Brain imaging signatures in amyotrophic lateral sclerosis: Correlation with peripheral motor degeneration.
This study aimed to explore the clinical significance of brain imaging signatures in the context of clinical neurological deficits in association with upper and lower motor neuron degeneration in amyotrophic lateral sclerosis (ALS). We performed brain MRI examinations to quantitatively evaluate (1) gray matter volume and (2) white matter tract fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD). Image-derived indices were correlated with (1) global neurological deficits of MRC muscle strength sum score, revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R), and forced vital capacity (FVC), and (2) focal scores of University of Pennsylvania Upper motor neuron score (Penn score) and the summation of compound muscle action potential Z scores (CMAP Z sum score). There were 39 ALS patients and 32 control subjects matched for age and gender. Compared to controls, ALS patients had a lower gray matter volume in the precentral gyrus of the primary motor cortex, which was correlated with FA of corticofugal tracts. The gray matter volume of the precentral gyrus was correlated with FVC, MRC sum score, and CMAP Z sum score, while the FA of the corticospinal tract was linearly associated with CMAP Z sum score and Penn score on multivariate linear regression model. This study indicated that clinical assessment of muscle strength and routine measurements on nerve conduction studies provided surrogate markers of brain structural changes for ALS. Furthermore, these findings suggested parallel involvement of both upper and lower motor neurons in ALS.


Predicting mortality in patients with cirrhosis of liver with application of neural network technology.
Prediction of mortality from cirrhosis is important in planning optimal timing of liver transplantation and other interventions. We evaluated the role of the Artificial Neural Network (ANN), which uses non-linear statistics for pattern recognition in predicting one-year liver disease-related mortality using information available during initial clinical evaluation. The ANN was constructed using software with data from a training set (n = 46) selected at random from a cohort of adult cirrhotics (n = 92). After training, validation was performed in the remaining patients (n = 46) whose outcome in terms of one-year mortality was unknown to the network. The performance of ANN was compared to those of a logistic regression model (LRM) and Child-Pugh's score (CPS). Death (related to cirrhosis/its complications) within one year of inclusion was the outcome variable. The ANN was also tested in an external validation sample (EVS, n = 62) from another hospital. Patients in the EVS were younger (mean age, 41 vs 45 years), infrequently of alcoholic etiology (5% vs 49%), had less severe disease (mean CPS 6.6 vs 10.8), and had lower one-year mortality (13 vs 46%). In the internal validation sample, ANN's accuracy was 91%, sensitivity 90% and specificity 92% in prediction of one-year mortality; area under the receiver-operating characteristic (ROC) curve was 0.94. The performance of the LRM (accuracy 74%) and the CPS (accuracy 55%) was significantly worse than ANN (P < 0.05, McNemar's test). Despite differences in the characteristics of the two groups, the ANN performed fairly well in the EVS (accuracy of 90%, area under curve 0.85). ANN can accurately predict one-year mortality in cirrhosis and is superior to CPS and LRM.


Correction: CTL-doxorubicin (DOX)-gold complex nanoparticles (DOX-AuGCs): from synthesis to enhancement of therapeutic effect on liver cancer model.
[This corrects the article DOI: 10.1039/D0NA00758G.].


Does Hospital Volume Really Affect the Surgical and Oncological Outcomes of Gastric Cancer in Korea?
The significance of hospital volume remains inconsistent and controversial. In particular, few studies have examined whether hospital volume is associated with the outcome of gastrectomy for gastric cancer in East Asia. This study examined the effect of hospital volume on the short-term surgical and long-term oncological outcomes of patients undergoing curative gastrectomy for gastric cancer. Between 2009 and 2011, 1,561 patients underwent curative gastrectomy for gastric cancer at Seoul St. Mary's Hospital (n=1,322) and Bucheon St. Mary's Hospital (n=239). We defined Seoul St. Mary's Hospital as a high-volume center and Bucheon St. Mary's Hospital as a low-volume center. The extent of resection, rate of combined resection, tumor stage, operating time, and hospital stay did not differ significantly between the 2 hospitals. In addition, the hospital volume was not significantly associated with the 30-day morbidity and mortality. When the overall and disease-free survival rates of the patients were stratified according to stage, hospital volume was not significantly associated with prognosis at any stage. Hospital volume might not be a decisive factor with respect to the surgical and oncological outcomes of patients if well-trained surgeons perform gastrectomy for gastric cancer.


Elective neck dissection for no neck during salvage total laryngectomy: findings, complications, and oncological outcome.
Optimum management of the clinically negative neck in the presence of primary site recurrence of laryngeal or hypopharyngeal cancer remains unclear. To examine the incidence of occult cervical nodal metastatic disease in patients undergoing salvage laryngectomy with necks clinically staged as N0 at the time of recurrence and to define the role of elective neck dissection in this population with regard to risk of complications and oncologic outcomes. Retrospective study of patients treated from 1996 through 2011. Academic teaching hospital. All patients undergoing salvage total laryngectomy for squamous cell carcinoma of larynx or hypopharynx after failed initial radiotherapy or chemoradiotherapy with radiographically N0 neck at time of recurrence. Primary outcome measure was incidence of cervical nodal metastases detected by means of pathological examination of elective neck dissection specimens. Secondary outcome measures were incidence of major postoperative complications and regional cancer control. Forty-five patients were included. Thirty-eight underwent elective unilateral (20) or bilateral (18) ND at the time of laryngectomy. Three patients (8%) had occult metastases (3 of 56 dissected heminecks [5%]). The incidence of major wound complications was significantly greater in patients undergoing bilateral ND (12 of 18 [67%]) than in patients undergoing unilateral or no ND (8 of 27 [30%]) (P = .03). There was no significant difference in regional control according to whether bilateral, unilateral, or no ND was performed. The incidence of occult metastatic disease in N0 necks in patients undergoing salvage surgery after radiotherapy is low. Neck dissection in this population does not seem to have a significant impact on regional cancer control. The need for elective ND, particularly bilateral ND, should be balanced against possible increased risk of morbidity in this group.


Change in the Gingival Margin Profile After the Single Flap Approach in Periodontal Intraosseous Defects.
The aim of the present study is to evaluate the association of patient-related and site-specific factors, as well as the adopted treatment modality, with the change in buccal (bREC) and interdental (iREC) gingival recession observed at 6 months after treatment of periodontal intraosseous defects with the single flap approach (SFA). Sixty-six patients contributing 74 intraosseous defects accessed with a buccal SFA and treated with different modalities were selected retrospectively. A two-level (patient and site) model was constructed, with the 6-month changes in bREC and iREC as the dependent variables. (1) Significant 6-month increases in bREC (-0.6 ± 0.7 mm) and iREC (-0.9 ± 1.1 mm) were observed. (2) bREC change was significantly predicted by presurgery interproximal probing depth (PD) and depth of osseous dehiscence at the buccal aspect. (3) iREC change was significantly predicted by presurgery interproximal PD and the treatment modality, with defects treated with SFA in combination with a graft material and a bioactive agent being less prone to iREC increase compared to defects treated with SFA alone. After buccal SFA, greater post-surgery increase in bREC must be expected for deep intraosseous defects associated with a buccal dehiscence. The combination of a graft material and a bioactive agent in adjunct to the SFA may limit the postoperative increase in iREC.


Generation of Monoclonal iPSC Lines with Stable Cas9 Expression and High Cas9 Activity.
CRISPR/Cas9-mediated gene editing has been rapidly and widely applied in many organisms for delicate genetic manipulation, including human-induced pluripotent stem cells (iPSCs). Gene editing in human iPSCs is promising for genetics and biomedical research due to that gene-edited iPSC still possesses the potential to be differentiated into any cell lineages. In many cases, the generation of Cas9 expressing cell lines is a prerequisite toward performing successful editing of multiplex genes of interest. Here, we describe a simple, effective method to generate stable Cas9 expressing human iPSCs with high Cas9 activity. In this method, stable Cas9 expressing monoclonal human iPSC lines were generated through lentiviral transduction of Cas9 cassette, followed by blasticidin selection and subcloning with low seeding density. After colonies isolation and expansion, a BFP-GFP reporter assay was applied to validate the Cas9 activities of multiple monoclonal lines by flow cytometry (FACS). These Cas9 expressing human iPSCs generated by our method are single cell-derived monoclonal lines with homogenous population and Cas9 activity of up to 99%.


Association of Asymmetric Dimethylarginine and Nitric Oxide with Cardiovascular Risk in Patients with End-Stage Liver Disease.
Endothelial dysfunction has been proposed to be an underlying mechanism of the pronounced cardiovascular morbidity in end-stage liver disease (ESLD), but clinical evidence is still limited. In this study, we investigated the association of circulating levels of asymmetric dimethylarginine (ADMA) and nitric oxide (NO) with estimated cardiovascular risk in patients with ESLD awaiting liver transplantation. ADMA and NO levels were measured in the sera of 160 adult ESLD patients. The severity of hepatic dysfunction was assessed by the model for end-stage liver disease (MELD) score. The cardiovascular risk was estimated with the European Society of Cardiology Systematic Coronary Risk Estimation (SCORE) index, which was used to dichotomize patients in the subgroups depicting higher and lower cardiovascular risk. Severe hepatic dysfunction (MELD ≥ 18) was present in 38% of the patients, and a higher cardiovascular risk was present in almost half of the patients (N = 74). ADMA and NO both significantly increased with the progression of liver disease and were independently associated with higher cardiovascular risk. Fasting glucose also independently predicted a higher cardiovascular risk, while HDL cholesterol and the absence of concomitant hepatocellular carcinoma were protective factors. These results suggest a remarkable contribution of the deranged arginine/NO pathway to cardiovascular risk in patients with end-stage liver disease.


Human polyomavirus type six in respiratory samples from hospitalized children with respiratory tract infections in Beijing, China.
HPyV6 is a novel human polyomavirus (HPyV), and neither its natural history nor its prevalence in human disease is well known. Therefore, the epidemiology and phylogenetic status of HPyV6 must be systematically characterized. The VP1 gene of HPyV6 was detected with an established TaqMan real-time PCR from nasopharyngeal aspirate specimens collected from hospitalized children with respiratory tract infections. The HPyV6-positive specimens were screened for other common respiratory viruses with real-time PCR assays. The prevalence of HPyV6 was 1.7 % (15/887), and children ≤ 5 years of age accounted for 80 % (12/15) of cases. All 15 HPyV6-positive patients were coinfected with other respiratory viruses, of which influenza virus A (IFVA) (8/15, 53.3 %) and respiratory syncytial virus (7/15, 46.7 %) were most common. All 15 HPyV6-positive patients were diagnosed with lower respiratory tract infections, and their viral loads ranged from 1.38 to 182.42 copies/μl nasopharyngeal aspirate specimen. The most common symptoms were cough (100 %) and fever (86.7 %). The complete 4926-bp genome (BJ376 strain, GenBank accession number KM387421) was amplified and showed 100 % identity to HPyV6 strain 607a. The prevalence of HPyV6 was 1.7 % in nasopharyngeal aspirate specimens from hospitalized children with respiratory tract infections, as analyzed by real-time PCR. Because the coinfection rate was high and the viral load low, it was not possible to establish a correlation between HPyV6 and respiratory diseases.


Outcome effect of adherence to operative principles of Nissen fundoplication by multiple surgeons. The Department of Veterans Affairs Gastroesophageal Reflux Disease Study Group.
Fifty-eight patients participated in a multi-institutional study designed to assess the outcome of Nissen fundoplication when performed for complicated disease by a variety of surgeons with varied skill and experience with compliance to established technical principles. All patients had an abnormal 24-hour pH study and mucosal injury on endoscopy. The surgical procedures were performed in 8 Veterans Administration hospitals by surgical residents supervised by surgical faculty, after initial agreement on 10 operative principles for the Nissen fundoplication. The mean symptomatic scores at 52 and 104 weeks improved significantly compared with the preoperative score (p < 0.0001). There was significant improvement in total percent time at pH below 4 at 52 weeks (p < 0.01) and 104 weeks (p < 0.01). There was significant improvement in the grade of esophagitis at 1 year (p < 0.0001). Compliance was greater than 90% for 7 of 10 principles of repair. In conclusion, a Nissen fundoplication resulted in relief of symptoms in 93% of patients and a 77% rate of healing of esophagitis. These results in complicated reflux disease were achieved by a variety of surgeons with varied experience in antireflux surgery.


Monitoring of the dilution rate during continuous in vivo blood sampling with a double lumen catheter.
A simple and non-destructive method for monitoring the dilution rate during continuous blood sampling is described. When the dilution rate is not constant, the proposed method based on electrical resistivity measurement provides a correction factor for further analysis.


Expression of the oxytocin and vasopressin genes in the rat hypothalamus during development: an in situ hybridization study.
Oxytocin (OT)- and vasopressin (VP)-mRNAs were detected in the hypothalamus, during development, by in situ hybridization with synthetic oligonucleotide probes. The presence of VP- and OT-mRNAs was first detected in the supraoptic nucleus at E16 and E17 respectively, and simultaneously at E18 in the paraventricular nucleus. VP- (but not OT-) mRNA then appeared in the suprachiasmatic nucleus at E21, and OT- (but not VP-) mRNA, in the anterior commissural nucleus at time of birth. In the different nuclei, the relative distribution of cells containing OT- or VP-mRNA was comparable, from the earliest stages on, with that observed in the adult. These data suggest that the later appearance of mature OT (E20), versus VP (E16), reported in immunocytochemical studies, may not be due to a delayed transcription. Moreover, since the presence of both OT- and VP-prohormones has been reported at E16, the results support the idea of a rapid translation of both OT- and VP-mRNAs. In no location could OT- and VP-mRNAs be detected before final cell settlement; the possible role of environmental factors in final non-proliferative differentiation is discussed.


Assembly of free-standing polypeptide films via the synergistic combination of hyperbranched macroinitiators, the grafting-from approach, and cross-chain termination.
Cross-linked polypeptide-based films are fabricated via a novel and robust method employing surface-initiated ring opening polymerization of α-amino acid N-carboxyanhydrides (NCA-ROP). The judicious combination of amine-based hyperbranched macroinitiators and benzyl ester-protected NCA derivatives promotes network formation by cross-chain terminations, which allows the formation of stable cross-linked peptide-based capsules in a one-pot system.


Randomized controlled trials of psychological and pharmacological treatments for nightmares: a meta-analysis.
A meta-analysis of treatments for nightmares is reported. The studies were identified by database searches and by an inspection of relevant reference lists. The inclusion criteria were: nightmares as a target problem, studies published in English, use of a randomized controlled trials and reporting of nightmare-relevant outcomes. A total of 19 studies, published between 1978 and 2012 were identified, which included 1285 participants. Effect sizes were calculated as Cohen's d. A statistically significant improvement for all studies combined (d = 0.47, 95% CI = 0.33-0.60, fixed effects model; d = 0.49, 95% CI = 0.32-0.66, random effects model) and for psychological treatments alone (d = 0.48, 95% CI = 0.36-0.60, random) and for prazosin alone (d = 0.50, 95% CI = 0.03-0.96, random) was found. Individual therapy format yielded a higher effect size than a self-help format (p = 0.03). Minimal interventions (relaxation, recording) yielded lower overall effect size than studies offering more extensive interventions (p = 0.02). It is concluded that there are both psychological and pharmacological interventions which have documented effects for the treatment of nightmares.


How wide is the clinical spectrum of the acrocallosal syndrome? Report of a mild case.
A boy presenting with an incomplete form of the acrocallosal syndrome is described. The syndrome shows clinical variability and it is stressed that none of the components is constant and facial dysmorphism is not always characteristic.


Raf-1 activates MAP kinase-kinase.
The normal cellular homologue of the acutely transforming oncogene v-raf is c-raf-1, which encodes a serine/threonine protein kinase that is activated by many extracellular stimuli. The physiological substrates of the protein c-Raf-1 are unknown. The mitogen-activated protein (MAP) kinases Erk1 and 2 are also activated by mitogens through phosphorylation of Erk tyrosine and threonine residues catalysed by a protein kinase of relative molecular mass 50,000, MAP kinase-kinase (MAPK-K). Here we report that MAPK-K as well as Erk1 and 2 are constitutively active in v-raf-transformed cells. MAPK-K partially purified from v-raf-transformed cells or from mitogen-treated cells can be deactivated by phosphatase 2A. c-Raf-1 purified after mitogen stimulation can reactivate the phosphatase 2A-inactivated MAPK-K over 30-fold in vitro. c-Raf-1 reactivation of MAPK-K coincides with the selective phosphorylation at serine/threonine residues of a polypeptide with M(r) 50,000 which coelutes precisely on cation-exchange chromatography with the MAPK-K activatable by c-Raf-1. These results indicate that c-Raf-1 is an immediate upstream activator of MAPK-K in vivo. To our knowledge, MAPK-K is the first physiological substrate of the c-raf-1 protooncogene product to be identified.


Prey selection by thaidid gastropods: some observational and experimental field tests of foraging models.
Field observations and experiments revealed that predatory intertidal gastropods of the genus Thais (or Nucella) were able both to recognize the expected food value of encountered prey (expected energy or growth potential gained per unit handling time) and to monitor their average yield over time (average energy or growth potential gained per unit foraging time). They appeared to discriminate not only among prey species, but also among different sized individuals of the same prey species. The evidence supporting these interpretations included: 1) field observations of snails feeding preferentially on prey types of higher expected food value even though lower value prey types were available and abundant, 2) a very limited number of direct underwater observations of foraging snails rejecting encountered items that were either of lower expected value than the item finally eaten or not measurably different from it, and 3) field (='arena') experiments in which both average yield, and the distribution and abundance of potential prey were controlled: snails conditioned at a high average yield fed preferentially on high value items, while those animals conditioned at a low yield consumed prey in the proportions that they were encountered. These behaviors are all consistent with a prey-selection decision motivated by energetic considerations. Further, the field experiments indicated that these predatory gastropods could select items from a diverse array of prey so as to maximize growth in their natural environment. The behaviors were not consistent with three alternative foraging hypotheses: non-selective foraging, frequency-dependent foraging on prey types (here, sizes of particular prey species), and frequency-dependent foraging on prey species. Deviations from some of the quantitative predictions of optimal foraging theory appeared related to learning and risk.


Blood Oxylipin Profiles as Markers of Oncological Diseases.
Oxylipins are signal lipid molecules formed from polyunsaturated fatty acids (PUFAs) in several multienzymatic metabolic pathways, such as cyclooxygenase (COX), lipoxygenase (LOX), epoxygenase (CYP), and anandamide pathways, as well as non-enzymatically. The pathways of PUFA transformation are activated in parallel, yielding a mixture of physiologically active substances. Although the association of oxylipins with carcinogenesis had been established a long time ago, only recently analytical methods have advanced to a degree allowing detection and quantification of oxylipins from different classes (oxylipin profiles). The review describes current approaches to the HPLC-MS/MS analysis of oxylipin profiles and compares oxylipin profiles from patients with oncological diseases (breast cancer, colorectal cancer, ovarian cancer, lung cancer, prostate cancer, liver cancer). The possibility of using blood oxylipin profiles as biomarkers in oncological diseases is discussed. Understanding the patterns of PUFA metabolism and physiological activity of combinations of oxylipins will improve early diagnostics of oncological diseases and evaluation of disease prognosis.


Carcinoid tumors of the alimentary tract. II. Angiographic diagnosis of small intestinal and colonic lesions.
The angiographic findings of five small intestinal and two colonic carcinoids are described and illustrated, together with a review of the pertinent literature. It is pointed out that the demonstration of a complex of angiographic findings related to the primary site, mesentery, and liver is highly specific. It helps in the preoperative diagnosis as well as in the localization and stage of development of the gastrointestinal carcinoid. The triad of findings is composed of: (a) faint to moderate staining at the primary site; (b) narrowing, obstruction of the distal mesenteric arcade, cluster of irregular kinked vessels, and encasement in the more central areas of mesentery; and (c) hypervascular liver metastasis. The colonic lesions examined are unique in the literature, and exhibited angiographic findings similar to the small bowel carcinoids.


Transanal total mesorectal excision for rectal carcinoma: short-term outcomes and experience after 80 cases.
Low anterior resection for distal and mid-rectal cancer is associated with high positive resection margins. Transanal total mesorectal excision (TaTME) is a new treatment in which the rectum is dissected transanally according to TME principles. The short-term results and oncological follow-up of the first 80 patients were described. Between June 2012 and September 2014, all patients in the Gelderse Vallei Hospital and the VU University Medical Center with histologically proven distal or mid-rectal carcinomas without evidence of distant metastases underwent TaTME. Patients with T4 tumors were excluded. Transanal mobilization was performed with the aid of a single port and endoscopic instruments according to TME criteria. Eighty patients were operated in a period of 2 years. Laparotomy was recommended and performed in four patients. Postoperative morbidity was 39%. Ten (12%) complications were graded as severe (Clavien-Dindo grade 3, 4 and 5) and needed re-intervention. Median operative time was 204 min (range 91-447). Median hospital stay was 8 days (range 3-41). Specimens were graded as complete in 88% of the patients, nearly complete in 9% and incomplete in 3%. A positive circumferential resection margin (<2 mm) was observed in two patients. During the two and half years study period, a local recurrence was observed in two patients. TaTME is a safe alternative to standard laparoscopic TME in selected low-risk patients with rectal carcinoma when treated by an experienced colorectal team. In the future, randomized trials are necessary to prove its oncological safety.


Foreign exchange forecasting and portfolio optimization strategy based on hybrid-molecular differential evolution algorithms.
At present, the COVID-19 epidemic is still spreading at home and abroad, and the foreign exchange market is highly volatile. From financial institutions to individual investors, foreign exchange asset allocation has become important contents worthy of attention. However, most intelligent optimization algorithms (hereinafter IOAS) adopt the existing data and ignore the forecasted one in the foreign exchange portfolio allocation, which will result in a huge difference between portfolio allocation and actual demand; at the same time, many IOAS are less adaptable and have lower optimization ability in portfolio problems. To solve the aforementioned problems, this paper first proposed a DETS based on hybrid tabu search and differential evolution algorithms (DEAs), which has excellent optimization ability. Subsequently, the DETS algorithm was applied to support vector machine (SVM) model. Experiments show that, compared with other algorithms, the MAE and RMSE obtained by using DETS optimization parameters are reduced by at least 3.79 and 1.47%, while the CTR is improved by at least 2.19%. Then combined with the DETS algorithm and Pareto sorting theory, an algorithm suitable for multi-objective optimization was further proposed, named NSDE-TS. Finally, by applying NSDE-TS algorithm, the optimal foreign exchange portfolio is acquired. The empirical analysis shows that the Pareto front obtained by this algorithm is better than that of NSGA-II. Since the lower the uniformity index and convergence index, the stronger the optimization performance of the corresponding algorithm, compared with NSGA-II, its uniformity and convergence index decreased by 15.7 and 39.6%.


Correlation of West Nile Virus Incidence in Donated Blood with West Nile Neuroinvasive Disease Rates, United States, 2010-2012.
Over the past decade, West Nile virus (WNV) has spread across the United States. We aggregated blood donor data from 2010-2012 and then calculated the incidence of WNV RNA-positive donations and compared the incidence with neuroinvasive disease (NID) case data from the ArboNET surveillance system. Of 10,107,853 donations, 640 were confirmed positive. The seasonal WNV incidence rate per 100,000 persons was 33.4 (95% CI 22-45) in 2010, 25.7 (95% CI 15-34) in 2011, and 119.9 (95% CI 98-141) in 2012. NID to blood donor ratios were 1 in 164 (95% CI 152-178) in 2010, 1 in 158 (95% CI 145-174) in 2011, and 1 in 131 (95% CI 127-136) in 2012. We updated estimates of the ratio of NID to WNV infection rates, demonstrating stable disease penetrance over the study period. Blood donor WNV RNA screening is a valuable public health tool for WNV surveillance.


Autonomous control of terminal erythropoiesis via physical interactions among erythroid cells.
In vitro erythropoiesis has been studied extensively for its application in the manufacture of transfusable erythrocytes. Unfortunately, culture conditions have not been as effective as in vivo growth conditions, where bone marrow macrophages are known to be a key regulator of erythropoiesis. This study focused on the fact that some erythroblasts are detached from macrophages and only contact other erythroblasts. We hypothesized that additional factors regulate erythroblasts, likely through either physical contact or secreted factors. To further elucidate these critical factors, human erythroblasts derived from cord blood were cultured at high density to mimic marrow conditions. This growth condition resulted in a significantly increased erythroid enucleation rate and viability. We found several novel contact-related signals in erythroblasts: intercellular adhesion molecule-4 (ICAM-4) and deleted in liver cancer-1 (DLC-1). DLC-1, a Rho-GTPase-activating protein, has not previously been reported in erythroid cells, but its interaction with ICAM-4 was demonstrated here. We further confirmed the presence of a secreted form of human ICAM-4 for the first time. When soluble ICAM-4 was added to media, cell viability and enucleation increased with decreased nuclear dysplasia, suggesting that ICAM-4 is a key factor in contact between cells. These results highlight potential new mechanisms for autonomous control of erythropoiesis. The application of these procedures to erythrocyte manufacturing could enhance in vitro erythrocyte production for clinical use.


Methods for measuring tissue protein breakdown rate in vivo.
To describe the latest innovations in measuring protein breakdown in vivo, particularly in muscle. The traditional method of using 3-methylhistidine excretion to measure muscle protein breakdown has been updated to include arteriovenous or microdialysis measurements, which address the concern that there are alternative sources of 3-methylhistidine in the body other than muscle. Several variations of a precursor-product method to measure fractional breakdown rate of tissues have been developed that are analogous to fractional synthesis rate of tissues. These methods are more generally applicable than the 3-methylhistidine methods and are less invasive than arteriovenous methods. The various precursor-product methods are distinguished by whether they require an isotopic steady state or multiple tracers and by how many biopsies are required. The new precursor-product methods have enabled assessment in clinical trials of protein breakdown for proteins other than myofibrillar proteins and in circumstances in which arteriovenous sampling is not feasible.


Development of benzophenone-based farnesyltransferase inhibitors as novel antimalarials.
The development of farnesyltransferase inhibitors directed against Plasmodium falciparum is a strategy towards new drugs against malaria. Previously, we described benzophenone-based farnesyltransferase inhibitors with high in vitro antimalarial activity but no in vivo activity. Through the introduction of a methylpiperazinyl moiety, farnesyltransferase inhibitors with in vivo antimalarial activity were obtained. Subsequently, a structure-based design approach was chosen to further improve the antimalarial activity of this type of inhibitor. As no crystal structure of the farnesyltransferase of the target organism is available, homology modeling was used to reveal differences between the active sites of the rat/human and the P. falciparum farnesyltransferase. Based on flexible docking data, the piperazinyl moiety was replaced by a N,N,N'-trimethylethylenediamine moiety. This resulted in an inhibitor with significantly improved in vitro and in vivo antimalarial activity. Furthermore, this inhibitor displayed a notable increase in selectivity towards malaria parasites relative to human cells.


Management of triple negative breast cancer in a centenarian.
There is limited clinical data to guide treatment for elderly patients with triple-negative breast cancer (TNBC). In the case of centenarians, there is almost no data for this age group. The diagnosis of TNBC portends a more challenging clinical course compared to hormone receptor positive breast cancers, especially in elderly patients. We present the case of a 102-year-old patient who was diagnosed with TNBC. Although our initial plan was observation, the tumor growth rate and the pain it caused resulted in us offering a right total mastectomy and a left partial mastectomy. Morbidity and mortality are higher in TNBC patients, and treatments are more limited, especially in elderly patients who may not be able to tolerate chemotherapy or surgery. As a result, management of breast cancer in elderly patients is largely individualized and treatment is generally more conservative. Focusing on quality of life is a key consideration when treating this patient population.


Effect of limited tryptic modification of a bacterial poly(3-hydroxybutyrate) depolymerase on its catalytic activity.
The extracellular poly(3-hydroxybutyrate) depolymerase of Alcaligenes faecalis T1, which hydrolyzes both hydrophobic poly(3-hydroxybutyrate) and water-soluble oligomers of D(-)-3-hydroxybutyrate, lost its hydrolyzing activity toward the hydrophobic substrate on mile trypsin treatment, but retained its activity toward water-soluble oligomers. The molecular mass of the trypsin-treated enzyme was 44 kDa, as estimated by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, which was 6 kDa smaller than that of the native enzyme (50 kDa). The trypsin-treated enzyme seemed to be less hydrophobic than the native one, because it was rather weakly adsorbed to a hydrophobic butyl-Toyopearl column compared with the native enzyme, and showed no ability to bind to poly(3-hydroxybutyrate), to which the native enzyme tightly bound. These results suggest that, in addition to a catalytic site, the enzyme has a hydrophobic site, which is not essential for the hydrolysis of water-soluble oligomers, but is necessary for the hydrolysis of hydrophobic substrates, and this hydrophobic site is removed from the enzyme by the action of trypsin.


Diagnostic value of anti-GM1 ganglioside serology and validation of the INCAT-ELISA.
The Inflammatory Neuropathy and Treatment (INCAT) group developed a standardized ELISA method for the detection of serum anti-GM1 antibodies. The diagnostic value of anti-GM1 antibodies determined by this method has not yet been established in large groups of patients. We assessed the reproducibility, sources of variation, optimal cut-off values and evaluated the diagnostic relevance of the INCAT-ELISA in various groups of patients and controls (N=1232). The coefficient of variance was 11.2% for IgM and 3.8% for IgG. High IgG titers were only found in Guillain-Barré syndrome (GBS) and other inflammatory polyneuropathies. High IgM titers were associated with GBS and multifocal motor neuropathy. Low IgM titers had no additional diagnostic value. The INCAT-ELISA is a reliable test with additional diagnostic value in specific clinical situations.


[Sonographic criteria of acute acalculous cholecystitis.Critical observation of the clinical records of sedated, ventilated and parenterally nourished patients].
After comparing the classical ultrasonographic findings of acute acalculous cholecystitis with our findings on 24 clinical and sonographic followed acute care unit patients, we have to pay attention to the possible reversibility of such phenomena as increased gallbladder wall thickness, low-level echo surrounding the gallbladder and sludge. In our experience, there is no correlation between a negative cholecystokinin stimulation test and an acute acalculous cholecystitis.


A Phase 2 trial of the liposomal DACH platinum L-NDDP in patients with therapy-refractory advanced colorectal cancer.
L-NDDP (Aroplatin) is a liposomal formulation of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II), a structural analogue of oxaliplatin. In a Phase 1 trial, the maximum tolerated dose (MTD) of L-NDDP was 312.5 mg/m2 with myelosuppression as dose limiting toxicity (DLT). We conducted a Phase 2 trial of L-NDDP in patients (pts) with advanced colorectal cancer (CRC) refractory to 5-fluorouracil/leucovorin or capecitabine and irinotecan to investigate the anti-tumor response of L-NDDP and to further characterize its toxicity profile in this population. L-NDDP was administered intravenously, once every 28 days. The starting dose was 300 mg/m2, with possible intra-patient dose escalation in the absence of grade 2 or higher drug-related toxicity. Patients were treated until disease progression or unacceptable toxicity. Of 20 eligible patients all were evaluable for toxicity and 18 were evaluable for response. Hematologic toxicities included anemia (grades 1-4) in 20% of pts and leucopenia, neutropenia and thrombocytopenia (grade 1/2) in 5% of patients each. Common non-hematologic toxicities included nausea (75%), vomiting (60%), and fatigue (70%), reversible infusion reactions (chest/back pain or shortness of breath; 40%), transient transaminase elevations (35%) and hyperbilirubinemia (20%). Grade 3-4 toxicities included infusion reaction (20%), vomiting (15%), fatigue (15%), anemia (10%) and ALT/AST elevation (5/15%). Peripheral neuropathy (grade 1/2) was seen in 15% of pts. One of 18 pts had a confirmed PR (5.6%), three (16.7%) had stable disease (> or =3 months) and 14 pts progressed. L-NDDP was well tolerated in this group of refractory patients and demonstrated evidence of anti-tumor activity. Further studies of L-NDDP, preferably in combination with other agents such as fluoropyrimidines, are warranted.


Association between early detection of soluble TNF-receptors and mortality in burn patients.
To describe early sequential profiling of circulating levels of tumor necrosis factor alpha (TNF-alpha), TNF-1 and TNF-2 soluble receptors (sTNFR1 and sTNFR2), and of endothelin (ET-1) in patients with severe burn injury, and its association with mortality. Prospective study. Intensive Care Burn Unit at a community hospital. Twenty patients with total burn surface area (TBSA)> or = 30%. None. Patients were enrolled within 6 h from the injury. Blood samples were drawn at zero, 6, 12, and 24 h for sequential ELISA measurement of plasma marker levels. Data are expressed as mean+/-SD. Age, TBSA, and inhalation injury were not significantly different between survivors ( n=9; 30+/-13 years, TBSA 40+/-12%) and nonsurvivors ( n=11, 38+/-15 years, TBSA 56+/-20%). sTNFR1 levels were increased in nonsurvivors (2937+/-1676 pg/ml; 4548+/-1436 pg/ml) as compared to survivors (1313+/-561 pg/ml; 2561+/-804 pg/ml) at 6 h and 24 h, respectively ( P=0.01 and 0.002). sTNFR2 levels were significantly increased in nonsurvivors (4617+/-1,876 pg/ml vs 2611+/-1,326 pg/ml) only at 6 h ( P=0.015). TNF-alpha and ET-1 levels were not different between nonsurvivors and survivors. After adjustment for TBSA, sTNFR1 and sTNFR2 remained significantly higher in nonsurvivors. Early and progressive increase in sTNFR1 and sTNFR2 levels is associated with higher risk for poor outcome in severely burned patients.


Reduction in insulin degludec dosing for multiple exercise sessions improves time spent in euglycaemia in people with type 1 diabetes: A randomized crossover trial.
To compare the time spent in specified glycaemic ranges in people with type 1 diabetes (T1D) during 5 consecutive days of moderate-intensity exercise while on either 100% or 75% of their usual insulin degludec (IDeg) dose. Nine participants with T1D (four women, mean age 32.1 ± 9.0 years, body mass index 25.5 ± 3.8 kg/m2 , glycated haemoglobin 55 ± 7 mmol/mol (7.2% ± 0.6%) on IDeg were enrolled in the trial. Three days before the first exercise period, participants were randomized to either 100% or 75% of their usual IDeg dose. Participants exercised on a cycle ergometer for 55 minutes at a moderate intensity for 5 consecutive days. After a 4-week wash-out period, participants performed the last exercise period for 5 consecutive days with the alternate IDeg dose. Time spent in specified glycaemic ranges, area under the curve and numbers of hypoglycaemic events were compared for the 5 days on each treatment allocation using a paired Students' t test, Wilcoxon matched-pairs signed-rank test and two-way ANOVA. Time spent in euglycaemia over 5 days was greater for the 75% IDeg dose versus the 100% IDeg dose (4008 ± 938 minutes vs. 3566 ± 856 minutes; P = 0.04). Numbers of hypoglycaemic events (P = 0.91) and time spent in hypoglycaemia (P = 0.07) or hyperglycaemia (P = 0.38) was similar for both dosing schemes. A 25% reduction in usual IDeg dose around regular exercise led to more time spent in euglycaemia, with small effects on time spent in hypo- and hyperglycaemia.


Nutritional requirements of keratinophilic fungi and dermatophytes for conidial germination.
Germination of spores of Chrysosporium crassitunicatum, Nannizzia fulva (+), Nannizzia fulva (-) and Trichophyton equinum was studied in the presence of various carbon and nitrogen sources. Effect of different temperatures on spore germination was also determined. Maximum spore germination within 24 hours was recorded when glucose was used as a carbon source for all the test fungi. Except sodium nitrate all the inorganic nitrogen sources enhanced the spore germination at 0.05% concentration. Most of the organic nitrogen sources used were found to be stimulatory for the spore germination of test fungi. Optimum temperature i.e. 28 degrees C supported maximum spore germination of all the test fungi within 24 hours. C. Crassitunicatum, N. fulva (+), N. fulva (-) could germinate upto 35 degrees C but beyond that no spore germination was noticed in these fungi. T. equinum could germinate at a higher temperature of 40 degrees C but the percentage of germination was very low.


Balance training in ataxic neuropathies. Effects on balance and gait parameters.
A rehabilitation program including foot sensory stimulation, balance and gait training with limited vision was followed by 30 patients with ataxic neuropathy in order to stimulate multi-sensory compensation in a no-controlled and no-blinded study. Ataxic neuropathy was graded by a pallesthetic score. The evaluation of patients and healthy subjects was performed with clinical tests (Berg Balance Scale, Functional Reach Test and Timed up and Go test) and instrumental tests for balance (force platform) and gait (Locometre). All patients exhibited impairments in balance and gait parameters compared to control group values. A high pallesthetic score correlated with increased sway area when standing with the eyes open on a firm surface. At the end of the training program, significant changes were observed in balance control assessed using the three clinical tests (Wilcoxon test, p<0.001). A tendency towards a reduction of the Romberg sign was noticed and limited changes were observed after training in instrumental tests for balance and for gait parameters. Age induced some limitations in balance and gait parameters but had no effect on training results. These results show that ataxic patients are impaired in balance and gait but can improve clinical balance parameters following training with a multisensory approach without limitation due to age or degree of sensory impairment. Only limited correlations were noticed between the pallesthetic score and some balance parameters, suggesting that various levels of compensation occur in these patients. The effectiveness of this training program has to be evaluated in the future in a controlled study to ascertain the contribution of the placebo effect in these data.


Efficacy and safety of various oral regimens (three oral doses) and schedules (daily v. monthly) of cholecalciferol in North Indian adults with low vitamin D status: evidence from a randomised controlled trial.
Vitamin D (VD) deficiency (serum 25 hydroxy vitamin D (25(OH)D) concentration of < 20 ng/ml), in endemic proportions, demands a supplementation strategy with optimal dosing regimens. A randomised parallel-group, active-controlled trial was conducted among apparently healthy, VD-deficient subjects, aged 18-60 years who received 600 μg/d (Group A), 1000 μg/d (Group B), 2000 μg/d (Group C) and 60 000 μg/month (Group D) of oral cholecalciferol. The intervention was carried in two phases (I and II) of 12 weeks each, with same dose, separated by a washout phase of 12 weeks. Serum 25(OH)D, intact parathyroid hormones (iPTH), Ca, phosphorous (PO4), alkaline phosphatase (ALP) and spot urine Ca/Cr were measured at baseline, 12, 24 and 36 weeks following the intervention, and adverse events were recorded at each occurrence and at 12, 24 and 36 weeks. A statistically significant time-group interaction was found in serum 25(OH)D concentration (P < 0·05). Serum 25(OH)D concentration increased significantly from baseline to 12 weeks (P < 0·05) in all the groups with no change at 24 weeks but further increase at 36 weeks (P < 0·05). At the end of the study, Group C had maximum increment in serum 25(OH)D concentration, while as Groups C and D (95 %, and 90 %) had higher proportion of subjects VD sufficient than Groups A and B (65 % and 78 %) (P < 0·05). No significant time-dose interactions were observed in serum iPTH, Ca, PO4 and ALP or urine Ca/Cr ratio. Three subjects (two in Group C and one in Group D) developed transient hypercalciuria. Supplementation with daily 2000 μg or monthly 60 000 μg of oral cholecalciferol among adults seems optimal and safe.


Intubation Performance of Advanced Airway Devices in a Helicopter Emergency Medical Service Setting.
This study attempts to determine if newer indirect laryngoscopes or intubating devices are superior to a standard laryngoscope for intubation success among helicopter emergency medical service (HEMS) personnel. Flight nurses and paramedics intubated standardized mannequins with a normal airway, a trauma airway, and a difficult airway using a standard laryngoscope, a gum elastic bougie, the Airtraq laryngoscope (King System Corp, Noblesville, IN), the Glidescope Ranger laryngoscope (Verathon Inc, Bothell, WA), and the S.A.L.T. device (Microtek Medical, Inc, Lehmberg, IN) in grounded helicopters wearing helmets and flight gear. Participant demographics, time to glottic view, the modified Cormack-Lehane score, total intubation time, number of attempts, and overall successful intubation were recorded for each type of airway. Two-hundred thirty-six subjects were initially enrolled across 107 bases in 15 states, and 177 completed the study. First-attempt success rates did not vary by device for the normal airway (P = .203), but the Airtraq laryngoscope and the S.A.L.T. device were highest in the difficult airway (82.0% and 85.0%, respectively; P < .0001). The time to first-attempt success in the difficult airway was lowest for the S.A.L.T. device and the Airtraq laryngoscope (mean = 9.72 seconds and 19.70 seconds, respectively; P < .0001). Using HEMS providers, the Airtraq laryngoscope and the S.A.L.T. device showed the fastest and highest intubation success on the first attempt in difficult simulated HEMS airway scenarios.


Detubularized sigmoid reservoir for bladder replacement after cystoprostatectomy. Preliminary report of new configuration.
A technique for total bladder replacement using a detubularized sigmoid segment is described. The procedure is technically straightforward and results in a highly compliant, low-pressure reservoir that allows both day and night-time continence.


Mapping the basal ganglia: fMRI evidence for somatotopic representation of face, hand, and foot.
To noninvasively investigate the somatotopy of the basal ganglia in humans. Functional MRI, 1.5-T, was performed on six normal right-handed volunteers during simple acoustically paced motor tasks involving the right hand, foot, and face. In a single-subject analysis, statistical parametric maps showed overlapping activation extending along the anteroposterior extent of the left lentiform nucleus (LLN) for the hand, foot, and face representations. Within the LLN, the centers of gravity of each body part, reflecting both the extent and gradient of activation, were all located in the retrocommissural portion of the putamen. Their spatial relationship followed a similar pattern across subjects-face was medial to toes and fingers, toes were dorsal and rostral to fingers. The somatotopic organization of hand, face, and foot representation in the human lentiform nucleus suggests a triangular pattern, rather than the linear pattern seen in primate studies. The overlap observed between the distinct body parts differs from the cortical sensorimotor representation, indicating a different organizational concept of the basal ganglia.


Author Reply: Comparison of Norepinephrine and Terlipressin vs Norepinephrine Alone for Management of Septic Shock: A Randomized Control Study.
How to cite this article: Sahoo P, Kothari N, Sharma A, Goyal S. Author Reply: Comparison of Norepinephrine and Terlipressin vs Norepinephrine Alone for Management of Septic Shock: A Randomized Control Study. Indian J Crit Care Med 2023;27(8):603-604.


Analysis of the impact of digital tomosynthesis on the radiological investigation of patients with suspected pulmonary lesions on chest radiography.
To assess the impact of digital tomosynthesis (DTS) on the radiological investigation of patients with suspected pulmonary lesions on chest radiography (CXR). Three hundred thirty-nine patients (200 male; age, 71.19 ± 11.9 years) with suspected pulmonary lesion(s) on CXR underwent DTS. Two readers prospectively analysed CXR and DTS images, and recorded their diagnostic confidence: 1 or 2 = definite or probable benign lesion or pseudolesion deserving no further diagnostic workup; 3 = indeterminate; 4 or 5 = probable or definite pulmonary lesion deserving further diagnostic workup by computed tomography (CT). Imaging follow-up by CT (n = 76 patients), CXR (n = 256) or histology (n = 7) was the reference standard. DTS resolved doubtful CXR findings in 256/339 (76 %) patients, while 83/339 (24 %) patients proceeded to CT. The mean interpretation time for DTS (mean ± SD, 220 ± 40 s) was higher (P < 0.05; Wilcoxon test) than for CXR (110 ± 30 s), but lower than CT (600 ± 150 s). Mean effective dose was 0.06 mSv (range 0.03-0.1 mSv) for CXR, 0.107 mSv (range 0.094-0.12 mSv) for DTS, and 3 mSv (range 2-4 mSv) for CT. DTS avoided the need for CT in about three-quarters of patients with a slight increase in the interpretation time and effective dose compared to CXR.


In this case report, a 68-year-old woman, with known insulin-dependent diabetes and myelomatosis, presented with ear pain in her right ear. Otomicroscopy showed exposed bone in the external auditory canal. The patient was examined with wound swab, biopsies, MRI and PET-CT scans to rule out necrotizing external otitis, cholesteatoma and malignancy. Later, the patient's bisphosphonate treatment for myelomatosis was suspected, because osteonecrosis of the external auditory canal is a rare side effect to this treatment. The bone lesion improved after local debridement and cessation of the bisphosphonate treatment.


Patch-clamp recordings of the light-sensitive dark noise in retinal rods from the lizard and frog.
In cell-attached recordings from rods in the intact lizard retina, light decreased a standing inward membrane current with a reversal potential approximately 60 mV more positive than the resting potential. The peak amplitude of saturating responses depended upon the area of recorded membrane and varied from cell to cell over approximately 100-fold range. Small patches of membrane gave variable responses to identical moderately intense flashes. Whole-cell voltage-clamp recordings were obtained on isolated frog rods with intact ellipsoids. Peak whole-cell photocurrent was related to flash intensity by a Michaelis equation with saturating response amplitudes ranging up to 30 pA in 0.1 mM-Ca2+ Ringer solution. In darkness the steady-state current-voltage relation, determined with whole-cell voltage clamp, showed outward rectification. Photocurrent had nearly constant amplitude between -80 and -10 mV, a mean reversal potential of +8 mV and recovered from flashes more slowly at positive holding potentials. Although it was not possible to resolve light-sensitive single-channel current events, power spectral analysis revealed both low- and high-frequency components of the light-sensitive noise in both cell-attached and whole-cell recordings. The low-frequency component was described by the product of two Lorentzians using time constants derived from the kinetics of the dim flash response. The high-frequency component of the light-sensitive noise was described by a single Lorentzian with a half-power frequency of 62 Hz in lizard and 212 Hz in frog. The half-power frequency was not appreciably affected by steady illumination. The Lorentzian nature of the noise suggests that the light-sensitive channel is a pore rather than a shuttle-type carrier. In cell-attached recordings the high-frequency component declined monotonically with increasing light intensity, suggesting that less than one-half of the channels are open in darkness. Furthermore, the ratio of the variance of the high-frequency noise to the mean photocurrent was independent of light intensity. Changing external Ca2+ from 0.1 to 0.5 mM reduced the ratio from 19.7 to 9.0 fA without a significant effect on the cut-off frequency of the noise. The results support the conclusion that the light-sensitive pore is opened by an internal transmitter that acts as an agonist and that both open and closed states of the pore may be blocked by external Ca2+. The conductance of the light-sensitive pore in the absence of external Ca2+ is estimated to be 1.25-2 pS.(ABSTRACT TRUNCATED AT 400 WORDS)


[+Gz protection of the on board oxygen generating system (OBOGS) and anti-G equipment].
To investigate the +Gz protection of the on board oxygen generating system (OBOGS) and anti-G equipment. Physical and physiological tests of the OBOGS and anti-G equipment were accomplished using human centrifuge. +Gz tolerance of ten male subjects with or without the anti-G suit, pressure breathing for G (PBG) and OBOGS were determined. The performance of the OBOGS and anti-G equipment fulfilled the requirements. The +Gz protections of the anti-G suit, PBG, and anti-G system were 2.08 G, 1.92 G, and 3.92 G, respectively. The +Gz protection of the OBOGS and anti-G equipment satisfy the performance requirements of high performance aircraft.


Bispectral index monitoring in healthy, cirrhotic, and end-stage liver disease patients undergoing hepatic operation.
The purpose of this study was to assess factors influencing the end-tidal concentrations of isoflurane within a bispectral index (BIS) range of 45-55 among healthy live liver donors (n = 11), chronic hepatitis B patients undergoing hepatectomy hepatocellular carcinoma (n = 10), and end-stage liver disease patients undergoing liver transplantation (n = 7). Patients data collected prospectively were compared among the groups using one-way analysis of variance as well as univariate and multivariate techniques. The results showed that end-stage liver disease patients required the least end-tidal isoflurane concentration. Patients with hepatocellular carcinoma with cirrhosis required intermediate end-tidal isoflurane concentrations; healthy live liver donors required the highest end-tidal isoflurane concentrations to provide sufficient anesthetic depth, as monitored by a target BIS (range, 45-55). Upon multivariate analysis, liver function was the only significant factor influencing the likelihood of lowering the end-tidal isoflurane concentration by 4 hours after anesthesia induction (P = .026). In conclusion, we recommend a preset target BIS within the range of 45-55 to monitor the depth of anesthesia during partial hepatectomy and liver transplantation because end-tidal isoflurane concentration requirements are different for patients with various liver status. This strategy may protect the patients from intraoperative recall or anesthesia over-depth as a consequence of insufficient or overdose of anesthesia, respectively.


Combined Heart-Lung Transplantation Outcomes in Asian Populations: National Database Analysis.
Heart-lung transplantation (HLTx) is a definitive surgical procedure for end-stage cardiopulmonary failure. Studies to understand the relationship between ethnicity and race and outcomes after HLTx are needed to uphold equitable HLTx access to the increasingly diverse U.S. population facing advanced cardiopulmonary failure. This study sought to examine the outcomes of HLTx recipients of Asian origin, with emphasis on the ethnic and racial disparities in the outcomes. We analyzed data from the United Network for Organ Sharing (UNOS) for patients of ≥18 years of age who underwent HLTx between 1987 and 2021. Propensity-score matching was performed between Asian and non-Hispanic Whites (NHWs), with a 1:3 matching ratio based on the propensity score of each patient estimated by multivariable logistic regression. We identified 42 Asian and Asian American heart-lung transplant recipients and 834 NHW recipients. In the pre-matched cohort, the median survival was 1,459 days (IQR: 1,080-2,692 days) in Asian recipients after transplantation, whereas it was 1,521 days (IQR: 1,262-1,841 days) in White recipients. Of the 876 recipients, 156 transplants were successfully matched (Asian, n = 36; NHW, n = 108). Among the post-transplantation outcomes, there were no significant differences in morbidity and mortality between Asian and NHW cohorts. This large-scale analysis in Asian patients will have important implications in Asian countries that have relatively fewer HLTx surgeries. An outcome equivalent to NHW in Asian patients, as demonstrated in our study, could be the driving force for further expansion of HLTx surgeries in Asian countries.


alpha-Bungarotoxin aggregates on radioiodination with chloramine-T but not with iodogen.
The presence of polymer(s) of radioiodinated bungarotoxin (Bgt) in preparations iodinated with chloramine-T or with iodogen, was investigated by chromatography on Sephadex-G50. In addition to a monomeric peak (P2), chloramine-T preparations showed a high content of polymeric forms (16-43%) eluting in the void volume (P1), present only to the extent of 1-3% in iodogen preparations. In purified [125I]Bgt prepared by the iodogen method, the content of P1 increased on treatment with chloramine-T, in the absence of radioiodine. The nonspecific binding of [125I]Bgt to DE-81 filter discs was high in the case of chloramine-T preparations and proportional to the content of P1 in each batch. Purified P1 (polymer) but not P2 (monomer) showed a concentration-dependent high degree of binding to DE-81 discs.


Management of carotid artery hemorrhage in middle ear surgery.
Iatrogenic injury to the carotid artery as it traverses the middle ear in its normal anatomic position is a rare but potentially life-threatening event. Predisposing factors include a thin or dehiscent plate of bone, which normally protects the artery at the level of the eustachian tube, erosive middle ear disease, or previous trauma. Prevention and management of carotid artery injuries in the middle ear are discussed with an applicable case report.


Oral Manifestation of Systemic Diseases.
The US Surgeon General's report Oral Health in America highlighted ways in which oral health and systemic conditions are associated with each other. An oral examination can reveal signs and symptoms associated with systemic diseases. In this article, multiple systemic diseases including but not limited to viral and immune modulated conditions and associated oral symptoms are discussed.


Testing a Theory of Implementation Leadership and Climate Across Autism Evidence-Based Interventions of Varying Complexity.
Prominent theories within the field of implementation science contend that organizational leaders can improve providers' fidelity to evidence-based practices (EBPs) by using focused implementation leadership behaviors that create an organizational climate for EBP implementation. However, this work has been criticized for overreliance on nonspecific, self-report fidelity measures and poor articulation of the boundary conditions that may attenuate leadership and climate's influence. This study tests the predictions of EBP implementation leadership and climate theory on observed fidelity to three school-based EBPs for autism that vary in complexity: pivotal response training (PRT), discrete trial training (DTT), and visual schedules (VS). Educators in kindergarten to third-grade autism support classrooms in 65 schools assessed their principals' EBP implementation leadership and school EBP implementation climate prior to the school year. Mid-school year, trained observers rated educator fidelity to all three interventions. Expert raters confirmed PRT was significantly more complex than DTT or VS using the Intervention Complexity Assessment Tool for Systematic Reviews. Linear regression analyses at the school level indicated principals' increased frequency of EBP implementation leadership predicted a higher school EBP implementation climate, which in turn predicted higher educator fidelity to PRT-however, there was no evidence of a relationship between implementation climate and fidelity to DTT or VS. Comparing principals whose EBP implementation leadership was ±1 SD from the mean, there was a significant indirect association of EBP implementation leadership with PRT fidelity through EBP implementation climate (d = 0.49, 95% CI [0.04, 0.93]). Strategies that target EBP implementation leadership and climate may support fidelity to complex behavioral interventions.


Specific and sensitive detection of nucleic acids and RNases using gold nanoparticle-RNA-fluorescent dye conjugates.
Gold nanoparticles were modified with RNA and utilized to detect specific DNA sequences and various RNA nucleases.


Applicability of Donnan equilibrium theory at nanochannel-reservoir interfaces.
Understanding ionic transport in nanochannels has attracted broad attention from various areas in energy and environmental fields. In most pervious research, Donnan equilibrium has been applied widely to nanofluidic systems to obtain ionic concentration and electrical potential at channel-reservoir interfaces; however, as well known that Donnan equilibrium is derived from classical thermodynamic theories with equilibrium assumptions. Therefore the applicability of the Donnan equilibrium may be questionable when the transport at nanochannel-reservoir interface is strongly non-equilibrium. In this work, the Poisson-Nernst-Planck model for ion transport is numerically solved to obtain the exact distributions of ionic concentration and electrical potential. The numerical results are quantitatively compared with the Donnan equilibrium predictions. The applicability of Donnan equilibrium is therefore justified by changing channel length, reservoir ionic concentration, surface charge density and channel height. The results indicate that the Donnan equilibrium is not applicable for short nanochannels, large concentration difference and wide openings. A non-dimensional parameter, Q factor, is proposed to measure the non-equilibrium extent and the relation between Q and the working conditions is studied in detail.


Multifocal malignant hemangioendothelioma presenting as acute hepatitis. A clinicopathologic study.
A patient with malignant hemangioendothelioma of the liver is described. The patient's clinical presentation and course were that of fulminant hepatic necrosis. Complications included upper gastrointestinal hemorrhage, hepatic encephalopathy, abnormal coagulation parameters and the hepatorenal syndrome. The duration of the illness from the onsetof symptoms to its fatal outcome was five weeks.


New brominated flame retardants and dechlorane plus in the Arctic: Local sources and bioaccumulation potential in marine benthos.
The aim of the present study was to investigate the presence and bioaccumulation of new flame retardants (nBFRs), polybrominated diphenyl ethers (PBDEs) and dechlorane plus (DDC-CO) in the marine environment close to an Arctic community. Passive sampling of air and water and grab sampling of sediment and amphipods was used to obtain samples to study long-range transport versus local contributions for regulated and emerging flame retardants in Longyearbyen, Svalbard. BDE-47 and -99, α- and β-tetrabromoethylcyclohexane (DBE-DBCH), syn- and anti-dechlorane plus (DDC-CO) were detected in all investigated matrices and the DDC-COss at higher concentrations in the air than reported from other remote Arctic areas. Water concentrations of ΣDDC-COSs were low (3 pg/L) and comparable to recent Arctic studies. ΣnBFR was 37 pg/L in the water samples while ΣPBDE was 3 pg/L. In biota, ΣDDC-COSs dominated (218 pg/g ww) followed by ΣnBFR (95 pg/g ww) and ΣPBDEs (45 pg/g ww). When compared with other areas and their relative distribution patterns, contributions from local sources of the analysed compounds cannot be ruled out. This should be taken into account when assessing long-range transport of nBFRs and DDC-COs to the Arctic. High concentrations of PBDEs in the sediment indicate that they might originate from a small, local source, while the results for some of the more volatile compounds such as hexabromobenzene (HBBz) suggest long-range transport to be more important than local sources. We recommend that local sources of flame retardants in remote areas receive more attention in the future.


Endoscopic Gastrojejunal Revisions Following Gastric Bypass: Lessons Learned in More Than 100 Consecutive Patients.
Weight regain and dumping after Roux-en-Y gastric bypass (RYGB) are long-term challenges thought to be due to dilation of the gastrojejunal anastomosis. The aim of this study was to analyze the feasibility, safety, and outcomes of endoscopic gastrojejunal revisions (EGRs) after its introduction in a tertiary bariatric surgery center. From January 2016 to March 2018, we reviewed the electronic records of all patients undergoing EGR with the OverStitch suturing device. Demographics, procedure details, and outcomes were recorded. There were 107 patients (M:F = 29:78) treated with 133 EGR procedures for weight regain (n = 81), dumping syndrome (n = 13), or both (n = 13) with mean age 47.3 years (R 22.0-72.9) and mean BMI 32.9 kg/m2 (R 22.2-49.8) at time of procedure. Mean procedure time was 17.8 min (R 12-41), with median 1 suture used (R 1-2). No intra-operative or 30-day complications were recorded. Mean follow-up time was 9.2 months (R 1-26.8). Patients lost a mean of 4.1, 5.8, and 8.0 kg at 3, 6, and 12 months, respectively, after the procedure. Weight loss outcomes were significantly better when two compared to one suture was used (p = 0.036), and for patients with higher starting BMI (p = 0.047). For patients with dumping syndrome, 90-100% had treatment response after one or two EGRs. EGR is feasible and safe for weight regain and dumping syndrome after RYGB. It can stabilize weight regain and improve dumping symptoms. Around 20% of patients will need repeat EGR within 1 year to achieve sufficient narrowing of the anastomosis.


Experience with new double J ureteral catheter stent.
Experience with a newly designed self-retaining silicone ureteral stent is presented. The stent is supplied in various lengths, has a J or hook molded into each end to prevent migration and has been designed specifically to be passed during an open operation as well as endoscopically. The device is used to provide free drainage to the bladder, reduce or eliminate urine leakage, provide stenting of the ureter and allow for earlier discharge from the hospital of patients without external catheters. In some cases the stent may be used instead of a nephrostomy tube to provide prolonged drainage with less chance of infection. It is removed easily in the outpatient facility by cystoscopy.


A multicentre phase II trial of vindesine in malignant melanoma.
Fifty-three evaluable patients with advanced malignant melanoma have been treated with vindesine 3 mg/m2 i.v. weekly for a minimum of 6 weeks. An objective response rate of 26% was attained with 17% complete remissions, 78% of which were in stage II disease. The treatment was well tolerated, with alopecia the only clinically significant side-effect (43% of patients). Vindesine is superior to DTIC and should be considered as the best currently available drug for malignant melanoma.


Cloning, E. coli overexpression, purification and binding properties of TraA and TraC, two proteins involved in the pheromone-dependent conjugation process in enterococci.
The bacteriocin encoding plasmid pPD1 from Enterococcus faecalis is involved in a mating response to the sex pheromone cPD1 produced by recipient bacterial cells devoid of pPD1. Previous studies showed that cPD1 is internalized into donor cells in a process in which TraC plays the role of cell surface pheromone receptor. Inside the recipient cells, the pheromone binds to the plasmid-encoded cytoplasmic protein TraA, able to recognize specific DNA sequences and to modulate the conjugation process. To avoid self-induction of the conjugation process, donor cells produce the inhibitor iPD1, which competes with cPD1. This study was designed to produce recombinant TraA and TraC in a functionally active state and to evaluate their main functional properties. We have isolated the sequences encoding TraA and TraC from the plasmid pPD1 and cloned them in suitable expression vectors. The two recombinant proteins were successfully obtained in a soluble form using Escherichia coli as expression host and a T7 inducible expression system. TraC and TraA were purified to homogeneity by three or two chromatographic steps, respectively, leading to a final yield up to 4mg/l of cell culture for TraC and up to 10mg/l of cell culture for TraA. The ability of TraA and TraC to bind the specific pheromone and inhibitor peptides has been assessed by means of ESI-mass spectrometry. Moreover, the ability of recombinant TraA to bind DNA has been demonstrated by means of electrophoretic mobility shift assay. Overall these results are consistent with the heterologously expressed TraC and TraA being functionally active.


Antiarrhythmic effects of JTV-519, a novel cardioprotective drug, on atrial fibrillation/flutter in a canine sterile pericarditis model.
Effect of JTV-519 on AF. A new cardioprotective drug, JTV-519, blocks Na+ current and inwardly rectifying K+ current and inhibits Ca2+ current. However, its role in atrial electrophysiology is unknown. We investigated the antiarrhythmic effects of JTV-519 on atrial fibrillation/flutter in the canine sterile pericarditis model. In nine dogs with sterile pericarditis, 38 episodes of sustained (>30 sec) atrial fibrillation (8 dogs) and 24 episodes of sustained atrial flutter (7 dogs) were induced by rapid atrial pacing. When atrial fibrillation or atrial flutter was sustained >15 minutes, it was cardioverted and reinduced. The inducibility of atrial fibrillation/flutter, the atrial effective refractory period, and the intra-atrial conduction time were compared before and after the continuous infusion of JTV-519 (0.03 mg/kg/min). JTV-519 significantly decreased the mean number of sustained atrial fibrillation episodes (from 4.2 +/- 2.9 to 0 +/- 0, P < 0.01). In contrast, atrial flutter was still inducible in 4 dogs after JTV-519 (from 2.7 +/- 2.5 to 1.6 +/- 2.1, P = NS). JTV-519 significantly prolonged effective refractory period (from 123 +/- 18 to 143 +/- 14 msec, from 127 +/- 18 to 151 +/- 12 msec, and from 132 +/- 13 to 159 +/- 9 msec at basic cycle lengths of 200, 300, and 400 msec, respectively, P < 0.01), but it did not affect the intra-atrial conduction time (from 47 +/- 11 msec to 48 +/- 11 msec, P = NS). JTV-519 had significant protective effects on atrial fibrillation in the canine sterile pericarditis model, mainly by increasing effective refractory period, suggesting that it may have potential as a novel antiarrhythmic agent for atrial fibrillation.


Refractory mixed proliferative and membranous lupus nephritis treated with the topoisomerase I inhibitor irinotecan as add-on therapy.
To evaluate the safety and effects of irinotecan, an inhibitor of topoisomerase I, on refractory lupus nephritis. A patient with refractory lupus nephritis under medication with mycophenolic acid, prednisolone, and hydroxychloroquine was treated with add-on low-dose irinotecan. Irinotecan was applied every fourth week at a dose of 50 mg/m2 for four cycles followed by 100 mg/m2 for another eight cycles. Renal function and anti-double-stranded DNA antibodies as well as blood count for evaluation of side effects were assessed during the treatment with irinotecan. Before starting the treatment with irinotecan, a urine protein/creatinine ratio of 1298 mg/g was determined. This declined to 613 mg/g after four cycles with 50 mg/m2 irinotecan and was further reduced to 198 mg/g when using the higher dose of irinotecan. Kidney function remained stable, with creatinine levels of 1.66 mg/dL at the beginning and 1.76 mg/dL at the end of treatment with irinotecan. Importantly, no side effects, such as diarrhoea or neutropenia, were observed during the entire course of treatment. Administration of low-dose irinotecan as add-on medication for the treatment of refractory lupus nephritis was shown to be safe. Clinical trials are needed to determine whether irinotecan can improve kidney function and the outcome of patients with refractory lupus nephritis.


Dose-effect relationships for the submandibular salivary glands and implications for their sparing by intensity modulated radiotherapy.
Submandibular salivary glands (SMGs) dysfunction contributes to xerostomia after radiotherapy (RT) of head-and-neck (HN) cancer. We assessed SMG dose-response relationships and their implications for sparing these glands by intensity-modulated radiotherapy (IMRT). A total of 148 HN cancer patients underwent unstimulated and stimulated SMG salivary flow rate measurements selectively from Wharton's duct orifices, before RT and periodically through 24 months after RT. Correlations of flow rates and mean SMG doses were modeled throughout all time points. IMRT replanning in 8 patients whose contralateral level I was not a target incorporated the results in a new cost function aiming to spare contralateral SMGs. Stimulated SMG flow rates decreased exponentially by (1.2%)(Gy) as mean doses increased up to 39 Gy threshold, and then plateaued near zero. At mean doses < or =39 Gy, but not higher, flow rates recovered over time at 2.2%/month. Similarly, the unstimulated salivary flow rates decreased exponentially by (3%)(Gy) as mean dose increased and recovered over time if mean dose was <39 Gy. IMRT replanning reduced mean contralateral SMG dose by average 12 Gy, achieving < or =39 Gy in 5 of 8 patients, without target underdosing, increasing the mean doses to the parotid glands and swallowing structures by average 2-3 Gy. SMG salivary flow rates depended on mean dose with recovery over time up to a threshold of 39 Gy. Substantial SMG dose reduction to below this threshold and without target underdosing is feasible in some patients, at the expense of modestly higher doses to some other organs.


Incidence of traumatic paraplegia and tetraplegia in Norway: a statistical survey of the years 1974 and 1975.
A survey based on interviews with all Norwegian hospitals, 62 in number, showed that in 1974 and 1975 respectively 65 and 66 traumatic spinal cord and cauda equina lesions were treated in Norway, a total of 131 or 16 . 5/million inhabitants/year.


The importance of coordination in preventing overdiagnosis: a retrospective analysis of unabsorbed oxidized regenerated cellulose.
Oxidized regenerated cellulose (ORC) is commonly used to control small intraoperative bleedings in lung cancer surgery. However, difficulties in its absorption may lead to complications that can mimic malignancy recurrence in the affected areas, and may require further examination. Between 2015 and 2022, patients who underwent malignant tumour resection and lymph node dissection and were subsequently evaluated for suspected lymph node recurrence and underwent EBUS-guided needle biopsy were included in the study. Pathology reports of these patients showed an ORC-related foreign body type granulomatous reaction. Such reactions, caused by delayed absorption of ORC, can mimic malignancy recurrence and result in unnecessary biopsies. In a total of 13 patients (10 males), pathology was observed in 18 lymph node areas after malignant resection and lymph node dissection, and ORC was detected in subcarinal and inferior paratracheal lymph node areas in all patients. The average age of the patients was calculated as 63.1 years (range 51-74). The mean SUVmax value observed in these lymph node areas on PET/CT was 5.22 (range 0-14.36). Although the SUVmax value decreased as the time between surgery and EBUS increased, no statistically significant difference was observed (p = 0.100). The study suggests that in cases of suspected unexpected lymph node recurrence in postoperative follow-up of lung cancer, it is important for clinicians to communicate with the surgeon and re-evaluate the use of ORC by reviewing the operative notes. This may help in determining an appropriate further investigation strategy.


Orthotopic transplantation of a tissue engineered diaphragm in rats.
The currently available surgical options to repair the diaphragm are associated with significant risks of defect recurrence, lack of growth potential and restored functionality. A tissue engineered diaphragm has the potential to improve surgical outcomes for patients with congenital or acquired disorders. Here we show that decellularized diaphragmatic tissue reseeded with bone marrow mesenchymal stromal cells (BM-MSCs) facilitates in situ regeneration of functional tissue. A novel bioreactor, using simultaneous perfusion and agitation, was used to rapidly decellularize rat diaphragms. The scaffolds retained architecture and mechanical properties and supported cell adhesion, proliferation and differentiation. Biocompatibility was further confirmed in vitro and in vivo. We replaced 80% of the left hemidiaphragm with reseeded diaphragmatic scaffolds. After three weeks, transplanted animals gained 32% weight, showed myography, spirometry parameters, and histological evaluations similar to native rats. In conclusion, our study suggested that reseeded decellularized diaphragmatic tissue appears to be a promising option for patients in need of diaphragmatic reconstruction.


Parent Emotion Regulation, Mindful Parenting, and Youth Attachment: Direct and Indirect Associations with Internalizing and Externalizing Problems.
The direct associations between two dimensions of parent emotion regulation within the parent-youth relationship (dysregulation; suppression), mindful parenting, and youth internalizing and externalizing problems were examined among 759 parents of youth with significant behavioural or emotional problems. The indirect associations of parent emotion regulation and mindful parenting with youth functioning through youth attachment anxiety and avoidance were also investigated. Parent dysregulation was associated with internalizing symptoms both directly and through attachment anxiety, and with externalizing symptoms directly and through attachment anxiety and avoidance. Parent suppression was associated with internalizing symptoms through attachment anxiety, and with externalizing symptoms through attachment anxiety and avoidance. Mindful parenting was associated with lower internalizing symptoms through attachment anxiety and with lower externalizing symptoms through attachment anxiety and avoidance. Emotion regulation within parent-child relationships and mindful parenting may be critical components of parenting programs aimed at promoting youth attachment security and mental health.


[Ribosome display: Evolution and acellular selection of molecular libraries for high affinity binder generation].
Ribosome display is a powerful method for selection and molecular evolution of proteins and peptides from large libraries. Displayed proteins are recovered from target molecules in multiple rounds of selection in order to enrich specific binders with the desired properties. Nowadays, ribosome display has become one of the most widely-used display technologies thanks to its advantages over cell-display as phage display. Ribosome display is an in vitro method, in which a stable ternary complex is formed between the mRNA, the ribosome and the nascent protein. A selection cycle can be performed in a few days and bacterial transformation is not necessary. Ribosome display has been used to screen and select peptides, proteins or molecular scaffolds in order to increase their affinity, specificity, catalytic activity or stability. In this review, ribosome display systems and their applications in selection and evolution of proteins are described.


Enhancement of gentamicin-induced nephrotoxicity by Mg deficiency in non-pregnant rats. Morphological, enzyme histochemical and immunohistochemical studies.
Non-pregnant rats fed an Mg-deficient diet showed some degenerated and calcified proximal tubules in the inner region of the medullary rays accompanied by reduced or absent enzyme activities. After gentamicin treatment some damaged convoluted proximal tubules occurred. Enzyme histochemistry revealed decreased activities for brush border and lysosomal hydrolases; using immunohistochemistry lesions were detectable for the cytoskeletal proteins keratin and vimentin. Administration of gentamicin to Mg-deficient rats led to a further decrease of hydrolase activities in obviously intact proximal tubules and drastic structural and enzymatic defects as well as alterations of the cytoskeletal proteins in the convoluted and straight segments of other proximal tubules and to a lesser degree also in glomeruli and further portions of the tubular apparatus including the collecting ducts.


Evolution of the RAG1-RAG2 locus: both proteins came from the same transposon.
The RAG1 and RAG2 proteins are essential subunits of the V(D)J recombinase that is required for the generation of the enormous variability of antibodies and T-cell receptors in jawed vertebrates. It was demonstrated previously that the 600-aa catalytic core of RAG1 evolved from the transposase of the Transib superfamily transposons. However, although homologs of RAG1 and RAG2 genes are adjacent in the purple sea urchin genome, a transposon encoding both proteins so far has not been reported. Here we describe such transposons in the genomes of green sea urchin, a starfish and an oyster. Comparison of the domain architectures of the RAG1 homologs in these transposons, denoted TransibSU, and other Transib superfamily transposases provides for reconstruction of the structure of the hypothetical TransibVDJ transposon that gave rise to the VDJ recombinases at the onset of vertebrate evolution some 500 million years ago.


A narrative review of staff views about dementia care in hospital through the lens of a systems framework.
Significant numbers of people with dementia are admitted into acute settings. They are likely to face poor health outcomes during hospitalisation. There is the need to fully understand the care provided to people with dementia through novel methods such as a systems approach (i.e. human interactions, policy, environment and equipment). The aim of this literature review is to explore hospital practitioners' views on dementia care and to analyse findings using a systems approach. We conducted a narrative review of primary studies that examined dementia care in acute settings. We analysed a total of 33 papers using Thomas and Harden's thematic synthesis guidelines. Thirty-three papers met the inclusion criteria for the review. The findings were as follows: (1) staff-patient relationships (e.g. coping with difficult behaviour), (2) staff-family relationships (e.g. the benefits of involving families in patient care), (3) staff-staff relationships (e.g. building a robust multidisciplinary team), (4) staff-patient care decisions (e.g. decisions directly related to the patient), (5) the environment (e.g. difficulty in adjusting to the hospital environment), (6) policies (e.g. hospital bureaucratic processes) and (7) equipment (e.g. pain assessment tools). The paper revealed multidimensional challenges in the provision of dementia care within hospitals. We conclude that training programmes, hospital policies and processes aimed at improving outcomes for patients with dementia should adopt a systems approach which focuses on the relational, environmental, procedural and instrumental aspects of the hospital system.


Thrombotic microangiopathy as first manifestation of acute human immunodeficiency virus infection: a case report and review of the literature.
We present the case of a patient with acute human immunodeficiency virus infection and a thrombotic microangiopathy as the first clinical manifestation, a presentation that has not, to the best of our knowledge, been previously reported. A 35-year-old Bolivian man presented with epistaxis and thrombocytopenia. We found microangiopathic anemia, lymphopenia, elevated lactate dehydrogenase, progressive acute renal failure, negative direct antiglobulin test, and normal activity of ADAMTS13. An human immunodeficiency virus ELISA test was negative, with an human immunodeficiency virus viral load of 10,000,000 RNA copies/mL. Antiretroviral therapy and three sessions of therapeutic plasma exchange were able to control thrombotic microangiopathy. Hematologic manifestations of human immunodeficiency virus infection are frequent. However, the debut of acute human immunodeficiency virus infection with thrombotic microangiopathy is a rare event. A high index of suspicion and early treatment is required.


Factors associated with asymptomatic infection in health-care workers with severe acute respiratory syndrome coronavirus 2 infection in Wuhan, China: a multicentre retrospective cohort study.
To describe the fraction of asymptomatic health-care workers (HCWs) in two designated hospitals for coronavirus disease 2019 (COVID-19) treatment in Wuhan and explore the factors associated with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. All HCWs in Wuhan Union Hospital and Wuhan Red Cross Hospital with either positive SARS-CoV-2 nucleic acid or positive antibody test before 18 April 2020 were included. Exposure, epidemiological and demographic information were retrospectively collected by a structured questionnaire. Medical records were also reviewed for clinical characteristics and CT images of HCWs. As of 18 April 2020, a total of 424 HCWs were identified. Among them, 276 (65.1%) were symptomatic and 148 (34.9%) were asymptomatic. Fifty-five (19.9%) families of the symptomatic HCWs and 16 (10.8%) families of the asymptomatic HCWs were infected with SARS-CoV-2. HCWs with infected family members tended to be symptomatic (OR 2.053, 95% CI 1.130-3.730; p 0.018). Multivariable logistic regression analysis exhibited that performing tracheal intubation or extubation (OR 4.057, 95% CI 1.183-13.909; p 0.026) was associated with an increased likelihood of symptomatic SARS-CoV-2 infection, whereas consistent use of N95 respirators (OR 0.369, 95% CI 0.201-0.680; p 0.001) and eye protection (OR 0.217, 95% CI 0.116-0.404; p < 0.001) were associated with an increased likelihood of asymptomatic SARS-CoV-2 infection. Asymptomatic SARS-CoV-2 infection in HCWs comprised a considerable proportion of HCW infections during the pandemic of COVID-19. Those who performed tracheal intubation or extubation were most likely to develop related symptoms, whereas those taking aggressive measures, including consistent use of N95 masks and eye protection, tended to be asymptomatic cases.


Mouse hepatoma and liver ferritins. Comparative structural studies.
Pure ferritin from male mouse liver produces a single band of monomers (RF = 0.199) with electrophoresis in polyacrylamide gels at pH 9.0. The five sub-bands within this monomeric band appear to represent charge isomers having the same molecular size. Ferritin from BH3 transplantable mouse hepatoma shows two overlapping bands of monomers (RFA = 0.208 and RFB = 0.240); further electrophoretic studies show that these bands represent two subpopulations of molecules differing both in charge and size. Sub-bands are not found in this hepatoma ferritin. The larger tumor ferritin reaches the same end migration position as all liver isoferritins on gradient gels, signifying a very similar or identical molecular size; however, the absence of sub-bands indicates that this hepatoma ferritin differs in charge from the homologous liver proteins. Liver and hepatoma ferritins both produce a single prominent subunit band corresponding to nominal molecular weights of 22 250 and 21 700, with polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and dithiothreitol. With electrophoresis on polyacrylamide gradient slabs containing sodium dodecyl sulfate and dithiothreitol, both liver and hepatoma ferritins now reveal two subunits bands situated at identical positions. The polypeptides of these two closely spaced bands have a nominal molecular weight difference of less than 1000. Neither the hepatoma nor the liver seems to produce the ferritins found in the other tissue. Nevertheless, all these ferritins are composed of the same two types of subunits, albeit in different relative amounts. Observed distinctions in the ferritins from these normal or neoplastic cells must reflect differences in assembly and processing, as well as in the regulated expression of the same ferritin genes.


Monitoring of multiple bacteriocins through a developed dual extraction protocol and comparison of HPLC-DAD with turbidometry as their quantification system.
The present study describes the development of a simple and efficient screening system that allows identification and quantification of nine bacteriocins produced by Lactococcus lactis. Cell-free L. lactis extracts presented a broad spectrum of antibacterial activity, including Gram-negative bacteria, Gram-positive bacteria, and fungi. The characterization of their sensitivity to pH, and heat, showed that the extracts retained their antibacterial activity at extreme pH values and in a wide temperature range. The loss of antibacterial activity following treatment of the extracts with lipase or protease suggests a lipoproteinaceous nature of the produced antimicrobials. The extracts were subjected to a purification protocol that employs a two phase extraction using ammonium sulfate precipitation and organic solvent precipitation, followed by ion exchange chromatography, solid phase extraction and HPLC. In the nine fractions that presented antimicrobial activity, bacteriocins were quantified by the turbidometric method using a standard curve of nisin and by the HPLC method with nisin as the external standard, with both methods producing comparable results. Turbidometry appears to be unique in the qualitative determination of bacteriocins but the only method suitable to both separate and quantify the bacteriocins providing increased sensitivity, accuracy, and precision is HPLC.


Stereophotogrammetric head shape assessment in neonates is feasible and can identify distinct differences between term-born and very preterm infants at term equivalent age.
The development of head shape and volume may reflect neurodevelopmental outcome and therefore is of paramount importance in neonatal care. Here, we compare head morphology in 25 very preterm infants with a birth weight of below 1500 g and / or a gestational age (GA) before 32 completed weeks to 25 term infants with a GA of 37-42 weeks at term equivalent age (TEA) and identify possible risk factors for non-synostotic head shape deformities. For three-dimensional head assessments, a portable stereophotogrammetric device was used. The most common and distinct head shape deformity in preterm infants was dolichocephaly. Severity of dolichocephaly correlated with GA and body weight at TEA but not with other factors such as neonatal morbidity, sex or total duration of respiratory support. Head circumference (HC) and cranial volume (CV) were not significantly different between the preterm and term infant group. Digitally measured HC and the CV significantly correlated even in infants with head shape deformities. Our study shows that stereophotogrammetric head assessment is feasible in all preterm and term infants and provides valuable information on volumetry and comprehensive head shape characteristics. In a small sample of preterm infants, body weight at TEA was identified as a specific risk factor for the development of dolichocephaly.


Neuroprotective flavonoids from Flemingia macrophylla.
Using an Abeta-induced neurotoxicity blocking assay to direct fractionation, three new flavonoids, fleminginin (1), flemingichromone (2), and flemingichalcone (3), and twenty known compounds were isolated from the active fractions of the aerial parts of Flemingia macrophylla. The structures of 1 - 3 were elucidated on the basis of spectroscopic data. When tested for neuroprotective activity, compound 2, osajin ( 4), 5,7,4'-trihydroxy-6,8-diprenylisoflavone (5), 5,7,4'-trihydroxy-6,3'-diprenylisoflavone (6), and aureole (7) protected neuronal cells from Abeta-induced damage with EC50 values of 31.43 +/- 3.16, 5.01 +/- 1.28, 11.25 +/-1.51, 4.47 +/- 0.65, 12.09 +/- 2.55 microM, respectively.


A technique for fabrication of an extracoronal attachment-retained removable partial denture to fit an existing fixed partial denture.
Precision attachments have been used for many years to retain removable partial dentures (RPDs). Common reasons for a failed attachment-retained RPD are fracture of the framework, fracture of the roots or teeth, and irretrievable decrease of retention. When an RPD framework major connector has been fractured, it should be remade. This article describes a technique to remake a fractured mandibular RPD using cast round profile attachment analogs without the need for replacement of the fixed partial denture.


Transient bone marrow oedema of the knee.
To evaluate the role of MRI in the diagnosis of transient bone marrow oedema of the knee. All cases were analysed with plain film and MR. Bone scan was performed to one of them. Laboratory tests were obtained in all 8 cases and core decompression was performed in two cases. The study includes 8 patients, 7 men and 1 woman with ages ranging from 33 to 74 years with severe knee pain, tenderness and slightly limited range of motion. Radiographs were unremarkable in terms of osteopenia because they were obtained early in the course of the disease and proved to be of no value in the diagnosis. MR is the imaging modality of choice showing low signal intensity in T1WI and increased signal intensity in T2WI with no joint destruction, fractures, bone death, periostitis or cortical disruption. Bone scan showed increase uptake of the affected area. Laboratory tests were normal. Spontaneous resolution was the rule. It should not be a diagnosis of exclusion and it should be ruled out every time a patient presents with pain and limited range of motion in the absence of history of trauma.


Postoperative Blepharoptosis After Pars Plana Vitrectomy Procedure.
To describe the frequency of blepharoptosis and factors affecting it after the pars plana vitrectomy (PPV) procedure. In a prospective study, patients were recruited consecutively from October 2016 to June 2018. Upper eyelid margin reflex distance 1 and 2 (MRD1 and 2), upper eyelid crease height, and levator function were measured before, 1 and at least 6 months after surgery by the same investigator. Clinical and Clinically significant ptosis were defined as ≥0.5 and ≥2 mm drop of MRD1. There were 60 eyes from 57 patients. The majority of surgeries were performed by the fellows (63.3%, 38/60) and under general anesthesia (95.0%, 57/60). Clinical and clinically significant ptosis following PPV were 47.2% (25/53) and 11.3% (6/53) at the last follow up (at least 6 months), respectively. MRD2 (p = 0.389) and eyelid crease height (p = 0.057) did not significantly change. Surgeons' level, time of the procedure and other variables were not significantly impacting the frequencies. Persistent clinically significant ptosis was observed in 11% of patients undergoing PPV. No variable was significantly associated with persistent postoperative ptosis after PPV.


Mutation of histone H3 serine 86 disrupts GATA factor Ams2 expression and precise chromosome segregation in fission yeast.
Eukaryotic genomes are packed into discrete units, referred to as nucleosomes, by organizing around scaffolding histone proteins. The interplay between these histones and the DNA can dynamically regulate the function of the chromosomal domain. Here, we interrogated the function of a pair of juxtaposing serine residues (S86 and S87) that reside within the histone fold of histone H3. We show that fission yeast cells expressing a mutant histone H3 disrupted at S86 and S87 (hht2-S86AS87A) exhibited unequal chromosome segregation, disrupted transcriptional silencing of centromeric chromatin, and reduced expression of Ams2, a GATA-factor that regulates localization of the centromere-specific histone H3 variant CENP-A. We found that overexpression of ams2(+) could suppress the chromosome missegregation phenotype that arose in the hht2-S86AS87A mutant. We further demonstrate that centromeric localization of SpCENP-A(cnp1-1) was significantly compromised in hht2-S86AS87A, suggesting synergism between histone H3 and the centromere-targeting domain of SpCENP-A. Taken together, our work presents evidence for an uncharacterized serine residue in fission yeast histone H3 that affects centromeric integrity via regulating the expression of the SpCENP-A-localizing Ams2 protein. [173/200 words].