesity. Many recent studies have shown that a poor diet and low cardiorespiratory fitness are associated with significant morbidity and an increased risk of all-cause mortality. There is evidence that those with higher cardiorespiratory fitness have lower annual healthcare costs. Despite continued research on the essential role of diet and exercise in optimal health, these vital health behaviors have been slow to change in the US population and do not receive adequate attention. We propose more objective screening, visible and monitored in the Electronic Health Record, to improve awareness, help educate patients, and monitor their progress over time. It would also help identify those individuals that would benefit from referral to interventional behavioral resources in the clinic and community. With an increased focus on preventive and population health measures, now is an ideal time to include both exercise and diet in health metrics. A few relatively simple changes could prompt providers to assess and educate patients about nutrition and fitness and promote a healthier population.


Use of acetaminophen and the risk of self-reported allergic symptoms and skin sensitization in Butajira, Ethiopia.
Studies in developed countries suggest that acetaminophen use is associated with increased risk of asthma, but it is unclear whether this association is causal. To determine the relation among acetaminophen use, asthma, and allergy, and to explore potential biases in acetaminophen use, in a developing country population. We surveyed 7649 adults and children from Butajira, Ethiopia, collecting data on self-reported symptoms of allergic disease, skin sensitization to Dermatophagoides pteronyssinus and cockroach, acetaminophen use, and potential confounders. We then collected detailed data on indications for acetaminophen use and reasons for aspirin avoidance in a nested follow-up study. Allergic symptoms increased significantly with frequency of acetaminophen use, with odds ratios in those using >3 tablets in the past month relative to none 1.89 (95% CI, 1.51-2.36) for wheeze, 2.14 (1.72-2.67) for nocturnal shortness of breath, 2.52 (1.99-3.20) for rhinitis, and 1.90 (1.39-2.61) for eczema. Cockroach sensitization was also more common in the highest acetaminophen category (odds ratio, 1.40; 95% CI, 1.10-1.79), but D pteronyssinus sensitization was not. Less than 1% of participants with asthma or wheeze in our nested study reported avoidance of aspirin because of asthma symptoms. None volunteered using acetaminophen to treat allergic symptoms. There is a dose-related association between acetaminophen use and self-reported allergic symptoms in this population that is not a result of aspirin avoidance, reverse causation, or other bias. Acetaminophen may therefore be involved in the etiology of asthma and allergic disease.


JTT-705 blocks cell proliferation and angiogenesis through p38 kinase/p27(kip1) and Ras/p21(waf1) pathways.
The excessive proliferation and migration of vascular smooth muscle cells (SMCs) participate in the growth and instability of atherosclerotic plaque. We examined the direct role of a newly developed chemical inhibitor of cholesteryl ester transfer protein, JTT-705, on SMC proliferation and angiogenesis in endothelial cells (ECs). JTT-705 inhibited human coronary artery SMC proliferation. JTT-705 induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular-signal-regulated kinases (ERK) in SMCs. In addition, the anti-proliferative effects of JTT-705 in SMCs were blocked by p38 MAPK inhibitor. JTT-705 induced the upregulation of p-p21(waf1), and this effect was blocked by dominant-negative Ras (N17), but not by inhibitors of p38 MAPK or ERK. In addition, JTT-705 also induced the upregulation of p27(kip1), and this effect was blocked by p38 MAPK inhibitor. Interestingly, culture medium from JTT-705-treated SMCs blocked human coronary artery EC tube formation in an in vitro model of angiogenesis indirectly via a decrease in vascular endothelial growth factor (VEGF) from SMCs and directly via an anti-proliferative effect in ECs. JTT-705 blocked the proliferation of SMCs through the activation of p38 kinase/p27(kip1) and Ras/p21(waf1) pathways, and simultaneously blocked EC tube formation associated with a decrease in VEGF production from SMCs and an anti-proliferative effect in ECs. Our results indicate that JTT-705 may induce a direct anti-atherogenic effect in addition to its inhibitory effect of CETP activity.


Yearly hypertension screening in women with a history of pre-eclampsia: a cost-effectiveness analysis.
Women with a history of preeclampsia are at increased risk for future hypertension and cardiovascular disease (CVD); until now it is not clear whether preventive measures are needed. A decision-analytic Markov model was constructed to evaluate healthcare costs and effects of screening and treatment (100 % compliance) for hypertension post preeclampsia based on the available literature. Cardiovascular events and CVD mortality were defined as health states. Outcomes were measured in absolute costs, events, life-years and quality-adjusted life-years (QALYs). Sensitivity and threshold analyses were performed to address uncertainty. Over a 20-year time horizon, events occurred in 7.2 % of the population after screening, and in 8.5 % of the population without screening. QALYs increased from 16.37 (no screening strategy) to 16.40 (screening strategy), an increment of 0.03 (95 % CI 0.01;0.05) QALYs. Total expected costs were € 8016 in the screening strategy, and € 9087 in the none screening strategy (expected saving of € 1071 (95 % CI - 3146;-87) per person). Annual hypertension screening and treatment in women with a history of preeclampsia may save costs, for at least a similar quality of life and survival due to prevented CVD compared with standard care.


Ten-year clinical outcomes from a randomized trial comparing new-generation everolimus-eluting stent versus first-generation Sirolimus-eluting stent: Results from the RESET extended study.
New-generation drug-eluting stents (DES) achieved technological innovations and reported clinical advantages as compared with first-generation DES in clinical trials with 3-5 years follow-up. However, detailed clinical outcome data in very long-term follow-up is still scarce. To evaluate 10-year clinical outcomes after first- and new-generation DES implantation. In this extende follow-up study of the RESET, which is a largest randomized trial comparing everolimus-eluting stent (EES) with Sirolimus-eluting stent (SES), the study population consisted of 2892 patients from 84 centers. The primary efficacy and safety endpoints were target lesion revascularization (TLR) and a composite of death or myocardial infarction (MI), respectively. Complete 10-year follow-up was achieved in 87.9% of patients. Cumulative 10-year incidences of TLR and non-TLR were not significantly different between EES and SES (13.9% vs. 15.7%, Log-rank p = 0.20, and 33.4% vs. 31.3%, Log-rank p = 0.30). The cumulative 10-year incidence of death/MI was also not significantly different between the groups (32.5% vs. 34.4%, Log-rank p = 0.18). Cumulative 10-year incidence of definite stent thrombosis was numerically lower in EES than in SES (1.0% vs. 1.7%, Log-rank p = 0.16). The lower risk of EES relative to SES was significant for a composite endpoint of target lesion failure (TLF: 19.6% vs. 24.9%, Log-rank p = 0.001) and target vessel failure (TVF: 26.7% vs. 31.4%, Log-rank p = 0.006). During 10-year of follow-up, the risks for primary efficacy and safety endpoints were not significantly different between new-generation EES and first-generation SES, although EES compared with SES was associated with a lower risk for composite endpoints such as TLF and TVF.


Self-renewal and phenotypic conversion are the main physiological responses of macrophages to the endogenous estrogen surge.
Beyond the physiology of reproduction, estrogen controls the homeostasis of several tissues. Although macrophages play a key role in tissue remodeling, the interplay with estrogen is still ill defined. Using a transcriptomic approach we first obtained a comprehensive list of genes that are differentially expressed in peritoneal macrophages in response to physiological levels of 17β-estradiol (E2) injected in intact female mice. Our data also showed the dynamic nature of the macrophage response to E2 and pointed to specific biological programs induced by the hormone, with cell proliferation, immune response and wound healing being the most prominent functional categories. Indeed, the exogenous administration of E2 and, more importantly, the endogenous hormonal surge proved to support macrophage proliferation in vivo, as shown by cell cycle gene expression, BrdU incorporation and cell number. Furthermore, E2 promoted an anti-inflammatory and pro-resolving macrophage phenotype, which converged on the induction of genes related to macrophage alternative activation and on IL-10 expression in vivo. Hormone action was maintained in an experimental model of peritoneal inflammation based on zymosan injection. These findings highlight a direct effect of estrogen on macrophage expansion and phenotypic adaptation in homeostatic conditions and suggest a role for this interplay in inflammatory pathologies.


Mutagenicity of some derivatives of dipyrido[1,2-a:3',2'-d]imidazoles in Salmonella typhimurium with metabolic activation by rat liver and small intestine subcellular fractions.
The mutagenic effect of 2-amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) was compared with that of the 3-amino, 3-nitro, or 3-N-hydroxylated derivatives of the same base ring with methyl groups at positions 4 and 6 of the molecule. The compounds were tested in Salmonella typhimurium strain TA98 without metabolic activation and in the presence of different concentrations of subcellular fractions from livers or small intestines of rats pretreated with different P448/P450 inducers. The 4,6-dimethyl compounds are always more mutagenic than Glu-P-2. Pretreatment with Aroclor 1254 (ARO) is the most effective inducer in the activation of the 2- and 3-amino compounds by liver S9, whereas the same fraction decreases the mutagenicity of the 3-nitro derivative. S9 from small intestine increased the mutagenic effect of the 3-nitro and 3-N-hydroxylated compounds, but it was unable to activate the amino compounds.


The use of adjuvant radiation therapy in patients with intermediate-risk Stages IC and II uterine corpus cancer: a patient care evaluation study from the American College of Surgeons National Cancer Data Base.
To determine the outcomes of patients with intermediate-risk Stages IC and II uterine corpus cancer treated with surgery alone or surgery followed by radiation therapy. Patients with uterine corpus cancer diagnosed in 1995 were identified from hospitals in the United States with tumor registry databases. Data were collected on histology, surgical treatment, radiation therapy, recurrence, and survival. Survival analysis was performed using life-table computational method. 713 hospitals submitted data on 10,726 patients with uterine corpus cancer. 9977 patients (93.0%) underwent surgery, and 2624 patients (26.3%) received radiation therapy. Patients with clinical Stages IC and IIA disease who underwent surgery followed by radiation therapy compared to surgery alone had a trend toward improved 5-year relative survival (RS) (81.2% vs. 92.5%; 74.3% vs. 96.0%, respectively). The 5-year RS of patients with surgical Stage IC disease was not statistically different between the surgery alone group and the radiation group (93.9% vs. 91.7%). Patients with surgical Stage IIA and IIB disease did not benefit from radiation therapy compared to surgery alone (5-year RS; 83.7% vs. 98.0% and 82.3% vs. 81.8%, respectively). There is a trend toward improved survival in patients with clinical Stages IC and IIA uterine corpus cancer when radiation therapy is utilized following surgery. The survival of patients with surgical Stages IC and II uterine corpus cancer is not improved with adjuvant radiation therapy.


Shigella Serotypes Associated With Carriage in Humans Establish Persistent Infection in Zebrafish.
Shigella represents a paraphyletic group of enteroinvasive Escherichia coli. More than 40 Shigella serotypes have been reported. However, most cases within the men who have sex with men (MSM) community are attributed to 3 serotypes: Shigella sonnei unique serotype and Shigella flexneri 2a and 3a serotypes. Using the zebrafish model, we demonstrate that Shigella can establish persistent infection in vivo. Bacteria are not cleared by the immune system and become antibiotic tolerant. Establishment of persistent infection depends on the O-antigen, a key constituent of the bacterial surface and a serotype determinant. Representative isolates associated with MSM transmission persist in zebrafish, while representative isolates of a serotype not associated with MSM transmission do not. Isolates of a Shigella serotype establishing persistent infections elicited significantly less macrophage death in vivo than isolates of a serotype unable to persist. We conclude that zebrafish are a valuable platform to illuminate factors underlying establishment of Shigella persistent infection in humans.


Topical pH Sensing NIR Fluorophores for Intraoperative Imaging and Surgery of Disseminated Ovarian Cancer.
Fluorescence-guided surgery (FGS) aids surgeons with real-time visualization of small cancer foci and borders, which improves surgical and prognostic efficacy of cancer. Despite the steady advances in imaging devices, there is a scarcity of fluorophores available to achieve optimal FGS. Here, 1) a pH-sensitive near-infrared fluorophore that exhibits rapid signal changes in acidic tumor microenvironments (TME) caused by the attenuation of intramolecular quenching, 2) the inherent targeting for cancer based on chemical structure (structure inherent targeting, SIT), and 3) mitochondrial and lysosomal retention are reported. After topical application of PH08 on peritoneal tumor regions in ovarian cancer-bearing mice, a rapid fluorescence increase (< 10 min), and extended preservation of signals (> 4 h post-topical application) are observed, which together allow for the visualization of submillimeter tumors with a high tumor-to-background ratio (TBR > 5.0). In addition, PH08 is preferentially transported to cancer cells via organic anion transporter peptides (OATPs) and colocalizes in the mitochondria and lysosomes due to the positive charges, enabling a long retention time during FGS. PH08 not only has a significant impact on surgical and diagnostic applications but also provides an effective and scalable strategy to design therapeutic agents for a wide array of cancers.


Previously undescribed pulpal and periodontal ligament calcifications in systemic sclerosis: a case report.
Systemic sclerosis (SSc), a multisystem autoimmune disease characterized by widespread fibrosis, vascular alterations, autoimmunity, and inflammation, has effects on the hard and soft tissues of the orofacial region. The most common oral radiographic features correspond to widening of the periodontal ligament space and to mandibular resorption. In this report, cone-beam computerized tomography (CBCT) confirmed not only the well described periodontal features associated with SSc but also revealed previously undescribed calcifications within the periodontal ligament space of most maxillary teeth. Moreover, CBCT showed pulp calcifications in some incisors and premolars with these calcifications leading to root canal obliterations. Such manifestations (which could be linked to different major pathogenic features of SSc such as calcinosis, vasculopathy, and fibrosis) contribute to the phenotypic spectrum of the disease.


Prenatal detection of fetal thymidine kinase activity in maternal plasma: normal values and clinical application in postterm pregnancy.
Deoxythymidine kinase is present in human cells in two forms: the cytosolar form (fetal thymidine kinase) and the mitochondrial form (adult thymidine kinase). The activity of thymidine kinase isozymes in plasma of preterm and term newborns has been previously reported to be related to gestational age, and fetal thymidine kinase activity was reported to be undetectable after the thirty-ninth week of gestation. Our purpose was to determine if similar changes in the activity levels of the thymidine kinase isozymes could be demonstrated in late third trimester maternal plasma. A cross-sectional sample of 35 patients was studied from week 34 of pregnancy to delivery. Significant differences between fetal and adult thymidine kinase activity patterns were observed. Adult thymidine kinase activity remained relatively constant throughout the evaluation interval, while fetal thymidine kinase activity decreased with advancing gestational age. Regression analysis of gestational age by neonatal examination (GAPED) and fetal thymidine kinase revealed a linear relationship (fetal thymidine kinase = 0.380 - 0.00745 GAPED; R2 = 0.2944; standard estimate of error = 0.0350; p less than 0.0008). Comparison of fetal thymidine kinase activity in term and postterm pregnancy plasma revealed a significant difference (p less than 0.0159). Our findings indicate that deoxythymidine kinase activity can be measured in maternal plasma, may relate to the fetoplacental growth rate, and may be useful in differentiating between term and postterm gestations.


Cytomorphometric changes in rat brain neurons after rapid eye movement sleep deprivation.
Rapid eye movement sleep plays a vital role in the survival of animals. Its deprivation causes alterations in brain functions and behaviors including activities of important enzymes, neurotransmitter levels, impairment of neural excitability and memory consolidation. However, there was a lack of knowledge regarding the effects of rapid eye movement sleep deprivation on neuronal morphology that may get affected much earlier than any permanent damage to the neurons. In the present study, some of these issues have been addressed by studying the effects of rapid eye movement sleep deprivation on various morphological parameters viz. neuronal perimeter, area and shape of neurons located in brain areas known to regulate rapid eye movement sleep and as a control in other brain areas which do not regulate rapid eye movement sleep. The results showed that rapid eye movement sleep deprivation differentially affected neurons depending on their physiological correlates of rapid eye movement sleep and neurotransmitter content. The effects could be reversed if the animals were allowed to recover from rapid eye movement sleep loss or by applying alpha1-adrenergic antagonist, prazosin. The findings in rats support reported data and help explaining previous observations.


Novel protein therapeutic joint retention strategy based on collagen-binding Avimers.
Designing drugs to treat diseases associated with articular joints, particularly those targeting chondrocytes, is challenging due to unique local environmental constraints including the avascular nature of cartilage, the absence of a closed joint compartment, and a highly cross-linked extracellular matrix. In an effort to address these challenges, we developed a novel strategy to prolong residence time of intra-articularly administered protein therapeutics. Avimer domains are naturally found in membrane polypeptides and mediate diverse protein-protein interactions. Screening of a phage Avimer domain library led to identification of several low affinity type II collagen-binding Avimers. Following several rounds of mutagenesis and reselection, these initial hits were transformed to high affinity, selective type II collagen-binding Avimers. One such Avimer (M26) persisted in rat knees for at least 1 month following intra-articular administration. Fusion of this Avimer to a candidate therapeutic payload, IL-1Ra, yielded a protein construct which simultaneously bound to type II collagen and to IL-1 receptor. In vitro, IL-1Ra_M26 bound selectively to cartilage explants and remained associated even after extensive washing. Binding appeared to occur preferentially to pericellular regions surrounding chondrocytes. An acute intra-articular IL-1-induced IL-6 challenge rat model was employed to assess in vivo pharmacodynamics. Whereas both IL-1Ra_M26 and native IL-1Ra inhibited IL-6 output when co-administered with the IL-1 challenge, only IL-1Ra_M26 inhibited when administered 1 week prior to IL-1 challenge. Collagen-binding Avimers thus represent a promising strategy for enhancing cartilage residence time of protein therapeutics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1238-1247, 2018.


In vivo behavior of acrylic bone cement in total hip arthroplasty.
Polymethylmethacrylate (PMMA) bone cement serves as the primary fixation material between bone and the prosthetic component in cemented total hip arthroplasty. In vivo degradation of bone cement may lead to a decrease in mechanical properties of PMMA and result in aseptic loosening. However, other factors such as porosity and location of the cement relative to the bone implant interface may also contribute to mechanical behavior in vivo. This study investigated the mechanical properties of Simplex cement retrieved from 43 patients undergoing revision total hip arthroplasty. The time in vivo was between 1 month and 27 years. The variables studied included fracture toughness (KIC), porosity, molecular weight, time in vivo of the cement, and relative in vivo location of the cement with respect to the implant and bone. KIC did not correlate with time in vivo of the samples or with molecular weight. This suggests that time in vivo may not be the limiting factor in the mechanical integrity of the bone cement, A significant and inverse relationship was found between porosity and KIC. This implies that porosity is the most important factor in the mechanical behavior of bone cement during in vivo use.


Steroid hormones and growth factors act in an integrated manner at the levels of hypothalamic astrocytes: a role in the neuroendocrine control of reproduction.
Several growth factors (e.g., transforming growth factors beta and alpha, basic fibroblast growth factor), produced by hypothalamic astrocytes, participate in the control of hypothalamic gonadotrophin-releasing hormone (GnRH) neurons. On this basis, we have hypothesized that steroid hormones, like estrogens and progestagens, influence the GnRH neurons by modulating in glial cells the synthesis and the release of these growth factors. Data reported here indicate that the expression of transforming growth factor beta 1 is modulated in hypothalamic astrocytes by a progesterone derivative (i.e., dihydroprogesterone), while estrogens modulate that of basic fibroblast growth factor. Moreover, it is interesting to highlight that the effect of estrogens on basic fibroblast growth factor is mediated by another growth factor (i.e., transforming growth factor alpha). Altogether, the present findings support the concept that steroid hormones and growth factors act in an integrated manner at the level of hypothalamic astrocytes, thus adding a further piece of knowledge in the understanding of the mechanisms controlling GnRH neurons.


The study on the evaluation of the pollution control situation of the sewage systems in the counties and cities of Taiwan by applying the VIKOR method.
Currently, the pollution control situation of the sewage systems across Taiwan can be divided into the two major sewage systems, namely, industrial area sewage and public community sewage. When the counties and cities of Taiwan cannot effectively control the sewage pollution situation, ecological pollution of the environment and personal health damage would result. Therefore, evaluating the pollution control situation of the sewage systems can help the environmental protection authorities developing strategies for the pollution control of the sewage systems in the future. In this study, the Vise Kriterijumska Optimizacija I Kompromisno Resenje (VIKOR) method was applied to evaluate the pollution control situation of the sewage systems. The water sample test qualification rate, the emission permit issuance rate, and the staff setting rate of the dedicated wastewater treatment company were used as the pollution control evaluation indexes. According to the results, the use of the VIKOR method to evaluate the pollution control situation of the sewage systems is effective. In cities and counties in Taiwan, public community sewage systems, dedicated to pollution control case, the public community should be actively coached in emission control technology to upgrade sewage capacity, the issuance of discharge permits, and the staff setting rate of the dedicated wastewater treatment, to improve public community sewage pollution control system capabilities. In Taiwan, the industrial area sewage systems, dedicated to pollution control situations, must pay attention to business units in raw materials, spare part inventory, and machine supplier of choice, and we must choose to meet environmental supply chain of green suppliers, which would be effective in reducing effluent produce and improve water sample test qualification rate. The VIKOR value of Yilan County is 1.0000, which is the worst in the pollution control of all the industrial area sewage systems, followed by Taoyuan County (0.2253) and Kaohsiung City (0.1334). Other cities and counties of Taiwan have good performance in the pollution control of the industrial area sewage systems. The VIKOR value of Kinmen County is 1.0000, which is the worst pollution control among the all public community sewage systems, followed by Hsinchu County (0.7458) and New Taipei City (0.5527). Among the cities and counties with good pollution control of the public community sewage systems, the best is Chiayi County (0.0000), followed by Kaohsiung City (0.0159) and Hsinchu City (0.0352). Chiayi County is a good performance compromise between all VIKOR values (0.0000), whether in industrial or public community area pollution control sewage systems. Yilan County industrial pollution control has the poorest performance of all the industrial area sewage systems in Taiwan, but in the public community, it ranked as fourth place of all the public community area sewage systems in Taiwan. The VIKOR method proposed in this study can effectively evaluate the pollution control situation of the sewage systems, and serve as a reference for the environmental protection authorities in developing the strategies for the pollution control of the sewage systems.


Functions of the aryl hydrocarbon receptor in the skin.
Among other functions, the skin serves as the barrier against the environment and provides vital protection from physical or chemical harm and from infection. Skin cells express the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor and sensor of environmental chemicals; at the same time, AHR ligands are abundant in skin from exogenous or endogenous sources. For example, solar radiation, in particular ultraviolet (UV) B, generates AHR ligands from tryptophan in the skin. Recent evidence has shown that AHR is involved in the (patho)physiology of skin including the regulation of skin pigmentation, photocarcinogenesis, and skin inflammation. We here provide a state-of-the-art summary of work which relates to the role of the AHR in (1) adaptive responses against environmental challenges such as UVB or topical chemicals and (2) intrinsic developmental roles for homeostasis of skin cells and (3) skin immunity. We also discuss the existing evidence that AHR antagonists or AHR ligands may be used for the prevention and/or treatment of skin disease.


Cardiac specific expression of the green fluorescent protein during early murine embryonic development.
We demonstrate the establishment of transgenic mice, where the expression of the green fluorescent protein (GFP) is under control of the human cardiac alpha-actin promoter. These mice display cardiac specific GFP expression already during early embryonic development. Prominent GFP fluorescence was observed at the earliest stage of the murine heart anlage (E8). Cardiomyocytes of different developmental stages proved GFP positive, but the intensity varied between cells. We further show that contractions of single GFP positive cardiomyocytes can be monitored within the intact embryo. At later stages of embryonic development, the skeletal musculature was also GFP positive, in line with the known expression pattern of cardiac alpha-actin. The tissue specific labeling of organs is a powerful new tool for embryological as well as functional investigations in vivo.


Inhibition of casein kinase I delta alters mitotic spindle formation and induces apoptosis in trophoblast cells.
The serine/threonine-specific casein kinase I delta (CKIdelta) is ubiquitously expressed in all tissues, is p53 dependently induced in stress situations and plays an important role in various cellular processes. Our immunohistochemical analysis of the human placenta revealed strongest expression of CKIdelta in extravillous trophoblast cells and in choriocarcinomas. Investigation of the functional role of CKIdelta in an extravillous trophoblast hybrid cell line revealed that CKIdelta was constitutively localized at the centrosomes and the mitotic spindle. Inhibition of CKIdelta with the CKI-specific inhibitor IC261 led to structural alterations of the centrosomes, the formation of multipolar spindles, the inhibition of mitosis and, in contrast to other cell lines, the induction of apoptosis. Our findings indicate that CKIdelta plays an important role in the mitotic progression and in the survival of cells of trophoblast origin. Therefore, IC261 could provide a new tool in treating choriocarcinomas.


Chemical characterization of glomerular and tubular basement membranes of cattle of different ages.
Glomerular and tubular basement membranes were isolated from fetal, neonatal, young and adult bovine kidneys. An isolation method with sieves for both glomeruli and tubules from the same kidney was developed. A detergent procedure appeared to give purer glomerular and tubular basement membrane preparations than the generally used sonication method. No large differences were found in the composition of glomerular and tubular basement membrane of adult animals. Glomerular and tubular basement membrane preparations of the four age groups showed an increase with age of hydroxylysine and both 3- and 4-hydroxyproline. The most marked increases appeared at different stages of development, that of tubular basement membrane being between fetal and neonatal stages and glomerular basement membrane between 18 weeks old and adult animals. The ratio of 3- to 4-hydroxyproline increased considerably during development. Total imino acid content was higher for both types of basement membrane from adult than from young animals, while total content of hydroxylysine plus lysine remained fairly constant. The increase in hydroxylation of lysine was accompanied by a corresponding change in glucose and galactose content so that the ratio of galactose to hydroxylysine or glucose to galactose remained constant. Fucose content of both types of basement membranes was the same for all age groups but content of aminosugars and mannose gradually increased with age.


Dendritic polyglycerol sulfate attenuates murine graft-versus-host disease.
Graft-versus-host disease (GvHD) is a severe immune reaction commonly occurring after hematopoietic stem cell transplantation. The outcome of patients who do not respond to the currently used immunosuppressive drugs is poor, thus there is an urgent need for the evaluation of new therapies. Heparin has a well-known anti-inflammatory effect and heparin analogues with a low anticoagulant effect are interesting candidates as new anti-inflammatory drugs. We explored the therapeutic potential of dendritic polyglycerol sulfates (dPGS), a novel class of heparin derivatives, on murine acute GvHD in vivo. The therapeutic effect of dPGS on murine GvHD was more intense after intravenous application compared to subcutaneous injection. An increased survival rate and improved clinical scores were observed in mice treated with 5 mg/kg once a week. In these animals, there was a reduction in the percentage of CD4(+) and CD8(+) T cells, which are the main effectors of GvHD. In addition, dPGS treatment decreased the number of tumor necrosis factor alpha (TNFα)-producing T cells. Increasing the dose of dPGS reversed the positive effect on survival as well as the clinical score, which indicates a small therapeutic range. Here, we report for the first time that dPGS have a significant immunosuppressive in vivo effect in a mouse model of severe acute GvHD. Therefore, we propose to study dPGS as promising candidates for the development of potential new drugs in the treatment of steroid-refractory GvHD patients first in larger animals and later in humans.


Relationship between multiple weight cycles and early weight loss in patients with obesity: a longitudinal study.
To assess the relationship between multiple weight cycling (WC) and early weight loss (e-WL). Using a longitudinal prospective design conducted between May 2017 and November 2019, early weight loss was assessed at month 2 of a weight management programme in 100 adult participants with overweight or obesity, at the Outpatient Clinic of the Department of Nutrition and Dietetics at Beirut Arab University (Lebanon). Weight cycling was defined as intentional weight loss of ≥ 3 kg followed by involuntary weight regain of ≥ 3 kg and participants were then categorized as multiple WC if they had experienced ≥ 2 cycles. Of the 100 participants with a median age of 34.90 (22.94-50.67) years and a median BMI of 35.25 (32.75-39.48) kg/m2, 75 met the criteria for WC and displayed a lower e-WL percentage than those without WC (4.69 ± 2.78% vs. 6.58 ± 2.80%; p = 0.006). Linear regression analysis showed that e-WL was lower by ≈ 2% (β = - 1.935; 95% CL - 3.221, - 0.648; p = 0.004) in the WC group compared to the non-WC group after adjusting for age, gender and baseline BMI. In a 'real-world' clinical setting, multiple WC decreases e-WL rates. New strategies could be adopted for these patients to improve this early clinical outcome, since e-WL predicts longer-term success. III, prospective longitudinal study.


Facial reanimation using the hypoglossal nerve and ansa cervicalis: a short-term retrospective analysis of surgical outcomes.
Transferring the hypoglossal nerve to the facial nerve using an end-to-end method is very effective for improving facial motor function. However, this technique may result in hemitongue atrophy. The ansa cervicalis, which arises from the cervical plexus, is also used for facial reanimation. We retrospectively reviewed cases where facial reanimation was performed using the ansa cervicalis to overcome the shortcomings of existing techniques of hypoglossal nerve transfer. The records of 15 patients who underwent hypoglossal nerve transfer were retrospectively reviewed. Three methods were used: facial reanimation with hypoglossal nerve transfer (group 1), facial nerve reanimation using the ansa cervicalis (group 2), and sural nerve interposition grafting between the hypoglossal nerve and facial nerve (group 3). In group 1, the ansa cervicalis was coapted to neurotize the distal stump of the hypoglossal nerve in a subset of patients. Clinical outcomes were evaluated using the House-Brackmann (H-B) grading system and Emotrics software. All patients in group 1 (n = 4) achieved H-B grade IV facial function and showed improvements in the oral commissure angle at rest (preoperative vs. postoperative difference, 6.48° ± 0.77°) and while smiling (13.88° ± 2.00°). In groups 2 and 3, the oral commissure angle slightly improved at rest (group 2: 0.95° ± 0.53°, group 3: 1.35° ± 1.02°) and while smiling (group 2: 2.06° ± 0.67°, group 3: 1.23° ± 0.56°). In group 1, reduced tongue morbidity was found in patients who underwent ansa cervicalis transfer. Facial reanimation with hypoglossal nerve transfer, in combination with hypoglossal nerve neurotization using the ansa cervicalis for complete facial palsy patients, might enable favorable facial reanimation outcomes and reduce tongue morbidity. Facial reanimation using the ansa cervicalis or sural nerve for incomplete facial palsy patients did not lead to remarkable improvements, but it warrants further investigation.


Seeking connection: a mixed methods study of mental well-being and community volunteerism among international migrants in Japan.
International migration is a stressful process for which non-Western nations are a growing destination. However, little attention has been paid to the psychological well-being of international residents or their local integration in such settings. Prosocial behavior, like volunteering in one's local community, has been demonstrated to improve mental health in native populations. Volunteerism may be a mental health promotion strategy applicable to non-native migrants as well. In order to assess such a hypothesis, this study investigated the mental well-being of international migrants living in Tokyo, Japan, who did or did not participate in formal volunteering. This convergent mixed-methods study assessed mental well-being with the Warwick-Edinburgh Mental Well-being Scale (WEMWBS) and qualitative follow-up interviews. Migrants who contributed their time to structured volunteering roles (formal volunteers, n = 150) were recruited from local non-profit organizations. Migrants who did not formally volunteer (n = 150) were recruited from social media sites. In parallel, a nested participant sample from both groups (n = 20) were interviewed about their satisfaction with life in Tokyo. After adjusting for sociodemographic characteristics, volunteering was not associated with higher mental well-being score (p = 0.215), but instead, not feeling isolated (p = 0.008), feeling connected to Japan (p = 0.001) and employment satisfaction (p < 0.001) were significantly associated with mental well-being. Follow-up interviews similarly demonstrated that migrants participated in various social activities to promote personal well-being and deeper social connections with Japanese, regardless of volunteering status. Volunteering status itself was not significantly associated with mental well-being score among international migrants in Japan after adjusting for potential confounding variables. Beyond volunteering, having deeper social connections with the Japanese community is a key to promoting migrant mental well-being.


Cat-Scratch Disease: Case Report and Review of the Literature.
Cat-scratch disease (CSD) is caused by Bartonella henselae and characterized by self-limited fever and granulomatous lymphadenopathy. In some cases signs of a visceral, neurologic, and ocular involvement can also be encountered. In this report we describe the development of CSD in a kidney transplant patient. Immunocompromised hosts are more susceptible to infection from Bartonella compared with the standard population. Infection of Bartonella should be considered as a differential diagnosis in kidney transplant patients with lymphadenopathy of unknown origin.


Sulfur is in the Air: Cyanolichen Marriages and Pollution.
Cyanolichens are symbiotic organisms involving cyanobacteria and fungi (bipartite) or with the addition of an algal partner (tripartite). Cyanolichens are known for their heightened susceptibility to environmental pollution. We focus here on the impacts on cyanolichens due to rising air pollution; we are especially interested in the role of sulfur dioxide on cyanolichen biology. Cyanolichens due to air pollution including sulfur dioxide exposure, show symptomatic changes including degradation of chlorophyll, lipid membrane peroxidation, decrease in ATP production, changes in respiration rate, and alteration of endogenous auxins and ethylene production, although symptoms are known to vary with species and genotype. Sulfur dioxide has been shown to be damaging to photosynthesis but is relatively benign on nitrogen fixation which proposes as a hypothesis that the algal partner may be more in harm's way than the cyanobiont. In fact, the Nostoc cyanobiont of sulfur dioxide-susceptible Lobaria pulmonaria carries a magnified set of sulfur (alkane sulfonate) metabolism genes capable of alkane sulfonate transport and assimilation, which were only unraveled by genome sequencing, a technology unavailable in the 1950-2000 epoch, where most physiology- based studies were performed. There is worldwide a growing corpus of evidence that sulfur has an important role to play in biological symbioses including rhizobia-legumes, mycorrhizae-roots and cyanobacteria-host plants. Furthermore, the fungal and algal partners of L. pulmonaria appear not to have the sulfonate transporter genes again providing the roles of ambient-sulfur (alkanesulfonate metabolism etc.) mediated functions primarily to the cyanobacterial partner. In conclusion, we have addressed here the role of the atmospheric pollutant sulfur dioxide to tripartite cyanolichen viability and suggest that the weaker link is likely to be the photosynthetic algal (chlorophyte) partner and not the nitrogen-fixing cyanobiont.


Polyomaviruses BK and JC DNA infection in peripheral blood cells from blood donors.
To investigate the prevalence of human polyomavirus (BK and JC viruses) infection in peripheral blood mononuclear cells of healthy blood donors. The study included 250 healthy blood donors. Five-milliliter blood was drawn into sterile EDTA tubes and PBMCs were isolated from whole blood. The isolated PBMCs were counted and stored at -70°C for future investigation. DNA was extracted and subjected to simple, sensitive and specific semi-nested PCR as well as QPCR using both general and specific primers for different assays. Of 250 blood samples, 66 (26.4%) were positive for BKV DNA (146-34,514 copies/106 cells). JC DNA was found in 45 (18%) blood samples (65-21,250 copies/106 cells). Co-infection with these viruses were found in 11 (4.4%) out of 250 blood samples. Our study provides important data on polyomavirus infection in peripheral blood mononuclear leukocytes in immunocompetent individuals. These data indicate significant differences between the prevalence of BKV and JCV infection in healthy blood donors. The prevalence of BK and JC virus infection is higher in the age range 30-39 years compared to other age ranges.


Drivers of microbial beta-diversity in wastewater treatment plants in China.
As one of the most well-documented biogeographic patterns, the distance-decay relationship provides insights into the underlying mechanisms driving biodiversity distribution. Although wastewater treatment plants (WWTPs) are well-controlled engineered ecosystems, this pattern has been seen among microbial communities in activated sludge (AS). However, little is known about the relative importance of environmental heterogeneity and dispersal limitation in shaping AS microbial community across China; especially they are related to spatial scale and organism types. Here, we assessed the distance-decay relationship based on different spatial scales and microbial phylogenetic groups by analyzing 132 activated sludge (AS) samples across China comprising 3,379,200 16S rRNA sequences. Our results indicated that the drivers of distance-decay pattern in China were scale-dependent. Microbial biogeographic patterns in WWTPs were mainly driven by dispersal limitation at both local and national scales. In contrast, conductivity, SRT, and pH played dominant roles in shaping AS microbial community compositions at the regional scale. Turnover rates and the drivers of beta-diversity also varied with microorganism populations. Moreover, a quantitative relationship between dispersal limitation ratio and AS microbial turnover rate was generated. Collectively, these results highlighted the importance of considering multiple spatial scales and micro-organism types for understanding microbial biogeography in WWTPs and provided new insights into predicting variations in AS community structure in response to environmental disturbance.


Sequential sparse autoencoder for dynamic heading representation in ventral intraparietal area.
To navigate in space, it is important to predict headings in real-time from neural responses in the brain to vestibular and visual signals, and the ventral intraparietal area (VIP) is one of the critical brain areas. However, it remains unexplored in the population level how the heading perception is represented in VIP. And there are no commonly used methods suitable for decoding the headings from the population responses in VIP, given the large spatiotemporal dynamics and heterogeneity in the neural responses. Here, responses were recorded from 210 VIP neurons in three rhesus monkeys when they were performing a heading perception task. And by specifically and separately modelling the both dynamics with sparse representation, we built a sequential sparse autoencoder (SSAE) to do the population decoding on the recorded dataset and tried to maximize the decoding performance. The SSAE relies on a three-layer sparse autoencoder to extract temporal and spatial heading features in the dataset via unsupervised learning, and a softmax classifier to decode the headings. Compared with other population decoding methods, the SSAE achieves a leading accuracy of 96.8% ± 2.1%, and shows the advantages of robustness, low storage and computing burden for real-time prediction. Therefore, our SSAE model performs well in learning neurobiologically plausible features comprising dynamic navigational information.


[Three cases of Dieulafoy's disease].
To increase the knowledge of Dieulafoy's disease and decrease the misdiagnosis rate. Three cases of Dieulafoy's disease were analyzed clinically and their therapeutic methods were discussed. Subtotal gastrectomy including the lesion is better than other methods. It is necessary to understand the clinical pattern and pathological characteristics in order to increase the diagnosis rate and decrease misdiagnosis rate. Subtotal gastrectomy or wide wedge resection of the lesion is recommended.


Evaluation of the ocular-irritation potential of 56 compounds.
The ocular irritancy of 56 chemicals was tested in the rabbit eye, with and without rinsing, using a procedure that complied with the main requirements of three protocols, namely those proposed by the Association Française de Normalisation (AFNOR) in 1982 and by the Organisation for Economic Co-operation and Development in 1979 for the testing of chemicals and that published by the French authorities (Journal Officiel 21 April 1971, p. 3862; ibid 5 June 1973, p. 3953) for the testing of cosmetics and toiletries. The results obtained were used to establish the extent to which the assessment of a chemical's irritation potential was affected by the differences between the three protocols in respect of the observation times prescribed, the inclusion and timing of rinsing, the number of animals used and the interpretation procedure. Conclusions were also drawn about the influence of the physical state and pH of a material on its potential irritancy and about the level of irritancy that necessitates the use of eye protection.


Nutritional and immunological assessment of patients with anorexia nervosa.
The nutritional and immunological status of patients with anorexia nervosa was assessed. Anthropometric measurements were found to be lowered as were the serum levels of zinc (p<0.01), copper (p<0.01) and ceruloplasmin (p<0.05) in comparison with the control group. However the serum levels of albumin, pre-albumin, transferrin and retinol binding protein, vitamins A and D and leucocyte vitamin C were generally found to be within normal limits. Lymphocyte transformation was measured in response to stimulation with the mitogens Con A, PHA and PWM. Responses were normal in all patients with the exception of one who showed a depressed response to Con A. Natural killer cell activity was measured against the target cell line K562 and was not found to differ significantly from controls. It is suggested that the relatively normal protein and vitamin status is responsible for maintaining the apparently normal cellular immune function in patients with anorexia nervosa.


Amineptine, response timing, and time discrimination in the albino rat.
Experiment 1 recorded the effects of single (doses of 1, 5, 10, and 20 mg/kg) and repeated intraperitoneal injections (10 mg/kg) of amineptine (a tricyclic antidepressant drug) on the performance of albino rats in differential reinforcement of low rate (DRL) of 30 s, fixed-interval (FI) of 60 s, and signalled continuous reinforcement (CRF-SD) schedules. In the second experiment, the effects of repeated (10 mg/kg) and single injections (20 mg/kg) were assessed on the discrimination of the duration of auditory stimuli (2 and 8 s). A dose-related increase in response rates was observed in FI and DRL, correlating with a dose-related impairment in the temporal regulation of performance. However, the drug remained without effect on duration discrimination. In other respects, decreases in response latency in CRF-SD or duration discrimination tended to indicate that the drug improved vigilance and reactivity to extraneous significant stimuli. Interpretations in terms of sensitization, tolerance, or dependency could be discarded. Our data support the hypothesis that drug effects on temporal regulation in FI and DRL are secondary to a nonspecific activation of motor activity. They question the plausibility of an antidepressant effect of the drug in humans via modulation of a timing mechanism.


Free circulating ICAM-1 in serum and cerebrospinal fluid of HIV-1 infected patients correlate with TNF-alpha and blood-brain barrier damage.
The mechanism for the initiation of blood-brain barrier damage and intrathecal inflammation in patients infected with the human immunodeficiency virus (HIV) is poorly understood. We have recently reported that tumour necrosis factor-alpha (TNF-alpha) mediates active neural inflammation and blood-brain barrier damage in HIV-1 infection. Stimulation of endothelial cells by TNF-alpha induces the expression of intercellular adhesion molecule-1 (ICAM-1), which is an important early marker of immune activation and response. We report herein for the first time the detection of high levels of free circulating ICAM-1 in serum and cerebrospinal fluid of patients with HIV-1 infection. Free circulating ICAM-1 in these patients correlated with TNF-alpha concentrations and with the degree of blood-brain barrier damage and were detected predominantly in patients with neurologic involvement. These findings have important implications for the understanding and investigation of the intrathecal inflammatory response in HIV-1 infection.


Ginkgolide B inhibits lung cancer cells promotion via beclin-1-dependent autophagy.
Ginkgolide B (GKB) is a major active component of the extracts of Ginkgo biloba leaves, and it has been used as an anti-cancer agent. However, it is unknown whether GKB has the therapeutic effects on lung cancer. Here, we studied the effects of GKB on lung cancer cells. The effects of GKB on lung cancer cell proliferation and invasion were analyzed by cell counting kit (CCK-8) and cell invasion assays, respectively. Apoptosis was detected by flow cytometry. Western blot analysis was used to confirm the expression of autophagy-associated proteins in GKB-treated cells. Immunofluorescence analysis was used to analyze the level of light chain 3B (LC3B). Treatment with GKB time-dependently inhibited the proliferation and decreased the invasive capacity of A549 and H1975 cells. GKB induced apoptosis of these cells, but there was no significant effect on apoptosis compared to the control treatment. GKB-induced inhibition of cell proliferation and GKB-induced cell death were due to autophagy rather than apoptosis. GKB-induced autophagy of lung cancer cells was dependent on beclin-1, and autophagy-induced inhibition of the NLRP3 inflammasome contributed to the anti-tumor effect of GKB. GKB-mediated autophagy of lung cancer cells is beclin-1-dependent and results in inhibition of the NLRP3 inflammasome. Therefore, GKB might be a potential therapeutic candidate for the treatment of lung cancer.