Conductive and enzyme-like silk fibers for soft sensing application.
A combination of supercritical carbon dioxide (scCO2) impregnation of pyrrole and sonochemical transformation of permanganate (KMnO4) was used to impart conductive and catalytic properties to silk fibers. The results indicated that the conductivity (from polypyrrole -PPy) and catalytic activities (from manganese dioxide -MnO2) were independent and complementary within the processing parameters used. The enhanced conductivity was attributed to scCO2 preferentially distributing the pyrrole monomers along with the silk internal fibrillar structure and hence, yielding a more linear PPy. The oxidative properties of the PPy-MnO2-silk hybrid showed an enzyme-like behavior for the degradation of hydrogen peroxide (H2O2) with a Km of about 13 mM and specific activity of 1470 ± 75 μmol/min/g. Finally, we demonstrated that the PPy-MnO2-silk hybrid could be used as soft working electrodes for the simultaneous degradation and detection of H2O2.


Scanning electron microscopy studies of the antennal sensilla of Metaphycus parasaissetiae Zhang & Huang (Hymenoptera: Encyrtidae).
Metaphycus parasaissetiae Zhang & Huang (Hymenoptera: Encyrtidae) is an important adult parasitoid of Parasaissetia nigra Nietner (Hemiptera: Coccoidea). The external morphology of the antennal sensilla of male and female M. parasaissetiae was examined using scanning electron microscopy. The geniculate antennae of male and female M. parasaissetiae were composed of a scape with a basal radicula, a barrel-shaped pedicel, and a long flagellum. Twelve morphologically distinct types of sensilla were identified, including multiporous placoid sensilla, campaniform sensilla, finger-like sensilla, multiporous basiconic sensilla (BS-1), three aporous types of basiconic sensilla (BS-2, BS-3, and BS-4), two types of aporous trichoid sensilla (TS-1 and TS-3), a type of multiporous trichoid sensilla (TS-2), and two types of sensilla chaetica (CH-1 and CH-2). Sex dimorphism in the sensilla composition of M. parasaissetiae is also observed. Major differences between the sexes were found in the number, distribution, shape, structure, and size of the identified sensilla. We also discuss on the functional aspects of these sensilla to elucidate the mechanisms involved in host searching and courtship behavior of M. parasaissetiae.


Review of Proxima DeLong amp; Freytag (Hemiptera: Cicadellidae: Gyponini) with description of two new species from Brazil and identification key to species.
The previously monotypic genus Proxima DeLong Freytag, 1975 is reviewed and new diagnostic characters are added. The type-species Proxima ocellata DeLong Freytag, 1975 described from the State of Esprito Santo, Brazil, is redescribed and newly recorded from the State of Minas Gerais. Also, two new species are described and illustrated: Proxima nigromaculata sp. nov. from the states of Esprito Santo, Maranho, Minas Gerais, Rio de Janeiro and Rio Grande do Sul and Proxima meloi sp. nov. from the states of Bahia and Minas Gerais. An identification key to the species of the genus is provided.


Plasma viscosity in isolated systolic hypertension: the role of pulse pressure.
Atherosclerosis is increasingly recognized as an inflammatory vascular disease, and high blood pressure (BP) has been suggested to exert a proinflammatory action. Whether plasma viscosity (PV), a major determinant of blood flow in microcirculation and a marker of systemic inflammation and cardiovascular risk, is increased in elderly subjects with isolated systolic hypertension is not known. In addition, the correlation of BP and its pulsatile component (ie, pulse pressure [PP]), with PV levels independent of the confounding effect of other cardiovascular risk factors has not been investigated. To this aim, we measured PV in 108 elderly men with never treated, uncomplicated isolated systolic hypertension, and in 60 healthy matched normotensive control subjects. The PV values were higher in hypertensive subjects than in controls (1.39+/-0.11 v 1.34+/-0.09 cP, P<.01). The PV showed a significant direct relation with both systolic BP (r=0.32) and PP (r=0.37, both P<.01), but not with diastolic BP (r=-0.03, P=.68). The PV was also directly associated with serum low-density lipoprotein cholesterol and triglycerides. In a multivariate analysis, PP was a significant predictor of PV levels when a consistent number of cardiovascular risk factors were simultaneously controlled for. In conclusion, PV is elevated in elderly subjects with isolated systolic hypertension. Systolic BP and PP appear to be major determinants of PV levels in these patients, independent of the potential proinflammatory action of traditional cardiovascular risk factors.


Expansion of human autologous cytotoxic T lymphocytes on fixed target tumor cells.
Human tumor specific cytotoxic T lymphocytes (CTL) were expanded on formalin-fixed autologous target tumor cells derived from glioblastoma multiforme. Growth response of the CTL restimulated with the fixed target cells was larger than those with live target cells. The results suggest that formalin-fixed tumor cells will be stable sources of tumor antigen for efficient autologous CTL expansion and be useful for adoptive immunotherapy of tumors.


Bayesian Meta-analysis of Safety Outcomes Using Blinded Clinical Trial Data.
During the development of an investigational new drug, identifying potential safety risks is imperative. Early detection, as well as federal regulations, requires safety monitoring procedures during clinical trials while the data are still blinded. We introduce a Bayesian meta-analytic approach for detecting a potential elevated safety risk conferred by an investigational treatment, as compared to control, using blinded data from multiple trials. Simulation studies of our approach demonstrate good operating characteristics when some relevant prior information is available. The utility of our procedure is demonstrated on data from a real clinical trial program with informative results based on blinded data compared with unblinded data. At any time during the drug development program, our approach provides easily interpretable posterior probability statements about the risk ratio for the safety event(s) of interest.


Detection of differentially regulated genes in ischaemic equine intestinal mucosa.
Colic is a serious disease syndrome in horses. Much of the mortality is associated with ischaemic-injured intestine during strangulating obstruction, yet there is limited understanding of the associated molecular events. Identification of differentially expressed genes during ischaemic injury should expand our understanding of colic and may lead to novel targeted therapeutic approaches in the future. To isolate and identify differentially expressed genes in equine jejunum following a 2 h ischaemic event compared to normally perfused jejunum. Suppressive subtractive hybridisation was used to clone genes that are differentially expressed in equine jejunum injured by 2 h of complete ischaemia as compared to time-matched control jejunal tissues. Expression of selected clones was further evaluated by northern blot analysis. Of the 384 clones selected, 157 were confirmed to possess cDNAs corresponding differentially expressed genes by dot blot analysis. Two genes, fatty acid binding protein 2 and calcium-activated chloride channel 4 were further confirmed to be differentially expressed by northern blot analysis. Suppressive subtractive hybridisation can be used to detect changes in expression of a broad array of genes, as confirmed by northern blot analysis of selected genes. These initial results have identified a pool of equine intestinal epithelial genes that are differentially expressed following a 2 h ischaemic event. In particular, genes indicative of deranged metabolic activity and those potentially involved in early repair events were identified and may ultimately provide clues as to the nature of epithelial ischaemic injury in horses.


Effect of particle sizes of biochar on CO2 emissions in a poplar plantation of ancient Yellow River channel, China.
Forest soil is a vital pool of organic carbon, which is sensitive to management. Biochar addition could change the CO2 emissions from soil, but its effects are still ambiguous. Moreover, the impacts of particle sizes of biochar on CO2 emissions are still unknown. In this study, a series of field experiments were conducted to investigate the effects of biochar addition on CO2 emissions in a poplar plantation (Populus nigra), China. Biochar with two application rates of (10 and 50 t/ha) and three particle sizes (3-1 mm, 1-0.1 mm, and <0.1 mm) was applied into the surface soil (0-10 cm), and the soil without biochar was set as control. The results showed that a high level of fine biochar addition (1-0.1 mm and <0.1 mm) had similar and positive effects on CO2 emissions by increasing the contents of soil ammonium, available phosphorus, easily oxidizable carbon, soil moisture, soil capillary pore, and the activity of β-glucosidase. However, biochar addition (1-0.1 mm and <0.1 mm) reduced the bioavailability of dissolved organic carbon (DOC), producing a negative relationship between DOC content and CO2 emissions. This investigation highlights the importance of biochar with different particle sizes in adjusting CO2 emissions from temperate soils.


Reproducibility of the Persian Version of the ABILOCO Questionnaire for Stroke Patients.
The ABILOCO is a questionnaire assessing and measuring the locomotion ability to perform activities daily living from easy to hard in stroke patients. The ABILOCO was translated into Persian and retranslated into English. Forty hemiplegic stroke patients with an average age (60 ± 7.5 years) participated in the study. The participants were interviewed using ABILOCO and were assessed by the interviewer and observer. The total logit score of the participants was also assessed by using the interclass correlation coefficient (ICC). The results were showed the high correlation between the first interview of interviewer and the observer (ICC = 0.8, P < 0.05). In addition, a strong relationship was observed between the interviewer's first and second interviews after a week (ICC = 0.85, P < 0.05). The Persian edition of ABILOCO is reliable to assess walking ability of stroke patients in clinics and studies.


Brachial plexus palsy: intrauterine onset.
A newborn had a combination of brachial plexus palsy and phrenic nerve palsy associated with a small left arm, deformed ribs on the left, and an area of subcutaneous calcification on the left side of the neck. These lesions represent a deformation syndrome due to uterine constraint in a bicornuate uterus. Appropriate diagnosis can initiate management to avoid problems in subsequent pregnancies.


Surgical Management of Peyronie's Disease.
When choosing a management strategy for a patient with Peyronie's disease (PD), it is critical to consider the phase of the disease, penile plaque characteristics, degree of curvature, associated deformities, stretched penile length, and baseline erectile function. Equally important is an understanding of the patient's goals and expectations. Treatment cost and duration may also be vital considerations for the patient. In this case, the degree of curvature and large calcified plaque make treatment with intralesional injection of collagenase Clostridium histolyticum unlikely to result in a functionally straight erection despite 6-7 mo of therapy. Conversely, surgery with either penile plication or plaque incision/partial excision and grafting can provide reliable straightening with 0-1 d of hospitalization and approximately 6 wk of recovery. With careful preoperative counseling and joint decision-making, surgical treatment of PD deformity can provide more complete correction in less time and at lower overall costs.


Generation of CHOPe003-A ESC line to study an ACTG2 variant affecting smooth muscle development and function.
Dysfunction of visceral smooth muscle ("visceral myopathy") impairs bowel, bladder, and uterine function. Symptoms of this life-threatening condition include massive intestinal distension with slow transit, vomiting, feeding intolerance, growth failure, poor bladder emptying, and difficult vaginal delivery. The most common genetic cause of visceral myopathy is a heterozygous point mutation (R257C) in gamma smooth muscle actin (ACTG2). We genetically modified the WAe0009-A human embryonic stem cell line to carry the c.769C>T p.R257C/+ mutation. This cell line will facilitate studies of how the ACTG2 R257C heterozygous variant affects smooth muscle development and function.


Cocaine hepatotoxicity: two different toxicity mechanisms for phenobarbital-induced and non-induced rat hepatocytes.
Hepatocytes isolated from both phenobarbital-induced and control rats were short-term cultured and exposed to cocaine (8-2000 microM) for varying times. Intracellular lactate dehydrogenase activity, free calcium levels ([Ca2+]i), reduced glutathione (GSH) and lipid peroxidation were investigated to evaluate the toxic effect of cocaine on hepatocytes. Cytochrome P450 induction by phenobarbital potentiated the in vitro cytotoxicity of cocaine by a factor of 13 (IC50 = 84 microM in induced cells vs 1100 microM in non-induced cells). This difference in the susceptibility of the two types of hepatocytes to cocaine correlated well with the activity of cytochrome P450 2B1/2. Rapid depletion of GSH, reaching 30% of the control levels, and massive lipid peroxidation thereafter were the two most remarkable phenomena preceding cell death in phenobarbital-induced hepatocytes. On the other hand, a sustained rise in [Ca2+]i starting 2 hr after incubation with cocaine was the most noteworthy finding in non-induced liver cells. We suggest two different pathways for cocaine hepatotoxicity: in phenobarbital-induced hepatocytes oxidative metabolism of the drug causes GSH depletion, subsequent extensive lipid peroxidation and cell death, at low concentrations of cocaine. In non-induced hepatocytes these changes are less relevant, and the major alteration caused by cocaine is a non-transient rise in [Ca2+]i that is evident at higher concentrations of the drug.


Estimation of noncompartmental parameters: a technical note.
Noncompartmental pharmacokinetic parameters are usually expressed in terms of the area under the so-called first moment curve and the area under the plasma concentration-time curve. These areas are normally computed by numerical integration. There is an inconsistency in the way in which they are presently estimated. This inconsistency is detailed and a consistent approach to the computation of noncompartmental parameters is outlined. The difference between the two methods is illustrated using some data from the literature.


Predictive modeling of groundwater nitrate pollution and evaluating its main impact factors using random forest.
Groundwater quality in plains and basins of arid and semi-arid regions with increased agriculture and urbanization development faces severe nitrate pollution, which is affected by both climate and anthropogenic activities. Here, shallow groundwater nitrate concentrations in the Yinchuan Region in central Yinchuan Plain were modeled during 2000, 2005, 2010, and 2015 using random forest. Multiple spatial environment factors were taken as predictor variables. The relative importance of these factors was also calculated using the constructed model. Remote sensing and GIS methods were used to compile various environmental factors to generate training and test sets for training and validation of the random forest model. Mean absolute error (MAE), root mean square error (RMSE), and coefficient of determination (R2) between the observed and predicted groundwater nitrate concentrations were used to measure the model performance. As indicated by these metrics, the random forest model for groundwater nitrate prediction was performed well. The relative importance of the predictor variables computed by the model indicated groundwater nitrate was mainly affected by the distance to the Yellow River, meteorological elements (precipitation, evaporation, and mean air temperature), and water level elevation. Additionally, urban and arable land were the two land use/land cover types that mainly influenced groundwater nitrate concentration in the Yinchuan Region, of which urban land was more influential than arable land as a result of intense expansion of urban land from 2000 to 2015. Overall, the current study provides an approach to integrate multiple environmental factors for groundwater quality study and is also significant for sustainable groundwater management in the Yinchuan Region.


Biofilm Producing Staphylococcus epidermidis (RP62A Strain) Inhibits Osseous Integration Without Osteolysis and Histopathology in a Murine Septic Implant Model.
Despite its presence in orthopaedic infections, Staphylococcus epidermidis's ability to directly induce inflammation and bone destruction is unknown. Thus, we compared a clinical strain of methicillin-resistant biofilm-producing S. epidermidis (RP62A) to a highly virulent and osteolytic strain of methicillin-resistant Staphylococcus aureus (USA300) in an established murine implant-associated osteomyelitis model. Bacterial burden was assessed by colony forming units (CFUs), tissue damage was assessed by histology and micro-computed tomography, biofilm was assessed by scanning electron microscopy (SEM), host gene expression was assessed by quantitative polymerase chain reaction, and osseous integration was assessed via biomechanical push-out test. While CFUs were recovered from RP62A-contaminated implants and surrounding tissues after 14 days, the bacterial burden was significantly less than USA300-infected tibiae (p < 0.001). In addition, RP62A failed to produce any of the gross pathologies induced by USA300 (osteolysis, reactive bone formation, Staphylococcus abscess communities, marrow necrosis, and biofilm). However, fibrous tissue was present at the implant-host interface, and rigorous SEM confirmed the rare presence of cocci on RP62A-contaminated implants. Gene expression studies revealed that IL-1β, IL-6, RANKL, and TLR-2 mRNA levels in RP62A-infected bone were increased versus Sterile controls. Ex vivo push-out testing showed that RP62A-infected implants required significantly less force compared with the Sterile group (7.5 ± 3.4 vs. 17.3 ± 4.1 N; p < 0.001), but required 10-fold greater force than USA300-infected implants (0.7 ± 0.3 N; p < 0.001). Taken together, these findings demonstrate that S. epidermidis is a commensal pathogen whose mechanisms to inhibit osseous integration are limited to minimal biofilm formation on the implant, and low-grade inflammation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:852-860, 2020.


Photodynamic therapy for superficial bladder cancer under local anaesthetic.
To evaluate the use of local anaesthesia (LA) in 5-aminolaevulinic acid (ALA) photodynamic therapy (PDT) for superficial transitional cell carcinoma (TCC) of the bladder, and to provide further toxicity and tolerability data on this new method within the context of a phase 1 trial. ALA PDT was administered to 19 patients with recurrent superficial TCC (stage Ta/carcinoma in situ, grades 1-3) using escalating doses of ALA (3-6%) and 633 nm laser light (25-50 J/cm2) under various LA (lignocaine) protocols. Pain was assessed using a linear analogue scale from 0 to 10. The endpoints of tolerability and toxicity were assessed for the different LA, light and ALA doses, with lignocaine levels. ALA PDT is painful and requires some form of anaesthesia. The discomfort was immediate, associated with bladder spasm, and was a function of the ALA concentration rather than the total light dose given. Simple passive diffusion (PD) of 2% lignocaine instilled for 40 min before PDT gave adequate anaesthesia with 3% ALA (n=8; median pain score 1, range 0-2). With 6% ALA the pain was dramatically increased using PD (n=6; median pain score 8, range 5-10) and therefore the more potent LA technique of electromotive drug administration (EMDA) of 2% lignocaine was used, with excellent results (n=3; median pain score 1, range 0-2). All patients had transient bladder irritability that typically lasted 9-12 days, with no subjective/objective change in long-term bladder function. No other toxicity was reported. Serum lignocaine levels were minimal. Bladder ALA PDT is both safe and feasible under LA. At a dose of 3% ALA, the procedure was well-tolerated using PD of lignocaine. At higher doses (6% ALA) more effective anaesthesia is required and this can be obtained satisfactorily with EMDA of lignocaine. With refinement, ALA PDT may be feasible as an outpatient treatment for superficial bladder TCC.


Skin Reactions to Immune Checkpoint Inhibitors.
The novelty of immune checkpoint inhibitors has only recently led to the characterization of cutaneous adverse events (AEs). This, along with the substantial rate of cutaneous reactions, has left many clinicians without sufficient familiarity to diagnose and treat. In the following chapter, we will review the categories of these drugs, common cutaneous effects, their grading, and management options.


Implementation of enhanced recovery after surgery pathway for patients undergoing mastectomy.
Mastectomy is still a common treatment for breast cancer. The introduction of the Enhanced Recovery After Surgery pathway (ERAS) having proven its benefits for major surgeries has not yet been validated for mastectomy without reconstruction. Our study was conducted to investigate the effects of implementing an ERAS pathway for mastectomies, including the length of hospital stay, postoperative complications and patient satisfaction. The study population included all patients who underwent mastectomy without immediate breast reconstruction in the gynecological surgery department of the Tours University Hospital during the year 2020. We compared patients who underwent an ERAS protocol with those who were managed in a standard manner. Of the 92 patients managed for mastectomy, 32 were managed in the ERAS group. The two groups were comparable. We found fewer postoperative complications with this protocol in multivariate analysis. We also obtained a 37% response rate to the satisfaction questionnaires. We did not find any significant difference between the 2 groups. There is a trend towards a decrease in the length of hospitalization associated with a decrease in postoperative complications thanks to the implementation of a ERAS protocol for the management of mastectomies. Future studies should focus on both objective clinical outcomes and patient-reported experiences to provide a comprehensive understanding of the effectiveness of ERAS protocols in mastectomy patients.


[Pseudomyxoma peritonei (PMP) secondary to mucinous carcinoma of the ovary: a case study].
Pseudomyxoma peritonei (PMP), also referred to as gelatinous ascites, is a rare disorder, described for the first time by R. Wyerth in 1884. It is characterized by diffuse peritoneal involvement, composed of mucinous ascites and multifocal mucinous epithelial implants. This disease mainly affects women. Its incidence is estimated at 2 cases per one million inhabitants. Pseudomyxoma peritonei can be asymptomatic, discovered during a laparotomy. The most common symptom is abdominal distension associated with diffuse abdominal pain. Abdominal CT scan is the most specific diagnostic tool. It shows pathognomonic signs of gelatinous ascites. Mucinous neoplasms of the appendix are the most frequent cause of pseudomyxoma peritonei accounting for 90% of cases. Pseudomyxoma peritonei of ovarian origin is very rare. There are essentially two types of treatment: multiple debulking surgery and cytoreductive surgery with perioperative intraperitoneal chemotherapy consisting of hyperthermic intraperitoneal chemotherapy with or without immediate postoperative intraperitoneal chemotherapy. We report a case of pseudomyxoma peritonei secondary to mucinous carcinoma of the left ovary.


Effect of alcohol dosage on long-term outcomes after alcohol septal ablation in patients with hypertrophic cardiomyopathy.
The aim of this study is to assess the long-term effects of alcohol dosage in alcohol septal ablation (ASA) on mortality and adverse arrhythmic events (AAE). ASA can be performed to reduce left ventricular outflow tract (LVOT) obstruction in patients with hypertrophic cardiomyopathy (HCM). However, the effect of alcohol dosage on long-term outcomes is unknown. This retrospective cohort study includes 296 HCM patients (age 60 ± 22 years, 58% male) who underwent ASA because of symptomatic LVOT obstruction. Twenty-nine patients (9.8%) were excluded because the alcohol dosage could not be retrieved. Primary endpoints were all-cause mortality and AAE. During 6.3 ± 3.7 years of follow-up, all-cause mortality and AAE rates were similar in patients who received ≤2.0 mL (n = 142) and >2.0 mL (n = 121) alcohol during ASA. Age was the only independent predictor of mortality (HR 1.1 95% CI 1.0-1.1, P < 0.001). Predictors of AAE were maximum CK-MB >240 U/L (HR 3.3 95% CI 1.5-7.2, P = 0.003), and sudden cardiac death survivor (HR 5.9 95% CI 1.7-20.3, P = 0.004). There was a mild to moderate correlation between CK-MB levels and amount of alcohol (Spearman's ρ 0.39, P < 0.001), cross-sectional area of the target septal branch ostium/ostia (Spearman's ρ 0.19, P = 0.003), and maximum ventricular wall thickness (Spearman's ρ 0.17, P = 0.006). Alcohol dosage appears not to have a long-term effect on mortality and AAE. A larger infarct size created by ASA increases the risk of AAE, and extended monitoring of these patients is advised. © 2016 Wiley Periodicals, Inc.


[Biomechanical study of a ventral stand-alone cage for the lumbar spine with and without additional posterior fixation].
Biomechanical study to examine the stability of a stand-alone cage (SAC; Topaz, Ulrich Medizintechnik, Ulm) incorporating integrated anterior fixation with and without additional posterior fixation. Six human spinal specimens (L4/5) were loaded in a spine tester in the three main motion planes in the following states: (a) intact, (b) defect (nucleotomy), (c) SAC, (d) SAC+internal fixator (IF), and (e) SAC+translaminar facet screws (TFS). Facet joint translation (FJT) and range of motion (ROM) were measured and used to evaluate the stability of the tested states. The SAC stabilized the segment in comparison to the intact (a) and defect-containing (b) segments. The most rigid fixation was found for SAC+IF compared with the other states (a, b, c, e). The ROM and FJT of the SAC with the additional IF (d) showed a significant higher stability in all three motion planes. All differences in ROM and FJT between the tested states were statistically significant (p<0.05) except for the FJT SAC and SAC+TFS. The ventral Topaz SAC is a stable implant for the lumbar spine. Additional dorsal stabilization is an option to increase the stability.


Human papillomavirus (HPV) infection in a case-control study of oral squamous cell carcinoma and its increasing trend in northeastern Thailand.
Human papillomavirus (HPV) is an independent risk factor for development of oral squamous cell carcinoma (OSCC). This study aimed to investigate the role of HPV infection and the trend in percentage of HPV-associated OSCC over a 5-year period in northeastern Thailand. In this case-control study, 91 exfoliated oral cell samples and 80 lesion cell samples from OSCC cases and exfoliated oral cells from 100 age/gender-matched controls were collected. HPV infection was investigated by PCR using GP5+/GP6+ primers followed by HPV genotyping using reverse line blot hybridization. Quantitative RT-PCR was used to evaluate HPV oncogene transcription. Temporal trends of HPV infection were evaluated in archived formalin-fixed paraffin-embedded (FFPE) OSCC tissues using in situ hybridization. HPV DNA was found in 17.5% (14/80) of lesion samples from OSCC cases and 29.7% (27/91) of exfoliated oral cell samples from the same cases. These values were significantly higher than in exfoliated oral cell samples from controls (13%, 13/100). HPV-16 was the genotype most frequently found in OSCC cases (92.8%, 13/14 infected cases). Interestingly, HPV oncogene mRNA expression was detected and correlated with OSCC cases (P < 0.005). Of 146 archived FFPE OSCC samples, 82 (56.2%) were positive for high-risk HPV DNA and 64 (43.8%) cases were positive for HPV E6/E7 mRNA expression. There was a trend of increasing percentage of HPV-associated OSCC from 2005 to 2010. This was especially so for females with well-differentiated tumors in specific tongue sub-sites. We suggest that HPV infection plays an important role in oral carcinogenesis in northeastern Thailand.


Regeneration pattern of cardiac and skeletal muscle after transplantation into a skeletal muscle bed in rats.
The ability of skeletal muscle to regenerate after injury is well established. In contrast, cardiac muscle is incapable of regeneration and recovery after injury. The aim of the present study was to evaluate and compare the regeneration pattern of cardiac and skeletal muscle after transplantation into a skeletal muscle bed in rats. The following group of transplants were performed at the site prepared by removing the host extensor digitorum longus (EDL) muscle. The first group consisted of cardiac muscle transplanted as one piece or after mincing into 1-mm pieces. The second group included cotransplants of cardiac and skeletal muscle minces that were intermixed. Entire EDL muscle or minced EDL muscle were also transplanted for comparison. Rats were sacrificed 3-30 days after transplantation for morphological analysis. The results demonstrated that skeletal muscle transplants underwent rapid regeneration, and by 30 days the entire muscle was filled with regenerated myofibers. In transplants of cardiac muscle significant inflammation, myocardial degeneration and necrosis were observed. In spite of the necrosis and fibrosis, the presence of a few regenerated myotubes in the outer region was observed. In cardiac and skeletal muscle cotransplants, the inflammation was restricted to cardiac tissue; however, by 30 days the entire cotransplant was filled with regenerated myotubes and myofibers. These results show that skeletal muscle is capable of growth, regeneration, and integration with the cardiac muscle after cotransplantation. Combination of skeletal and cardiac muscle may prove useful in defining the cellular processes necessary for enhancing cardiac repair after injury.


Laparoscopy in 533 patients with abdominal malignancy.
Laparoscopy in patients with intra-abdominal malignancy remains controversial. This study evaluates the incidence of tumor recurrence at the port site after laparoscopy in patients with intra-abdominal malignancy. The medical records of all patients with nongynecologic malignancies who underwent laparoscopic procedures between May 1, 1990, and June 30, 1996, at the University of Texas M.D. Anderson Cancer Center were reviewed. Data on extent of tumor, histologic findings, primary location, procedures performed, and complications were recorded. During this time, 533 patients with known intra-abdominal malignancies underwent laparoscopy. Mean follow-up time was 13.2 +/- 0.5 months (range 1 to 71 months; median 10.6 months). Four recurrences at the port site were identified (0.8%). Three of these patients had advanced intra-abdominal disease at the time of laparoscopy; 1 patient without advanced disease at the time of laparoscopy had a recurrence at the port site as the only site of recurrent disease (0.19%). The incidence of port site recurrences among patients with advanced intra-abdominal disease at the time of laparoscopy (3/71) was significantly greater than the risk of development of a recurrence at the port site among patients without advanced intra-abdominal disease at the time of laparoscopy (1/462; P < .0003, by chi-square analysis). Recurrence at the port site is very rare. When implantation at the port site does occur, it is most commonly associated with advanced intra-abdominal disease.


Ion-selective reversing aggregation-caused quenching - Maximizing optodes signal stability.
An alternative optical signal transduction mechanism for ion-selective optodes is proposed. The nanostructural sensors benefit from ion-selective reversing aggregation caused quenching yielding turn-on, bright and highly stable optical signals. Selective incorporation of analyte results in transformation of the polymer dye from aggregate to a micelle structure, affecting spatial arrangement of chromophore groups in the nanostructure. Formation of micelles, induced by ion-selective interactions, is coupled with pronounced increase of emission due to decrease of aggregation caused quenching, characteristic for dispersed phase formation. The formed micelles are highly stable in solution, offering constant in time (days scale) emission signal. The important difference from other known systems is that the analyte binding induced change does not affect the chromophore group, but occurs in distant, terminal position of the side chain of the polymer. As a model system calcium selective optodes have been prepared. Thus obtained probes were characterized with broad analyte concentration range (from 10-7 to 10-3 M) emission signal increase. The turn-on response was observed within broad range of pH (6.3-8.9), with no sign of optical signal deterioration during 5 days contact with the analyte or more than two weeks storage.


Diethylstilbestrol-related clear-cell adenocarcinoma in women with initial examinations demonstrating no malignant disease.
The DES Screening Center of Queens, Nassau, and Suffolk counties has screened approximately 2000 diethylstilbestrol (DES)-exposed women since its inception in 1979. Four women, who at their initial visit were noted to have only nonmalignant DES-related changes, subsequently developed clear-cell adenocarcinoma while under observation, between 18-81 months after their first colposcopy. The age at diagnosis ranged from 16-31. Three patients had been receiving close follow-up; one had not. These cases emphasize the need for frequent follow-up for these patients using careful inspection and palpation, vaginal and cervical cytology, colposcopy, and colposcopically directed biopsy of suspicious areas.


Factors Associated With Neurocognitive Impairment Following Chemoradiotherapy in Patients With High-Grade Glioma: Results of a Prospective Trial.
High-grade gliomas (HGG) are highly fatal tumors despite advanced multimodality management. They are also associated with neurocognitive impairment, both due to disease pathology and treatment. We aimed to assess various risk factors responsible for neurocognitive decline in HGG patients undergoing adjuvant chemoradiation. Newly diagnosed HGG patients who underwent maximal safe resection were included. Patients received volumetric modulated arc therapy to a dose of 60 Gy in 30 fractions, along with concurrent temozolomide (TMZ) at a dose of 75 mg/m²/day orally; thereafter adjuvant TMZ (150-200 mg/m² for 5 days), given every 28 days for 6 to 8 cycles. The Mini-Mental State Examination questionnaire was used to measure cognitive impairment of each study patient at various time points. Cox regression model was used for univariate and multivariable analysis of data to establish possible risk factors. Fifty-three patients were enrolled and analyzed. At a median follow-up of 15 months, 30 patients (56.6%) developed cognitive impairment, and 23 patients (43.4%) did not. On univariate analysis, HGG with WHO grade 4, glioblastoma and diffuse midline glioma histology, IDH-wild type, recursive partitioning analysis class IV/V, and only biopsy of primary tumor were significantly associated with neurocognitive impairment, but none of them were independent risk factors on multivariable analysis. Planning target volume and dose received by ipsilateral hippocampus were also significantly correlated with cognitive decline in HGG patients. Decline in neurocognitive functions in HGG patients is multifactorial and can be attributed to an amalgam of various tumor, patient, and treatment-related factors.


A non-covalent method of attaching antibodies to liposomes.
A novel non-covalent method of attaching antibodies to liposomes which exploits the high affinity of streptavidin for biotin, is described. The two-step coupling protocol involves the initial attachment of streptavidin to liposomes containing biotin PE, followed by the coupling of biotinated antibodies to streptavidin-liposomes. The association of streptavidin with liposomes containing biotinated PE is rapid (less than 5 min), resulting in a maximum association of 40 molecules of streptavidin per 100 nm vesicle. In the presence of equimolar cholesterol, the amount of streptavidin bound is twice that observed when biotin PE/egg PC liposomes are used. Irrespective of the mole ratio of biotin to antibody (e.g. for 1-6 biotins per antibody), or the molar ratio of antibody to streptavidin in the second incubation step, equimolar amounts of antibody bind to streptavidin. It is shown that anti-rat-erythrocyte IgG or F(ab')2 complexed to liposomes via the streptavidin linker bind specifically to rat erythrocytes but not to human erythrocytes. This coupling protocol can be readily extended to other biotinated antibodies.


Examining Equity in Access and Utilization of a Freely Available Meditation App.
Digital interventions have the potential to alleviate mental health disparities for marginalized and minoritized communities. The current study examined whether disparities in access and utilization of meditation in the United States (US) were reduced for a freely available meditation app. We analyzed demographic and usage data from US-based users of the Healthy Minds Program (HMP; N = 66,482) between October 2019 and July 2022. College education was associated with a greater likelihood of accessing (65.0% of users vs. 32.9% of the US population) and continuing to utilize the app (β = .11-.17). Conversely, identifying as African American was associated lower likelihood of accessing (5.3% vs. 13.4% of US population) and continuing to utilize the app (β = -.02-.03). African Americans were more likely to access content from an African American meditation teacher, but this did not appear to increase utilization. Additional efforts are warranted to identify factors which might reduce disparities.


Transport of K+ by Na(+)-Ca2+, K+ exchanger in isolated rods of lizard retina.
Transport of K+ by the photoreceptor Na(+)-Ca2+, K+ exchanger was investigated in isolated rod outer segments (OS) by recording membrane current under whole-cell voltage-clamp conditions. Known amounts of K+ were imported in the OS through the Ca(2+)-activated K+ channels while perfusing with high extracellular concentration of K+, [K+]o. These channels were detected in the recordings from the OS, which probably retained a small portion of the rest of the cell. The activation of forward exchange (Na+ imported per Ca2+ and K+ extruded) by intracellular K+, Ki+, was described by first-order kinetics with a Michaelis constant, Kapp(Ki+), of about 2 mM and a maximal current, Imax, of about -60 pA. [Na+]i larger than 100 mM had little effect on Kapp(Ki+) and Imax, indicating that Nai+ did not compete with Ki+ for exchange sites under physiological conditions, and that Na+ release at the exchanger intracellular side was not a rate-limiting step for the exchange process. Exchanger stoichiometry resulted in one K+ ion extruded per one positive charge imported. Exchange current was detected only if Ca2+ and K+ were present on the same membrane side, and Na+ was simultaneously present on the opposite side. Nonelectrogenic modes of ion exchange were tested taking advantage of the hindered diffusion found for Cai2+ and Ki+. Experiments were carried out so that the occurrence of a putative nonelectrogenic ion exchange, supposedly induced by the preapplication of certain extracellular ion(s), would have resulted in the transient presence of both Cai2+ and Ki+. The lack of electrogenic forward exchange in a subsequent switch to high Nao+, excluded the presence of previous nonelectrogenic transport.


[Patient experience in emergency departments: What do children and adolescents think?]
Improving patient experience must become a priority in paediatric emergency departments. This experience is often studied by surveying parents, and not children directly. The aim of this study was to assess the patient experience of children attended in a Paediatric Emergency Department (PED). A prospective descriptive study was conducted using a survey based on the Picker questionnaire on the patient experience. From January to May 2014, children 8-17 years seen in the Paediatric Emergency Department and admitted to the hospital were asked to complete the questionnaires anonymously, within 24hours of admission. A total of 217 patients completed the survey. The responses showed the 19.4% had to wait longer than expected, with 46.2% saying that there was not enough for children of their age group to do while waiting to be seen. As regards care and treatment, 4.6% of participants said staff did not fully explain what they were doing, and 23% said that they were not given enough privacy when being examined. Overall, 99.1% of patients said that they were well treated. Overall patient experience in the PED was positive. Some aspects have to be improved (activities in the waiting room, and privacy during the examination).


Impact of 5 fluorouracil chemotherapy on gut inflammation, functional parameters, and gut microbiota.
Emerging evidence suggests that gut microbiota may influence the response to chemotherapy. We sought to characterize the effects of 5 fluorouracil (5FU) chemotherapy on colon inflammation and functional measures in colorectal cancer (CRC) and to further determine whether gut microbiota can influence this response. 50 C57BL/6 were randomized into four groups; Control + Vehicle (n = 10), Control + 5FU (n = 10), AOM/DSS + Vehicle (n = 15), and AOM/DSS + 5FU (n = 15). CRC was induced chemically by a single 10 mg/kg injection of azoxymethane (AOM) followed by two cycles (2% and 1%) of dextran sodium sulfate (DSS). Mice were then treated with 3 cycles of vehicle or 5FU (cycle 1: 40 mg/kg, cycle 2 + 3: 20 mg/kg). Functional tests (grip strength and run-to-fatigue) were performed prior to 5FU treatment (baseline) and at the completion of the second cycle of 5FU. Following the third 5FU cycle, mice were euthanized and the colon was evaluated for expression of inflammatory genes using RT-qPCR and stool samples were profiled using 16S rRNA sequencing. A second experiment used fecal microbiota transplantation from 5FU treated mice to control mice (n = 10-15/group) to determine whether 5FU associated changes in the microbiota could influence functional measures and colon inflammation. 5FU reduced grip strength (p < 0.05) and caused a trending decrease in run-to-fatigue performance in cancer mice (p = 0.06). Select intestinal inflammatory genes were significantly elevated with 5FU treatment and this was further exacerbated with cancer (p < 0.05). Microbiota analysis revealed increased dissimilarity and alterations in bacterial taxonomy in 5FU and AOM/DSS-treated mice (p < 0.05). Fecal transplant from 5FU treated mice reduced functional performance (p < 0.05) and altered select colon inflammatory markers (p < 0.05). This study provides evidence of an effect of 5FU on inflammatory responses and functional measures in a mouse model of CRC and suggests that gut microbes may play a role in some, but not all, 5FU related perturbations.


Anticonvulsant activity of two novel piperazine derivatives with potent kainate antagonist activity.
Two dicarboxylic piperazine derivatives, 1-(p-chlorobenzoyl)-piperazine-2,3-dicarboxylic acid (pCB-PzDA) and 1-(p-bromobenzoyl)-piperazine-2,3-dicarboxylic acid (pBB-PzDA), that block excitation at glutamate receptors have been evaluated as anticonvulsants in rodent models of epilepsy by i.c.v. or i.p. injection. In DBA/2 mice, pBB-PzDA (0.01 mumol i.c.v.) or pCB-PzDA (0.03 mumol i.c.v.) protects against the clonic and tonic seizures induced by loud sound. Protection is also seen following i.p. injection of pBB-PzDA (0.33-1.0 mmol/kg) or pCB-PzDA (0.66-1.0 mmol/kg). In Swiss S mice suppression of seizure activity induced by i.c.v. injection of excitatory amino acid agonists shows that both compounds are preferentially active against alpha-kainate, with the following rank orders (for pBB-PzDA); alpha-kainate greater than quisqualate greater than N-methyl-D-aspartate greater than quinolinate greater than L-glutamate; and (for pCB-PzDA): alpha-kainate greater than quinolinate greater than N-methyl-D-aspartate greater than quisqualate greater than L-glutamate. These compounds are the most potent preferential alpha-kainate antagonists so far tested. The relationship between antagonism at the various receptor subtypes and anticonvulsant action is not adequately defined.


Insights into the prokaryotic communities of the abyssal-hadal benthic-boundary layer of the Kuril Kamchatka Trench.
The Kuril-Kamchatka Trench (maximum depth 9604 m), located in the NW Pacific Ocean, is among the top seven deepest hadal trenches. The work aimed to investigate the unexplored abyssal-hadal prokaryotic communities of this fascinating, but underrated environment. As for the bacterial communities, we found that Proteobacteria (56.1-74.5%), Bacteroidetes (6.5-19.1%), and Actinobacteria (0.9-16.1%) were the most represented bacterial phyla over all samples. Thaumarchaeota (52.9-91.1%) was the most abundant phylum in the archaeal communities. The archaeal diversity was highly represented by the ammonia-oxidizing Nitrosopumilus, and the potential hydrocarbon-degrading bacteria Acinetobacter, Zhongshania, and Colwellia were the main bacterial genera. The α-diversity analysis evidenced that both prokaryotic communities were characterized by low evenness, as indicated by the high Gini index values (> 0.9). The β-diversity analysis (Redundancy Analysis) indicated that, as expected, the depth significantly affected the structure of the prokaryotic communities. The co-occurrence network revealed seven prokaryotic groups that covaried across the abyssal-hadal zone of the Kuril-Kamchatka Trench. Among them, the main group included the most abundant archaeal and bacterial OTUs (Nitrosopumilus OTU A2 and OTU A1; Acinetobacter OTU B1), which were ubiquitous across the trench. This manuscript represents the first attempt to characterize the prokaryotic communities of the KKT abyssal-hadal zone. Our results reveal that the most abundant prokaryotes harbored by the abyssal-hadal zone of Kuril-Kamchatka Trench were chemolithotrophic archaea and heterotrophic bacteria, which did not show a distinctive pattern distribution according to depth. In particular, Acinetobacter, Zhongshania, and Colwellia (potential hydrocarbon degraders) were the main bacterial genera, and Nitrosopumilus (ammonia oxidizer) was the dominant representative of the archaeal diversity.


Friend or foe, the role of EGR-1 in cancer.
Early growth response-1 (EGR-1), also termed NEFI-A and Krox-24, as a multi-domain protein is implicated in several vital physiological processes, including development, metabolism, cell growth and proliferation. Previous studies have implied that EGR-1 was producing in response to the tissue injury, immune response and fibrosis. Meanwhile, emerging studies stressed the pronounced correlation of EGR-1 and human cancers. Nevertheless, the intricate mechanisms of cancer-reduce EGR-1 alteration still poorly characterized. In the review, we evaluated the effects of EGR-1 in tumor cell proliferation, apoptosis, migration, invasion and tumor microenvironment, and then, we dwell on the intricate signaling pathways that EGR-1 involved in. The aberrantly expressed of EGR-1 in cancers are expected to provide a new cancer therapy strategy or a new marker for assessing treatment efficacy.


Serial measurements of transient evoked otoacoustic emissions (TEOAEs) in healthy newborns and in newborns with perinatal infection.
Detection of hearing impairment in early childhood is difficult. We serially recorded transient evoked otoacoustic emissions (TEOAEs) to search for signs of ototoxicity in term, healthy newborns and compared the results to a second group of term babies treated for perinatally acquired bacterial infection with ampicillin plus either cefotaxime or plus aminoglycoside. At initial evaluation, in the group of 45 healthy children born at term, well reproducible emissions were observed in all but two children. In each of these two, initially well reproducible TEOAEs were detected in one ear only. At the time of the second recording (mean at day 8.5) excellent emissions were seen in all ears of all children. Similarly, in the second group receiving ampicillin plus either cefotaxime or plus aminoglycoside, the height of emissions as well as TEOAE-reproducibility was equal or even increased at the time of the second evaluation in all 17 patients. In the following group of 59 patients, all receiving ampicillin plus aminoglycoside, again TEOAEs were equal or improved at the time of follow-up examinations. In all patients, a reduced general condition tended to be associated with less reproducible TEOAEs. We conclude that at conventional doses in low-risk infants, aminoglycosides are unlikely to cause ototoxicity and that in early childhood serial TEOAE-recording may be useful for evaluation of inner ear function.


Three-dimensional organization of lymphatics and its relationship to blood vessels in rat small intestine.
The lymphatic organization and its relationship to the vascular system in the rat small intestine was studied by scanning electron microscopy of corrosion casts and freeze-fractured tissues, and by light microscopy of injected preparations. The villus possessed 3-10 or more central lacteals depending upon the villous width. The lacteals in each villus possessed interconnections between adjacent ones and were surrounded externally by the villous capillary network. At the villous base, the lacteals fused and formed a wide sinus, from which 2 or 3 lymphatics descended and led into the submucosal ones. In the muscularis externa there was a coarse lymphatic network which, together with the submucosal one, drained into collecting lymphatics continuous with the mesenteric ones. The central lacteals and the sinus were lined with thin endothelial cells with cytoplasmic leaves interdigitating with those of adjacent ones. There were tissue channels in the villous interstitial space, which opened through the gaps between the lymphatic endothelial cells into the central lacteals. The voluminous lacteals in the villi suggest their great potential for lymph formation. The existence of collecting lymphatics with valves in the muscularis externa suggests that contraction of the layer is involved in transporting lymph towards the efferent lymphatics.


Universal prophylactic rectal nonsteroidal anti-inflammatory drugs with a policy of selective pancreatic duct stenting significantly reduce post-endoscopic retrograde cholangiopancreatography pancreatitis.
Although rectal nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to be effective for the prevention of post-ERCP (endoscopic retrograde cholangiopancreatography) pancreatitis (PEP) in high-risk patients, the benefit in average-risk patients is unclear. We aimed at assessing the benefit of prophylactic rectal NSAIDs in unselected consecutive patients to prevent PEP. All patients undergoing index ERCP procedures from January 2018 until March 2020 were included. All patients received prophylactic rectal diclofenac. A prophylactic pancreatic duct (PD) stent was placed if there was repeated PD cannulation, at the discretion of the endoscopist. The frequency of PEP was compared with historical controls. Of 769 patients who underwent ERCP, 34 (4.4%) developed PEP (mild in 29 [85.3%], moderate in four [11.8%] and severe in one [2.9%]). Female gender, precut sphincterotomy, inadvertent PD cannulation and procedural time of > 30 minutes predicted PEP in univariate analysis. Inadvertent PD cannulation (OR 4.6, 95% CI: 1.8-11.7; p < 0.001) and procedural time of > 30 minutes (OR 8.5, 95% CI: 3.7-10.1; p < 0.001) were independent risk factors on multivariate analysis. When compared with historical controls, the odds of PEP with prophylactic use of rectal NSAIDs and selective PD stenting was 0.54 (CI: 0.31-0.93, p = 0.027). The number needed to treat (NNT) was 22 to prevent one PEP with prophylactic rectal NSAIDs. Routine use of prophylactic rectal NSAIDs effectively prevents the occurrence of PEP in unselected consecutive patients in a real-world scenario.


Results of hyperthermia, alone or combined with irradiation, in chest wall recurrences of breast cancer.
In the period between September 1983 and July 1987, 28 locoregional recurrences (about 86% in the chest wall) of breast cancer in 19 patients were treated with external microwave hyperthermia. Of these, 11 lesions were treated with hyperthermia alone and 17 with the combination of heat and external irradiation. Hyperthermia was induced in most cases with 915 MHz microwave (at least 42 degrees C for 30-45 min, for 6-10 sessions). Radiation was administered using photon or electron beams with total doses varying from 2000 to 5000 cGy. Complete and partial response rates on the whole series of patients were 53.6% and 42.9%, respectively. Of 17 lesions treated with combined treatment, 10 had a complete (58.8%) and 7 a partial response; of 11 lesions treated with hyperthermia alone, 5 had a complete (45.5%), 5 a partial (45.5%), and 1 no response. Complete responses were long lasting in all but 3 cases, which recurred after 4 months (2 cases) and 1 year, respectively.


B72.3 immunoreactivity in benign abdominal lymph nodes associated with gastrointestinal disease.
Immunolocalization of the tumor-associated glycoprotein 72 antigen with the monoclonal antibody B72.3 has been used as a "cancer marker" in radioimmunoscintigraphy and radioimmunoguided surgery (RIGS). Radioimmunoscintigraphy and RIGS have been used to detect occult metastatic deposits from colorectal adenocarcinoma. It has been suggested that RIGS is superior to histologic examination in detecting lymph node metastases from colorectal cancer. To determine the specificity of immunodetection of the tumor-associated glycoprotein-72 antigen as a marker for metastatic adenocarcinoma, we studied benign intra-abdominal lymph nodes with B72.3 and an immunohistochemical technique. Formaldehyde-fixed, paraffin-embedded sections of 276 benign abdominal lymph nodes, resected with 35 cases of colonic adenocarcinoma and 33 cases of benign gastrointestinal disorders, were evaluated for B72.3 immunoreactivity using an avidin-biotin complex immunohistochemical technique. Lymph nodes from cases of colonic carcinoma were also studied with cytokeratin immunostaining to help eliminate occult micrometastases. B72.3 immunoreactivity was seen in the germinal centers of benign lymph nodes associated with 49 percent of the cases of colonic adenocarcinoma and 12 percent of the cases of benign gastrointestinal disease. B72.3 immunoreactivity can be seen in benign abdominal lymph nodes associated with gastrointestinal disease. We advise caution in the use of diagnostic techniques that equate B72.3 immunoreactivity with the presence of adenocarcinoma.


Correction to: Esogastro-Pleuro-Bronchial Fistula: An Unusual Complication After Sleeve Gastrectomy.
Due to a Production error Figs. 1 and 2 were omitted from the original article.


Predictive model for treatment outcomes of peripheral T-cell lymphoma, not otherwise specified, in Taiwanese patients.
We aimed to explore the clinical outcomes and prognostic factors for PTCL-NOS patients in the real world. Clinical data were retrospectively collected from adult patients with PTCL-NOS treated at a single center in Taiwan. 104 PTCL-NOS patients with a median age of 53.0 years were enrolled. Patients with the International Prognostic Index (IPI) or prognostic index for peripheral T-cell lymphoma (PIT) scores of zero had a longer overall survival (OS) and progression free survival (PFS), while patients with IPI or PIT scores ≥1 did poorly. For patients who are eligible for transplantation, the use of pralatrexate as salvage chemotherapy has shown better OS (2-year OS 83.3% vs. 24.4%, P = 0.011) compared to patients who did not. By multivariate analysis, age >60 years, male, B symptoms, ECOG >1, lung involvement, and thrombocytopenia were independent adverse factors for OS. Incorporating factors in multivariate analysis, we established a novel predictive index for PTCL-NOS which efficiently stratifies patients into low (0-1 factor), intermediate-1 (2 factors), intermediate-2 (3 factors), and high risk (4-6 factors) groups with 2-year OS rates of 81.5%, 32.9%, 8.8%, and 0%, respectively (P < 0.001). PTCL-NOS patients have a dismal prognosis in Taiwan. Novel agents may improve the outcomes of PTCL-NOS patients. The usefulness of the novel prognostic index for PTCL-NOS needs further validation.


A starch-based controlled-release targeted nutrient agent to stimulate the activity of volatile chlorinated hydrocarbon-degrading indigenous microflora present in groundwater.
Volatile chlorinated hydrocarbons (VCHs) contaminated groundwater has a low indigenous microorganism population, and lack of nutrient substrates involved in degradation reactions, resulting in a weak natural remediation ability of groundwater ecosystems. In this study, based on the principle of degradation of VCHs by indigenous microorganisms in groundwater, and combined with biostimulation and controlled-release technology, we developed a starch-based encapsulated targeted bionutrient (YH-1) with easy uptake, good stability, controllable slow-release migration, and long timeliness for the remediation of groundwater contaminated by VCHs by indigenous microorganisms. The results showed that YH-1 is easily absorbed by microorganisms and can rapidly initiate itself to stimulate the microbial degradation of VCHs, and the degradation rate of various VCH components within 7 days was 82.38-92.38 %. The release rate of nutrient components in YH-1 increases with increasing VCH concentrations in groundwater; this could effectively prolong the action time of nutrient components, while also improving the degradation efficiency of pollutants with a sustained effect of more than 15 days. Simultaneously, owing to the fluidity, water solubility, and biodegradability of YH-1 in lithologic media, YH-1 injection did not cause blockage of the lithologic media in the aquifer. Through YH-1 stimulation, indigenous microorganisms grew rapidly in the underground environment, the diversity of microbial communities and the total number of species increased, and the correlation between genera strengthened. Simultaneously, YH-1 improved the ability of microbial community to convert inorganic electron donors/acceptors, thereby strengthening the co-metabolic mechanism between microorganisms. Additionally, there was a significant increase in the percentage of many microorganisms (e.g., Sphingomonas, Janthinobacterium, Duganella, etc.) that mediated the reductive dechlorination process and were redox inorganic electron donors/acceptors. This was conducive to the reductive dechlorination process of VCHs and achieved the efficient degradation of VCHs.


A simple technique to open the posterior wall of the third ventricle.
Third ventriculostomy is an operating technique which is mostly used in benign adult aqueductal stenosis. The most important stage of this operation is the manipulation of the basal membrane of the third ventricle. A technique which facilitates the opening of the posterior wall of the third ventricle is presented.


Optokinetic circular vection: a test of visual-vestibular conflict models of vection nascensy.
The propensity to experience circular vection (the illusory perception of self-turning evoked by a rotating scene, CV) as reflected by its onset latency exhibits considerable interindividual variation. Models of CV nascensy have linked this delay to the time it takes the visual-vestibular conflict to disappear. One line of these "conflict models" (Zacharias and Young in Exp Brain Res 41:159-171, 1981) predicts that, across individuals, CV latency (CVL) correlates positively with the vestibular time constant (TC) and negatively with the vestibular motion detection threshold (vTHR). A second type of models (Mergner et al. in Arch Ital Biol 138:139-166, 2000) predicts only an increase in CVL with TC. We here examine which of these predictions can be experimentally substantiated. Also, we ask whether the relative weight W O of the optokinetic contribution to the perception of real self-turning could also be a factor influencing CVL. We conducted 5 experiments in 29 subjects measuring: (1) CVL, (2) the TCs of velocity perception and of accompanying nystagmus during rotation in darkness and (3) likewise for displacement perception, (4) vTHR, and (5) W O as revealed by discordant visual-vestibular stimulation. CVL correlated with the nystagmus TC recorded during velocity estimation but with none of the other vestibular TCs nor with vTHR. Confirming earlier findings, CVL shortened with rising scene velocity. Finally, CVL correlated inversely with W O: the larger an individual's optokinetic weight, the shorter was his CVL. Taken together, our data favour the second type of models which invoke an antagonism between CV inhibition by the optokinetic-vestibular conflict and disinhibition by optokinetic stimulation. Idiosyncratic factors appear to strongly modulate the balance between inhibition and disinhibition, thus increasing CVL variability and obscuring the expected relation between CVL and TC.


Prevalence of rheumatoid arthritis in Edmonton and Northern Alberta.
The purpose of this study was to compare and contrast the prevalence of rheumatoid arthritis in Northern Alberta estimated by health administrative data and data from a rheumatologist-based prescription database. The study was performed using administrative health data from the province of Alberta through the local health authority. The cases and population identified in the database were reported from the year 2016. Rheumatology prescribing data was accessed through the Physician Learning Program and based on Alberta health billing data of actively practicing rheumatologists between the years 2012 and 2016. Ethics was provided by the Conjoint Health Research Ethics Boards at the University of Calgary (REB 13-0459). The total population of the area examined was determined to be 2,086,181. The administrative health database identified 42,354 cases of RA based on their case definition with a prevalence of 2.08%. Based on rheumatologist diagnosis and prescribing data, the number of cases identified was 11,273 cases of RA with a prevalence of 0.542%. The average percentage of identified RA patients being seen by a rheumatologist was determined to be 26.7% with the range of 19.8 to 39.9%. In conclusion, this study compares and contrasts the prevalence of rheumatoid arthritis reported by administrative data versus identification by specialists. Our study again illustrates that accuracy of case definitions when studying chronic conditions such as rheumatoid arthritis is paramount. The results also suggest a lack of access to rheumatologist services in Northern Alberta and reiterate the need for ongoing recruitment of new rheumatologists as has been highlighted previously. Key Points • The main contribution of this paper is to compare and contrast the prevalence of rheumatoid arthritis as reported by administrative data versus identification by specialists. • Our study also shows the distribution of rheumatoid arthritis in a large geographical area and illustrates a lack of access to subspecialty care in certain regions.


Management of oropharyngeal squamous cell carcinoma.
This article reviews the various treatment options, by primary or postoperative external radiotherapy and by brachytherapy for the p16-negative oropharyngeal squamous cell carcinoma. Dose levels, fractionation and association with systemic treatments are presented. The need for neck node dissection post local treatment is discussed, as well as specificities for the management of p16-positive tumours. Guidelines for target volume selection and delineation are thoroughly elaborated. Last, the management by radiotherapy of locoregional recurrences is discussed.


The effect of fasting on 5-hydroxytryptamine metabolism in brain regions of the albino rat.
The turnover of 5-hydroxytryptamine (5-HT) in the whole brain and different brain regions was studied in rats fasted for 24 h. These rats showed an increased tissue concentration of the amine in the whole brain and of its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the whole brain, the striatum, the combined pons-medulla and the cerebral cortex. The accumulation of 5-HIAA after probenecid was increased by fasting in the regions mentioned above except for the striatum. The effect of probenecid was also increased by fasting in the midbrain, the hypothalamus and the hippocampus. In the striatum, the administration of probenecid produced a smaller increase in 5-HIAA concentration in fasted than in fed rats. The decay of 5-HT following p-chlorophenylalanine (PCPA) was increased in the hypothalamus of fasted rats at 16 h, but not at 4 h, after the intraperitoneal administration of the inhibitor. In the midbrain, the striatum and the combined pons-medulla, food deprivation did not modify the decrease induced by PCPA. However, the inhibitor induced a reduction of food consumption in the fed group, which made this group rather similar to the fasted one and complicated the interpretation of the results in these last three cerebral areas. Our results confirm that food deprivation increases the turnover of brain 5-HT and point out that the increase probably occurs in all brain areas. This increased turnover appears to be accompanied, in the hypothalamus, by an increased neuronal release of the amine. In the striatum, fasting probably blocks the active transport system which removes acid metabolites from the brain.


Congenital Heart Surgery Program Variable Case Mix: Risk Associated With Adjusted Mortality Rate.
Congenital heart operations are categorized into risk categories based on The Society of Thoracic Surgeons-European Association of Cardio-Thoracic Surgery Congenital Heart Surgery (STAT) Mortality Categories. The adjusted mortality rate should adjust for case mix. The Society of Thoracic Surgeons Congenital Heart Surgery Public Reporting data were extracted for the top 50 U.S. News & World Report Cardiology and Heart Surgery Programs in 2021 (operations from January 2015 to December 2018). Variability in STAT 1 as a percentage of total operations and as a ratio to STAT 4+5 operations was evaluated. STAT 1 cases varied between centers from 18% to 37% of total. The ratio of STAT 1 to STAT 4+5 varied from 0.52 to 1.97. There was an inverse relationship between the STAT 1:STAT 4+5 ratio and adjusted mortality rate that did not reach statistical significance (P = .12). When programs (n = 12) in the quartiles with the highest vs lowest STAT 1:STAT 4+5 ratio were compared, a significant difference was found in the median adjusted mortality rate (2.2% vs 2.95%, P = .03). There is a 4-fold difference in the ratio of STAT 1 to STAT 4+5 cases among congenital heart surgery programs, even when smaller programs are excluded, suggesting significant differences in the decision-making philosophy. Programs with the highest proportion of STAT 1 cases had lower adjusted mortality rate, suggesting that The Society of Thoracic Surgery Congenital Heart Surgery Database mortality risk model adjusts well but not completely for case-mix variability between programs.


Structure-Activity Relationship Studies of Pyridine-Based Ligands and Identification of a Fluorinated Derivative for Positron Emission Tomography Imaging of Cannabinoid Type 2 Receptors.
The cannabinoid type 2 (CB2) receptor has emerged as a valuable target for therapy and imaging of immune-mediated pathologies. With the aim to find a suitable radiofluorinated analogue of the previously reported CB2 positron emission tomography (PET) radioligand [11C]RSR-056, 38 fluorinated derivatives were synthesized and tested by in vitro binding assays. With a Ki (hCB2) of 6 nM and a selectivity factor of nearly 700 over cannabinoid type 1 receptors, target compound 3 exhibited optimal in vitro properties and was selected for evaluation as a PET radioligand. [18F]3 was obtained in an average radiochemical yield of 11 ± 4% and molar activities between 33 and 114 GBq/μmol. Specific binding of [18F]3 to CB2 was demonstrated by in vitro autoradiography and in vivo PET experiments using the CB2 ligand GW-405 833. Metabolite analysis revealed only intact [18F]3 in the rat brain. [18F]3 detected CB2 upregulation in human amyotrophic lateral sclerosis spinal cord tissue and may thus become a candidate for diagnostic use in humans.


Simulations of membranes and other interfacial systems using P2(1) and Pc periodic boundary conditions.
We demonstrate the ease and utility of simulating heterogeneous interfacial systems with P2(1) and Pc periodic boundary conditions which allow, for example, lipids in a membrane to switch leaflets. In preliminary tests, P2(1) was shown to yield equivalent results to P1 in simulations of bulk water, a water/vacuum interface, and pure DPPC bilayers with an equal number of lipids per leaflet; equivalence of Pc and P1 was also demonstrated for the former two systems. P2(1) was further tested in simulations involving the spreading of an octane film on water, and equilibration of a DPPC bilayer from an initial condition containing different numbers of lipids in the two leaflets. Lastly, a simulation in P2(1) of a DOPC/melittin membrane showed significant passage of lipids to the melittin-containing leaflet from the initial distribution, and lends insight into the condensation of lipids by melittin.


Signal relay by CC chemokine receptor 2 (CCR2) and formylpeptide receptor 2 (Fpr2) in the recruitment of monocyte-derived dendritic cells in allergic airway inflammation.
Chemoattractant receptors regulate leukocyte accumulation at sites of inflammation. In allergic airway inflammation, although a chemokine receptor CCR2 was implicated in mediating monocyte-derived dendritic cell (DC) recruitment into the lung, we previously also discovered reduced accumulation of DCs in the inflamed lung in mice deficient in formylpeptide receptor Fpr2 (Fpr2(-/-)). We therefore investigated the role of Fpr2 in the trafficking of monocyte-derived DCs in allergic airway inflammation in cooperation with CCR2. We report that in allergic airway inflammation, CCR2 mediated the recruitment of monocyte-derived DCs to the perivascular region, and Fpr2 was required for further migration of the cells into the bronchiolar area. We additionally found that the bronchoalveolar lavage liquid from mice with airway inflammation contained both the CCR2 ligand CCL2 and an Fpr2 agonist CRAMP. Furthermore, similar to Fpr2(-/-) mice, in the inflamed airway of CRAMP(-/-) mice, DC trafficking into the peribronchiolar areas was diminished. Our study demonstrates that the interaction of CCR2 and Fpr2 with their endogenous ligands sequentially mediates the trafficking of DCs within the inflamed lung.


Coenzyme Q10 Supplementation in Reducing Inflammation: An Umbrella Review.
The purpose of this study was to review meta-analyses on the effectiveness of coenzyme Q10 supplementation in reducing inflammation through changes in the inflammatory biomarkers C-reactive protein, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α). An umbrella review of all published meta-analyses was performed. A PubMed search from January 1, 1980, to December 31, 2021, was conducted using the following search strategy: "(coenzyme q10 OR CoQ10 OR ubiquinone OR ubiquinol) AND (meta-analysis OR systematic review)". Only English language publications that provided quantitative statistical analysis on coenzyme Q10 supplementation and markers of inflammation were retrieved. Seven meta-analyses were retrieved for inclusion in this umbrella review, and for all 3 inflammatory biomarker marker groups, the median intake of supplemental coenzyme Q10 was 200 mg/d for a median duration of 12 weeks. For C-reactive protein, only 3 of the 7 meta-analyses presented with statistically significant reductions, while statistically significant reductions in IL-6 and TNF-α for were observed in 4 of the 5 meta-analyses and 3 of the 4 meta-analyses, respectively. However, statistically significant heterogeneity was observed in the majority of these meta-analyses. The majority of included meta-analyses showed that coenzyme Q10 supplementation significantly decreased the proinflammatory cytokines IL-6 and TNF-α. However, heterogeneity was observed in the majority of these meta-analyses, and therefore the results should be interpreted with caution.


C1-esterase inhibitor reduces reperfusion injury after lung transplantation.
Activation of the complement system and polymorphonuclear neutrophilic leukocytes plays a major role in mediating reperfusion injury after lung transplantation. We hypothesized that early interference with complement activation would reduce lung reperfusion injury after transplantation. Unilateral left lung autotransplantation was performed in 6 sheep. After hilar stripping the left lung was flushed with Euro-Collins solution and preserved for 2 hours in situ at 15 degrees C. After reperfusion the right main bronchus and pulmonary artery were occluded, leaving the animal dependent on the reperfused lung (reperfused group). C1-esterase inhibitor group animals (n = 6) received 200 U/kg body weight of C1-esterase inhibitor as a short infusion, half 10 minutes before, the other half 10 minutes after reperfusion. Controls (n = 6) underwent hilar preparation only. Pulmonary function was assessed by alveolar-arterial oxygen difference and pulmonary vascular resistance. The release of beta-N-acetylglucosaminidase served as indicator of polymorphonuclear neutrophilic leukocyte activation. Extravascular lung water was an indicator for pulmonary edema formation. Biopsy specimens were taken from all groups 3 hours after reperfusion for light and electron microscopy. In the reperfused group, alveolar-arterial oxygen difference and pulmonary vascular resistance were significantly elevated after reperfusion. All animals developed frank alveolar edema. The biochemical marker beta-N-acetylglucosaminidase showed significant leukocyte activation. In the C1-esterase inhibitor group, alveolar-arterial oxygen difference, pulmonary vascular resistance, and the level of polymorphonuclear neutrophilic leukocyte activation were significantly lower. Treatment with C1-esterase inhibitor reduces reperfusion injury and improves pulmonary function in this experimental model.


Isolation of 15-acetoxyscirpendiol from culture ofFusarium poae on corn.
The main toxic metabolites of a strain ofFusarium poae, isolated from oats, were diacetoxyscirpenol (DAS) and a monoacetoxyscirpendiol. An accurate(1)H and 13C NMR analysis allowed to identify the monoacetoxyscirpendiol as the 15-acetoxy-3α, 4 β - di hydroxy -12,13 - epoxy trichothec - 9 - ene (15-acetoxyscirpendiol). This is the first report on the production of 15 - acetoxyscirpendiol byFusarium poae.


The tumour-promoting role of protein homeostasis: Implications for cancer immunotherapy.
Protein homeostasis, an important aspect of cellular fitness that encompasses the balance of production, folding and degradation of proteins, has been linked to several diseases of the human body. Multiple interconnected pathways coordinate to maintain protein homeostasis within the cell. Recently, the role of the protein homeostasis network in tumorigenesis and tumour progression has gradually come to light. Here, we summarize the involvement of the most prominent components of the protein quality control mechanisms (HSR, UPS, autophagy, UPR and ERAD) in tumour development and cancer immunity. In addition, evidence for protein quality control mechanisms and targeted drugs is outlined, and attempts to combine these drugs with cancer immunotherapy are discussed. Altogether, combination therapy represents a promising direction for future investigations, and this exciting insight will be further illuminated by the development of drugs that can reach a balance between the benefits and hazards associated with protein homeostasis interference.


Haptoglobin interacts with the human mast cell line HMC-1 and inhibits its spontaneous proliferation.
Haptoglobin (Hp) is an acute phase reactant produced by hepatocytes. There is evidence for an immunomodulatory potential of Hp, though there is no clear evidence yet about the mechanisms of this action. We have previously shown that Hp interacts with the beta2-integrin CD11b/CD18. In addition, other investigators reported the binding of Hp to B lymphocytes through the CD22 receptor, and to neutrophils through two different receptors. In the present study, we investigated the interaction of haptoglobin with the human mast cell line HMC-1. We report that fluorescein isothiocyanate (FITC)-labelled haptoglobin binds to this cell line and that binding is increased by calcium in a dose- and time-dependent manner. Hp binding sites on HMC-1 were upregulated upon stimulation with phorbol myristate acetate (PMA)/A23187 and after treatment with anti-CD43 and anti-CD44 monoclonal antibodies (MoAbs). HMC-1 cells do not express either CD11b/CD18 or CD22 receptors, indicating that the haptoglobin-binding receptor on this cell line is different from the known receptors. Assessment of cell function showed that Hp inhibits the spontaneous growth of HMC-1 up till 40% at higher Hp concentrations, but it did not exhibit any effect on the expression of CD54 on the release of either tryptase or IL-1ra. In conclusion, haptoglobin binds specifically to human mast cells via a receptor different from CD11b/CD18 and CD22, and may play a role in the modulation of mast cell functions. Exploration of Hp effects in mast cell-dependent diseases such as allergic rhinitis and urticaria seems warranted.


Trimethyl-ammonium 2,6-dioxo-5-(2,4,6-trinitro-phen-yl)-1,2,3,6-tetra-hydro-pyrimidin-4-olate.
IN THE TITLE BARBITURATE SALT (TRIVIAL NAME: trimethyl-ammonium 2,4,6-trinitro-phenyl-barbiturate), C(3)H(10)N(+)·C(10)H(4)N(5)O(9) (-), the asymmetric unit contains two sets of anion-cation moieties. The dihedral angle between the rings in the anions are 44.0 (3) and 45.7 (3)°. Adjacent anions are connected into ribbons along [100] through R(2) (2)(8) ring motifs formed by N-H⋯O hydrogen bonds involving the barbiturate rings. Attached to both sides of these ribbons via N-H⋯O hydrogen bonds are the trimethyl-ammonium cations. C-H⋯O hydrogen bonds are also observed.


Integration of acoustic and electric hearing is better in the same ear than across ears.
Advances in cochlear implant (CI) technology allow for acoustic and electric hearing to be combined within the same ear (electric-acoustic stimulation, or EAS) and/or across ears (bimodal listening). Integration efficiency (IE; the ratio between observed and predicted performance for acoustic-electric hearing) can be used to estimate how well acoustic and electric hearing are combined. The goal of this study was to evaluate factors that affect IE in EAS and bimodal listening. Vowel recognition was measured in normal-hearing subjects listening to simulations of unimodal, EAS, and bimodal listening. The input/output frequency range for acoustic hearing was 0.1-0.6 kHz. For CI simulations, the output frequency range was 1.2-8.0 kHz to simulate a shallow insertion depth and the input frequency range was varied to provide increasing amounts of speech information and tonotopic mismatch. Performance was best when acoustic and electric hearing was combined in the same ear. IE was significantly better for EAS than for bimodal listening; IE was sensitive to tonotopic mismatch for EAS, but not for bimodal listening. These simulation results suggest acoustic and electric hearing may be more effectively and efficiently combined within rather than across ears, and that tonotopic mismatch should be minimized to maximize the benefit of acoustic-electric hearing, especially for EAS.


Exploration of an objective and simple index as the outcome of nutrition support for elderly patients and identification of risk factors.
The study aimed to explore the risk factors for the outcome of nutrition support teams (NSTs) for elderly patients. Previously identified risk factors lack general versatility owing to slightly subjective judgment standards; this study aimed to explore an objective and simple index of NST outcome and identify the risk factors for NST outcome. This retrospective observational study analyzed, 372 elderly patients enrolled in the NST between January 2014 and July 2018. We identified that the energy fill rate to total energy expenditure (%TEE) at the time of NST termination (post-%TEE) < 75.0% was the most valid index for the outcome in our previous study. The cutoff values of continuous variables at the time of NST enrollment (pre-) were set for post-%TEE < 75.0% using receiver operating characteristic curve analysis, and hazard ratios (HRs) were calculated. From the multivariable Cox proportional hazard analysis, pre-%TEE < 62.6% (HR: 1.96; 95% confidence interval [95% CI]: 1.29-2.99; p = 0.002), presence of pressure ulcers (HR: 1.74; 95% CI: 1.02-2.98; p = 0.042), pre-prognostic nutritional index (PNI) < 32.7 (HR: 1.78; 95% CI: 1.13-2.82; p = 0.014), and presence of pre-peripheral parenteral nutrition (PPN) (HR: 1.74; 95% CI: 1.19-2.56; p = 0.005) were identified as independent risk factors for post-%TEE < 75.0%. Post-%TEE < 75.0% was the objective and simple index for NST outcomes. Patients with low pre-%TEE, pressure ulcers, low pre-PNI, or pre-PPN require early nutritional intervention.


Contamination of patients' files in intensive care units: an indication of strict handwashing after entering case notes.
The extent to which bedside patients' files become contaminated and the range of bacterial flora attributable to contamination in high-risk areas of the hospital are not known with certainty. The aim of the present study was to determine the degree of contamination of the patient's files and also to analyze and compare the spectrum of contaminant bacterial flora between the intensive care unit (ICU) and surgical wards, the 2 most high-risk areas for nosocomial transmission of infection. Microbiologic samples were collected from the exposed outer surface of the patients' files kept bedside in the ICU and surgical wards with sterile swabs moistened with sterile normal saline. Swabs were cultured within an hour of collection on blood agar and MacConkey's agar plates, which were incubated at 37 degrees C for 48 hours. Gram-negative bacilli were identified by Gram's stain, catalase, oxidase tests, and API 20E and API 20NE. Staphylococcus species were identified by Gram's stain, catalase test, and tube coagulase test. Antibiotic susceptibility of the isolated bacteria was determined by the disk diffusion technique according to the criteria of National Committee for Clinical Laboratory Standards (NCCLS). In ICU, 85.2% (87/102) and, in surgical wards, 24.7% (22/89) of patient's files were found to be contaminated with pathogenic and potentially pathogenic bacteria (OR, 17.664; 95% CI: 8.050-39.423; P < .0001). Pseudomonas aeruginosa was the most commonly isolated bacteria (32.3%, 33/102) in ICUs, whereas Staphylococcus aureus was the peak contaminant (11.2%, 10/89) of the files in surgical wards. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from 6.8% (7/102) of ICU patient's files, whereas only 1.1% (1/89) of patient's files in surgical wards were contaminated with MRSA (OR, 6.484; 95% CI: 3.215-13.463; P < .0001). The multidrug-resistant P aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, and Serretia marcesens isolated from the patient's files had the same antibiotic resistance pattern as of these bacteria isolated from the patients. The majority of the patient's files in ICUs were contaminated often with multidrug-resistant bacteria and even MRSA. Contaminated files could be a source of transmission of infection. To prevent this, handwashing practice should be strictly followed after attending the patient and before entering the case notes in the patient's file. The maintenance of good hand hygiene by the health care workers (HCWs) after handling contaminated files should perhaps be the most prudent approach to prevent patient-patient transmission of infection in high-risk areas including ICU and surgical wards.


Extended sigmoid-shaped free jejunal patch for reconstruction of the oral base and pharynx after total glossectomy with laryngectomy.
The procedure for reconstruction of the extensive defect after total glossectomy with total laryngectomy has not been standardised so far. We have devised a new method in which a free jejunal patch is extended to a sigmoid-shaped form specifically optimised for reconstruction of the defect that consists of the entire floor of the mouth and the antero-lateral walls of the pharyngoesophageal tract. After a jejunal segment of about 40 cm has been longitudinally opened in full length, the proximal quarter is folded parallel to the second quarter, which is then folded parallel to the third quarter in the opposite direction, to be laid out in a S-shaped form. Side-by-side sutures are then placed along each of the folded borders and corrective trimming is done to fit the defect. This widely extended patch replaces the whole oral base, whereas the remaining distal quarter of the patch replaces the antero-lateral walls of the hypopharynx and cervical esophagus. Because of the encouraging functional results with satisfactory restoration of oral alimentation, this procedure is considered to be ideal for the reconstruction of the defect which follows total glossectomy with total laryngectomy.


Arsenic uptake and transport of Pteris vittata L. as influenced by phosphate and inorganic arsenic species under sand culture.
In order to understand the similarity or difference of inorganic As species uptake and transport related to phosphorus in As-hyperaccumulator, uptake and transport of arsenate (As(V)) and arsenite (As(III)) were studied using Pteris vittata L. under sand culture. Higher concentrations of phosphate were found to inhibit accumulation of arsenate and arsenite in the fronds of P. vittata. The reduction in As accumulation was greater in old fronds than in young fronds, and relatively weak in root and rhizome. Moderate increases, from 0.05 to 0.3 mmol/L, in phosphate reduced uptake of As(III) more than As(V), while the reverse was observed at high concentrations of phosphate (> or = 1.0 mmol/L). Phosphate apparently reduced As transport and the proportion of As accumulated in fronds of P. vittata when As was supplied as As(V). It may in part be due to competition between phosphorus and As(V) during transport. In contrast, phosphate had a much smaller effect on As transport when the As was supplied as As(III). Therefore, the results from present experiments indicates that a higher concentration of phosphate suppressed As accumulation and transport in P. vittata, especially in the fronds, when exposed to As(V); but the suppression of phosphate to As transport may be insignificant when P. vittata exposed to As(III) under sand culture conditions. The finding will help to understand the interaction of P and As during their uptake process in P.


Inflammation-induced transgene expression in genetically engineered equine mesenchymal stem cells.
Osteoarthritis, a chronic and progressive degenerative joint disorder, ranks amongst the top five causes of disability. Given the high incidence, associated socioeconomic costs and the absence of effective disease-modifying therapies of osteoarthritis, cell-based treatments offer a promising new approach. Owing to their paracrine, differentiation and self-renewal abilities, mesenchymal stem cells (MSCs) have great potential for regenerative medicine, which might be further enhanced by targeted gene therapy. Hence, the development of systems allowing transgene expression, particularly when regulated by natural disease-dependent occuring substances, is of high interest. Bone marrow-isolated equine MSCs were stably transduced with an HIV-1 based lentiviral vector expressing the luciferase gene under control of an inducible nuclear factor κB (NFκB)-responsive promoter. Marker gene expression was analysed by determining luciferase activity in transduced cells stimulated with different concentrations of interleukin (IL)-1β or tumour necrosis factor (TNF)α. A dose-dependent increase in luciferase expression was observed in transduced MSCs upon cytokine stimulation. The induction effect was more potent in cells treated with TNFα compared to those treated with IL-1β. Maximum transgene expression was obtained after 48 h of stimulation and the same time was necessary to return to baseline luciferase expression levels after withdrawal of the stimulus. Repeated cycles of induction allowed on-off modulation of transgene expression without becoming refractory to induction. The NFκB-responsive promoter retained its inducibility also in chondrogenically differentiated MSC/Luc cells. The results of the present study demonstrate that on demand transgene expression from the NFκB-responsive promoter using naturally occurring inflammatory cytokines can be induced in undifferentiated and chondrogenically differentiated equine MSCs. Copyright © 2016 John Wiley & Sons, Ltd.


Interactions between heparin and factor Xa. Inhibition of prothrombin activation.
The effects of heparin on prothrombin activation have been examined. Heparin was found to inhibit the rate of prothrombin activation by Factor Xa, calcium and phospholipid. In the absence of phospholipid, heparin had no effect on the rate of prothrombin activation. In contrast, heparin was found to increase the rate of activation of prethrombin-1 and prethrombin-2. Initial velocity studies indicated that heparin blocks lipid stimulation of prothrombin activation. In accord with this, binding studies demonstrated that heparin could displace Factor Xa, and in separate experiments, prothrombin, from phospholipid vesicles.


Growth of corticospinal axons on prosthetic substrates introduced into the spinal cord of neonatal rats.
Nitrocellulose implants treated with biological materials known to support neurite growth in vitro were introduced at thoracolumbar levels of the neonatal rat spinal cord before the arrival of growing corticospinal tract (CST) axons. Implant placement was designed to interrupt the normal CST growth path and provide a potential, alternative growth path. Subsequent growth of CST axons within the spinal cord in the vicinity of the implants was evaluated by labeling the axons with the anterograde transport of horseradish peroxidase. Untreated implants either blocked further CST axon growth or deflected CST axons to abnormal positions. Implants bearing living cells from spinal cord primary cultures were able to support the adhesion and growth of CST axons. Similarly, acellular implants coated with laminin, but not with poly-L-lysine supported the adhesion and growth of CST axons, suggesting that laminin or some other adhesive factor produced by immature neuroglial cells may be normally involved in CST axon growth and guidance.


Differences in thermal adaptation of infants delivered at primary or tertiary care facilities in India.
To compare the pattern of thermal stabilization seen in infants born at a rural primary health center (PHC) with that of infants born in an modern urban tertiary care hospital (TCH). Abdominal temperature (Ta) and foot temperature (Tf) of healthy term newborn infants were monitored and electronically recorded continuously from birth in the delivery room (DR) until 12 h of life in the postnatal ward (PNW) at two sites. A total of 71 infants were enrolled in the study: 51 infants at the PHC and 20 infants at the TCH. In infants delivered at TCH the maximum mean (±s.d.) Ta of 36.4 ° C ± 0.48 was reached by 12 h, while at PHC maximum mean Ta was 35.4 °C (1.98) by 10.5 h. The mean Tf improved from the lowest value of 29.7 °C ± 1.3 at 4.5 h to 32.9 °C±1.6 by 12 h of life in infants delivered at TCH, whereas in infants delivered at PHC Tf remained low (maximum 30.7 °C) all through 12 h. The mean Td (Ta-Tf) gradually decreased from a maximum of 5.9 °C ± 1.6 at 4.5 h to 3.5 °C ± 1.5 by 12 h of life in infants born at TCH, but the Td remained at >5 °C even after 6 h of life in infants born at PHC, which was statistically significant (P<0.05). The calculated area between the Ta and Tf, a proxy for metabolic stress was greater in babies born at PHC than those born at TCH. Our study shows that although both groups of newborn infants experienced significant thermal stress, infants delivered at PHC experienced significantly greater thermal stress than babies born at TCH. This difference could be attributed to the differences in thermal environment of DR and PNW between PHC and TCH.


Use of split-thickness dermal graft in the surgical treatment of corneal and scleral defects.
We used split-thickness dermal grafts for the surgical treatment of corneal and scleral perforations in two patients and obtained excellent results. Patient 1 had severe lye burns and bilateral corneal perforations and Patient 2 had scleromalacia perforans. The dermal graft self-epithelializes and, thus, does not need to be covered by conjunctiva; is supple, without the bulkiness of other materials, particularly cartilage and periosteum; is hearty and flourishes on avascular surfaces such as cornea and sclera; has good tensile strength; and is autogenous.


Two rare cases of central nervous system opportunistic mycoses.
This article presents two cases of opportunistic mycoses (OMs) of the central nervous system (CNS) caused by Cryptococcus neoformans and Aspergillus nidulans, respectively. The patients were hospitalised in local hospitals between 2009 and 2011 because of unspecific symptoms (fever, headache, and/or weight lost). Duration of symptoms varied from 4 days to over 2 weeks. The patients were treated with antibiotics and symptomatically. OM was not suspected in any of them. The patients became critically ill with symptoms of CNS involvement and were transferred to the Intensive Care Unit (ICU) of the University Hospital for Infectious diseases (UHID) in Zagreb. None of the patients belonged to the high-risk population for developing OMs. They were not HIV-infected, had no transplantation of bone marrow or solid organ, and were not on severe immunosuppressive chemotherapy. Fungi were isolated from cerebrospinal fluid (CSF) samples and, in one patient, from aspirate of cerebral abscess. Isolation and mycological identification of all fungal isolates and in vitro antifungal susceptibility testing of these isolates were done at the Reference Centre for Mycological Diagnostics of Systemic and Disseminated Infections (RCMDSDI) in Zagreb. The patient with cryptococcal meningitis was treated with amphotericin B and fluconazole and the patient with cerebral aspergilloma with voriconazole.


[Replacement of the iliac veins and the infrarenal vena cava regment with heterologous grafts in animal tests (author's transl)].
A bovine collagen graft was implanted in 30 dogs for the replacement of the femoral vein, the iliac vein and the inferior vena cava. During the observation period up to 210 days six thromboses of the graft were observed. Histological results after 30 days: development of a "neo-intima" with collagen type III, originating from the anastomosis. After 90 to 210 days: Continuous endothelial layer of the graft with appearance of smooth muscle fibers in the neo-intima. From the graft bed there was found resorption of the bovine collagen and replacement by new collagen type III fibers.


Safety profiles of aromatase inhibitors and selective estrogen-receptor modulators in the treatment of early breast cancer.
For the medical treatment of early breast cancer, aromatase inhibitors (AIs) such as anastrozole, letrozole, and exemestane are more effective than selective estrogen-receptor modulators (SERMs) such as tamoxifen (TAM). However, the adverse events associated with AIs are different from those associated with SERMs. Hot flushes, gynecological disorders, and thrombosis are more frequent in patients treated with TAM than in those treated with AIs. Conversely, osteoporosis, fractures, joint symptoms, and myalgia are more common in patients receiving AIs. Osteoporosis and bone fractures resulting from osteoporosis are important issues for patients treated with AIs. The precise management of bone health, in strict accordance with clinical guidelines, is vital in patients receiving AIs. AI-related joint symptoms are also one of the most important considerations for patients taking AIs. AI-related joint symptoms are the most common reason for the discontinuation of AIs. Confirmed management strategies for AI-related joint symptoms are unavailable at present. In patients receiving AIs, long-term adverse events (for example, those occurring as a result of changing lipid metabolism) remain unclear. There is a clear need to elucidate AI-related adverse events over the long term and to establish management strategies for AI-related adverse events, such that AIs can be used safely in patients with breast cancer over long periods of time.