Diffuse periventricular leukomalacia in preterm children: assessment of grey matter changes by MRI.
Preterm children may have cognitive deficits and behavioural disorders suggestive of grey matter (GM) injury. The prevalence is higher in preterm children with diffuse periventricular leukomalacia (dPVL). Evaluate changes in the volume of 116 GM areas in preterm children with dPVL. Eleven preterm children with dPVL, gestational age 32.8 ± 2.6 weeks, examined at corrected age 22.0 ± 18.2 months and 33 matched preterm controls with normal brain MRI were studied. Volumes of 116 individual GM areas, and white matter/cerebrospinal fluid (WM/CSF) ratio were calculated on T1-weighted high-resolution images after segmentation. Relative to controls, children with dPVL had decreased GM volume of the hippocampus, amygdala, and frontal lobes and temporal middle gyrus (P < 0.05); increased GM volume of the putamen, thalamus, globus pallidum, superior temporal gyrus and of the parietal and occipital lobes (P < 0.05) and lower WM volume/higher CSF volume (P < 0.05). WM/CSF ratios also differed (P < 0.05). Preterm children with dPVL have increased regional GM volume in some areas probably related with a process of brain plasticity-regeneration and reduced GM volume in areas associated with cognition and memory.


The solution structure of concanavalin A probed by FT-IR spectroscopy.
The secondary structural properties of various forms of concanavalin A in solution were investigated by Fourier-transform infrared spectroscopy in the Amide I region. As in the crystal, the solution structure of the native protein consists mainly of antiparallel beta-sheet. Carbohydrate binding does not produce major changes in the overall secondary structure of concanavalin A, but affects infrared bands due to loops and beta-turns. Upon demetallization, the spectrum of concanavalin A shows only a small change in the Amide I band, indicating that whereas the beta-sheet structure is conserved, the tertiary properties may be altered. There are also changes in the bands from the tyrosine residues which are compatible with local changes in structure. Confirming tertiary structural differences, the cation-depleted apoprotein is much less stable, denaturing around 63 degrees C, while the native protein denatures only at temperatures around 85 degrees C. Tetramerization proceeds without significant secondary structural change. However, aggregation of the tetramers leads to a significant decrease of the bands corresponding to beta-sheet structure, and changes in the tyrosine bands.


Task-dependent functional connectivity of pain is associated with the magnitude of placebo analgesia in pain-free individuals.
Task-based functional connectivity (FC) of pain-related regions resulting from expectancy-based placebo induction has yet to be examined, limiting our understanding of regions and networks associated with placebo analgesia. Fifty-five healthy pain-free adults over 18 (M = 22.8 years, SD = 7.75) were recruited (65.5% women; 63.6% non-Hispanic/Latino/a/x; 58.2% White). Participants completed a baseline followed by a placebo session involving the topical application of an inactive cream in the context of an expectancy-enhancing instruction set. Noxious heat stimuli were applied to the thenar eminence of the right palm using an fMRI-safe thermode. Stimulus intensity was individually calibrated to produce pain ratings of approximately 40 on a 100-point visual analogue scale. A total of 67.3% of the participants showed a reduction in pain intensity in the placebo condition with an average reduction in pain across the whole sample of 12.7%. Expected pain intensity was associated with reported pain intensity in the placebo session (b = 0.32, p = 0.004, R2 = 0.15). Voxel-wise analyses indicated seven clusters with significant activation during noxious heat stimulation at baseline (pFDR < 0.05). Generalized psychophysiological interaction analysis suggested that placebo-related FC changes between middle frontal gyrus-superior parietal lobule during noxious stimulation were significantly associated with the magnitude of pain reduction (pFDR < 0.05). Results suggest that stronger expectancy-based placebo responses might be underpinned by greater FC among attentional and somatosensory regions. This article provides support and insight for task-dependent functional connectivity differences related to the magnitude of placebo analgesia. Our findings provide key support that the magnitude of expectation-based placebo response depends on the coupling of regions associated with somatosensory and attentional processing.


Reproducibility of the Structural Connectome Reconstruction across Diffusion Methods.
Analysis of the structural connectomes can lead to powerful insights about the brain's organization and damage. However, the accuracy and reproducibility of constructing the structural connectome done with different acquisition and reconstruction techniques is not well defined. In this work, we evaluated the reproducibility of the structural connectome techniques by performing test-retest (same day) and longitudinal studies (after 1 month) as well as analyzing graph-based measures on the data acquired from 22 healthy volunteers (6 subjects were used for the longitudinal study). We compared connectivity matrices and tract reconstructions obtained with the most typical acquisition schemes used in clinical application: diffusion tensor imaging (DTI), high angular resolution diffusion imaging (HARDI), and diffusion spectrum imaging (DSI). We observed that all techniques showed high reproducibility in the test-retest analysis (correlation >.9). However, HARDI was the only technique with low variability (2%) in the longitudinal assessment (1-month interval). The intraclass coefficient analysis showed the highest reproducibility for the DTI connectome, however, with more sparse connections than HARDI and DSI. Qualitative (neuroanatomical) assessment of selected tracts confirmed the quantitative results showing that HARDI managed to detect most of the analyzed fiber groups and fanning fibers. In conclusion, we found that HARDI acquisition showed the most balanced trade-off between high reproducibility of the connectome, higher rate of path detection and of fanning fibers, and intermediate acquisition times (10-15 minutes), although at the cost of higher appearance of aberrant fibers.


Bioactive polar lipids from Chroococcidiopsis sp. (Cyanobacteria).
Many studies indicate that various bioactive metabolites subsist in cyanobacteria. Glycolipids of cyanobacteria are reported as molecules that exert specific bioactivities. In this study, total lipids of Chroococcidiopsissp., a coccoid cyanobacterium isolated from a Greek cave, were separated into neutral and polar-lipids and the latter were further fractionated by high-performance liquid chromatography (HPLC). Each polar lipid fraction was tested in vitro for its ability to inhibit platelet-activating factor (PAF)- and thrombin-induced washed rabbit platelet aggregation and/or to cause platelet aggregation. The structures of the most active fractions were elucidated by biological assays and identified by electrospray mass spectrometry. One fraction was a potent inhibitor of PAF-induced platelet aggregation. Structural studies of this fraction indicated the existence of phospho-glyco analog of ceramide. Another fraction that was a potent inhibitor of PAF- as well as of thrombin-induced platelet aggregation was structurally elucidated as a phospho-acetylated glyco-analog of diglyceride. The fraction that induced platelet aggregation was identified as a phospho-acetylated-glyco analog of ceramide. These novel bioactive polar lipids in cyanobacteria in regard to the structure and biological activity may contribute to the allergic character of cyanobacteria.


Understanding obstructive sleep apnea in children with CHARGE syndrome.
CHARGE syndrome occurs in approximately 1 in 8500 live births and is diagnosed clinically by combinations of major characteristics: choanal atresia, coloboma, characteristic ears, cranial nerve abnormalities and distinct temporal bone anomalies. More than 50% of children with CHARGE syndrome experience sleep disturbances, with obstructive sleep apnea being one diagnosis. Objectives of this study were to develop a better understanding of the prevalence, symptomatology and treatments of sleep apnea in CHARGE syndrome. Secondary aims were to determine the usefulness of questionnaires examining obstructive sleep apnea in a CHARGE syndrome population. Parents of 51 children with CHARGE syndrome (aged 0-14 years) were recruited between May 2010 and July 2011. Genetic testing and/or clinical criteria confirmed diagnosis of CHARGE syndrome. Questionnaires completed by parents included one covering CHARGE characteristics and three previously validated questionnaires: the Brouilette Score Questionnaire, the Pediatric Sleep Questionnaire and the OSA-18 Quality of Life Questionnaire. SPSS 19.0 was used for statistical calculations. Previous diagnosis of obstructive sleep apnea was present in 65% of the study population. Treatments included continuous positive airway pressure, tonsillectomy and/or adenoidectomy, and tracheostomy. Brouilette scores identified the presence of obstructive sleep apnea in the CHARGE syndrome population studied and indicated statistically significant (p=<0.001) improvements following treatment, which were comparable to the general population. Only the subscales of snoring and daytime sleepiness were useful in identifying obstructive sleep apnea using the Pediatric Sleep Questionnaire. The OSA-18 Questionnaire indicated that residual symptoms affecting quality of life may be present in the CHARGE syndrome population after treatment for obstructive sleep apnea. Obstructive sleep apnea appears to be prevalent in children with CHARGE syndrome. All conventional treatments for obstructive sleep apnea reduce symptomatology. Brouilette scores are useful in identifying obstructive sleep apnea in the CHARGE syndrome population. The Pediatric Sleep Questionnaire could be useful once modified. The OSA-18 Questionnaire would be most useful as a means to measure quality of life gains following treatment.


Separation of estrogen glucorinides, sulphates and phosphates on ion-exchange cellulose by high-pressure liquid chromatography.
In continuation of previous work, the selectivity of anion-exchange cellulose systems with respect to thirty estrogen conjugates was studied. The influence of the type and particle size of cellulose anion exchangers, the type and concentration of the counter anion, pH and temperature was investigated. On the basis of the results the optimal choice of the ion-exchange material, the eluent and the operating conditions is demonstrated. The results of the optimization are exemplified by a number of chromatograms showing rapid separations, including the determination of the estrogen conjugate profile of human pregnancy urine.


Challenges and opportunities for Iranian global health diplomacy: lessons learned from action for prevention and control of noncommunicable diseases.
The steady rise in noncommunicable diseases (NCDs) worldwide has been a key global health challenge. Governments have the primary responsibility for taking action to prevent and control NCDs. Given the growing importance of globalization of healthcare as well as the increasing use of soft power, governments need to identify challenges and opportunities to enhance global health diplomacy (GHD) for NCD prevention and control. The purpose of this qualitative research was to explain the challenges and opportunities of GHD for NCDs in Iran. This study was conducted in 2020 using a qualitative approach and through in-depth, semi-structured interviews with 21 experts and specialists in related fields such as health policy, healthcare management, epidemiology and other related specialties. The participants were selected from all levels of diplomacy, including global, regional and national levels, with at least 3 years of experience in managerial, executive and scientific activities. Data analysis was performed by content analysis with an inductive approach. Data were analysed using inductive content analysis. The identified challenges were categorized into five main themes, including content challenges, structural challenges, process challenges, governance challenges and cultural challenges. Opportunities extracted from the interviews were also categorized into four main themes, including strong political will, utilizing the capacity of nongovernmental organizations (NGOs), multisectoral collaborations and a well-developed health system. NCD prevention and control requires a multilateral collaboration-based solution. Recognition of the challenges and opportunities in GHD can help draw significant lessons for building the necessary capacities and implementing more effective policies to prevent and control NCDs.


Cysteine mutations cause defective tyrosine phosphorylation in MEGF10 myopathy.
Recessive mutations in MEGF10 are known to cause a congenital myopathy in humans. Two mutations in the extracellular EGF-like domains of MEGF10, C326R and C774R, were associated with decreased tyrosine phosphorylation of MEGF10 in vitro. Y1030 was identified to be the major tyrosine phosphorylation site in MEGF10 and is phosphorylated at least in part by c-Src. Overexpression of wild-type MEGF10 enhanced C2C12 myoblast proliferation, while overexpression of Y1030F mutated MEGF10 did not. We conclude that MEGF10-mediated signaling via tyrosine phosphorylation helps to regulate myoblast proliferation. Defects in this signaling pathway may contribute to the disease mechanism of MEGF10 myopathy.


Maternal vitamin A supplementation increases natural antibody concentrations of preadolescent offspring in rural Nepal.
B1a lymphocytes-which constitutively produce most natural antibodies (NAb)-arise from an early wave of progenitors unique to fetal life. Vitamin A regulates early lymphopoiesis. In animals, deficiency during this critical period compromises B1 cell populations. The aim of this study was to investigate the effect of maternal supplementation with vitamin A or β-carotene from preconception through lactation on NAb concentrations of offspring. Participants (N = 290) were born to participants of a cluster-randomized, placebo-controlled trial of weekly maternal vitamin A or β-carotene supplementation (7000 μg retinol equivalents) conducted in Sarlahi, Nepal (1994-1997) and assessed at ages 9 to 13 y (2006-2008). Serum retinol was measured by reversed-phase high-performance liquid chromatography at mid-pregnancy and 3 mo of age. Enzyme-linked immunosorbent assay (ELISA) was used to measure children's plasma NAb concentrations at 9 to 13 y. Unadjusted geometric mean concentrations were 20.08 U/mL (95% confidence interval [CI], 17.82-22.64) in the vitamin A group compared with 17.64 U/mL (95% CI, 15.70-19.81) and 15.96 U/mL (95% CI, 13.43-18.96) in the β-carotene and placebo groups (P = 0.07), respectively. After adjustment, maternal vitamin A supplementation was associated with a 0.39 SD increase in NAb concentrations (P = 0.02). The effect was mediated by infant serum retinol in our statistical models. Although girls had 1.4-fold higher NAb concentrations (P < 0.001), sex did not modify the vitamin A effect. In an undernourished population, maternal vitamin A supplementation enhanced NAb concentrations of preadolescent children. We posit that this was due to a greater allotment of B1a precursors during fetal life and a sustained higher count of NAb-secreting B1a cells.


Relation of fasting insulin plasma levels to restenosis after elective coronary stent implantation in patients without diabetes mellitus.
The results of this study in 172 patients without diabetes who underwent elective stent implantation showed a significant correlation between preprocedural fasting insulin serum levels and angiographic late lumen loss (correlation coefficient 0.49, p <0.0001). Furthermore, the waist-to-hip ratio and C-peptide and hemoglobin A1c serum levels were associated with the occurrence of binary angiographic restenosis.


SubQ-Sim: A Subcutaneous Physiologically Based Biopharmaceutics Model. Part 1: The Injection and System Parameters.
To construct a detailed mechanistic and physiologically based biopharmaceutics model capable of predicting 1) device-formulation-tissue interaction during the injection process and 2) binding, degradation, local distribution, diffusion, and drug absorption, following subcutaneous injection. This paper is part of a series and focusses on the first aspect. A mathematical model, SubQ-Sim, was developed incorporating the details of the various substructures within the subcutaneous environment together with the calculation of dynamic drug disposition towards the lymph ducts and venous capillaries. Literature was searched to derive key model parameters in healthy and diseased subjects. External factors such as body temperature, exercise, body position, food or stress provide a means to calculate the impact of "life events" on the pharmacokinetics of subcutaneously administered drugs. The model predicts the tissue backpressure time profile during the injection as a function of injection rate, volume injected, solution viscosity, and interstitial fluid viscosity. The shape of the depot and the concentrations of the formulation and proteins in the depot are described. The model enables prediction of formulation backflow following premature needle removal and the resulting formulation losses. Finally, the effect of disease (type 2 diabetes) or the presence of recombinant human hyaluronidase in the formulation on the injection pressure, are explored. This novel model can successfully predict tissue back pressure, depot dimensions, drug and protein concentration and formulation losses due to incorrect injection, which are all important starting conditions for predicting drug absorption from a subcutaneous dose. The next article will describe the absorption model and validation against clinical data.


Pregnancy-associated plasma protein-A (PAPP-A) inhibits thrombin-induced coagulation of plasma.
Concentrations of immunoreactive PAPP-A have been found significantly lower in the serum as compared to heparin or EDTA plasma from the same patients. After coagulation significant amounts of PAPP-A remain associated with the clot. Purified PAPP-A inhibits thrombin induced coagulation of plasma. This inhibition cannot be attributed to a direct effect of PAPP-A on thrombin. It is exerted via an activation of endogenous antithrombin III since the inhibitory effect of PAPP-A on thrombin induced coagulation in a euglobulin system can be observed only if antithrombin III is added. The fact that protamine sulphate is capable of neutralizing the inhibitory effects of PAPP-A made us postulate that PAPP-A, like heparin, possesses strongly acidic residues which bind to protamine.


Interpleural location of chest drain on ultrasound excludes pneumothorax and associates with a low degree of chest drain foreshortening on the antero-posterior chest X-ray.
The role of chest drain (CD) location by bedside imaging methods in the diagnosis of pneumothorax has not been explored in a prospective study yet. Covid-19 ARDS patients with pneumothorax were prospectively monitored with chest ultrasound (CUS) and antero-posterior X-ray (CR) performed after drainage in the safe triangle. CD foreshortening was estimated as a decrease of chest drain index (CDI = length of CD in chest taken from CR/depth of insertion on CD scale + 5 cm). The angle of inclination of the CD was measured between the horizontal line and the CD at the point where it enters pleural space on CR. Of the total 106 pneumothorax cases 80 patients had full lung expansion on CUS, the CD was located by CUS in 69 (86%), the CDI was 0.99 (0.88-1.06). 26 cases had a residual pneumothorax after drainage (24.5%), the CD was located by CUS in 31%, the CDI was 0.76 (0.6-0.93),p < 0.01. The risk ratio for a pneumothorax in a patient with not visible CD between the pleural layers on CUS and an associated low CDI on CR was 5.97, p˂0.0001. For the patients with a steep angle of inclination (> 50°) of the CD, the risk ratio for pneumothorax was not significant (p < 0.17). A continued air leak from the CD after drainage is related to the risk for a residual pneumothorax (RR 2.27, p = 0.003). Absence of a CD on CUS post drainage, low CDI on CR and continuous air leak significantly associate with residual occult pneumothorax which may evade diagnosis on an antero-posterior CR.


An evaluation of the Cobra Perilaryngeal Airway: study halted after two cases of pulmonary aspiration.
The Cobra Perilaryngeal Airway (Engineered Medical Systems, Indianapolis, IN) is a new supraglottic airway designed for spontaneous and controlled ventilation. It is not yet commercially available in the UK. Our aim was to evaluate the performance of the Cobra Perilaryngeal Airway in a cohort study and in a randomised, controlled, crossover comparison study with the Classic Laryngeal Mask Airway. After studying 29 patients, both studies were suspended and later stopped after two cases of significant pulmonary aspiration had occurred in patients whilst using the Cobra Perilaryngeal Airway. These cases raised concern about both the design and the safety of the Cobra Perilaryngeal Airway, particularly during controlled ventilation. We suggest that the Cobra Perilaryngeal Airway should not be marketed for controlled ventilation until more safety data are available.


Insight into the activation mechanism of Escherichia coli octaprenyl pyrophosphate synthase derived from pre-steady-state kinetic analysis.
Octaprenyl pyrophosphate synthase (OPPs) catalyzes the sequential condensation of five molecules of isopentenyl pyrophosphate with farnesyl pyrophosphate to generate all-trans C40-octaprenyl pyrophosphate, which constitutes the side chain of ubiquinone. Due to the slow product release, a long-chain polyprenyl pyrophosphate synthase often requires detergent or another factor for optimal activity. Our previous studies in examining the activity enhancement of Escherichia coli undecaprenyl pyrophosphate synthase have demonstrated a switch of the rate-determining step from product release to isopentenyl pyrophosphate (IPP) condensation reaction in the presence of Triton [12]. In order to understand the mechanism of enzyme activation for E. coli OPPs, a single-turnover reaction was performed and the measured IPP condensation rate (2 s(-1)) was 100 times larger than the steady-state rate (0.02 s(-1)). The high molecular weight fractions and Triton could accelerate the steady-state rate by 3-fold (0.06 s(-1)) but insufficient to cause full activation (100-fold). A burst product formation was observed in enzyme multiple turnovers indicating a slow product release.


Laparoscopic management of caliceal diverticular calculi.
We describe laparoscopic techniques for the definitive management of symptomatic caliceal diverticular stone disease. Five patients underwent retroperitoneoscopic management of a symptomatic, stone bearing caliceal diverticulum. Techniques for intraoperative localization of the stone bearing diverticulum included retrograde injection of indigo carmine, fluoroscopy and/or laparoscopic ultrasound. In 2 cases the patent neck of the diverticulum was sutured via laparoscopy. Complete stone clearance and obliteration of the diverticular cavity was achieved in all cases without any open conversion. Mean operative time was 133.8 minutes. Mean estimated blood loss was less than 50 cc in 4 cases and 150 cc in 1. Mean hospital stay was 36 hours. There were no laparoscopic or postoperative complications. The laparoscopic approach to symptomatic caliceal diverticula represents an effective and minimally invasive modality for complete clearance of the stone burden and definitive management of the anatomical abnormality. However, patient selection is paramount. We reserve the laparoscopic approach for symptomatic caliceal diverticula with thin overlying renal parenchyma, or for anterior lesions inaccessible to or unsuccessfully managed by endourological techniques. A decision tree algorithm for managing symptomatic caliceal diverticular calculi is proposed.


A strategy for aromatic hydrocarbon bioremediation under anaerobic conditions and the impacts of ethanol: a microcosm study.
Increased use of ethanol-blended gasoline (gasohol) and its potential release into the subsurface have spurred interest in studying the biodegradation of and interactions between ethanol and gasoline components such as benzene, toluene, ethylbenzene and xylene isomers (BTEX) in groundwater plumes. The preferred substrate status and the high biological oxygen demand (BOD) posed by ethanol and its biodegradation products suggests that anaerobic electron acceptors (EAs) will be required to support in situ bioremediation of BTEX. To develop a strategy for aromatic hydrocarbon bioremediation and to understand the impacts of ethanol on BTEX biodegradation under strictly anaerobic conditions, a microcosm experiment was conducted using pristine aquifer sand and groundwater obtained from Canadian Forces Base Borden, Canada. The initial electron accepter pool included nitrate, sulfate and/or ferric iron. The microcosms typically contained 400 g of sediment, 600 approximately 800 ml of groundwater, and with differing EAs added, and were run under anaerobic conditions. Ethanol was added to some at concentrations of 500 and 5000 mg/L. Trends for biodegradation of aromatic hydrocarbons for the Borden aquifer material were first developed in the absence of ethanol, The results showed that indigenous microorganisms could degrade all aromatic hydrocarbons (BTEX and trimethylbenzene isomers-TMB) under nitrate- and ferric iron-combined conditions, but not under sulfate-reducing conditions. Toluene, ethylbenzene and m/p-xylene were biodegraded under denitrifying conditions. However, the persistence of benzene indicated that enhancing denitrification alone was insufficient. Both benzene and o-xylene biodegraded significantly under iron-reducing conditions, but only after denitrification had removed other aromatics. For the trimethylbenzene isomers, 1,3,5-TMB biodegradation was found under denitrifying and then iron-reducing conditions. Biodegradation of 1,2,3-TMB or 1,2,4-TMB was slower under iron-reducing conditions. This study suggests that addition of excess ferric iron combined with limited nitrate has promise for in situ bioremediation of BTEX and TMB in the Borden aquifer and possibly for other sites contaminated by hydrocarbons. This study is the first to report 1,2,3-TMB biodegradation under strictly anaerobic condition. With the addition of 500 mg/L ethanol but without EA addition, ethanol and its main intermediate, acetate, were quickly biodegraded within 41 d with methane as a major product. Ethanol initially present at 5000 mg/L without EA addition declined slowly with the persistence of unidentified volatile fatty acids, likely propionate and butyrate, but less methane. In contrast, all ethanol disappeared with repeated additions of either nitrate or ferric iron, but acetate and unidentified intermediates persisted under iron-enhanced conditions. With the addition of 500 mg/L ethanol and nitrate, only minor toluene biodegradation was observed under denitrifying conditions and only after ethanol and acetate were utilized. The higher ethanol concentration (5000 mg/L) essentially shut down BTEX biodegradation likely due to high EA demand provided by ethanol and its intermediates. The negative findings for anaerobic BTEX biodegradation in the presence of ethanol and/or its biodegradation products are in contrast to recent research reported by Da Silva et al. [Da Silva, M.L.B., Ruiz-Aguilar, G.M.L., Alvarez, P.J.J., 2005. Enhanced anaerobic biodegradation of BTEX-ethanol mixtures in aquifer columns amended with sulfate, chelated ferric iron or nitrate. Biodegradation. 16, 105-114]. Our results suggest that the apparent conservation of high residual labile carbon as biodegradation products such as acetate makes natural attenuation of aromatics less effective, and makes subsequent addition of EAs to promote in situ BTEX biodegradation problematic.


Rat hepatocyte engraftment in severe combined immunodeficient x beige mice using mouse-specific anti-fas antibody.
Hepatocyte transplantation holds promise as a treatment for acute and chronic liver failure; however, robust model systems needed to study xenogeneic hepatocyte transfer are lacking. Severe combined immunodeficient x beige (SCID/bg) hybrid mice readily accept foreign tissue. Repopulation of C.B-17 SCID/bg mouse liver with rat hepatocytes was studied following induction of mouse hepatocyte apoptosis using an anti-mouse agonistic fas monoclonal antibody (Jo2 mAb) that does not engage xenogeneic fas. SCID/bg mice were transplanted with 1 x 10(6) fresh adult rat hepatocytes intrasplenically and treated with various doses, routes and frequencies of Jo2 mAb. Rat cell repopulation was characterized by quantitative immunofluorescent antibody (q-IFA) staining specific for rat dipeptidyl peptidase type IV (DPP-IV) and leucine amino peptidase, amplification of rat genomic DNA using polymerase chain reaction and histopathological and serum biochemistry analyses. Analysis of liver sections from mice treated twice weekly for 12 weeks with 0.4 mg/kg Jo2 mAb intraperitoneally consistently demonstrated >50% rat hepatocytes in the parenchymal mass by q-IFA. Rat hepatocyte engraftment protected mice from Jo2 mAb-mediated liver hemorrhage and hepatocyte apoptosis. Serum liver enzyme levels did not increase in Jo2 mAb-treated mice that were highly engrafted with rat hepatocytes, in contrast to matched non-engrafted mice. At 12 weeks post-engraftment, minimal fibrosis and inflammation were apparent and liver architecture had returned to near normal. Jo2 mAb did not induce histopathological abnormalities in other tissues known to express fas antigen (i.e. heart, lung). This novel model represents a simple and robust system of xenogeneic hepatocyte transplantation that could be applied to studies of liver biology, regeneration and hepatocyte transplantation.


Therapeutic potential of Curcuma oil and its terpenoids in gynecological cancers.
Gynecological cancers encompass all uncontrolled and aberrant cell growth in the female reproductive system, therapeutic interventions are constantly evolving, but there is still a high death rate, significant side effects and medication resistance, making the task of treatment challenging and complex. The essential oil extracted from the rhizome of Curcuma longa is a promising natural drug, which has excellent biological activity on cancer cells and is to be developed as a new type of anti-gynecological tumor therapeutic agent. To systematically summarize the available evidence for the efficacy of Curcuma oil and its terpenoids (β-elemene, curcumol, furanodiene, and germacrone) in gynecological cancers, primarily malignancies of the reproductive system, involving ovarian, cervical, and endometrial cancers, explain the underlying mechanisms of preventing and treating gynecological cancers, and assess the shortcomings of existing work. Through several signaling channels, Curcuma oil and its terpenoids can not only stop the growth of ovarian cancer, cervical cancer, and endometrial cancer cells, limit the formation of tumors, but also raise the effectiveness of chemotherapy drugs and improve the quality of life for patients. It provides a preclinical basis for the efficacy of Curcuma oil as a broad-spectrum anti-tumor agent for the prevention and treatment of gynecological cancers. Even so, further efforts are still needed to improve the bioavailability of Curcuma oil and upgrade related experiments.


Stimulatory effects of ethanol in C57BL/6 mice.
Although ethanol stimulation is well documented in several species including humans, there is some controversy about whether the stimulation occurs in the highly inbred mouse strain, C57BL/6. Since inbred mouse strains are frequently used to elucidate mechanisms for individual differences in reaction to alcohol, the present study was undertaken to more completely characterize the behavioral effects of ethanol and to help resolve some of the controversy regarding the drug's stimulatory effect on C57 mice. Activity of female C57BL/6cr mice was assessed in either a lighted or dark environment for 20 min after injections of water or ethanol at doses of 0.5, 1.0, 2.0, 4.0 g/kg. Elevated activity (stimulation) was observed in mice injected with relatively low ethanol doses and tested in the light. The 2.0 g/kg dose produced a transient elevation in activity which declined rapidly across time. Animals tested under the dark condition were not stimulated by the drug but had activity reductions to high doses of ethanol. The detection of ethanol-induced stimulation appears to be related to the performance of control mice rather than a light-related difference in ethanol sensitivity.


Prevalence of hepatitis C antibodies in patients with clotting disorders in Victoria. Relationship with other blood borne viruses and liver disease.
To elucidate the seroepidemiology of hepatitis C in patients with clotting disorders in comparison with other blood borne infections; to examine the effects of hepatitis C on liver function; and to assess the effectiveness of current screening and inactivation procedures used in preventing the transmission of blood borne viruses by clotting factor preparations. A retrospective analysis of the prevalence of antibodies to hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) by means of commercially available enzyme immunoassays (for antibodies to HCV and HIV) or radioimmunoassays (for HBV antibodies and surface antigen). An analysis was made of serum transaminase levels where such information was available and this was correlated with HCV status. Panels of sera were collected from adults and children with clotting disorders attending two Melbourne haemophilia treatment centres in 1973 (n = 33), 1980 (n = 33), 1984-1985 (n = 111) and 1987-1990 (n = 217) and tested for antibodies to HCV, HBV and HIV. The prevalence of antibodies to HCV in the four panels tested was 45%, 74%, 75% and 76%, and the prevalence of markers of infection with HBV was 66%, 74%, 62% and 65% respectively. No antibodies to HIV were found in sera in Panels I and II but the prevalence in Panels III and IV was 23% and 36% respectively. In subjects in whom liver function test results were available, there was a significant association between the presence of antibodies to HCV and raised transaminase levels. Since heat inactivation of clotting factors was commenced in Australia in 1984, no new cases of transmission of HIV by clotting factors has been detected, but transmission of HCV in 19 subjects and HBV in one subject could not be excluded. Hepatitis C infection in haemophiliacs has been a very frequent event, and the presence of antibodies to HCV is associated with an increased incidence of raised transaminase levels. Screening and heat inactivation of clotting factors has prevented further HIV transmission, but exposure to HBV and HCV has not been eliminated.


Facing the future of transit ridership: shifting attitudes towards public transit and auto ownership among transit riders during COVID-19.
Public transit agencies face a transformed landscape of rider demand and political support as the COVID-19 pandemic recedes. We explore people's motivations for returning to or avoiding public transit a year into the pandemic. We draw on a March 2021 follow-up survey of over 1,900 people who rode transit regularly prior to the COVID-19 pandemic in Toronto and Vancouver, Canada, and who took part in a prior survey on the topic in May 2020. We investigate how transit demand changes associated with the pandemic relate to changes in automobile ownership and its desirability. We find that pre-COVID frequent transit users between the ages of 18-29, a part of the so-called "Gen Z," and recent immigrants are more attracted to driving due to the pandemic, with the latter group more likely to have actually purchased a vehicle. Getting COVID-19 or living with someone who did is also a strong and positive predictor of buying a car and anticipating less transit use after the pandemic. Our results suggest that COVID-19 may have increased the attractiveness of auto ownership among transit riders likely to eventually purchase cars anyway (immigrants, twentysomethings), at least in the North American context. We also conclude that getting COVID-19 or living with someone who did is a positive predictor of having bought a car. Future research should consider how having COVID-19 transformed some travelers' views, values, and behaviour. The online version contains supplementary material available at 10.1007/s11116-022-10344-2.


Changes in trace metal concentrations throughout the phosphogypsum lifecycle.
Phosphogypsum (PG) samples from four distinct sources in the Southeastern US were analyzed to explore the variation in total metal content between newly generated (fresh) PG and PG disposed of in phosphogypsum stacks for different lengths of time (stack). Fresh PG exhibited greater total metal concentrations relative to stack PG, including those identified in the literature as important from a risk assessment perspective (As, Cd, Co, Cr, Cu, Pb, and Zn). The pH varied between fresh and stack PG, with some stack samples exhibiting lower pH than fresh samples, however the relationship between pH and age of sample was not linear. Stack samples with pH values similar to fresh samples possessed lower concentrations of total inorganic metals than fresh samples suggesting that process water drainage and stack location play an important role in the reusability of PG as they can affect the pH of stack PG and total inorganic metal concentrations. Overall observations show that stacking PG for three or more years prior to beneficial reuse provides a construction material with lower total metal concentrations than fresh PG.


The significance of histologic findings in predicting nodal metastases in invasive squamous cell carcinoma of the vulva.
The significance of tumor differentiation, depth of stromal penetration, and vascular channel involvement in predicting nodal metastases was studied in 62 patients with invasive squamous cell carcinoma of the vulva treated with radical vulvectomy and bilateral inguinal and femoral lymphadenectomy. The pattern of arrangement of vulvar neoplastic cells at the interface with stroma was used as a criterion for histologic grading. Patients with less differentiated tumors had a higher incidence of nodal metastasis within each stage of disease. No nodal metastases were noted in patients with Grade III tumors who had Stage I disease. No well-differentiated tumor with less than 5 mm of stromal penetration was associated with nodal metastases. In this study, the degree of tumor differentiation and the depth of stromal penetration were important predictors of nodal metastases. It was concluded that a subgroup of patients with Stage I well-differentiated vulvar carcinoma invading less than 5 mm into the underlying stroma may benefit by less radical surgery without compromising cure.


What constitutes an Arabian Helicobacter pylori? Lessons from comparative genomics.
Helicobacter pylori, the human gastric pathogen, causes a variety of gastric diseases ranging from mild gastritis to gastric cancer. While the studies on H. pylori are dominated by those based on either East Asian or Western strains, information regarding H. pylori strains prevalent in the Middle East remains scarce. Therefore, we carried out whole-genome sequencing and comparative analysis of three H. pylori strains isolated from three native Arab, Kuwaiti patients. H. pylori strains were sequenced using Illumina platform. The sequence reads were filtered and draft genomes were assembled and annotated. Various pathogenicity-associated regions and phages present within the genomes were identified. Phylogenetic analysis was carried out to determine the genetic relatedness of Kuwaiti strains to various lineages of H. pylori. The core genome content and virulence-related genes were analyzed to assess the pathogenic potential. The three genomes clustered along with HpEurope strains in the phylogenetic tree comprising various H. pylori lineages. A total of 1187 genes spread among various functional classes were identified in the core genome analysis. The three genomes possessed a complete cagPAI and also retained most of the known outer membrane proteins as well as virulence-related genes. The cagA gene in all three strains consisted of an AB-C type EPIYA motif. The comparative genomic analysis of Kuwaiti H. pylori strains revealed a European ancestry and a high pathogenic potential.


Correlates and spatial distribution of the co-occurrence of childhood anaemia and stunting in Ghana.
Childhood anaemia and stunting are major public health concerns in Ghana. Using the 2014 Ghana Demographic and Health Survey, we evaluated whether childhood anaemia (Haemoglobin concentration < 110 g/L) and stunting (height-for-age z score < -2) co-occur beyond what is expected in Ghana, and employed spatial analysis techniques to determine if their co-occurrence is spatially correlated. There was no statistically significant difference between the observed and expected frequency of co-occurrence. Among 24-35 month and 36-59-month-old children, belonging to a high wealth household compared to low wealth household was associated with lower odds of the co-occurrence of childhood anaemia and stunting (OR, 95% CI: 0.3[0.1, 0.8] and 0.2[0.1, 0.5], respectively). Children aged 6-23 months with caregivers who had formerly been in union compared to their counterparts with caregivers who have never been in union had higher odds of co-occurrence of anaemia and stunting (5.1, [1.1, 24.3]). Overall, households with high wealth and having a mother with secondary or more education were associated with lower odds of the co-occurrence of childhood anaemia and stunting (OR, 95% CI: 0.4[0.2, 0.8] and 0.5[0.3, 0.9], respectively). There was substantial spatial clustering of co-occurrence, particularly in the northern region of the country. Interventions purposed to improve linear growth and anaemia must identify the specific factors or context which contribute to childhood anaemia and stunting.


Repeat corneal collagen cross-linking after failure of primary cross-linking in keratoconus.
Primary corneal collagen cross-linking (CXL) stabilises 96% of progressive keratoconus. There is limited evidence for the treatment of choice when this fails. We present 10 years of repeat CXL and compare with our published experience of primary CXL to (1) identify perioperative risk factors of primary CXL failure and (2) demonstrate the safety and efficacy of repeat CXL. Patients undergoing repeat accelerated epithelium-off CXL at St James's University Hospital, Leeds, UK January 2012-August 2022 were identified through electronic patient record, and compared with a previously published cohort of primary CXL patients at the same site. Twenty-one eyes underwent repeat CXL. The mean interval between primary and repeat CXL treatments was 47.1 months (SD 22.5). Twenty (95%) eyes stabilised after repeat CXL at a mean follow-up of 29.9 months. These cases were compared with 151 cases of primary CXL from our previous study. Patients failing primary CXL were significantly younger (21.3 years (SD 7.0) vs 26.7 years (SD 6.5), p=0.0008). Repeat CXL and primary CXL induced a similar amount of flattening of Kmax (-1.2 D (SD 3.9) vs -0.7 D (SD 4.4), p=0.22). A small, but clinically insignificant, improvement in best-corrected visual acuity was found in the repeat CXL group (-0.04 (SD 0.17) vs -0.05 (SD 0.13), p=0.04). No complications of repeat CXL were noted. Younger age may be associated with failure of primary CXL. Repeat CXL is an effective and safe treatment for progressive keratoconus despite primary CXL.


Enzymatic in situ determination of stereospecificity of NAD-dependent dehydrogenases.
Amino acid racemases inherently catalyze the exchange of alpha-hydrogen of amino acids with deuterium during racemization in 2H2O. When the reactions catalyzed by alanine racemase (EC 22.214.171.124) and L-alanine dehydrogenase (EC 18.104.22.168), which is pro-R specific for the C-4 hydrogen transfer of NADH, are coupled in 2H2O, [4R-2H]NADH is exclusively produced. Similarly, [4S-2H]NADH is made in 2H2O with amino-acid racemase with low substrate specificity (EC 126.96.36.199) and L-leucine dehydrogenase (EC 188.8.131.52), which is pro-S specific. We have established a simple procedure for the in situ analysis of stereospecificity of C-4 hydrogen transfer of NADH by an NAD-dependent dehydrogenase by combination with either of the above two couples of enzymes in the same reaction mixture. When the C-4 hydrogen of NAD+ is fully retained after sufficient incubation, the stereospecificity of hydrogen transfer by a dehydrogenase is the same as that of alanine dehydrogenase or leucine dehydrogenase. However, when the C-4 hydrogen of NAD+ is exchanged with deuterium, the enzyme to be examined shows the different stereospecificity from alanine dehydrogenase or leucine dehydrogenase. Thus, we can readily determine the stereospecificity by 1H NMR measurement without isolation of the coenzymes and products.


Human autologous mixed lymphocyte reactions (a review).
The literature concerning the autologous mixed lymphocyte reactions has been reviewed. This analysis supports the following conclusions: human subjects have self-responsive cells which are capable of proliferating when co-cultured with irradiated autologous non-T or Ia+ T cells. Since monoclonal antibodies recognizing distinct determinants of Ia antigen have different effects on AMLR with non-T cells and on Ia+ type AMLR, there is the possibility that different Ia molecule determinants have different functional role in the process of cell-to-cell interaction. The presence of AMLR abnormalities in disease strongly suggests that reactivity among different cell subsets plays a role in immunological homeostasis.


Helicity Induction in Three π-Conjugated Chromophores by Planar Chirality of Calixamide.
Shall we twist? Three-dimensional arrangement of π-conjugated chromophores with triple-stranded helicity was achieved by using the planar chirality of m-calix[3]amide. Based on spectroscopic data and theoretical calculations, the dynamic and preferred helical characters of bithiophene units embedded in the tubular molecule were elucidated, and the absolute configuration was determined.


Changes in excitability properties associated with axonal regeneration in human neuropathy and mouse Wallerian degeneration.
The aim of this study was to investigate changes in excitability properties associated with axonal regeneration in human neuropathy and a mouse Wallerian degeneration model. Threshold tracking was used to measure axonal excitability indices such as strength-duration time constant (SDTC), threshold electrotonus, supernormality in median motor axons at the wrist of 13 patients with vasculitic neuropathy in their recovery phase, and in tibial motor axons at the ankle of mice with sciatic nerve crush. In the mouse model, excitability testing was performed 4, 8, 12, and 20weeks after the nerve crush. In patients, there were longer SDTC, greater threshold changes at 0.2ms in latent addition, and greater threshold changes in depolarizing and hyperpolarizing threshold electrotonus, compared with controls. The pattern of changes in excitability indices was similar to those in experimental nerve crush, in which the indices remained abnormal for 20weeks after the crush. These changes suggest an increase in nodal persistent sodium currents, whereas multiple factors may also contribute to changes in excitability properties, such as axonal hyperpolarization, increased internodal resistance, and altered potassium currents. Excitability properties in regenerating axons are characterized by increased nodal persistent currents with variable combination of changes in passive properties, membrane potential, and potassium currents. Increased persistent sodium currents are potential reasons for positive symptoms in patients with axonal neuropathy. Sodium channel blockers could be considered a treatment option.


Points to consider when choosing a biopsy method in cases of pleurisy of unknown origin.
Blind pleural needle biopsy and diagnostic thoracoscopy are procedures sometimes used in the work-up of a patient with pleural effusion of unknown origin. We reviewed 203 diagnostic thoracoscopies in patients with malignant pleural effusion to show the different location of pleural metastasis, some out of the reach of blind needle biopsy. Based on these data, we find diagnostic thoracoscopy a superior procedure because of its higher reliability, faster diagnostic results, slight or no complications, and the possibility of carrying out pleurodesis in the same examination.


Acoustic distortion products in rabbit ear canal. I. Basic features and physiological vulnerability.
In contrast to evoked otoacoustic emissions, acoustic distortion products (DPs) recorded from the ear canal are present at predictable frequencies with respect to their primary tones, f1 and f2. Such specificity may provide detailed frequency-place information concerning the functional state of limited regions of the organ of Corti following experimental intervention. However, to date, it is not clear whether emitted DPs solely reflect activity at the basilar-membrane regions of primary tones or if the remote DP site makes a significant contribution to the emitted signal measured in the ear canal. We have investigated a number of the general features of acoustic-DP generation in the rabbit so that, in later experiments, the contributions of specific basilar-membrane regions involved in generating these DPs can be identified using techniques designed to manipulate their normal properties. The first report describes the outcome of systematic manipulations of a number of stimulus conditions and alterations to the physiological state of the cochlea by exposure to fatiguing sound or anoxia. Experimental findings for the 2f1-f2 DP showed that, in general, the relations of the levels and frequency of the primary tones to DP magnitude were consistent with previously published data from other mammalian species. Additional observations for other odd-order intermodulation DPs at the 3f1-2f2 and 2f2-f1 frequencies suggested that the basic attributes of the acoustic DPs were similarly affected by systematic manipulation of the basic parameters of the primary tones and the general metabolic state of the cochlea. General anesthesia, however, did not affect DP amplitude. A companion paper describes the results of a series of subsequent experiments using response-suppression, interfering-tone, and temporary threshold shift techniques which address more directly the issue of which basilar-membrane sites contribute to the generation of different acoustic DPs.


Unusual presentation of lateral sural cutaneous nerve schwannoma: An exceptional case report.
Schwannoma is the most common benign nerve sheath tumor. Peripheral nerves of the lower extremity are rarely involved and usually asymptomatic. We report the case of a misleading clinical presentation of lateral sural cutaneous nerve schwannoma. To the best of our knowledge, no case has been reported about the location of schwannoma in the lateral sural cutaneous nerve. MRI and anatomopathologic assessment, after microscopic enucleation, are required to confirm diagnosis. Care must be taken to not miss a schwannoma of lateral sural cutaneous nerve by meticulous clinical examination and appropriate imaging using MRI in unexplained L5 sciatica.


The Impact of HIV-Associated Neurocognitive Impairment on Driving Performance in Commercial Truck Drivers.
Driving ability can be diminished amongst people with HIV with associated neurocognitive impairment (NCI). We explore the relationship between HIV status, NCI and driving ability in professional truck drivers. Forty male professional drivers (20 HIV-positive; mean age = 39.20 ± 7.05) completed a neuropsychological test battery, two driving simulator tasks that assessed driving ability, and a driving history and habits questionnaire. A higher proportion of HIV-positive drivers exhibited impaired overall cognitive performance (p ≤ 0.001). Overall, drivers with NCI (defined as z ≤ 1.00) were more likely than those without NCI to crash (p = 0.002). There were no significant between-group (HIV-positive versus HIV-negative) differences with regard to self-reported on-road driving events. Professional drivers with NCI, as measured on a driving simulator, are at increased risk of making driving errors under high-risk conditions compared to their neurocognitively normal counterparts. These data should inform driver health management with regard to annual medical screening and surveillance.


[New anticoagulant drugs for atrial fibrillation. Feasibility and necessity of monitoring].
Two novel oral anticoagulants, namely the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitor rivaroxaban, have recently been approved for treatment of atrial fibrillation. They differ in many ways from vitamin K antagonists, including rapid onset of action, shorter half-life, fewer drug-drug interactions, lack of a need for monitoring and no need for titration or dose adjustments. Commonly available global coagulation time assessments (e.g. prothrombin time and activated partial thromboplastin time) are highly influenced by rivaroxaban and dabigatran but these assays are relatively insensitive. Ideally these anticoagulant agents would be assessable using a sensitive and standardized test with a linear dose-response curve. Optimized assays are currently under investigation and may quantify the anticoagulant effect. At present the therapeutic ranges for dose adjustment have not yet been established.


Novel curcumin analogs targeting TNF-induced NF-kappaB activation and proliferation in human leukemic KBM-5 cells.
Novel curcumin analogs were synthesized using Knoevenagel condensation to convert enolic diketones of curcumin into non-enolizable ones and Schiff bases were prepared using a bioactive thiosemicarbazide pharmacophore. Copper(II) conjugates of all synthesized ligands were prepared and structurally characterized as well as evaluated for their potential of inhibiting TNF-induced NF-kappaB activation and proliferation in human leukemic KBM-5 cells wherein compound 13 was found to be more potent than curcumin. Compounds were further examined on other tumor cell lines such as Jurkat, H1299, and MM1, respectively.


An HIT-Supported Care Coordination Framework for Reducing Structural Racism and Discrimination for Patients With ADRD.
Black and Latinx Americans are disproportionately at greater risk for having Alzheimer's disease and related dementias (ADRD) than White Americans. Such differences in risk for ADRD are arguably explained through health disparities, social inequities, and historical policies. Structural racism and discrimination (SRD), defined as "macro-level conditions that limit opportunities, resources, and well-being of less privileged groups," have been linked with common comorbidities of ADRD, including hypertension, obesity, diabetes, depression. Given the historical impact of SRD-including discriminatory housing policies resulting in racial residential segregation that has been shown to limit access to education, employment, and healthcare-Black and Latinx populations with ADRD are directly or indirectly negatively affected by SRD in terms of access, quality and cost for healthcare. Emerging studies have brought to light the value of structural-level hospital and public health collaboration on care coordination for improving healthcare quality and access, and thus could serve as a macro-level mechanism for addressing disparities for minoritized racial and ethnic populations with ADRD. This paper presents a conceptual framework delineating how care coordination can successfully be achieved through health information technology (HIT) systems and ultimately address SRD. To address health inequities, it is therefore critical that policy initiatives invest in HIT capacities and infrastructures to promote care coordination, identify patient needs and preferences, and promote engagement of patients with ADRD and their caregivers.


Ellagic acid modulates cisplatin toxicity in DMH induced colorectal cancer: Studies on membrane alterations.
Systemic toxicity due to chemotherapy contributes to poor prognosis in patients receiving chemotherapy. The present study, therefore, explores the role of Ellagic acid, a phytochemical, in modulating cisplatin (CP) toxicity in dimethylhydrazine-induced colorectal cancer. Colons excised from DMH administered animals showed abnormal crypts and bulges over the mucosal surface. SEM revealed significant alterations and dysplastic lesions in DMH administered mice. Animals receiving combined treatment showed improvement in colonic epithelium with lesser irregularities. DMH and CP administration disturbed the membrane dynamics and integrity as observed with the fluorescent probes DPH and pyrene. However, EA co-supplementation with CP proved to be beneficial in normalizing the altered membrane. Ellagic acid co-supplementation along with CP; therefore, showed great promise and helped restore the membrane alterations in the colon caused due to CP-induced toxicity and DMH insult. These observations could pave way towards developing a combination therapy targeting colon carcinogenesis in future.


Initiatives and evaluations: the life of a lymphoedema researcher.
Ioan Humphreys, Research Assistant, College of Human and Health Sciences, Swansea University ( firstname.lastname@example.com ), describes his involvement in evaluating some exciting initiatives to improve care.


Single-cell analyses reveal novel molecular signatures and pathogenesis in cutaneous T cell lymphoma.
Sézary syndrome (SS) is a rare and aggressive type of cutaneous T cell lymphoma (CTCL) with a poor prognosis. Intra-tumoral heterogeneity caused by different disease compartments (e.g., skin, blood) and poor understanding of the pathogenesis has created obstacles to the precise diagnosis and targeted treatment of the disease. Here we performed a comprehensive analysis by integrating single-cell transcriptomic data of 40,333 peripheral blood mononuclear cells (PBMCs) and 41,580 skin cells, as well as single-cell chromatin accessibility data of 11,058 PBMCs from an SS patient and matched healthy controls (HCs). Validation and functional investigation were carried out in an independent cohort consisting of SS patients, mycosis fungoides (MF) patients, psoriatic erythroderma patients, and HCs, as well as multiple cell lines. The analysis revealed that skin-derived Sézary cells (SCs) had a shifting trend to more advanced mature phenotypes compared to blood-derived SCs. A series of specific marker genes (TOX, DNM3, KLHL42, PGM2L1, and SESN3) shared in blood- and skin-derived SCs were identified, facilitating the diagnosis and prognosis of MF/SS. Moreover, luciferase reporter assays and gene knockdown assays were used to verify that KLHL42 was transcriptionally activated by GATA3 in SS. Functional assays indicated that KLHL42 silencing significantly inhibited aggressive CTCL cell proliferation and promoted its apoptosis. Therefore, targeting inhibition KLHL42 might serve as a promising therapeutic approach in CTCL.


Inhibitory effect of digoxin on testosterone secretion through mechanisms involving decreases of cyclic AMP production and cytochrome P450scc activity in rat testicular interstitial cells.
1. In vivo and in vitro experiments were performed to examine inhibitory effects of digoxin on testosterone secretion and to determine possible underlying mechanisms. 2. A single intravenous injection of digoxin (1 microg kg(-1)) decreased the basal and human chorionic gonadotropin (hCG)-stimulated plasma testosterone concentrations in adult male rats. 3. Digoxin (10(-7) - 10(-4) M) decreased the basal and hCG-stimulated release of testosterone from rat testicular interstitial cells in vitro. 4. Digoxin (10(-7) - 10(-4) M) also diminished the basal and hCG-stimulated production of cyclic 3':5'-adenosine monophosphate (AMP) and attenuated the stimulatory effects of forskolin and 8-Br-cyclic AMP on testosterone production by rat testicular interstitial cells. 5. Digoxin (10(-4) M) inhibited cytochrome P450 side chain cleavage enzyme (cytochrome P450sec) activity (conversion of 25-hydroxy cholesterol to pregnenolone) in the testicular interstitial cells but did not influence the activity of other steroidogenic enzymes. 6. These results suggest that digoxin inhibits the production of testosterone in rat testicular interstitial cells, at least in part, via attenuation of the activities of adenylyl cyclase and cytochrome P450sec.


Neural correlates of humor detection and appreciation.
Humor is a uniquely human quality whose neural substrates remain enigmatic. The present report combined dynamic, real-life content and event-related functional magnetic resonance imaging (fMRI) to dissociate humor detection ("getting the joke") from humor appreciation (the affective experience of mirth). During scanning, subjects viewed full-length episodes of the television sitcoms Seinfeld or The Simpsons. Brain activity time-locked to humor detection moments revealed increases in left inferior frontal and posterior temporal cortices, whereas brain activity time-locked to moments of humor appreciation revealed increases in bilateral regions of insular cortex and the amygdala. These findings provide evidence that humor depends critically upon extant neural systems important for resolving incongruities (humor detection) and for the expression of affect (humor appreciation).


Endoscopically Assisted Myectomy for Intramuscular Lipoma of Pronator Quadratus.
Intramuscular lipoma is usually growing infiltratively and can affect any muscle, although the proximal muscles of the extremities are mostly commonly involved. This lesion can occur in the pronator quadratus. Because of muscle is small and deep seated, the intramuscular lipoma usually involves the whole muscle and even has an extramuscular component before it presents clinically. In this Technical Note, we report the technique of endoscopically assisted myectomy of the pronator quadratus for infiltrating intramuscular lipoma of the muscle. This has the advantage of minimally invasive surgery of minimal soft tissue dissection and fewer soft tissue complications.


Enhanced radiosensitivity of LNCaP prostate cancer cell line by gold-photoactive nanoparticles modified with folic acid.
Conventional cancer treatment methods suffer from many limitations such as non-specificity in discrimination between healthy and malignant cells. The aim of this study was to investigate the role of polymeric gold-photoactive nanoparticles (PGPNPs) conjugated with folic acid (FA) as theranostic nanoparticles for active targeting, real-time fluorescence tracing and radiosensitivity inducition in LNCaP prostate cancer cells. The cellular uptake and cytotoxicity effect of gold nanoparticles (PGPNPs and PGPNPs-FA) after 2 and 24 h treatment were evaluated in in both cancer (LNCaP) and normal (HUVEC) cells using fluorescent microscopy, Induced coupled plasma optical emission spectrometry (ICP-OES) and Tetrazolium bromide dye (MTT), respectively. The therapeutic efficacy was analyzed on the LNCaP cells. For this purpose, LNCaP cells were treated by nanoparticles and ionizing radiation, and the synergistic effect of treatment methods were evaluated by colony formation assay (CFA) and Flow cytometry analysis. The results of fluorescence imaging and ICP-OES data showed that the LNCaP cells absorbed PGPNP-FA nanoparticles more than PGPNP (P < 0.001). Also, the uptake of nanoparticles was significantly greater in cancer cells than in healthy ones (P < 0.01). MTT assay results indicated higher cytotoxic effect of nanoparticles conjugated with FA in folate-receptor overexpressing LNCaP cancer cells compared to HUVEC normal cells (P < 0.01). Furthermore, CFA and Flow cytometry results demonstrated that combinatorial therapy of polymeric gold nanoparticles with/without FA and ionizing radiation at various doses (2, 4 and 6 Gy) had a synergistic effect on survival fraction and induction of apoptotic and necrotizing cell death (P < 0.01). PGPNPs-FA nanoparticles led to higher and more specific uptake and accumulation of nanoparticles in LNCaP cells, thereby increasing the ability of gold nanoparticles as radio-sensitizer.


Characterization of the explosive triacetone triperoxide and detection by ion mobility spectrometry.
The improvised explosive triacetone triperoxide (TATP) was synthesized and characterized by 1H-nuclear magnetic resonance (NMR), 13C-NMR, Raman and infrared (IR) spectroscopy. Triacetone triperoxide was subsequently analyzed by ion mobility spectrometry (IMS) in positive ion mode, and detected as a cluster of three peaks with a drift time of the most intense peak at 13.06 ms. Triacetone triperoxide was then analyzed after dissolution in toluene, where a dramatic increase in peak intensity was observed, at a flight time of 12.56 ms (K0=2.71 cm2V(-1)s(-1)). Triacetone triperoxide was subsequently analyzed by coupling the ion mobility spectrometer to a triple quadrupole mass spectrometer, where a single peak at m/z of 223 atomic mass units identified the species present in the ion mobility spectra as being triacetone triperoxide.


Lateral striatal cholinergic mechanisms involved in oral motor activities in the rat.
These experiments were undertaken to determine if local injection of pilocarpine in the neostriatum of the rat produces oral motor activities that are similar to those produced by systemic administration. In the first experiment, IP administration of 2.0-8.0 mg/kg pilocarpine increased chewing movements and tongue protrusions. In the second experiment, chronic guide cannulae were implanted bilaterally in ventromedial or ventrolateral striatum, and rats were injected with saline, 30, and 60 micrograms pilocarpine (per side). A dose-related increase in vacuous chewing was induced by injections of pilocarpine in the ventrolateral but not the ventromedial striatum. Tongue protrusions were induced by injections of pilocarpine into the ventromedial and the ventrolateral striatum. A third experiment demonstrated that this response was blocked completely by 10 micrograms scopolamine co-administered via the same cannulae, but the response was not reduced significantly by 10 micrograms haloperidol. These results indicate that ventrolateral striatal cholinergic mechanisms are involved in oral motor activities in the rat. This syndrome may provide a model for human clinical phenomena such as parkinsonian tremor.


Flavonoid compounds are potent inhibitors of cyclic AMP phosphodiesterase.
The inhibitory activity of 19 flavonoid molecules on cyclic AMP breakdown by a commercial beef heart phosphodiesterase preparation is reported. 7 compounds are active in the micromolar range, 2 of which have a potency equivalent to that of papaverine. Some structure activity relationships are drawn.


Structural basis for the relaxed substrate selectivity of Leishmania mexicana broad specificity aminotransferase.
Leishmania species are early branching eukaryotic parasites that cause difficult-to-treat tissue-damaging diseases known as leishmaniases. As a hallmark of their parasitic lifestyle, Leishmaniae express a number of aminotransferases that are involved in important cellular processes and exhibit broader substrate specificity than their mammalian host's counterparts. Here, we have determined the crystal structure of the broad specificity aminotransferase from Leishmania mexicana (LmexBSAT) at 1.91Å resolution. LmexBSAT is a homodimer and belongs to the α-branch of family-I aminotransferases. Despite the fact that the protein was crystallized in the absence of substrates and has lost the pyridoxal-5'-phosphate (PLP) cofactor during crystallization, the structure resembles the closed, ligand-bound form of related enzymes such as chicken cytosolic aspartate aminotransferase. Its broader substrate specificity seems to be rooted in increased flexibility of a substrate-binding arginine (R291) and the interactions of this residue with the N-terminus of the second chain of the dimer.


The polar lipids of group B Streptococci. II. Composition and positional distribution of fatty acids.
1. The polar lipids from group B Streptococci have been isolated. Unless overlapping fractions are worked up on each step molecular species can be lost resulting in a fatty acid composition different from the original one. 2. The lipids were shown to be 1(3),2-diacyl-3(1)-O-alpha-D-glucopyranosyl-sn-glycerol, 1(3),2-diacyl-3(1)-O-[alpha--D-glucopyranosyl-(1,2)-O-alpha-D-glucopyranosyl]-sn-glycerol, 1,2-diacyl-sn-glycero-3-phospho-1'-sn-glycerol, lysylphosphatidylglycerol and 1'-3'-bis(1,2-diacyl-sn-glycero-3-phospho-glycerol. The sterochemical configuration of the phospholipids was achieved by combinations of chemical degradations. 3. The fatty acid composition of group B Streptococci lipids is qualitatively the same as in other Streptococci, but differs by a high content of stearic acid and by a low degree of unsaturation and cyclopropanization. 4. The forementioned polar lipids as well as the glucosyldiphsphatidylglycerol,, which is also found in this organism, showed a very similar composition and the same non-radom positional distribution of fatty acids. Apart from short chain fatty acids the positioning differentiates between saturated and unsaturated fatty acids: short chain and unsaturated fatty acids are accumulated at Position 2, saturated acids are preferentially linked to Position 1. 5. The uniform fatty acid make-up in all polar lipids favours the hypothesis that their diacylglycerol portions are derived from a common phosphatidic acid precursor with negligible postsynthetic rearrangements of the constituent fatty acids.


Simple application of anterior jig or leaf gauge in routine clinical practice.
Utilization of either of the two described methods by dentists is recommended as a simple means to routinely record or provide centric relation closures. The leaf gauge (1 to 6 mm thick) can be made from plastic or x-ray film or it can be purchased. The anterior acrylic resin jig can be made in a few minutes directly in the mouth by the dentist or an assistant or by a technician using mounted casts. Both methods avoid adaptive mandibular closure patterns and dentist-guided jaw closure as well as other commonly unrecognized errors in assessing occlusal contacts.


The Perruche case and the issue of compensation for the consequences of medical error.
The case of Nicolas Perruche gave rise to a national debate in France over compensation for serious consequences of medical error. Ultimately, legislation was enacted banning the cause of action known in Anglo-American law as wrongful life, and an agency was established to adjudicate subsequent claims. As other developed nations continue to wrestle with rapid increases in the cost of professional liability coverage and health care in general, a review of the Perruche case and its influence on French health policy may advance the discussion beyond the current stalemate of hardened advocacy positions.


Visual tracking at 4 months in preterm infants predicts 6.5-year cognition and attention.
Visual tracking of moving objects requires sustained attention and prediction of the object's trajectory. We tested the hypothesis that measures of eye-head tracking of moving objects are associated to long-term neurodevelopment in very preterm infants. Visual tracking performance was assessed at 4 month's corrected age in 57 infants with gestational age <32 weeks. An object moved in front of the infant with sinusoidal or triangular (i.e. abrupt) turns of the direction. Gaze gain, smooth pursuit gain, and timing of gaze to object motion were analyzed. At 6.5 years the Wechsler Intelligence Scale for Children (WISC-IV), the Brown Attention Deficit Disorder (Brown ADD), and visual examination were performed. Gaze gain and smooth pursuit gain at 4 months were strongly related to all WISC-IV parameters at 6.5 years. Gaze gain for the triangular and sinusoidal motion patterns related similarly to the cognitive scores. For the sinusoidal motion pattern, timing related to most Brown ADD parameters. There were no statistically significant differences in associations dependent on motion pattern. Visual function did not influence the results. The ability to attend to and smoothly track a moving object in infancy is an early marker of cognition and attention at 6.5 years. Potential long-term implications of infant visual tracking of moving objects for school-age neurodevelopment has not been previously studied in very preterm infants. Early coordination of eye and head movements in gaze gain, smooth pursuit, and timing of gaze to object motion are closely associated with cognition and attention at 6.5 years. As related functions at 6.5 years include perceptual and verbal skills, working memory, processing speed and attention, predictive elements in gaze tracking of moving objects might be a suitable target for future intervention studies.


Explaining excessive rates of cesareans and other childbirth interventions: contributions from contemporary theories of gender and psychosocial development.
The current rate of cesarean sections in the U.S. is too high. Numerous mothers and babies are being placed at unnecessary risk of medical, behavioral and psychological complications. The problem has proven resistant to solution on a large scale, despite serious efforts on the part of a variety of individuals and groups. This paper considers reports on the interactions between obstetricians and mothers in labor in light of findings and theory in the areas of gender and psychosocial development. Examination of processes and standards of care in light of these findings and theory leads to the conclusion that the present model of obstetric services is consistent with a masculine style, and offers far less than optimal care for women. In fact, the gender-inappropriate elements of the model itself probably contribute to the excessive rates of interventions in labor. Social, political and historical factors are seen to support the obstetric model as is, leading to some pessimism about the possibility that the model could be modified sufficiently without major social change. The obstetric model is compared briefly with the more gender appropriate model of care provided by midwives.


Effects of prostacyclin on bronchoconstriction and neutropenia induced by inhaled platelet-activating factor in man.
We studied the effects of prostacyclin (PGI2) on the airway responses to platelet-activating factor (PAF) in a randomized and crossover study in eight normal subjects. PGI2 or diluent (glycine buffer) was continuously infused on 2 separate days. Two breaths of PAF (21 micrograms) were inhaled three times every 15 minutes and airflow at 30% of vital capacity from partial flow-volume curves (Vp30) was measured. PGI2 (4 ng/kg/min) had no effect on Vp30 or blood pressure, whereas heart rate increased from 70.3 +/- 3.9 to 73.7 +/- 4.0 beats/min (mean +/- SEM; p less than 0.01). Two subjects did not complete the study because of transient hypotension. PGI2 had no effect on PAF-induced bronchoconstriction with maximal decreases in Vp30 of 42.0 +/- 8.0% (p less than 0.01) during PGI2 and 49.8 +/- 14.2% (p less than 0.02) during diluent infusion. Ex vivo platelet aggregation to PAF (10(-9) to 10(-7) mol/L) was significantly inhibited by PGI2. Circulating neutrophils decreased from 4.7 +/- 0.9 x 10(9)/L to 1.5 +/- 0.3 x 10(9)/L (p less than 0.05) 5 minutes after the first PAF inhalation during diluent infusion, whereas there was no significant change with PGI2. Thus, PGI2 does not influence PAF-induced bronchoconstriction in man despite causing marked inhibition of ex vivo PAF-induced platelet aggregation and preventing the fall of neutrophils.


Dynamics of cerebral blood flow velocities during normal human sleep.
Bilateral flow patterns of the middle cerebral artery (MCA) were recorded continuously throughout the night in 18 healthy male subjects (mean age 27.4 years) by a computer-assisted pulsed Doppler (2 MHz) system together with simultaneous polysomnography. After inception of sleep, mean flow velocity (MFV) decreased steadily during deepening sleep stages reaching -15.0 +/- 3.6% (p < 0.001) in the right MCA and -16.2 +/- 3.4% in the left MCA (p < 0.001) in stage 4 of the first sleep cycle compared to the waking state. Lowest MFV values were found in stage 2 preceding the last REM period (right MCA: -19.2 +/- 4.1%: left MCA: -19.7 +/- 5.1%). Changing from non-REM into REM sleep, a sudden rise of MFV, which varied from 8.9% (first sleep cycle, left MCA) to 18% (last sleep cycle, right MCA), could be consistently detected indicating a coupling of cerebral electrical activity and cerebral perfusion in REM sleep. During non-REM sleep this concomitant change of MFV and EEG activity was only found in the first sleep cycle, whereas no parallel changes could be observed in later sleep cycles. These results indicate a decoupling of EEG measured cerebral electrical activity and perfusion and suggest that factors other than metabolic mechanisms contribute to the regulation of cerebral perfusion during human non-REM sleep.


Estrogen replacement therapy decreases plasma adiponectin but not resistin in postmenopausal women.
The effects of estrogen replacement therapy (ERT) to cardiovascular disease risk are still unclear. Low adiponectin and high resistin plasma concentrations are reported to be associated with atherosclerosis. However, it is not known how ERT affects plasma adiponectin and resistin concentrations. Seventy-three hysterectomized, nondiabetic, postmenopausal women were randomized in a double-blind, double-dummy study to receive either peroral estradiol valerate or transdermal 17beta-estradiol gel for 6 months. Biochemical measurements were determined from samples taken before and after the therapy. Peroral estradiol valerate therapy decreased adiponectin concentrations from 13.6 to 11.6 mg/L (P = .008), whereas transdermal 17beta-estradiol gel had no effect (12.7 vs 12.2 mg/L). Neither treatment changed the resistin concentrations significantly. Plasma concentrations of estradiol and estrone did not correlate with adiponectin or resistin concentrations before or after therapy. The change in adiponectin concentration correlated significantly with the changes in waist-hip ratio, very low-density lipoprotein triglycerides, and insulin-like growth factor 1 in the peroral estradiol valerate group. The changes in these variables and the change in estradiol concentration explained 43.1% (P = .001) of the variability in the change of plasma adiponectin, the change in very low-density lipoprotein triglycerides being the strongest determinant (beta = -.407, P = .011). The results show that peroral ERT can decrease plasma adiponectin levels. However, ERT does not seem to influence plasma resistin concentrations.


Association between Pre-Treatment Biological Indicators and Compliance to Neoadjuvant/Perioperative Chemotherapy in Operable Gastric Cancer.
Perioperative treatment is currently the gold standard approach in Europe for locally advanced gastric cancer (GC). Unfortunately, the phenomenon of patients dropping out of treatment has been frequently observed. The primary aims of this study were to verify if routine blood parameters, inflammatory response markers, sarcopenia, and the depletion of adipose tissues were associated with compliance to neoadjuvant/perioperative chemotherapy. Blood samples were considered before the first and second cycles of chemotherapy. Sarcopenia and adipose indices were calculated with a CT scan before starting chemotherapy and before surgery. Odds ratios (OR) from univariable and multivariable models were calculated with a 95% confidence interval (95% CI). A total of 84 patients with locally advanced GC were identified between September 2010 and January 2021. Forty-four patients (52.4%) did not complete the treatment according to the number of cycles planned/performed. Eight patients (9.5%) decided to suspend chemotherapy, seven patients (8.3%) discontinued because of clinical decisions, fourteen patients (16.7%) discontinued because of toxicity and fifteen patients (17.9%) discontinued for miscellaneous causes. Seventy-nine (94%) out of eighty-four patients underwent gastrectomy, with four patients having surgical complications, which led to a suspension of treatment. Sarcopenia was present in 38 patients (50.7%) before chemotherapy began, while it was present in 47 patients (60%) at the CT scan before the gastrectomy. At the univariable analysis, patients with basal platelet to lymphocyte ratio (PLR) ≥ 152 (p = 0.017) and a second value of PLR ≥ 131 (p = 0.007) were more frequently associated with an interruption of chemotherapy. Patients with increased PLR (p = 0.034) compared to the cut-off were associated with an interruption of chemotherapy, while patients with increased monocytes between the first and second cycles were associated with a lower risk of treatment interruption (p = 0.006); patients who underwent 5-fluorouracil plus cisplatin or oxaliplatin had a higher risk of interruption (p = 0.016) compared to patients who underwent a 5-fluorouracil plus leucovorin, oxaliplatin and docetaxel (FLOT) regimen. The multivariable analysis showed a higher risk of interruption for patients who had higher values of PLR compared to the identified cut-off both at pretreatment and second-cycle evaluation (OR: 5.03; 95% CI: 1.34-18.89; p = 0.017) as well as for patients who had a lower PLR than the identified cut-off at pretreatment evaluation and had a higher PLR value than the cut-off at the second cycle (OR: 4.64; 95% CI: 1.02-21.02; p = 0.047). Becker regression was neither affected by a decrease of sarcopenia ≥ 5% (p = 0.867) nor by incomplete compliance with chemotherapy (p = 0.281). Changes in PLR values which tend to increase more than the cut-off seem to be an immediate indicator of incomplete compliance with neoadjuvant/perioperative treatment. Fat loss and sarcopenia do not appear to be related to compliance. More information is needed to reduce the causes of interruption.


Septate junctions between digestive vacuoles in human malacoplakia.
Typical septate junctions between digestive vacuoles in phagocytic cells of human malacoplakia are described in this paper. Evidence for a honeycomb pattern of hexagonal subunits is presented for their cleft material. Junctions were not observed between other organelles or in cells other than phagocytes. It is assumed that the septate junctions described here may reflect a pathological change in the organization of the membrane components of digestive organelles.


Heat inhibition of reticulocyte protein synthesis. Evidence for a mechanism independent of the hemin-controlled repressor.
Incubation of rabbit reticulocytes at 45 degrees C results in a prompt but reversible decrease in protein synthesis and a concomitant conversion of polyribosomes to smaller aggregates. These effects occur even in the presence of 100 micrometer hemin in the incubation medium. There is also inhibition of heme synthesis but this occurs at a later time than the effect on protein synthesis. The inhibtion of heme synthesis results from a decrease in activity of beta-aminolevulinic acid synthetase. This decrease of heme synthesis appears to be secondary to the inhibition of protein synthesis with resultant accumulation of intramitochondrial heme (which will decrease beta-aminolevulinic acid synthetase activity). An inhibitor of reticulocyte cell-free protein synthesis formed in the postribosomal supernatants of cells incubated at both 45 and 37 degrees C but not at 0 degrees C. No temporal or quantitative differences in the amount of this inhibitor from cells treated at either 37 or 45 degrees C was apparent. The inhibitor was not found in the fraction where the hemin-controlled repressor is isolated. It is concluded that heat inactivation of intact reticulocyte protein synthesis does not depend upon a decrease in heme synthesis, heme concentration or generation of the hemin-controlled repressor. Furthermore, it appears that the inhibitor formed in the post-ribosomal supernatant cannot be the sole cause of the heat inhibition of protein synthesis.


Relative efficacy of chelating agents as antidotes for acute gallium nitrate intoxication.
Twelve chelating agents were administered to mice by IP injection to compare their relative effectiveness in preventing death after a single IP injection of gallium nitrate. Na2Ca-ethylenediaminetetraacetate (EDTA), Na3Ca-diethylenetriaminepentaacetate (DTPA), dimercaptosuccinic acid (DMSA), 4,5-dihydroxy-1,3-benzene-disulfonic acid (Tiron), sodium diethyldithiocarbamate (DDC), L-cysteine and sodium salicylate were not effective for acute gallium nitrate intoxication. The therapeutic indices of the effective chelators were: 25.4 (deferoxamine mesylate), 35.7 (citric acid), 42.3 (succinic acid), 52.2 (malic acid) and 111.1 (oxalic acid).


Abnormal growth factor modulation of beta1-integrin-mediated adhesion in chronic myelogenous leukaemia haematopoietic progenitors.
Abnormal progenitor circulation and extramedullary haematopoiesis are characteristic features of chronic myelogenous leukaemia (CML). Growth factor (GF) and beta1-integrin interactions play an important role in regulation of progenitor trafficking to and from the marrow space. CML progenitors demonstrate abnormal beta1-integrin-mediated adhesion to fibronectin (FN). In the present study we investigated whether GF modulation of beta1-integrin-mediated adhesion and migration was altered in CML progenitors. Culture with low concentrations of GF enhanced normal progenitor adhesion to FN compared with no GF, but failed to enhance CML progenitor adhesion to FN. Similarly, high concentrations of selected GF rapidly enhanced beta1-integrin-mediated adhesion of normal progenitors to FN through a phosphotidylinositol-3 (PI-3) kinase-dependent mechanism, but failed to increase CML progenitor adhesion. Exposure to a BCR-ABL tyrosine kinase inhibitor restored GF modulation of CML progenitor adhesion. CML colony-forming cells (CFC) demonstrated increased migration across FN-coated transwells compared with normal CFC in the absence of GF. The addition of stem cell factor resulted in enhanced migration of CML and normal CFC on FN. In conclusion, GF stimulation failed to enhance integrin-mediated adhesion but enhanced migration in CML progenitors on FN. BCR-ABL induced abnormalities in GF-integrin interactions could contribute to abnormal circulation and microenvironmental localization of CML progenitors.


Obstacles to penicillin use in treating pneumococcal infection.
To determine the pattern of penicillin use in the treatment of pneumococcal pneumonia, and factors contributing to the use of alternative antibiotics. This study included all adult inpatients of St. Vincent's Hospital and Medical Center who had documented pneumococcal pneumonia between December 1998 and October 1999. St. Vincent's is a 600 bed tertiary teaching hospital in New York City. Patients who had Streptococcus pneumoniae isolated from a respiratory tract specimen were identified through microbiology laboratory records. A retrospective chart review of these patients was conducted, and those identified with clinical pneumonia were included in this study. Antibiotic use, patient demographics, resistance data, and clinician awareness of the antibiotic susceptibility results were noted. Sixty adult patients hospitalized with documented pneumococcal pneumonia were identified. Thirteen (21.6%) of the 60 patients received penicillin or ampicillin. Susceptibility results were not noted in the medical record in 21 (35.0%) of the 60 patients, and none received penicillin. High rates of reported penicillin allergy in 8 (13.3%) of the 60 patients, and reluctance to use penicillin when isolates demonstrated intermediate susceptibility in 8 (13.3%) of the 60 patients were observed. Several remediable obstacles to penicillin use were identified in this study. An increased awareness of susceptibility results by physicians and education of practitioners could have increased the use of penicillin as therapy to two-thirds of these patients.


Effects of an oil enriched in gamma linolenic acid on locomotor activity and behaviour in the Morris Maze, following in utero ethanol exposure in rats.
Ethanol is known to decrease the quantity of polyunsaturated fatty acids in brain membranes possibly as the repercussion of an inhibition of delta-5- and delta-6-desaturases. Consequently behavioural changes may occur. Evening Primrose Oil (EPO) which is rich in gamma linolenic acid (10% 8:3 (n-6)) was proposed to try to circumvent these deleterious effects of ethanol. An animal model of the foetal alcohol syndrome was used in which ethanol was administered throughout gestation and into the weaning period, in a milk diet. EPO was administered concurrently with ethanol to establish the effect of this essential fatty acid and ethanol on the animal's behaviour. Animals were tested at approximately 60 days of age for their responses in two different behavioural paradigms, i.e. the stressful memory task of the Morris Maze and the non-stressful activity monitor. In this study we report an increase in learning ability in male (Control-EPO and alcohol-EPO versus their control: P less than 0.00001 and P less than 0.01, respectively) and female rats (Control-EPO and alcohol-EPO versus control: P less than 0.0001 and P less than 0.00001, respectively) after administration of EPO. It was also found that ethanol plus EPO administration consistently raised the activity scores of the rats in the activity monitor (daytime activity scores for male and female rats were P less than 0.00001 and P less than 0.0001, respectively), while ethanol alone decreased the scores (male and female rats P less than 0.00001 and P less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)


Preoperative factors affecting the operative outcomes of laparoscopic nephrectomy.
Laparoscopic radical nephrectomy is the standard surgery for localized renal cell carcinoma. Both tumor and patient factors affect the difficulty of laparoscopic radical nephrectomy. Obesity is a major factor influencing technical difficulty in surgical procedures. This study examined preoperative tumor and patient factors affecting the operating time. The data of 123 patients who underwent laparoscopic radical nephrectomy at our institution between January 2014 and December 2018 were retrospectively analyzed. The operating time was determined based on the median pneumoperitoneum time. Surgical procedures with a pneumoperitoneum time of ≥130 min were defined as having prolonged pneumoperitoneum time. Multiple logistic regression analyses were performed to identify the preoperative factors affecting the prolonged pneumoperitoneum time, and risk stratification was performed based on these factors. Multiple logistic regression analyses revealed that a total number of renal pedicle blood vessels ≥3 and a visceral fat volume ≥3000 cm3 were associated with prolonged pneumoperitoneum time of laparoscopic radical nephrectomy. Based on the multivariate analysis results, these factors were considered individually, and the cohort was stratified into three risk groups: low (0 point), intermediate (1 point), and high (2 points) risk groups. The pneumoperitoneum time was significantly prolonged as the number of risk factors increased. We developed a risk stratification model using preoperative factors to predict the prolonged pneumoperitoneum time of laparoscopic radical nephrectomy, which can help select suitable cases that are appropriate for each surgeon's skill level.


Retinal nerve fibre layer imaging: comparison of Cirrus optical coherence tomography and Heidelberg retinal tomograph 3.
The purpose of this study was to analyze the relationship between retinal nerve fibre layer thickness measured by spectral domain optical coherence tomography and confocal scanning laser ophthalmoscope. Prospective, cross-sectional study. Hospital setting. One hundred seventy-three subjects (85 glaucoma and 88 normal subjects). One eye from each individual was selected randomly for imaging by the spectral domain Cirrus optical coherence tomography and Heidelberg retinal tomograph 3. Global thickness and measurements at the four quadrants around the optic disc. Measurements as determined by Heidelberg retinal tomograph 3 were significantly larger than measurements done by Cirrus optical coherence tomography (respectively in mm, for global thickness: 200.0 ± 87.2 and 80.7 ± 14.7; for temporal quadrant: 75.3 ± 31.9 and 59.1 ± 13.8; for superior quadrant: 223.2 ± 128.4 and 97.7 ± 20.9; for nasal quadrant: 208.0 ± 102.9 and 66.8 ± 11.8; and for inferior quadrant: 224.4 ± 116.9 and 99.1 ± 26.6, for all P < 0.01). Significant correlation was found for all measurements (P ≤ 0.009), but a pattern of proportional bias was demonstrated. The agreement of categorical classification (within normal limits, borderline or outside normal limits) ranged between poor and fair. The thickness easurements by the two technologies are strongly correlated but significantly different. The differences are substantial and proportional to the retinal nerve fibre layer thickness. The normative diagnostic classification of the two technologies may not agree. The results preclude interchangeable use of these measurements in clinical practice.


The predictive value of multi-targeted fluorescent in-situ hybridization in patients with history of bladder cancer.
UroVysion (Abbott Molecular Inc., Des Plaines, IL) is a multi-target fluorescent in-situ hybridization (FISH) assay that detects aneuploidy of chromosomes 3, 7, and 17, and loss of the 9p21 locus in exfoliated cells in urine. In this study, we evaluated if UroVysion can predict tumor recurrence in patients with negative cystoscopy and urinary cytology at the time of (FISH) assay. The study population included patients with history of non-muscle invasive bladder cancer treated by transurethral resection. Follow-up included cystoscopy, barbotage, urinary cytology, and UroVysion testing. Patients were followed for at least 6 months after their initial UroVysion testing. A total of 64 patients (37 males) were enrolled into the study. Mean patient age was 62 years (S.D. 13.2 years). Initial highest tumor stage was Ta in 42 patients (65.6%), T1 in 21 patients (33%), and isolated Tis in a single patient. Abnormal UroVysion results were observed in 40 patients (62.5%). After a median follow-up of 13.5 months, 21 patients (33%) developed tumor recurrence (Ta in 13 patients, T1 in 5, and Tis in 3). Recurrent tumors developed in 45% of the patients with abnormal UroVysion test compared with 12.5% of the patients with normal assay (P = 0.01). An abnormal UroVysion result preceded the diagnosis of tumor recurrence in 18/21 cases (86%), including all high-grade recurrences. This data suggest that UroVysion may be a useful tool for predicting tumor recurrence. Cystoscopy may be spared and surveillance intervals widened in patients with history of low grade tumors and a normal UroVysion test.


Synthesis, microstructure, anti-corrosion property and biological performances of Mn-incorporated Ca-P/TiO2 composite coating fabricated via micro-arc oxidation.
In this work, a Mn-incorporated Ca-P/TiO2 composite coating was produced through the facile one-step micro-arc oxidation (MAO) method. It is revealed that only when the concentration of Na2Mn-EDTA reaches 0.02 mol/L, the Ca-P phase could form on Mn-incorporated TiO2 coating, which is associated with the combined effect of EDTA complex and Mn species. The Ca-P phase is amorphous, which may contain hydroxyapatite phases whereas the underlying Mn-incorporated TiO2 coating contains two separate layers, including the Mn-rich outer layer and Mn-depleted inner layer. The biological investigation of the Mn-incorporated Ca-P/TiO2 composite coating suggests that it exhibits desirable osteogenesis with certain capability to inhibit the growth of S. aureus bacteria. Hence, a promising composite coating with superior bone formability could be produced using the one-step micro-arc oxidation method in the electrolyte containing Na2Mn-EDTA.


Simulated Increase in Monoarticular Hip Muscle Strength Reduces the First Peak of Knee Compression Forces During Walking.
Reducing compressive knee contact forces (KCF) during walking could slow the progression and reduce symptoms of knee osteoarthritis. A previous study has shown that compensating for the hip flexion/extension moment could reduce the KCF peak occurring during early stance (KCFp1). Therefore, this study aimed to identify if monoarticular hip muscle could allow this compensation while considering different walking strategies. Gait trials from 24 healthy participants were used to make musculoskeletal models, and five load-cases were examined: (I) Normal, (II) with an applied external moment compensating for 100% of the hip flexion/extension moment, and (III-V) three conditions with isolated/combined 30% increase of peak isometric strength of gluteus medius and maximus. Knee contact forces, hip muscle forces, and joint moments were computed. A cluster analysis of the Normal condition was performed with hip and knee flexion/extension moment during KCFp1 as input to examine the influence of different walking strategies. The cluster analysis revealed two groups having significantly different hip and knee moments in early-stance (p < 0.01). The reduction in KCFp1 from the Normal condition, although present in both groups, was greater for the group with the highest hip and lowest knee flexion/extension moments for all conditions tested (II: -21.82 ± 8.71% versus -6.03 ± 6.68%, III: -3.21 ± 1.09% versus -1.59 ± 0.96%, IV: -3.00 ± 0.89% versus -1.76 ± 1.04%, V: -6.12 ± 1.69 versus -3.09 ± 1.95%). This reduction in KCFp1 occurred through a shift in force developed by the hamstrings during walking (biarticular) to the gluteus medius and maximus (monoarticular), whose isometric strength was increased. The differences between the groups suggest that this reduction depends on the walking strategy.