Transvaginal cervical length scans to prevent prematurity in twins: a randomized controlled trial.
Twin pregnancies are associated with an increased risk of perinatal morbidity and mortality primarily due to spontaneous preterm deliveries. The mean gestational age for delivery is 35.3 weeks and twins account for 23% of preterm births <32 weeks. A number of strategies have been proposed to prevent preterm deliveries: tocolytics, bed rest, hospitalization, home uterine activity monitoring, cerclage, and most recently, progesterone. Unfortunately, none have proven effective. Recent metaanalyses and reviews suggest that transvaginal cervical length (TVCL) ultrasound in the second trimester is a powerful predictor of preterm birth among asymptomatic women. Indeed, TVCL has the highest positive and negative predictive values for determining the risk of spontaneous preterm delivery in twin pregnancies. It follows that TVCL assessment may allow identification of a subset of twin pregnancies that re better candidates for interventions intended to prevent prematurity. We sought to determine whether use of TVCL prolongs gestation in twin pregnancies. This is a multicenter, randomized, controlled trial of 125 dichorionic or monochorionic/diamniotic twin pregnancies without prior preterm birth <28 weeks. The study group (n = 63) had TVCL and digital exams monthly from 16-28 weeks and were managed with a standard algorithm for activity restriction and cerclage. The control group (n = 62) had monthly digital cervical examinations but no routine TVCL ultrasound examinations. The primary outcome was gestational age at delivery. Secondary outcomes included percentage of deliveries <35 weeks, and maternal and neonatal outcomes. The mean gestational age at delivery was 35.7 weeks (95% confidence interval [CI], 35.2-36.2) among those managed with TVCL and 35.5 weeks (95% CI, 34.7-36.4) among the control patients. The Kaplan-Meier estimates of deliveries <38 weeks were not significantly different between groups. This was true whether we compared curves with a log-rank test (P = .67), Breslow test (P = .67), or Tarone-Ware test (P = .64). The percentage of deliveries <35 0/7 weeks did not differ: 27.4% for subjects managed with routine TVCL and 28.6% for control subjects (relative risk, 0.96; 95% CI, 0.60-1.54). Our study had an 80% power to detect a 12-day difference in the gestational age at delivery with 95% confidence. The overall mean length of gestation and the percentage of women delivering <35 weeks did not differ between twin gestations managed with TVCL and digital exams monthly from 16-28 weeks with a standard algorithm for activity restriction and cerclage and controls who had monthly digital cervical examinations but no routine TVCL. Routine second-trimester transvaginal ultrasound assessment of cervical length is not associated with improved outcomes when incorporated into the standard management of otherwise low-risk twin pregnancies.


Mathematical modelling of ATP, K+ and Na+ interactions with (Na+ + K+)-ATPase occurring under equilibrium conditions.
The controlling effect of ATP, K+ and Na+ on the rate of (Na+ + K+)-ATPase inactivation by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-C1) is used for the mathematical modelling of the interaction of the effectors with the enzyme under equilibrium conditions. 1. Of a series of conceivable interaction models, designed without conceptual restrictions to describe the effector control of inactivation kinetics, only one fits the experimental data described in a preceding paper. 2. The model is characterized by the coexistence of two binding sites for ATP and the coexistence of two separate binding sites for K+ and Na+ on the enzyme-ATP complex. On the basis of this model, the effector parameters fitting the experimental data most closely are estimated by means of nonlinear least-squares fits. 3. The apparent dissociation constants for ATP fo the enzyme-ATP complex or of the enzyme-(ATP)2 complex are computed to lie near 0.0024 mM and 0.34 mM, respectively, irrespective of whether K+ and Na+ were absent or K+ and K+ plus Na+, respectively, were present in the experiments. 4. The origin of the high and the low affinity site for binding of ATP to the (Na+ + K+)-ATPase molecule is traced back to the coexistence of two catalytic centres which, although primarily equivalent as to the reactivity of their thiol groups with NBD-C1, are induced into anticooperative communication by ATP binding and thus show an induced geometric asymmetry. 5. On the basis of the interaction model outlined under item 2 the apparent dissociation constant for K+ or Na+ in the (K+ + Na+)-liganded enzyme-ATP complex are computed to be 1.7 mM and 3.5 mM, respectively. 6. The conclusions concerning the coexistence of two primarily equivalent but anticooperatively interacting catalytic centres and the coexistence of two separate ionophoric centres for Na+ and K+ correspond to the appropriate basic postulates of the flip-flop concept of (Na+ + K+)-ATPase mechanism.


Dorsal-ventral differentiation in Simonsiella and other aspects of its morphology and ultrastructure.
The morphology and ultrastructure of the aerobic, Gram-negative multicellular-filamentous bacteria of the genus simonsiella were investigated by scanning and transmission electron microscopy. The flat, ribbon-shaped, multicellular filaments show dorsal-ventral differentiation with respect to their orientations to solid substrata. The dorsal surface, orientated away from the substrate, is convex and possesses an unstructured capsule. The ventral surface, on which the organisms adhere and glide, is concave and has an extracellular layer with fibrils extending at right angles from the cell wall. The cytoplasm in the ventral region contains a proliferation of intracytoplasmic membranes and few ribosomes in comparison to the cytoplasm in other parts of the cell. Centripetal cell wall formation is asymmetrical and commences preferentially in the ventral region. Quantitative differences in morphology and cytology exist among selected Simonsiella strains. Functional aspects of this dorsal-ventral differentiation are discussed with respect to the colonization and adherence of Simonsiella to mucosal squamous epithelial cells in its ecological habitat, the oral cavities of warm-blooded vertebrates.


MicroRNA-802 plays a tumour suppressive role in tongue squamous cell carcinoma through directly targeting MAP2K4.
Tongue squamous cell carcinoma (TSCC) is the most common oral tumours. MicroRNAs play crucial roles in many cell processes including cell viability, development, apoptosis, migration and invasion. The role of miR-802 in the TSCC is still unknown. The miR-802 expression in TSCC tissues and cell lines was determined by quantitative real-time polymerase chain reaction. CCK-8 assay was performed to measure the cell viability, while the cell invasion assay was used to determine the cell invasion. Dual-luciferase reporter and western blot were used to confirm the potential target gene of miR-802. In our study, we demonstrated that miR-802 expression was downregulated in TSCC tissues and cell lines. Elevated expression of miR-802 suppressed the TSCC cell viability and invasion. Moreover, enforced expression of miR-802 increased the expression of E-cadherin, while suppressed the expression of N-cadherin, Snail and Vimentin in the TSCC cell. In addition, we identified the mitogen-activated protein kinase 4 (MAP2K4) as a direct target gene of miR-802 in the TSCC cell. We also demonstrated that the expression of MAP2K4 was higher in the TSCC tissues than that in the adjacent normal tissues. Furthermore, the expression level of MAP2K4 was inversely associated with the expression of miR-802 in TSCC tissues. We also demonstrated that the MAP2K4 expression was upregulated in TSCC cell lines. Elevated expression of miR-802 inhibited TSCC cell viability and invasion through inhibiting MAP2K4 expression. Our data revealed that miR-802 played as a tumour suppressor gene and might act as a therapeutic target in TSCC patients.


Apoptosis induced by hydrogen peroxide is mediated by decreased superoxide anion concentration and reduction of intracellular milieu.
Hydrogen peroxide (H2O2) is considered to be a mediator of apoptotic cell death but the mechanism by which it induces apoptosis is unclear. Here, we show that cells undergoing apoptosis from exposure to H2O2 display a significant decrease in intracellular concentration of superoxide (O2-) which is associated with a reduction of the intracellular milieu, as measured by an increase in the GSH/GSSG ratio and a decrease in intracellular pH. The notion that a decrease in intracellular O2- concentration triggers apoptosis is supported by the observation that H2O2-mediated apoptosis could be retarded in cells in which the intracellular O2- concentration is maintained at or above the cellular baseline level by inhibition of the major O2- scavenger superoxide dismutase (Cu/Zn SOD). Taken together, our observations indicate that a decrease in the intracellular O2- concentration, reduction and acidification of the intracellular milieu constitute a signal for H2O2-mediated apoptosis, thereby inducing a reductive as opposed to an oxidative stress.


Perinatal risk factors for infantile hypertrophic pyloric stenosis: A meta-analysis.
Infantile hypertrophic pyloric stenosis (IHPS) is the most common surgical cause of nonbilious vomiting in infancy. The etiology of IHPS is not completely understood. Hence, we performed a meta-analysis to investigate the association between perinatal factors and IHPS onset. The MEDLINE, EMBASE, PubMed and Cochrane Library databases were searched for studies published in English before December 2016. The combined odd ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. Fifteen studies were included. Several perinatal factors, including first-born (OR 1.19, 95% CI: 1.07-1.33), cesarean section delivery (OR 1.63, 95% CI: 1.53-1.73), preterm birth (OR 1.37, 95% CI: 1.12-1.67), and bottle-feed (OR 2.46, 95% CI: 1.76-3.43), were significantly associated with the IHPS onset. Among these, bottle-feed was the most significantly risk factor for IHPS onset. Although few studies have evaluated the relationship between perinatal factors and IHPS, they have major limitations including retrospective collection of data on perinatal events and testing of multiple hypotheses without appropriate statistical corrections. First-born, cesarean section delivery, preterm birth, and bottle-feed are associated with the development of IHPS. Well-designed future studies are needed to help understand the etiology of IHPS. Systematic reviews and meta-analyses. Level III.


Removal of low concentration Cr(VI) from aqueous solution by magnetic-fluids fixed bed using the high gradient magnetic separation.
The focus of this paper was a novel model of Cr(VI) extraction process. The original so-called "magnetic-fluids fixed bed" (MFFB), which bridged the solvent extraction and the fixed-bed extraction by the theory of the high gradient magnetic separation (HGMS), has been explained. The MFFB integrated the advantages of the two above mentioned classical extraction methods and overcame their drawbacks. The feasibility of this method was studied by extraction experiments of Cr(VI) from aqueous solution. The influences of the design of ferromagnetic steel wires in magnetic separation column, the pH value of feed solution, TBP concentration in magnetic fluids, and flow rate of aqueous solution in column were investigated. Under the optimum conditions, the proposed method obtained high extraction efficiency with continuous process.


Synthesis of mixed musks via Eschenmoser-Tanabe fragmentation, enyne metathesis and Diels-Alder reaction as key steps.
Musk analogues containing different macrocyclic ring systems as well as different annulated ring systems were synthesised by a simple and useful strategy. This strategy includes Eschenmoser-Tanabe fragmentation, enyne metathesis and Diels-Alder reaction as key steps. Starting from easily available (n) macrocyclic ketones, (n + 3) macrocyclic systems were assembled using the basic organic reactions.


A simple colorimetric method for ascorbic acid determination in blood plasma.
The paper describes a simple method for determination of ascorbic acid using acid phosphotungstate. The reagent has been found to be specific and sensitive to ascorbic acid and can be used for ascorbic acid determination in plasma with good reproducibility.


Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes.
Increased flux of glucose through the hexosamine biosynthetic pathway (HSP) is believed to mediate hyperglycemia-induced insulin resistance in diabetes. The end product of the HSP, UDP beta-N-acetylglucosamine (GlcNAc), is a donor sugar nucleotide for complex glycosylation in the secretory pathway and for O-linked GlcNAc (O-GlcNAc) addition to nucleocytoplasmic proteins. Cycling of the O-GlcNAc posttranslational modification was blocked by pharmacological inhibition of O-GlcNAcase, the enzyme that catalyzes O-GlcNAc removal from proteins, with O-(2-acetamido-2-deoxy-d-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc). PUGNAc treatment increased levels of O-GlcNAc and caused insulin resistance in 3T3-L1 adipocytes. Insulin resistance induced through the HSP by glucosamine and chronic insulin treatment correlated with increased O-GlcNAc levels on nucleocytoplasmic proteins. Whereas insulin receptor autophosphorylation and insulin receptor substrate 2 tyrosine phosphorylation were not affected by PUGNAc inhibition of O-GlcNAcase, downstream phosphorylation of Akt at Thr-308 and glycogen synthase kinase 3 beta at Ser-9 was inhibited. PUGNAc-induced insulin resistance was associated with increased O-GlcNAc modification of several proteins including insulin receptor substrate 1 and beta-catenin, two important effectors of insulin signaling. These results suggest that elevation of O-GlcNAc levels attenuate insulin signaling and contribute to the mechanism by which increased flux through the HSP leads to insulin resistance in adipocytes.


Ecological degradation of an inland river basin and an evaluation of the spatial and distance effect on willingness to pay for its improvement.
Improvements in the ecological attributes of inland rivers have been projected to provide considerable non-market benefits, and the monetary valuation of these attributes has steadily increased over the past several decades. The present study addresses the spatial heterogeneity of the public's preference for ecological attributes and the distance-decay effect of willingness to pay (WTP) to improve various attributes of the river basin. The results revealed that spatial heterogeneity exists among the individuals; for example, the respondents of Liangzhou County prefer a large improvement in the natural landscape, forest coverage, and eco-tourism and are willing to pay 491.89, 369.32, and 338.37 yuan per year, respectively, for one unit improvement in these ecological attributes. Similarly, the respondents of Jinchang County value and are willing to pay 447.60, 431.81, and 318.18 yuan for one unit improvement in tourism, forest coverage, and natural landscape, respectively. Furthermore, the results from the random parameter logit model show a significant distance-decay effect of the household WTP for ecological attributes. For example, the respondents living within 5 km of the river are willing to pay more money, that is, 832.61, 365.62, and 353.05 yuan per year for improving the natural landscape, water quantity, and grass cover, respectively. As the distance from the river increases, the corresponding WTP decreases, meaning that the respondents (users) living near the Shiyang River Basin are willing to pay more for ecological attribute improvement than those living far away from the river.


Mechanisms of gastroesophageal reflux in children with sequelae of birth asphyxia.
Patterns of childhood gastroesophageal reflux (GER) have been studied extensively; however, the mechanisms underlying its occurrence in neurologically impaired children (NIC) are poorly understood. Concurrent esophageal manometry and pH monitoring was conducted in 10 un-operated children (7 male; mean age: 59.5 months) with sequelae birth asphyxia and esophagitis. Reflux episodes were scored when esophageal pH decreased to <4 for at least 5 s. When the rate of decrease of lower esophageal sphincter (LES) pressure was >1 mmHg/s, the decrease of LES pressure was defined as LES relaxation. The time relationship of the pharyngeal manometric swallowing signal to LES relaxation onset was then evaluated in order to distinguish between LES relaxations associated with swallowing (type II or III, associated with one or more swallows, respectively) and those that occurred independently of swallowing (type I). Esophageal manometry and pH monitoring were conducted for a mean duration of 91.5 min. Basal LES pressure averaged (+/-SD) 9.2+/-4.8 mmHg; in 4 of 10 patients (40%) the LES pressure was largely undetectable, varying between 0 and 2 mmHg. Mean LES pressure was inversely correlated with age (r=0.7, P=0.02). The total number of reflux episodes/h averaged 32.1+/-12.1 LES pressure reached 0 mmHg in 98% of reflux episodes. Type I LES relaxations were present in 3.15+/-1.1 reflux episodes/h, whereas type II LES relaxation occurred in 2.3+/-2.4 episodes/h. Acid reflux episodes appeared during absent basal LES tone periods, without phasic LES relaxations, in 74%. Absent basal LES tone is the main mechanism of GER in a subgroup of NIC, especially in older children. Transient LES relaxation, the most common known event associated with acid reflux in neurologically normal children, seems to precede a minority of reflux events in NIC.


Anticancer activity of silver-N-heterocyclic carbene complexes: caspase-independent induction of apoptosis via mitochondrial apoptosis-inducing factor (AIF).
Fourteen silver(I) complexes bearing N-heterocyclic carbene (NHC) ligands were prepared and evaluated for anticancer activity. Some of these were found to exhibit potent antiproliferative activity toward several types of human cancer cell lines, including drug-resistant cell lines, with IC(50) values in the nanomolar range. An initial investigation into the mechanism of cell death induced by this family of silver(I) complexes was carried out. Cell death was shown to result from the activation of apoptosis without involvement of primary necrosis. In HL60 cells, silver-NHCs induce depolarization of the mitochondrial membrane potential (ΔΨ(m)) and likely allow the release of mitochondrial proteins to elicit early apoptosis. This effect is not related to the overproduction of reactive oxygen species (ROS). In addition, apoptosis is not associated with the activation of caspase-3, but is triggered by the translocation of apoptosis-inducing factor (AIF) and caspase-12 from mitochondria and the endoplasmic reticulum, respectively, into the nucleus to promote DNA fragmentation and ultimately cell death. No modification in cell-cycle distribution was observed, indicating that silver-NHCs are not genotoxic. Finally, the use of a fluorescent complex showed that silver-NHCs target mitochondria. Altogether, these results demonstrate that silver-NHCs induce cancer cell death independent of the caspase cascade via the mitochondrial AIF pathway.


Identifying phases of investigation helps planning, appraising, and applying the results of explanatory prognosis studies.
To present an explanatory framework for understanding prognosis and illustrate it using data from a systematic review. A framework including three phases of explanatory prognosis investigation was adapted from earlier work and a discussion of causal understanding was integrated. For illustration, prognosis studies were identified from electronic and supplemental searches of literature between 1966 and December 2006. We extracted characteristics of the populations, exposures, and outcomes and identified three phases of explanatory prognosis investigation: Phase 1, identifying associations; Phase 2, testing independent associations; and Phase 3, understanding prognostic pathways. The purpose of each phase is exploration, confirmation, and development of understanding, respectively. It is important to consider a framework of explanatory prognosis studies for: (1) defining the study objectives, (2) presenting the study methods and data, and (3) interpreting and applying the results of the study. When conducting and reporting prognosis studies, researchers should consider the approach to prognosis (explanatory or outcome prediction) and phase of investigation, use best methods to limit biases, report completely, and cautiously interpret results. Readers of health care research will then be better able to evaluate the goals and interpret and appropriately use the results of prognosis studies.


Treating Gang-Involved Patients: Embodied Trauma & How to Heal from Life on the Street.
People involved with gangs experience a disproportionate amount of violence and trauma which can lead to the development of mental health and substance use disorders. This paper arms social workers with knowledge and skills to assess and intervene with gang-involved patients. A review of the rates of mental health and substance use disorders within the population is provided, including a discussion of theoretical frameworks to understand how gang involvement relates to mental health and substance use disorders. Finally, a review of evidence-based practices for treating gang-involved patients is provided.


Paracetamol overdose: protective effect of concomitantly ingested antimuscarinic drugs and codeine.
Twelve cases of paracetamol overdose are reported. Nine patients ingested antimuscarinic agents and/or codeine concomitantly. Our findings indicate that 'mixed' overdose of this type gives rise to marked attenuation of the rate of paracetamol absorption and, apparently, reduced morbidity associated with paracetamol poisoning. It is speculated that suitable antimuscarinic agents may be incorporated into paracetamol formulations to achieve inhibition of gastric emptying and to confer a degree of protection in case of overdose.


Apoptosis of peripheral human blood lymphocytes induced by physical-chemical influences and generation of reactive oxygen species.
The sensitivity of peripheral blood lymphocytes of healthy people (blood donors) to induced apoptotic processes and reactive oxygen species production under physical-chemical influences was evaluated in vitro.


Anesthetic Management and Considerations for Electrophysiology Procedures.
The number of electrophysiology (EP) procedures being performed has dramatically increased in recent years. This escalation necessitates a full understanding by the general anesthesiologist as to the risks, specific considerations, and comorbidities that accompany these now common procedures. Procedures reviewed in this article include atrial fibrillation and flutter ablation, supraventricular tachycardia ablation, ventricular tachycardia ablation, electrical cardioversion, pacemaker insertion, implantable cardioverter-defibrillator (ICD) insertion, and ICD lead extraction. General anesthetic considerations as well as procedure-specific concerns are discussed. Knowledge of these procedures will add to the anesthesiologist's armamentarium in safely caring for patients in the EP laboratory.


Alkylation mutagenesis in Saccharomyces cerevisiae: lack of evidence for an adaptive response.
We have found no evidence for an adaptive response for either lethality or mutagenesis following treatment of Saccharomyces cerevisiae with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The rad6 and rad52 mutants of S. cerevisiae are highly defective in MNNG and ethyl methanesulfonate induced mutagenesis of both stationary and exponential phase cells. These and other observations indicate that the mechanisms of repair of alkylation damage and mutagenesis differ markedly between S. cerevisiae and Escherichia coli.


Treatment of lateral instability of the ankle--a new modification of the Evans repair.
A modification of the Evans repair using only half of the peroneus brevis tendon was applied in the treatment of 34 patients with chronic functional lateral instability of the ankle. With a median follow-up of 25 months, 32 patients were examined. Functional stability was achieved in all but one patient. This modification of Evans' repair is recommended, as it is technically easy, gives good functional stability, and has the theoretical advantage of saving an important pronator of the foot.


Tropism in nerve regeneration in vivo. Attraction of regenerating axons by diffusible factors derived from cells in distal nerve stumps of transected peripheral nerves.
We re-examined the hypothesis of Cajal3, later refuted by Weiss and Taylor20, that cells in distal stumps of transected peripheral nerves exert an attractive (tropic) effect on regenerating axons. This question was re-assessed in vivo using surgical materials and assay procedures not available to those workers. Proximal stumps of transected rat sciatic or cat peroneal nerves were inserted into the single inlet end of a hollow, Y-shaped Silastic implant. Regenerating axons were provided with alternative targets consisting of a vacant arm vs one occupied by a sciatic nerve graft (rat), or a tibial (Tout) vs peroneal (Pout) distal nerve stump (cat). In some cases Pout was rendered metabolically compromised relative to Tout by exposing the former to dry ice and inhibitors of DNA and RNA synthesis. At 4.5 or 6 weeks postoperatively, the number of regenerating axons in each fork of the implant was assessed by morphometric analysis (total number of non-myelinated and myelinated axons greater than 1 micron in diameter at 4.5 weeks, and total number of myelinated axons at 6 weeks postoperatively), or by quantification of an axonally transported label. Rat sciatic nerve fibers exclusively regenerated toward the nerve graft, suggesting the existence of a neurotropic lure. In cats, morphometric analysis revealed a 10-(4.5 week) and 6-fold (6 week) greater number of axons growing towards untreated Tout vs treated Pout. When both distal stumps were untreated, more axons were seen in forks leading to Pout. Analysis of transported label confirmed the preferential growth of axons towards untreated Tout vs treated Pout for both motor and sensory axons. In separate experiments, Nuclepore filters (0.2 microns, pore size) were inserted between distal nerve stumps and outlet ends of Silastic implants. Preferential regeneration toward untreated stumps was observed if the distance between proximal and distal nerve stumps was equal to but not greater than 4-5 mm. These results suggest that peripheral nerve fiber regeneration in vivo can be directed by cells in distal stumps of transected nerves, and that this effect can be mediated over distances of several millimeters via diffusible factors.


Immunohistochemical detection of lymph node microinvolvement in node-negative gastric cancer.
BACKGROUND: Despite curative resection of the primary tumor with extensive dissection of lymph nodes, some patients with node-negative gastric cancer die of local relapse or metastatic disease. Microinvolvement of regional lymph nodes may play an important role in the prognosis.METHODS: To evaluate the incidence and prognostic implications of regional lymph node microinvolvement in node-negative gastric cancer, we retrospectively analyzed tissue samples from 51 patients operated on for primary gastric cancer. They had tumors that invaded beyond the muscularis propria, but without metastasis to the lymph nodes, shown by the conventional H&E staining method. The regional lymph nodes were examined immunohistochemically, using monoclonal antibodies against cytokeratin.RESULTS: Microinvolvement was found in 4.8% of lymph nodes (67/1390) and in 43.2% of the patients (22/51). The clinical outcome of the patients with microinvolvement was not significantly different from those without it. However, no patient died in the no-microinvolvement group, while three patients in the microinvolvement group died of recurrence.CONCLUSION: The incidence of microinvolvement in conventionally negative lymph nodes cannot be ignored, and detecting microinvolvement may be important for predicting recurrence of gastric cancer.


The volume-outcome relationship in laparoscopic cholecystectomy: a population-based study using propensity score matching.
The volume-outcome relationship has been validated previously for surgical procedures and cancer treatments. However, no studies have longitudinally compared the relationships between volume and outcome, and none have systematically compared laparoscopic cholecystectomy (LC) surgery outcomes in Taiwan. This study purposed to explore the relationship between volume and hospital treatment cost after LC. This cohort study retrospectively analyzed 247,751 LCs performed from 1998 to 2009. Hospitals were classified as low-, medium-, and high-volume hospitals if their annual number of LCs were 1-29, 30-84, ≥85, respectively. Surgeons were classified as low-, medium-, and high-volume surgeons if their annual number of LCs were 1-10, 11-24, ≥25, respectively. Hierarchical linear regression model and propensity score were used to assess the relationship between volume and hospital treatment cost. The mean hospital treatment cost was US $2,504.53, and the average hospital costs for high-volume hospitals/surgeons were 33/47% lower than those for low-volume hospitals and surgeons. When analyzed by propensity score, the hospital treatment cost differed significantly between high-volume hospitals/surgeons and low/medium-volume hospitals/surgeons (2,073.70 vs. 2,350.91/2,056.73 vs. 2,553.76, P < 0.001). Analysis using a hierarchical linear regression model and propensity score found an association between high-volume hospitals and surgeons and hospital treatment cost in LC patients. Moreover, the significant factors associated with hospital resource utilization for this procedure include age, gender, comorbidity, hospital type, hospital volume, and surgeon volume. Additionally, analysis of the treatment strategies adopted at high-volume hospitals or by high-volume surgeons may improve overall hospital treatment cost.


No effect of preoperative ulceration on outcomes of tibiotalocalcaneal arthrodesis.
Tibiotalocalcaneal (TTC) arthrodesis is a commonly performed operation for complex hindfoot pathology, but the effect of preoperative ulceration on TTC outcomes has been debated. This study aims to examine infection rates in patients undergoing TTC arthrodesis with internal fixation with and without concomitant hindfoot ulceration. We conducted a retrospective review of 31 patients who underwent a TTC arthrodesis between June 2016 and February 2021 with a fellowship-trained foot and ankle surgeon at an academic medical center. Nine (29.0%) patients had preoperative ulceration. Mean follow-up duration was 1.49 (range, 0.51-4.28) years. Other data collected included demographics, comorbidities, surgical approach, fixation method, and complication and reoperation rates. There was no difference in overall complication (ulcer [U]=66.7%, no ulcer [NU]=50.0%; p = .397), infection (U=33.3%, NU=31.8%; p = .935), or reoperation (U=55.6%, NU=27.3%; p = .135) rates between groups. TTC arthrodesis with internal fixation appears to be a reasonable treatment method for patients with a preoperative ulcer.


The effect of cryopreservation on canine menisci: a biochemical, morphologic, and biomechanical evaluation.
This study evaluated the effect of cryopreservation on the structural organization, biosynthetic activity, and material properties of canine menisci. The menisci were cryopreserved by incubating them in a 4% solution of dimethyl sulfoxide (DMSO) in physiologic media and freezing them to -100 degrees C using a controlled rate freezing system. The menisci were then stored for varying periods of time from zero to 12 weeks in liquid nitrogen (-196 degrees C). Following rapid thawing, changes in the histological appearance and biosynthetic activity of the menisci were evaluated as functions of storage time. In addition, the effects of the cryopreservation process on the tensile strength and modulus of the meniscal tissue were assessed. Although cryopreservation and short-term storage did not appear to affect the morphological appearance or biomechanical character of the menisci, biosynthetic activity, as determined by Na2S35SO4 incorporation, was diminished to less than 50% of normal control values immediately following cryopreservation and thawing. Autoradiographic examination of these tissues revealed that only approximately 10% of the meniscal cells were metabolically active, however, indicating that a marked increase in the metabolic activity of individual cells occurs following the freeze-thaw cycle. Total metabolic activity continued to decline with storage time.


SnapShot: Olfactory Classical Conditioning of Drosophila.
This SnapShot summarizes current knowledge about the molecules and circuitry that mediate olfactory memory formation in Drosophila, with emphasis on neural circuits carrying the learned sensory information; the molecular mechanisms for acquisition, memory storage, and forgetting; and the output pathways for memory expression. To view this SnapShot, open or download the PDF.


The new residency curriculum: professionalism, patient safety, and more.
Graduate medical education programs are facing unprecedented challenges. Public expectations for professionalism and patient safety are at an all-time high. A new graduate medical education accreditation system is under way. The author discusses ways to modify the current residency curriculum and assessment tools to include greater emphasis on professionalism and patient safety in the learning environment.


[Renal insufficiency and cardiovascular risk].
Patients with chronic renal insufficiency often show symptoms that are atypical for cardiovascular problems. The correct interpretation of the symptoms is crucial in order to correctly assess the risk of a heart-related emergency and to take preventive measures and initiate the right therapy. Biomarkers such as NT-proBNP, troponin T or hsCRP (highly sensitive CRP) are independent predictors of mortality, but do not replace instrument-based diagnostics. Patients with renal insufficiency often have stiff vessels which, due to the premature reflection of the pulse wave, can lead to left ventricular dysfunction and ultimately to heart failure.


7-T Magnetic Resonance Imaging in the Management of Brain Tumors.
This article provides an overview of the current status of ultrahigh-field 7-T magnetic resonance (MR) imaging in neuro-oncology, specifically for the management of patients with brain tumors. It includes a discussion of areas across the pretherapeutic, peritherapeutic, and posttherapeutic stages of patient care where 7-T MR imaging is currently being exploited and holds promise. This discussion includes existing technical challenges, barriers to clinical integration, as well as our impression of the future role of 7-T MR imaging as a clinical tool in neuro-oncology.


Rare central nervous system manifestation of granulomatosis with polyangiitis in a 12-year-old child: A case report.
To share a unique case of granulomatosis with polyangiitis (GPA) identified in a child with CNS involvement, specifically PRES (posterior reversible encephalopathy syndrome). Discuss this uncommon manifestation's clinical characteristics, diagnostic process, and treatment. We are currently discussing a 12-year-old female patient who presented with a chronic cough, shortness of breath, and a new-onset fever. Upon further examination, the patient was diagnosed with GPA, confirmed through positive cytoplasmic antineutrophil cytoplasmic antibodies (C-ANCA), a renal biopsy, and multiple lung cavitary lesions. During her hospitalization, the patient also experienced neurological symptoms, including a severe headache, blurred vision, loss of consciousness, and an abnormal neurological exam, which led to brain MR imaging. The imaging revealed evidence of small vessel vasculitis with confluent T2 hyper signal intensity of gray-white matter junctions in both parietooccipital and frontal lobes containing hemorrhagic components, suggesting Posterior reversible encephalopathy syndrome. This case of Wegener's granulomatosis is noteworthy due to its occurrence in a pediatric patient with CNS involvement, specifically (posterior reversible encephalopathy syndrome). This event highlights the importance of recognizing that autoimmune disorders can present infrequently in young patients. Diagnosing Wegener's granulomatosis can be challenging, particularly when the CNS is affected. However, when appropriate treatment is initiated promptly, favorable outcomes can be achieved, as evidenced by the patient's improved condition with the prednisolone, captopril, and Rituximab treatment plan. Further research is necessary to understand better the underlying pathophysiology and optimal management of CNS involvement in GPA, particularly in the pediatric population.


[Hemorrhagic skin necrosis in intravascular precipitation of cryoglobulin by lymphocytic malignant lymphoma].
A 82 year old woman developed wide spread hemorrhagic skin gangrene in the face and on the extremities as cutaneous manifestation of IgG-IgM cryoglobulinemia, in this case a concomitant phenomenon of lymphocytic malignant lymphoma.


Expression Levels of the Oxidative Stress Response Gene ALDH3A2 in Granulosa-Lutein Cells Are Related to Female Age and Infertility Diagnosis.
Oxidative stress (OS) plays an important role in all physiological processes. The effect of OS on cellular processes is modulated by the ability of the cell to express genes implicated in the reversal of lipid, protein, and DNA injury. Aldehyde dehydrogenase 3, member A2 (ALDH3A2) is a ubiquitous enzyme involved in lipid detoxification. The objective of this study was to investigate the expression ofALDH3A2in human granulosa-lutein (GL) cells of women undergoing in vitro fertilization (IVF) and its relationship with age, infertility diagnosis, and IVF outcome variables. Relative expression levels ofALDH3A2were determined by quantitative reverse transcription-polymerase chain reaction. To investigate the effect of age onALDH3A2expression, 72 women between 18 and 44 years of age with no ovarian factor (NOF) were analyzed. To evaluate the effect of infertility diagnosis onALDH3A2expression, the following groups were analyzed: 22 oocyte donors (ODs), 24 women >40 years old (yo) with tubal or male factor and no ovarian pathology, 18 poor responders (PRs), 19 cases with endometriosis (EM), and 18 patients with polycystic ovarian syndrome (PCOS). In NOF,ALDH3A2expression correlated positively with age and with the doses of follicle-stimulating hormone and luteinizing hormone administered and negatively with the number of total and mature oocytes. When different groups were analyzed,ALDH3A2expression levels were higher in patients >40 yo and in PR compared to OD. On the contrary, EM and PCOS levels were lower than expected for age. These data suggest that GL cellALDH3A2expression levels correlate with age, cause of infertility, and ovarian response to stimulation.


Immune checkpoint inhibitor nephrotoxicity: what do we know and what should we do?
Immune checkpoint inhibitors have dramatically improved cancer therapy for many patients. These humanized monoclonal antibodies against various immune checkpoints (receptors and ligands) effectively treat a number of malignancies by unleashing the immune system to destroy cancer cells. These drugs are not excreted by the kidneys or liver, have a long half-life, and undergo receptor-mediated clearance. Although these agents have greatly improved the prognosis of many cancers, immune-related end organ injury is a complication that has come to light in clinical practice. Although less common than other organ involvement, kidney lesions resulting in acute kidney injury and/or proteinuria are being described. Acute tubulointerstitial nephritis is the most common lesion seen on kidney biopsy, while acute tubular injury and glomerular lesions occur less commonly. Clinical findings and laboratory tests are suboptimal in predicting the underlying renal lesion, making kidney biopsy necessary in the majority of cases to definitely diagnose the lesion and potentially guide therapy. Immune checkpoint inhibitor discontinuation and corticosteroid therapy are recommended for acute tubulointerstitial nephritis. Based on a handful of cases, re-exposure to these drugs in patients who previously developed acute tubulointerstitial nephritis has been mixed. Although it is unclear whether re-exposure is appropriate, it should perhaps be considered in patients with limited options. When this approach is taken, patients should be closely monitored for recurrence of acute kidney injury. Treatment of cancer in patients with a kidney transplant with immune checkpoint inhibitors risks the development of acute rejection in some patients and requires close surveillance.


Solar cycles and malignant melanoma.
There has been a sixfold increase in the incidence of malignant melanoma in the State of Connecticut during the past forty years. Superimposed on a steady incidence rise are cycles of markedly increased incidence rates which follow periods of maximum sunspot activity. We propose that the effect of sunspot cycles on human melanoma occurrence is mediated by modulation of stratospheric ozone and thus indirectly affects UV flux at the earth's surface. This hypothesis would predict a time lag in melanoma incidence cycles, relative to sunspot activity, with increasing distance from polar caps. This appears to be the case. The increase in melanoma incidence related to a given reduction in ozone depletion in this hypothesis, is in great excess of existing models relating anthropogenic ozone depletion and skin cancer.


Race differences in professional help seeking.
Using data from two national surveys, findings from this research indicated that blacks were more likely than whites to seek help from mental health professionals, particularly for economic and physical health problems. Blacks also sought help more often than whites from other sources of professional help, such as teachers, lawyers, social workers and emergency rooms. On the other hand, whites were more likely to seek help from medical sources for all types of problems, and from clergy members.


Risk of autoimmune diseases following COVID-19 and the potential protective effect from vaccination: a population-based cohort study.
Case reports suggest that SARS-CoV-2 infection could lead to immune dysregulation and trigger autoimmunity while COVID-19 vaccination is effective against severe COVID-19 outcomes. We aim to examine the association between COVID-19 and development of autoimmune diseases (ADs), and the potential protective effect of COVID-19 vaccination on such an association. A retrospective cohort study was conducted in Hong Kong between 1 April 2020 and 15 November 2022. COVID-19 was confirmed by positive polymerase chain reaction or rapid antigen test. Cox proportional hazard regression with inverse probability of treatment weighting was applied to estimate the risk of incident ADs following COVID-19. COVID-19 vaccinated population was compared against COVID-19 unvaccinated population to examine the protective effect of COVID-19 vaccination on new ADs. The study included 1,028,721 COVID-19 and 3,168,467 non-COVID individuals. Compared with non-COVID controls, patients with COVID-19 presented an increased risk of developing pernicious anaemia [adjusted Hazard Ratio (aHR): 1.72; 95% Confidence Interval (CI): 1.12-2.64]; spondyloarthritis [aHR: 1.32 (95% CI: 1.03-1.69)]; rheumatoid arthritis [aHR: 1.29 (95% CI: 1.09-1.54)]; other autoimmune arthritis [aHR: 1.43 (95% CI: 1.33-1.54)]; psoriasis [aHR: 1.42 (95% CI: 1.13-1.78)]; pemphigoid [aHR: 2.39 (95% CI: 1.83-3.11)]; Graves' disease [aHR: 1.30 (95% CI: 1.10-1.54)]; anti-phospholipid antibody syndrome [aHR: 2.12 (95% CI: 1.47-3.05)]; immune mediated thrombocytopenia [aHR: 2.1 (95% CI: 1.82-2.43)]; multiple sclerosis [aHR: 2.66 (95% CI: 1.17-6.05)]; vasculitis [aHR: 1.46 (95% CI: 1.04-2.04)]. Among COVID-19 patients, completion of two doses of COVID-19 vaccine shows a decreased risk of pemphigoid, Graves' disease, anti-phospholipid antibody syndrome, immune-mediated thrombocytopenia, systemic lupus erythematosus and other autoimmune arthritis. Our findings suggested that COVID-19 is associated with an increased risk of developing various ADs and the risk could be attenuated by COVID-19 vaccination. Future studies investigating pathology and mechanisms would be valuable to interpreting our findings. Supported by RGC Collaborative Research Fund (C7154-20GF).


Lamivudine compared with lamivudine and adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B.
We aimed to evaluate nucleoside/nucleotide combination therapy in treatment-naïve HBeAg-positive patients with chronic hepatitis B (CHB). One hundred and fifteen HBeAg-positive patients received lamivudine 100 mg daily plus placebo (monotherapy) or lamivudine 100 mg plus adefovir dipoxil 10 mg daily (combination therapy) for 104 weeks in a randomized double-blind study. Time-weighted average change in serum HBV DNA from baseline up to week 16 was -4.20 log(10)copies/mL for both groups (p=0.936). At week 104, median serum HBV DNA change from baseline (log(10)copies/mL) for monotherapy and combination therapy was -3.41 versus -5.22, respectively. HBV DNA breakthrough was detected in 44% of monotherapy and 19% of combination therapy patients. The M204V/I mutation was detected in 43% (15/35) and 15% (6/41) of each group, respectively. ALT normalization at week 100 and 104 was 34% (19/56) in the monotherapy group and 45% (23/51) in the combination therapy group (p=0.018). By week 104, HBeAg seroconversion occurred in 20% of monotherapy and 13% of combination therapy patients. Both regimens were well tolerated. Lower rates of resistance to lamivudine, lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years. However, serological outcomes were similar.


Improvement of heavy metal stress and toxicity assays by coupling a transgenic reporter in a mutant nematode strain.
Previous studies have demonstrated that wild type Caenorhabditis elegans displays high sensitivity to heavy metals in a lethality test at a level comparable to that of other bioindicator organisms. Taking advantage of the genetics of this model organism, we have tested a number of mutant strains for enhanced sensitivity in heavy metal induced lethality and stress response. These mutants are defective in genes controlling dauer formation, longevity or response to reactive oxygen species (ROS). Among the tested mutants, a double mutant daf-16 unc-75 strain was identified to have superior sensitivity. It has a 6-, 3- and 2-fold increase in sensitivity to cadmium, copper and zinc, respectively, as compared with that of wild type animals. When a fluorescent reporter transgene was coupled with this double mutant for stress detection, a 10-fold enhancement of sensitivity to cadmium over the wild type strain was observed. These transgenic animals, superior to most of the model organisms currently used in bioassays for environmental pollutants, offer a fast and economic approach to reveal the bioavailability of toxic substance in field samples. This study also demonstrates that combination of genetic mutations and transgenesis is a viable approach to identify sensitive indicator animals for environmental monitoring.


Survival and functional results after a mean follow-up of 9 years with the Ceragyr® highly congruent mobile-bearing TKA.
Fixed-bearing total knee arthroplasty (TKA) implants have excellent long-term survival. Mobile-bearing implants were developed to reduce bone-implant interface stresses and polyethylene insert wear. The primary objective of this study was to analyze the survival rate of a highly congruent mobile-bearing TKA implant (Ceragyr(®)) in patients having a minimum follow-up of 7 years. We hypothesized that the survival rate would be 95-100% at that time point. A single-center prospective study included all the patients operated for a primary TKA procedure with a Ceragyr(®) implant between 2000 and 2003. All the implants were cemented. Patellar resurfacing was not carried out systematically, but could be carried out secondarily in cases of persistent anterior knee pain. Clinical and radiological data were collected before the surgery, at 3 months postoperative, at 1 year and then at a minimum follow-up of 7 years. The primary endpoint was the overall revision-free survival rate. Secondary endpoints were the survival without mechanical failure, IKS scores, knee range of motion and implant positioning. One hundred and thirty-four patients (143 Ceragyr(®) TKA cases) were included; 9 patients (10 TKA) were lost to follow-up (6.7%) and the remaining 125 patients (133 TKA) were contacted. At the final review, 7 of the 133 TKA cases (5.3%) had been revised (6 men, 1 women; P = 0.002), 2 (1.5%) because of mechanical failure and 5 (3.8%) because of an infection. The overall revision-free survival rate was 94.8% [95% CI: 89.3-97.5]; survival was 98.4% [95% CI: 93.8-99.6] with mechanical failure as an endpoint. An in-person assessment was conducted on 76 patients (80 TKA cases) (49 women; 27 men) who had an average age of 70.3 ± 8.4 years at the time of the arthroplasty procedure. The patella had been resurfaced during the initial procedure in 49 cases, and was either not resurfaced or secondarily resurfaced in 31 cases. The average follow-up was 8.7 ± 1.1 years. The IKS score had significantly improved relative to the preoperative values (P < 0.00001). Knee flexion and the IKS knee score remained stable over time (P > 0.05). Patients who underwent patella resurfacing during the initial TKA procedure had better clinical results (P = 0.03). After a minimum follow-up of 7years, the overall revision-free survival rate for the Ceragyr(®) was 94.8%; the survival was 98.4% with mechanical failure as an endpoint. The results were stable over time.


Excretion of urinary Tamm-Horsfall glycoprotein in girls with recurrent urinary tract infections.
Tamm-Horsfall glycoprotein (THG) might constitute a bacteria-fixing mucus which contributes to the non-immunological anti-infectious mechanisms of the lower urinary tract. To evaluate the role of THG in girls with idiopathic recurrent lower urinary tract infections, the THG excretion and concentration in 24-h urine were measured by a radial immunodiffusion method in 16 patients with a median age of 9 years and in 14 healthy age-matched girls. The results showed no significant differences in the THG excretion or concentration between the patients and the controls. Transiently decreased THG excretion rates as well as functional changes in the ability and/or capacity to trap bacteria, however, may leave girls periodically prone to colonization of the bladder. Thus, further studies are warranted to evaluate the importance of THG in the bladder defence mechanism.


Pathogen inactivation of red cell concentrates using Inactine chemistry.
The INACTINE process is a promising approach for improving the pathogen safety of red cell concentrates. Clinical trials are ongoing to characterize the viability of the pathogen inactivated red cells in humans. The presentation will update the audience on the preclinical and clinical trials conducted to date.


Morphological and electrophysiological studies of human hippocampal transplants in the anterior eye chamber of athymic nude rats.
Human fetal hippocampal tissue from normal women was obtained following elective abortion in the 8th to the 11th week of gestation. The hippocampal tissue was transplanted to the anterior chamber of the eye of adult athymic nude rats, where it was allowed to develop for up to 9 months before histological and electrophysiological evaluation. The transplants were revascularized from the host iris and many grew extensively in oculo. Large neurons were present in all transplants. Immunohistochemical studies revealed glutamic acid decarboxylase-containing terminals and clusters of gamma-aminobutyric acid-positive nerve cell bodies within the transplants, as well as scattered tyrosine hydroxylase-positive and acetylcholinesterase-containing fibers. Single neurons recorded extracellularly from transplants 4-9 months in oculo showed a slow spontaneous discharge, with both complex and single action potentials. Stimulation of the transplant surface evoked a small initial wave followed by a larger and longer-lasting field potential, similar to that seen in hippocampus in situ. A conditioning-testing paradigm was used to evaluate the presence of inhibitory circuitry in the hippocampal transplants. Significant suppression of the evoked test response was seen with interstimulus intervals ranging from 20 to 500 ms. Superfusion of enkephalin (100-300 nM) or penicillin (1600 U/ml) increased slow-wave activity, as did tetanic electrical stimulation. These treatments appeared to generate ictal-like activity, which in some cases persisted as interictal spikes. Illumination of the retina also increased neuronal activity, presumably by reflex activation of cholinergic afferents from the parasympathetic innervation of the iris. Taken together, our data suggest that fragments of hippocampus from aborted first trimester human fetuses, grafted to the eye chamber of rodent hosts, develop many organotypic histological and physiological features. This preparation may provide a unique means for the study of neurobiological properties of human brain in both normal and disease states.


The production of reactive oxygen species in tacrolimus-treated glial cells.
After organ transplantation, some patients suffer from mild neurological symptoms, such as tremor, to severe complications, including seizures and encephalopathy. These neurological side effects can be caused by immunosuppressants such as tacrolimus. However, the mechanism of encephalopathy by tacrolimus is not fully understood. We measured the production of reactive oxygen species (ROS) in glioma cells after tacrolimus treatment. Tacrolimus added to glioma cells was incubated for 60 minutes at 37 degrees C. The production of ROS was evaluated by measuring the fluorescent product from the oxidation of an oxidant-sensitive 2',7'-dichlorofluorescin using VICTOR3TM multilabel counter. Tacrolimus resulted in the production of the ROS in glioma cells. The production of the ROS was increased in time-dependent fashion. These findings indicated that the tacrolimus may contribute the neurological side effects by ROS production.


Towards a structural understanding of the fibrillization pathway in Machado-Joseph's disease: trapping early oligomers of non-expanded ataxin-3.
Machado-Joseph's disease is caused by a CAG trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract in the protein ataxin-3. Except for the polyglutamine region, proteins associated with polyglutamine diseases are unrelated, and for all of these diseases aggregates containing these proteins are the major components of the nuclear proteinaceous deposits found in the brain. Aggregates of the expanded proteins display amyloid-like morphological and biophysical properties. Human ataxin-3 containing a non-pathological number of glutamine residues (14Q), as well as its Caenorhabditis elegans (1Q) orthologue, showed a high tendency towards self-interaction and aggregation, under near-physiological conditions. In order to understand the discrete steps in the assembly process leading to ataxin-3 oligomerization, we have separated chromatographically high molecular mass oligomers as well as medium mass multimers of non-expanded ataxin-3. We show that: (a) oligomerization occurs independently of the poly(Q)-repeat and it is accompanied by an increase in beta-structure; and (b) the first intermediate in the oligomerization pathway is a Josephin domain-mediated dimer of ataxin-3. Furthermore, non-expanded ataxin-3 oligomers are recognized by a specific antibody that targets a conformational epitope present in soluble cytotoxic species found in the fibrillization pathway of expanded polyglutamine proteins and other amyloid-forming proteins. Imaging of the oligomeric forms of the non-pathological protein using electron microscopy reveals globular particles, as well as short chains of such particles that likely mimic the initial stages in the fibrillogenesis pathway occurring in the polyglutamine-expanded protein. Thus, they constitute potential targets for therapeutic approaches in Machado-Joseph's disease, as well as valuable diagnostic markers in disease settings.


Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti-inflammatory FMS inhibitors.
A series of pyrimidinopyridones has been designed, synthesized and shown to be potent and selective inhibitors of the FMS tyrosine kinase. Introduction of an amide substituent at the 6-position of the pyridone core resulted in a significant potency increase. Compound 24 effectively inhibited in vivo LPS-induced TNF in mice greater than 80%.


Gastric emptying rates of solid food in relation to body size.
The relationship of body size to rates of gastric emptying of solid food was investigated in order to obtain data that may allow this variable to be considered when populations of varying size are studied. Rates of gastric emptying were measured using a beef stew meal to which were added pieces of chicken liver tagged with [99mTc]sulfur colloid, and following the passage of the isotope through the gastrointestinal tract with intermittent gamma-imaging. Results showed an inverse linear relationship between gastric emptying rates and body surface area, and between gastric emptying rates and body weight. The variable of body size must be taken into account when measurements of gastric emptying of solid food are measured.


Development and spike timing-dependent plasticity of recurrent excitation in the Xenopus optic tectum.
Much of the information processing in the brain occurs at the level of local circuits; however, the mechanisms underlying their initial development are poorly understood. We sought to examine the early development and plasticity of local excitatory circuits in the optic tectum of Xenopus laevis tadpoles. We found that retinal input recruits persistent, recurrent intratectal synaptic excitation that becomes more temporally compact and less variable over development, thus increasing the temporal coherence and precision of tectal cell spiking. We also saw that patterned retinal input can sculpt recurrent activity according to a spike timing-dependent plasticity rule, and that impairing this plasticity during development results in abnormal refinement of the temporal characteristics of recurrent circuits. This plasticity is a previously unknown mechanism by which patterned retinal activity allows intratectal circuitry to self-organize, optimizing the temporal response properties of the tectal network, and provides a substrate for rapid modulation of tectal neuron receptive-field properties.


High-performance cholesterol sensor based on the solution-gated field effect transistor fabricated with ZnO nanorods.
A high-performance cholesterol sensor based on solution-gated field-effect-transistor (FET) was fabricated by using the vertically aligned ZnO nanorods (ZnO NRs) grown selectively on pre-patterned substrate in solution. The structural characterization showed that the as-grown ZnO NRs are vertically aligned, high purity single crystalline. The active layer of ZnO NRs between source and drain electrodes was immobilized with cholesterol oxidase (ChOx) enzyme. The performance of the fabricated FET sensor has been examined with the cholesterol solutions with and without electroactive species, the human serum (H4522), and the freshly drawn blood sample. The FET sensor provided a real-time response towards a wide range of cholesterol concentration (0.001-45 mM) with high sensitivity (10 μA cm(-2) mM(-1)) and selectivity.


Stabilization effect of resin on the production of potent proteasome inhibitor NPI-0052 during submerged fermentation of Salinispora tropica.
Addition of acrylic resin Amberlite XAD-7 during the fermentation of Salinispora tropica significantly enhanced the production of NPI-0052 by 69 fold. Examination of the time course of resin addition to the Salinispora tropica fermentation demonstrated that the increase in the production of NPI-052 is due to the stabilization effect by resin but not the removal of an end product feedback repression. Delay in resin addition to the fermentation led to decreases in the production of NPI-0052 to the amounts that are synthesized prior to the resin addition.


L-Tryptophan's effects on brain chemistry and sleep in cats and rats: a review.
In this review I shall discuss published and unpublished work from my laboratory dealing with L-tryptophan's effects on brain monoamines and sleep in cats and rats. From our work it appears that normal animals may not be suitable subjects for testing sleep-inducing effect of tryptophan since their slow-wave sleep (SWS) latency is relatively short. In polyphasic sleepers like cats, we did not observe tryptophan's hypnotic effect with any dosage used (10, 30 or 135 mg/kg). However, we found small, but statistically significant, sleep-inducing effect of tryptophan (30 mg/kg, IP) in normal rats. We have tried, therefore, to create insomniac cats with long sleep latencies by using methysergide, a serotonin receptor blocker. The results show that in insomniac cats hypnotic effect of tryptophan, a precursor to brain serotonin, was observed. It involved not only reduction of sleep latencies but also an increase in SWS. It seems likely that tryptophan's partial reversal of methysergide's effect in cats occurred via a dual mechanism of serotonergic activation and catecholaminergic deactivation, while its sleep-inducing effect in normal rats may have been due to the attenuation of the activity of brain catecholamines.


Ciglitazone, a hypoglycemic agent: early effects on the pancreatic islets of ob/ob mice.
Chronic administration of ciglitazone (5-4[1-methyl-cyclohexylmethoxy)-benzyl]-thiazolidine-2,4 dione) decreased both plasma glucose and insulin concentrations in ob/ob mice. When given as an admixture to the feed, blood glucose levels were reduced as early as 12 hours after initiation of treatment. Concomitant with the decrease in circulating insulin, there was an increased hormone content in the beta-cells as judged by RIA and aldehyde-fuchsin staining. Acute oral dosing with ciglitazone produced a 41% reduction in circulating insulin at a time when glucose concentrations were as yet unaffected. Ciglitazone also inhibited glucose-stimulated insulin secretion in vitro. The results suggest that the hypoglycemic agent, ciglitazone, may reduce plasma glucose and insulin concentrations at least partially as the result of independent mechanisms.


The discursive context of medical aid in dying: A paradox of control?
Individual agency is central to late modern and neoliberal concepts of the self and notions of a good death. Assisted dying can be understood as a reflection of these ideas in that control over death resides with the individual. The aim of this article is to explore individual agency and control and employ concepts of biopower and freedom to illustrate the paradoxes inherent within assisted dying. Assisted dying is currently of wide interest due to legislative change. At the time of research, the New Zealand Parliament was passing the End of Life Choice Act, yet there had been no research with people approaching the end of life about assisted dying. Through the media we recruited and interviewed 14 people approaching the end of life who would have considered choosing assisted dying if it were available to them. Interviews were analyzed using an immersion/crystallization thematic analysis. Assisted dying appealed to participants because it offered control. This article examines the discursive context of control as well as the participants' perception of control to offer insights into how paradoxically, a medical regime of assisted dying reinforces health professionals as in control of the circumstances of dying. We argue that although legalized medical assisted dying is highly regulated and monitored, thus limiting freedom, the option of assisted dying also increases freedom for the dying person. Within this paradox of control, there is still scope for choice and an ethical making of the self, although limited by the biopolitical regime, that equates to a degree of freedom for participants.


Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma.
Lung cancer is the number one cancer killer of both men and women in the United States. Three quarters of lung cancer patients are diagnosed with regionally or distantly disseminated disease; their 5-year survival is only 15%. DNA hypermethylation at promoter CpG islands shows great promise as a cancer-specific marker that would complement visual lung cancer screening tools such as spiral CT, improving early detection. In lung cancer patients, such hypermethylation is detectable in a variety of samples ranging from tumor material to blood and sputum. To date the penetrance of DNA methylation at any single locus has been too low to provide great clinical sensitivity. We used the real-time PCR-based method MethyLight to examine DNA methylation quantitatively at twenty-eight loci in 51 primary human lung adenocarcinomas, 38 adjacent non-tumor lung samples, and 11 lung samples from non-lung cancer patients. We identified thirteen loci showing significant differential DNA methylation levels between tumor and non-tumor lung; eight of these show highly significant hypermethylation in adenocarcinoma: CDH13, CDKN2A EX2, CDX2, HOXA1, OPCML, RASSF1, SFPR1, and TWIST1 (p-value << 0.0001). Using the current tissue collection and 5-fold cross validation, the four most significant loci (CDKN2A EX2, CDX2, HOXA1 and OPCML) individually distinguish lung adenocarcinoma from non-cancer lung with a sensitivity of 67-86% and specificity of 74-82%. DNA methylation of these loci did not differ significantly based on gender, race, age or tumor stage, indicating their wide applicability as potential lung adenocarcinoma markers. We applied random forests to determine a good classifier based on a subset of our loci and determined that combined use of the same four top markers allows identification of lung cancer tissue from non-lung cancer tissue with 94% sensitivity and 90% specificity. The identification of eight CpG island loci showing highly significant hypermethylation in lung adenocarcinoma provides strong candidates for evaluation in patient remote media such as plasma and sputum. The four most highly ranked loci, CDKN2A EX2, CDX2, HOXA1 and OPCML, which show significant DNA methylation even in stage IA tumor samples, merit further investigation as some of the most promising lung adenocarcinoma markers identified to date.


Factors influencing the growth in knowledge of trainees in general practice.
The relation between the content of postgraduate training for general practice and the outcome in terms of the growth in knowledge of trainees was investigated. The training variables included were: (1) the number of patients seen per day, (2) the trainer, (3) the practice and (4) the theoretical curriculum. Subjects were 58 trainee-trainer pairs. Growth in knowledge was assessed by two written tests administered with eight months interval. Training variables were evaluated by means of questionnaires and logbook-registration. The correlation was explored between each of the training variables and the knowledge tests scores. To correct for interactional effects, a step-wise multiple regression analysis was performed with the second test as dependent variable and the first test as well as the training variables as independent variables. Significant growth in knowledge was demonstrated. Non of all training variables investigated explained the variance in scores on the second test equally good or better than the scores on the entry test. The impact of the separate training-components on the growth in knowledge, remains unclear. We may speculate, that the sort of knowledge assessed with the written literature based true/false test is different from the sort of knowledge transferred during every day training: evidence based knowledge versus experience based knowledge. Equally valid is the conclusion that these findings fit into the theory that in adult learning the outcome is more learner than teacher dependent.


Homozygous mutation in murine retrovirus integration site 1 gene associated with a non-syndromic form of isolated familial achalasia.
Achalasia is a condition characterized by impaired function of esophageal motility and incomplete relaxation of the lower esophagus sphincter, causing dysphagia and regurgitation. Rare cases of early-onset achalasia appear often in combination with further symptoms in a syndromic form as an inherited disease. Whole genome sequencing was used to investigate the genetic basis of isolated achalasia in a family of Tunisian origin. We analyzed the function of the affected protein with immunofluorescence and affinity chromatography study. A homozygous nonsense mutation was detected in murine retrovirus integration site 1 (MRVI1) gene (Human Genome Organisation Gene Nomenclature Committee (HGNC) approved gene symbol: IRAG1) encoding the inositol 1,4,5-trisphosphate receptor 1 (IP3 R1)-associated cyclic guanosine monophosphate (cGMP) kinase substrate (IRAG). Sanger sequencing confirmed co-segregation of the mutation with the disease. Sequencing of the entire MRVI1 gene in 35 additional patients with a syndromic form of achalasia did not uncover further cases with MRVI1 mutations. Immunofluorescence analysis of transfected COS7 cells revealed GFP-IRAG with the truncating mutation p.Arg112* (transcript variant 1) or p.Arg121* (transcript variant 2) to be mislocalized in the cytoplasm and the nucleus. Co-transfection with cGMP-dependent protein kinase 1 isoform β (cGK1β) depicted a partial mislocalization of cGK1β due to mislocalized truncated IRAG. Isolation of protein complexes revealed that the truncation of this protein causes the loss of the interaction domain of IRAG with cGK1β. In individuals with an early onset of achalasia without further accompanying symptoms, MRVI1 mutations should be considered as the disease-causing defect.


Carcinoid tumors of the appendix. Mesoappendiceal extension and nodal metastases.
Carcinoid of the appendix occurred in 92 of 400,000 surgical pathology specimens covering 70 years, and followed previously reported incidences by age, sex, symptoms, size, localization and histology. Invasion of the mesoappendix occurred in 13 cases, and in two of these, a reoperative ileocolectomy demonstrated regional node metastases. No distant metastases or fatalities appeared. Tumor size correlated with mesoappendiceal invasion. Carcinoid invasion of the mesoappendix may provide a valuable marker for more distant tumor spread, and justify an aggressive surgical approach in selected patients.


Unusual location and function of the operator in the Escherichia coli galactose operon.
The operator of the gal operon is located about 60 base pairs preceding the startpoints of the transcription of the two gal promoters. This location contrasts with the location of the operator in other phage or bacterial operons where the repressor binds more closely to the respective transcription initiation sites. Models explaining how the repressor-operator interactions may control the two gal promoters are presented.


[Crusted scabies: A review].
Crusted scabies is a rare and severe form of infestation by Sarcoptes scabies var. hominis. It is characterized by profuse hyperkeratosis containing over 4000 mites per gram of skin, with treatment being long and difficult. The condition is both direct and indirectly contagious. It has a central role in epidemic cycles of scabies, the incidence of which is on the rise in economically stable countries. Recent discoveries concerning the biology of mites, the pathophysiology of hyperkeratosis and the key role of IL-17 in this severe form open up new therapeutic perspectives.


Erratum: Exploratory Graph Analysis of the Strengths and Difficulties Questionnaire for Aboriginal and/or Torres Strait Islander Children.
[This corrects the article DOI: 10.3389/fpsyg.2021.573825.].


Derivation and characterization of alveolar epithelial cells from murine embryonic stem cells in vitro.
We present a protocol that has been developed for induction of the differentiation of murine embryonic stem (ES) cells to alveolar type II cells. With this protocol, undifferentiated murine ES cells are induced to form embryoid bodies (EBs). The 10-d-old EBs are transferred to adherent culture conditions and are fed with high-glucose Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% v/v fetal bovine serum, 2 mM L-glutamine, and 0.1 mM 2-mercaptoethanol for 20 d without splitting. Then, the cells are fed with a medium designed for the maintenance and growth of mature distal airway epithelial cells (small airway growth medium, SAGM) for 3 d. Characterization of the alveolar type II cells was done using real-time reverse transcriptase polymerase chain reaction detection of surfactant protein C mRNA and immunocytochemical detection of prosurfactant protein C. Real-time reverse transcriptase polymerase chain reaction revealed that SAGM increases the mRNA expression level of SPC by a factor of 8 when compared to that of cells grown in supplemented high-glucose DMEM (p < 0.05, Student t-test). Immunocytochemistry revealed that proSPC-expressing cells comprised 2.8 +/- 0.23% of the total cell population in SAGM-treated samples and 0.5 +/- 0.1% in samples treated with supplemented high-glucose DMEM (p < 0.05, chi2 test).


TILE-12 index: an interpretable instrument for identifying older adults at risk for transitions in living environment within the next 12-months.
Few evidence-based tools exist to support identification of older community dwelling adults at risk for unwanted transitions in living environment leading to missed opportunities to modify care plans to support aging-in-place and/or establish end-of-life care goals. An interpretable and actionable tool for assessing a person's risk of experiencing a transition is introduced. Logistic regression analysis of 14,772 transition opportunities (i.e. 12-month periods) for 4,431 respondents to the National Health and Aging Trends Study (NHATS) rounds 1-7. Results were visualized in a nomogram. Unmarried males of increasing age with chronic disease, greater functional dependence, overnight hospitalizations, not living in a single-family home, and limited social network, have elevated risk of experiencing a transition in living environment in a 12-month period. Homecare nurses are uniquely qualified to identify social determinants of health and can use this evidence-based tool to identify individuals who may benefit from transitional care assistance.


FIRRM/C1orf112 is synthetic lethal with PICH and mediates RAD51 dynamics.
Joint DNA molecules are natural byproducts of DNA replication and repair. Persistent joint molecules give rise to ultrafine DNA bridges (UFBs) in mitosis, compromising sister chromatid separation. The DNA translocase PICH (ERCC6L) has a central role in UFB resolution. A genome-wide loss-of-function screen is performed to identify the genetic context of PICH dependency. In addition to genes involved in DNA condensation, centromere stability, and DNA-damage repair, we identify FIGNL1-interacting regulator of recombination and mitosis (FIRRM), formerly known as C1orf112. We find that FIRRM interacts with and stabilizes the AAA+ ATPase FIGNL1. Inactivation of either FIRRM or FIGNL1 results in UFB formation, prolonged accumulation of RAD51 at nuclear foci, and impaired replication fork dynamics and consequently impairs genome maintenance. Combined, our data suggest that inactivation of FIRRM and FIGNL1 dysregulates RAD51 dynamics at replication forks, resulting in persistent DNA lesions and a dependency on PICH to preserve cell viability.


Artificial intelligence deep learning model assessment of leukocyte counts and proliferation in endometrium from women with and without polycystic ovary syndrome.
To study whether artificial intelligence (AI) technology can be used to discern quantitative differences in endometrial immune cells between cycle phases and between samples from women with polycystic ovary syndrome (PCOS) and non-PCOS controls. Only a few studies have analyzed endometrial histology using AI technology, and especially, studies of the PCOS endometrium are lacking, partly because of the technically challenging analysis and unavailability of well-phenotyped samples. Novel AI technologies can overcome this problem. Case-control study. University hospital-based research laboratory. Forty-eight women with PCOS and 43 controls. Proliferative phase samples (26 control and 23 PCOS) and luteinizing hormone (LH) surge timed LH+ 7-9 (10 control and 16 PCOS) and LH+ 10-12 (7 control and 9 PCOS) secretory endometrial samples were collected during 2014-2019. None. Endometrial samples were stained with antibodies for CD8+ T cells, CD56+ uterine natural killer cells, CD68+ macrophages, and proliferation marker Ki67. Scanned whole slide images were analyzed with an AI deep learning model. Cycle phase differences in leukocyte counts, proliferation rate, and endometrial thickness were measured within the study populations and between the PCOS and control samples. A subanalysis of anovulatory PCOS samples (n = 11) vs. proliferative phase controls (n = 18) was also performed. Automated cell counting with a deep learning model performs well for the human endometrium. The leukocyte numbers and proliferation in the endometrium fluctuate with the menstrual cycle. Differences in leukocyte counts were not observed between the whole PCOS population and controls. However, anovulatory women with PCOS presented with a higher number of CD68+ cells in the epithelium (controls vs. PCOS, median [interquartile range], 0.92 [0.75-1.51] vs. 1.97 [1.12-2.68]) and fewer leukocytes in the stroma (CD8%, 3.72 [2.18-4.20] vs. 1.44 [0.77-3.03]; CD56%, 6.36 [4.43-7.43] vs. 2.07 [0.65-4.99]; CD68%, 4.57 [3.92-5.70] vs. 3.07 [1.73-4.59], respectively) compared with the controls. The endometrial thickness and proliferation rate were comparable between the PCOS and control groups in all cycle phases. Artificial intelligence technology provides a powerful tool for endometrial research because it is objective and can efficiently analyze endometrial compartments separately. Ovulatory endometrium from women with PCOS did not differ remarkably from the controls, which may indicate that gaining ovulatory cycles normalizes the PCOS endometrium and enables normalization of leukocyte environment before implantation. Deviant endometrial leukocyte populations observed in anovulatory women with PCOS could be interrelated with the altered endometrial function observed in these women.


Serologic diagnosis of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis through the detection of immunoglobulin G to Aspergillus fumigatus.
Allergic bronchopulmonary aspergillosis (ABPA) is seen in approximately 10% of patients with cystic fibrosis (CF) and can be difficult to diagnose. Consensus criteria require the presence of multiple elevated immunologic markers such as total immunoglobulin E (IgE), Aspergillus IgE and Aspergillus IgG, or precipitins for a robust diagnosis. There is some degree of standardization of total IgE and Aspergillus IgE levels, but there is no standardization in the measurement of IgG antibodies or precipitins to Aspergillus. The interpretation of results may, therefore, be confusing. Eighty-seven patients with CF were categorized as having ABPA or as controls, using the consensus criteria and an in-house enzyme immunoassay to measure IgG levels to Aspergillus. All sera from patients were then analyzed by commercial fluorescent immunoassay (FEIA) for the quantitative detection of anti-Aspergillus IgG. FEIA results were analyzed against the consensus conference minimum diagnostic criteria to ascertain a cutoff point, which could predict a diagnosis of ABPA in CF. Eighty patients with CF and with no or incomplete evidence of ABPA had a mean FEIA score of 51.1 mg/L, whereas 7 CF patients with ABPA had a mean FEIA score of 132.5 mg/L. Using receiver operator characteristic curve analysis of the ImmunoCAP (Phadia) IgG score on ABPA versus all other patients gave an area under the curve of 0.933 (estimated SE, 0.027). This analysis provisionally suggested that a score of 90 mg/L may be used as a cutoff point, which would give a sensitivity of 91% and specificity of 88.0% for the diagnosis of ABPA, though this requires further validation. This quantitative approach to Aspergillus IgG measurement in patients with CF along with the results of other tests will hopefully provide a more accurate approach to the diagnosis of ABPA.


[Neovascular glaucoma treatment in 2012: role of anti-VEGF agents].
Neovascular glaucoma is a serious pathology with a variety of causes. It results from the secretion by hypoxic retinal tissue of growth factors, including vascular endothelial growth factor (VEGF). Anterior segment involvement begins in the iris, followed by the development of a fibrovascular membrane in the angle, with resultant goniosynechiae. Treatment of the underlying disease consists most often of panretinal photocoagulation. As for the secondary sequelae, current treatment consists of intravitreal injection of anti-VEGF agents. The most utilized agent is bevacizumab or Avastin, off-label. Avastin is effective against neovascularization and ocular hypertension, especially in the early stages. It also represents an adjunct to filtering surgery. It appears to be very well tolerated.


Clinical considerations during spontaneous coronary artery dissection in the post-partum period: a case report.
Spontaneous coronary artery dissection (SCAD) is a common and under-recognized cause of myocardial infarction during the post-partum period. We report a case of a young women presenting with chest pain in the post-partum period. Her clinical appearance was that of a myocardial infarction, and angiography was indicative of a Type 2 SCAD. The patients had persistent chest pain, reduced left ventricular function, and critical left anterior descending artery stenosis. Percutaneous coronary intervention was done with caution. Shared decision-making with the patient helped guide the medical treatment plan and follow-up. We discuss the clinical considerations surrounding the management of this patient.


Menstrual disorders in patients undergoing chronic hemodialysis.
To investigate the etiology of menstrual disorders in patients undergoing chronic hemodialysis (CHD). The menstrual histories, along with hormonal, biochemical, and hematological data, were investigated in 25 reproductive-aged CHD patients. All subjects had had regular menstrual cycles before entering CHD therapy. Of the 20 women who developed amenorrhea after beginning CHD therapy, 8 showed a return to their regular cycles and 6 improved to oligomenorrhea, 3 months to 66 months later, while 6 remained amenorrheic. The serum prolactin (PRL) levels were significantly higher in the patients (n = 9) with normogonadotropic amenorrhea or oligomenorrhea than in patients (n = 13) with regular cycles (53.6 +/- 36.2 vs 27.8 + 15.2 ng/ml, p < 0.05). The serum LH levels were high in both groups. In a cross-sectional study, the serum PRL levels gradually decreased with longer duration of dialysis. Patients undergoing CHD are likely to develop menstrual disorders. Hyperprolactinemia in part contributes to these menstrual disorders. However, menstrual disorders in CHD patients tend to improve during long-term follow-up, because of the gradual decrease in serum PRL levels during long-term CHD therapy.


Prognostic efficacy of the RTN1 gene in patients with diffuse large B-cell lymphoma.
Gene expression profiling has been vastly used to extract the genes that can predict the clinical outcome in patients with diverse cancers, including diffuse large B-cell lymphoma (DLBCL). With the aid of bioinformatics and computational analysis on gene expression data, various prognostic gene signatures for DLBCL have been recently developed. The major drawback of the previous signatures is their inability to correctly predict survival in external data sets. In other words, they are not reproducible in other datasets. Hence, in this study, we sought to determine the gene(s) that can reproducibly and robustly predict survival in patients with DLBCL. Gene expression data were extracted from 7 datasets containing 1636 patients (GSE10846 [n = 420], GSE31312 [n = 470], GSE11318 [n = 203], GSE32918 [n = 172], GSE4475 [n = 123], GSE69051 [n = 157], and GSE34171 [n = 91]). Genes significantly associated with overall survival were detected using the univariate Cox proportional hazards analysis with a P value < 0.001 and a false discovery rate (FDR) < 5%. Thereafter, significant genes common between all the datasets were extracted. Additionally, chromosomal aberrations in the corresponding region of the final common gene(s) were evaluated as copy number alterations using the single nucleotide polymorphism (SNP) data of 570 patients with DLBCL (GSE58718 [n = 242], GSE57277 [n = 148], and GSE34171 [n = 180]). Our results indicated that reticulon family gene 1 (RTN1) was the only gene that met our rigorous pipeline criteria and associated with a favorable clinical outcome in all the datasets (P < 0.001, FDR < 5%). In the multivariate Cox proportional hazards analysis, this gene remained independent of the routine international prognostic index components (i.e., age, stage, lactate dehydrogenase level, Eastern Cooperative Oncology Group [ECOG] performance status, and number of extranodal sites) (P < 0.0001). Furthermore, no significant chromosomal aberration was found in the RTN1 genomic region (14q23.1: Start 59,595,976/End 59,870,966).


Long-term visual damage after acute methanol poisonings: Longitudinal cross-sectional study in 50 patients.
Visual disturbances due to the toxic effect of formic acid in acute methanol poisonings are generally transient. The subjective symptoms of visual toxicity may resolve within few weeks and fundoscopic signs of acute optic neuropathy subside within 1-2 months; therefore, the prevalence of long-term visual sequelae in the population of survivors of poisonings may be underestimated. To study the prevalence and character of long-term visual sequelae of acute methanol poisonings based on the data from the Czech mass methanol outbreak in 2012. A total of 50 patients with confirmed methanol poisoning were included in this longitudinal cross-sectional study, median age: 48 (range, 23-73) years. The following tests were performed: optical coherence tomography or OCT with evaluation of the retinal nerve fibers layer (RNFL), visual evoked potentials (VEP), magnetic resonance imaging (MRI) of brain, complete ocular examination (visual acuity/field, color vision, contrast sensitivity, and fundus), neurological examinations, and biochemical tests. Of 50 patients, 7/50 (14%) were discharged with diagnosed visual sequelae and 6/50 (12%) were discharged with both visual and central nervous system sequelae of poisoning. On the follow-up examination, 20/50 (40%) of the patients had long-term visual sequelae, with 8% of blindness. A total of 38% of the patients had abnormal (28% borderline) findings on RNFL, and 40% had abnormal (18% borderline) VEP. Among the patients discharged without detected visual sequelae, 8/37 (22%) had abnormal RNFL and VEP. Patients with visual sequelae had brain lesions more often (70% vs. 27%, p < 0.01). MRI identified optic nerve lesions in 2/20 cases with abnormal VEP only. The groups with and without visual sequelae differed in serum methanol, ethanol, HCO3-, formate, pH, anion gap, and base deficit (all p < 0.01). Visual disturbances on admission and coma were more prevalent in the patients with visual sequelae (p < 0.05). Patients with positive serum ethanol on admission were 93% less likely to have optical axonal damage (OR: 0.07 (95% CI: 0.01-0.8); p < 0.05). No association was found between visual sequelae and type of antidote administered, mode of hemodialysis, or folate substitution. Pre-hospital administration of ethanol seemed beneficial: these patients were 90% less likely to have abnormal RNFL findings (OR: 0.10 (95% CI: 0.02-0.52); p < 0.01). The long-term visual sequelae were clearly underestimated on discharge, suggesting a significantly higher amount of patients with long-term sequelae than earlier reported. Thorough examinations before discharge and during follow-up will likely uncover a higher morbidity also after methanol poisonings in general.


Spinal cord mediation of the opioid analgesia of pregnancy.
It has been demonstrated that during pregnancy and labor in rats and humans there is an opioid-mediated elevation in the threshold for responsiveness to aversive stimuli which reaches a maximum at term. Acute administration of the opiate antagonist, naltrexone, into the lumbar intrathecal (i.t.) space of pregnant rats (day 20 of gestation) significantly reduces the threshold for reflexive jumping in response to electric footshock. The i.t. administration of the inactive stereoisomer of a closely related narcotic antagonist, (+)-naloxone, is devoid of any effect on pain threshold. No effect on the pain threshold is observed following intrathecal saline administration to pregnant rats, i.t. naltrexone administration to non-pregnant rats or following systemic administration of an intrathecally effective dose of naltrexone to pregnant rats. These data indicate that the analgesia observed during gestation is mediated, at least in part, via a spinal opioid pathway which is activated by some aspect of the pregnant condition.


Cisplatin neuropathy: clinical course and neurophysiological findings.
Sixteen patients treated with cisplatin (CDDP) 40 mg/m2 on days 1-5 every 4 weeks for three courses (cumulative dose 600 mg/m2) were clinically and neurophysiologically tested before, during and 1, 3, 6, 9 and 12 months after CDDP administration. The first symptoms of polyneuropathy occurred in 4 of 9 patients after the second course (cumulative dose 400 mg/m2). One month after treatment 1 of 9 patients was asymptomatic, 5 complained of symptoms and 3 showed clinical and neurophysiological signs of polyneuropathy. Three months after CDDP all patients were affected. Clinical and neurophysiological signs of severity progression were noted up to 6 months after treatment with CDDP.


Ferredoxin requirement for electron transport from the carbon monoxide dehydrogenase complex to a membrane-bound hydrogenase in acetate-grown Methanosarcina thermophila.
Cell extracts from acetate-grown Methanosarcina thermophila contained CO-oxidizing:H2-evolving activity 16-fold greater than extracts from methanol-grown cells. Following fractionation of cell extracts into soluble and membrane components, CO-dependent H2 evolution and CO-dependent methyl-coenzyme M methylreductase activities were only present in the soluble fraction, but addition of the membrane fraction enhanced both activities. A b-type cytochrome(s), present in the membrane fraction, was linked to a membrane-bound hydrogenase. CO-oxidizing:H2-evolving activity was reconstituted with: (i) CO dehydrogenase complex, (ii) a ferredoxin, and (iii) purified membranes with associated hydrogenase. The ferredoxin was a direct electron acceptor for the CO dehydrogenase complex. The ferredoxin also coupled CO oxidation by CO dehydrogenase complex to metronidazole reduction.


Biological treatment of tannery wastewater by using salt-tolerant bacterial strains.
High salinity (1-10% w/v) of tannery wastewater makes it difficult to be treated by conventional biological treatment. Salt tolerant microbes can adapt to these saline conditions and degrade the organics in saline wastewater. Four salt tolerant bacterial strains isolated from marine and tannery saline wastewater samples were identified as Pseudomonas aeruginosa, Bacillus flexus, Exiguobacterium homiense and Staphylococcus aureus. Growth factors of the identified strains were optimized. Tannery saline wastewater obtained from a Common Effluent Treatment Plant (CETP) near Chennai (southern India) was treated with pure and mixed consortia of four salt tolerant bacterial strains. Experiments with optimized conditions and varying salt content (between 2 and 10% (w/v) were conducted. Salt inhibition effects on COD removal rate were noted. Comparative analysis was made by treating the tannery saline wastewater with activated sludge obtained from CETP and with natural habitat microbes present in raw tannery saline wastewater. Salt tolerant bacterial mixed consortia showed appreciable biodegradation at all saline concentrations (2%, 4%, 6%, 8% and 10% w/v) with 80% COD reduction in particular at 8% salinity level the consortia could be used as suitable working cultures for tannery saline wastewater treatment.


Definitions of Long-Term Weight Regain and Their Associations with Clinical Outcomes.
The prevalence and clinical significance of weight regain after bariatric surgery remains largely unclear due to the lack of a standardized definition of significant weight regain. The development of a clinically relevant definition of weight regain requires a better understanding of its clinical significance. To assess rates of weight regain 5 years after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), applying six definitions and investigating their association with clinical outcomes. Patients were followed up until 5 years after surgery and weight regain was calculated. Regression techniques were used to assess the association of weight regain with health-related quality of life (HRQoL) and the presence of comorbidities. A total of 868 patients participated in the study, with a mean age of 46.6 (± 10.4) years, of which 79% were female. The average preoperative BMI was 44.8 (± 5.9) kg/m2 and the total maximum weight loss was 32% (± 8%). Eighty-seven percent experienced any regain. Significant weight regain rates ranged from 16 to 37% depending on the definition. Three weight regain definitions were associated with deterioration in physical HRQoL (p < 0.05), while associations between definitions of weight regain and the presence of comorbidities 5 years after surgery were not significant. These results indicate that identifying one single categorical definition of clinically significant weight regain is difficult. Additional research into the clinical significance of weight regain is needed to inform the development of a standardized definition that includes all dimensions of surgery success: weight, HRQoL, and comorbidity remission.


Nonstented Tubularized Incised Plate Distal Hypospadias Repair: A Single Center 5 Years' Experience.
To report our immediate and delayed outcomes of nonstented tubularized incised plate (TIP) distal hypospadias repair. We retrospectively reviewed all charts of children who underwent distal hypospadias repair in a single children's hospital from 2013 to 2018. Patients' demographics, hypospadias characteristics, operative technique, and immediate and delayed outcomes were recorded. Of 280 consecutive distal hypospadias repairs that were identified, 74 were excluded due to the use of a repair other than TIP. Eleven stented TIP repairs were excluded as well. Of 195 nonstented repairs, immediate postoperative voiding complications were recorded in 11 (5.6%) and included multiple/split stream in 6 (3%), dysuria and voiding difficulty in 2 (1%), urinary retention in 2 (1%), and gross hematuria that spontaneously resolved in 1 (0.5%). Late follow up was recorded in 142 of 195 (72.8%) repairs. Delayed urethroplasty/glansplasty complications were recorded in 12 (8.5%) and included urethrocutaneous fistula in 10 (7.0%), meatal stenosis in 6 (4.2%) and glans/urethroplasty dehiscence in 2 (1.4%). Avoiding postoperative urethral stents in distal hypospadias TIP repair reduces the morbidity associated with the stent and is a feasible option that carries acceptable immediate and delayed complication rates. Avoiding the stent eliminates stent-related bladder spasms, the need for other medications, and the short-term office visit for stent removal, therefore reducing parental anxiety, patient discomfort, and reducing cost.


Surgical procedure long terms recognition from Chinese literature incorporating structural feature.
With rapid development of technologies in medical diagnosis and treatment, the novel and complicated concepts and usages of clinical terms especially of surgical procedures have become common in daily routine. Expected to be performed in an operating room and accompanied by an incision based on expert discretion, surgical procedures imply clinical understanding of diagnosis, examination, testing, equipment, drugs and symptoms, etc., but terms expressing surgical procedures are difficult to recognize since the terms are highly distinctive due to long morphological length and complex linguistics phenomena. To achieve higher recognition performance and overcome the challenge of the absence of natural delimiters in Chinese sentences, we propose a Named Entity Recognition (NER) model named Structural-SoftLexicon-Bi-LSTM-CRF (SSBC) empowered by pre-trained model BERT. In particular, we pre-trained a lexicon embedding over large-scale medical corpus to better leverage domain-specific structural knowledge. With input additionally augmented by BERT, rich multigranular information and structural term information is transferred from Structural-SoftLexicon to downstream model Bi-LSTM-CRF. Therefore, we could get a global optimal prediction of input sequence. We evaluate our model on a self-built corpus and results show that SSBC with pre-trained model outperforms other state-of-the-art benchmarks, surpassing at most 3.77% in F1 score. This study hopefully would benefit Diagnostic Related Groups (DRGs) and Diagnosis Intervention Package (DIP) grouping system, medical records statistics and analysis, Medicare payment system, etc.