[Use of a semisynthetic broad-spectrum penicillin (ampicillin) in surgical practice].
Parenterally ampicillin was used for the treatment of 87 patients with lung and abdominal diseases, liver abscesses, extremity phlegmonas, osteomyelitis and other diseases. The antibiotic was administered intravenously and intramuscularly. High efficacy of the treatment was observed in all the cases with ampicillin sensitive microflora. In some cases a satisfactory therapeutic effect was observed only with the use of ampicillin in combination with other antibiotics and aminoglycosides in particular. No side effects of the antibiotic were registered.


Guillain-Barré syndrome associated with preceding hepatitis E virus infection.
The aim of the study was to determine whether Guillain-Barré syndrome (GBS) is associated with preceding hepatitis E virus infection. The frequency of hepatitis E virus (HEV) infections was determined by anti-HEV serology in a cohort of 201 patients with GBS and 201 healthy controls with a similar distribution in age, sex, and year of sampling. Blood samples from patients with GBS were obtained in the acute phase before treatment. In a subgroup of patients with GBS, blood, stool, and CSF samples were tested for HEV RNA. An increased ratio of anti-HEV immunoglobulin (Ig) M antibodies was found in 10 patients with GBS (5.0%) compared with 1 healthy control (0.5%, odds ratio 10.5, 95% confidence interval 1.3-82.6, p = 0.026). HEV RNA was detected in blood from 3 of these patients and additionally in feces from 1 patient. Seventy percent of anti-HEV IgM-positive patients had mildly increased liver function tests. All CSF samples tested negative for HEV RNA. The presence of anti-HEV IgM in patients with GBS was not related to age, sex, disease severity, or clinical outcome after 6 months. In the Netherlands, 5% of patients with GBS have an associated acute HEV infection. Further research is required to determine whether HEV infections also precede GBS in other geographical areas.


A call to action: training public health students to be effective agents for social change.
In the 21st century, we face enormous public health challenges that differ fundamentally from those of the last century, because these challenges involve widespread societal change and complexity. To address these challenges, public health professionals need to be able to place their work in a larger social context, understand local and global perspectives on a deeper level, and effectively engage a wide variety of stakeholders. To confer these skills, we need to change the way we train our students. We present two examples of low-cost innovative approaches to teaching public health that promote active engagement with individuals across a wide range of backgrounds and fields and that train students to be effective agents for change.


Pharmacokinetics of dexmedetomidine after intravenous administration of a bolus to cats.
To characterize the pharmacokinetics of dexmedetomidine after IV administration of a bolus to conscious healthy cats. 5 healthy adult spayed female cats. Dexmedetomidine was administered IV as a bolus at 3 doses (5, 20, or 50 μg/kg) on separate days in a random order. Blood samples were collected immediately before and at various times for 8 hours after drug administration. Plasma dexmedetomidine concentrations were determined with liquid chromatography-mass spectrometry. Compartment models were fitted to the concentration-time data by means of nonlinear regression. A 2-compartment model best fit the concentration-time data after administration of 5 μg/kg, whereas a 3-compartment model best fit the data after administration of 20 and 50 μg/kg. The median volume of distribution at steady-state and terminal half-life were 371 mL/kg (range, 266 to 435 mL/kg) and 31.8 minutes (range, 30.3 to 39.7 minutes), respectively, after administration of 5 μg/kg; 545 mL/kg (range, 445 to 998 mL/kg) and 56.3 minutes (range, 39.3 to 68.9 minutes), respectively, after administration of 20 μg/kg; and 750 mL/kg (range, 514 to 938 mL/kg) and 75.3 minutes (range, 52.2 to 223.3 minutes), respectively, after administration of 50 μg/kg. The pharmacokinetics of dexmedetomidine was characterized by a small volume of distribution and moderate clearance and had minimal dose dependence within the range of doses evaluated. These data will help clinicians design dosing regimens once effective plasma concentrations are established.


[A Case of Angiomyolipoma Occurring in the Mesentery of the Transverse Colon and Treated Using Laparoscopic Excision].
A 65-year-old woman had received chemotherapy for malignant lymphoma since 2011. After the 8th course, computed tomography revealed the disappearance of lymph node metastasis, except for 22mm of the mass located on the tail side of the antrum. MRI showed a low intensity mass on the T1 and T2-weighted images. FDG-PET did not show abnormal uptake in the tumor. EUS-FNA did not reveal a definitive diagnosis. We performed a laparotomy for diagnosis and treatment. Intraoperative findings showed that the tumor occurred in the mesentery of the transverse colon. The pathological diagnosis was angiomyolipoma. The patient has been free from recurrent disease for 2 years and 6 months. Angiomyolipoma originating in the transverse mesentery region is rare and, due to various percentage of tissue factors, there are no fixed view of image findings. Furthermore, a large tissue volume is need for histological diagnosis. Laparotomy is useful for diagnosis and therapy for angiomyolipoma occurring in the mesentery of the transverse colon.


The entorhinal cortex of the Megachiroptera: a comparative study of Wahlberg's epauletted fruit bat and the straw-coloured fruit bat.
This study describes the organisation of the entorhinal cortex of the Megachiroptera, straw-coloured fruit bat and Wahlberg's epauletted fruit bat. Using Nissl and Timm stains, parvalbumin and SMI-32 immunohistochemistry, we identified five fields within the medial (MEA) and lateral (LEA) entorhinal areas. MEA fields E(CL) and E(C) are characterised by a poor differentiation between layers II and III, a distinct layer IV and broad, stratified layers V and VI. LEA fields E(I), E(R) and E(L) are distinguished by cell clusters in layer II, a clear differentiation between layers II and III, a wide columnar layer III and a broad sublayer Va. Clustering in LEA layer II was more typical of the straw-coloured fruit bat. Timm-staining was most intense in layers Ib and II across all fields and layer III of field E(R). Parvalbumin-like staining varied along a medio-lateral gradient with highest immunoreactivity in layers II and III of MEA and more lateral fields of LEA. Sparse SMI-32-like immunoreactivity was seen only in Wahlberg's epauletted fruit bat. Of the neurons in MEA layer II, ovoid stellate cells account for approximately 38%, polygonal stellate cells for approximately 8%, pyramidal cells for approximately 18%, oblique pyramidal cells for approximately 6% and other neurons of variable morphology for approximately 29%. Differences between bats and other species in cellular make-up and cytoarchitecture of layer II may relate to their three-dimensional habitat. Cytoarchitecture of layer V in conjunction with high encephalisation and structural changes in the hippocampus suggest similarities in efferent hippocampal --> entorhinal --> cortical interactions between fruit bats and primates.


Hepatitis B viral genotypes: clinical relevance and molecular characteristics.
Hepatitis B virus (HBV) infection is a global health problem and the clinical outcome of chronic HBV infection depends on the frequency and severity of hepatitis flares in the immune clearance phase. Currently, four subtypes and seven genotypes of HBV are identified and most have specific geographic distributions. The impact of HBV genotypes on the clinical outcome of chronic HBV infection has been partially clarified. In Taiwan, genotype C is associated with more severe liver disease and genotype B is associated with the development of hepatocellular carcinoma (HCC) in young non-cirrhotic patients. In contrast, genotype B has a relatively good prognosis in Japan and China and is rarely associated with the development of HCC. Similarly, genotype D is associated with more severe liver disease than genotype A in India and may predict occurrence of HCC in young patients. Although superinfection of HBV on top of hepatitis B carriers occurs in Taiwan, it is rarely associated with acute exacerbations. As to the response to antiviral treatment, genotypes C and D are associated with a lower response rate to interferon therapy compared with genotypes B and A. In addition, the subtype adw is reported to be associated with a higher risk of lamivudine resistance than ayw. In HBV subtype adw-infected HCC patients, genotype B responds better to embolization therapy and has a lower rate of HCC recurrence than genotype C. In summary, pathogenic and therapeutic differences do exist among HBV genotypes and determining the genotype in patients with chronic HBV infection would help gain further information for etiologic, clinical, virologic and anthropologic investigations. Further studies to clarify the molecular virological factors that contribute to these differences are awaited.


[Successful brachial replantation in a child after a traction-type traumatic amputation].
The article deals with certain aspects of managing patients presenting with extremital bone-and-vascular injuries known for utter severity and a high incidence rate of postoperative complications. Suggested herein, as the authors believe, is an optimal for both the patient and surgeon policy of emergency reconstruction. Emphasis is placed on the necessity to follow a certain sequence while restoring the anatomical structures destroyed. The conclusions drawn include compulsorily considering a possibility to spare the damaged segment, followed by restoring adequate blood circulation and prevention of wound infection, carrying out osteosynthesis with obligatory shortening of the bones, and postponing orthopaedic measures for the remote postoperative period. Also presented in the article is a photograph-illustrated clinical case report of a successful brachial replantation.


Importance of flexible bronchoscopy in decannulation of tracheostomy patients.
To evaluate the importance of flexible bronchoscopy in tracheostomy patients in the process of decannulation to assess the incidence and types of laryngotracheal injury and compare the presence of such lesions with clinical criteria used for decannulation. We studied 51 tracheostomized patients aged between 19 and 87 years, with tracheal stent for a mean of 46 ± 28 days and with clinical criteria for decannulation. They were submitted to tracheostomy tube occlusion tolerance testfor 24 hours, and then to flexible bronchoscopy. We described and classified the diagnosed laryngotracheal changes. We compared the clinical criteria for decannulation indication with the bronchoscopy-diagnosed laryngotracheal injuries that contraindicated decannulation. We identified the factors that could interfere in decannulation and evaluated the importance of bronchoscopy as part of the process. Forty (80.4%) patients had laryngotracheal alterations. Of the 40 patients considered clinically fit to decannulation, eight (20%) (p = 0.0007) presented with laryngotracheal injuries at bronchoscopy that contraindicated the procedure. The most frequent laryngeal alteration was vocal cords lesion, in 15 (29%) individuals, and granuloma, the most prevalent tracheal lesion, in 14 (27.5%) patients. flexible bronchoscopy showed a large number of laryngotracheal injuries, the most frequent being the vocal cords injury in the larynx and the granuloma in the trachea, which contributed to increase the decannulation procedure safety.


Relationships of birth weight and pre-nursing concentrations of serum albumin to survival and growth rate in swine.
Data from 29 litters of swine were analyzed to estimate the relationships of birth weight and pre-nursing concentrations of serum albumin to survival and daily gain from birth to 14 d and from 14 to 28 d. Means and standard deviations of birth weight and serum albumin were calculated within each litter and used as analytical units. Positive linear partial regression coefficients were detected for effects of serum albumin on birth weight (P less than .01) and daily gains (P less than .05). As both serum albumin and birth weight increased, survival also increased but at a decreasing rate (P less than .05). Survival decreased as the standard deviations of serum albumin (P less than .05) and the birth weight (P less than .10) increased. Daily gain from 14 to 28 d of age increased (P less than .10) as the standard deviation of serum albumin varied above or below about .5 mg/ml. The linear effect of birth weight on daily gain from birth to 14 d of age was positive (P less than .01), whereas daily gain from 14 to 28 d of age increased as birth weight varied above or below about 1.3 kg (P less than .01). Daily gains during the first and second periods also increased as the standard deviation of birth weight varied above or below .3 kg (P less than .05) and .25 kg (P less than .001), respectively. Fitting birth weight and serum albumin simultaneously into the statistical model accounted for 57% of the variation in survival, a level at least twice as great as previously reported. It is speculated that use of a marker of physiological maturity, such as pre-nursing concentrations of serum albumin, might facilitate selection for survival.


Early identification of anthracycline cardiomyopathy: possibilities and implications.
The number of survivors of childhood cancer affected by anthracycline cardiomyopathy is steadily increasing, despite efforts to limit cardiotoxicity by dose restriction. Cardiac function was evaluated prospectively in 125 children during treatment to attempt to identify individual susceptibilities to cardiotoxicity and hence any potential for treatment modification. Left ventricular shortening fraction was used as an index of cardiotoxicity. Shortening fraction declined as cumulative anthracycline dose increased, at an average rate of 1% per 100 mg/m2. Six patients (5%) developed heart failure. Twenty four patients (19%) had abnormal shortening fraction (< 30%) by the end of treatment, and their rate of fall of shortening fraction was significantly steeper throughout treatment than in patients finishing with normal function (shortening fraction > or = 30%). This differential susceptibility to cardiotoxicity was apparent from very early in treatment, interquartile ranges of the two shortening fraction groups separating at doses > 200 mg/m2. Patients at high risk of risk of important anthracycline cardiotoxicity may be identifiable early in treatment by regular and careful monitoring of shortening fraction. However, frequent assessment is required and this has significant resource implications.


Effect of placental tissue on inhibition of uterine contraction by nitric oxide donors.
Our purpose was to test the hypothesis that placental tissue modulates the effect of nitric oxide on spontaneous uterine contractility in pregnant rats. Rings (approximately 4 mm) of uterus taken from rats on day 14 (midpregnancy, n = 6), day 18 (late pregnancy, n = 4), and day 22 (term, n = 4) of gestation were placed in organ chambers filled with Krebs-bicarbonate buffer bubbled with 5% carbon dioxide in air (37 degrees C, pH approximately 7.4) for isometric tension recording. In some rings a piece of placenta was left attached to the uterine wall. In the other rings the fetuses, placentas, and membranes were removed completely. Change of spontaneous contractions of the rings (percentage change of basal integral activity for 10 minutes) in response to cumulative concentrations of the nitric oxide donors diethylamine-nitric oxide and nitroglycerin (10(-6) mol/L to 10(-4) mol/L) were compared between rings with and without placenta. Diethylamine-nitric oxide and nitroglycerin inhibited spontaneous uterine contractions in rings from midpregnancy, in both the absence and the presence of placenta. In rings from midpregnancy, the maximal inhibition of contractions by diethylamine-nitric oxide but not by nitroglycerin was significantly (P <.05) higher in the presence (26.7% +/- 3.5% of basal activity) than in the absence (39. 6% +/- 3.3%) of placenta. Inhibition of contraction by nitric oxide donors in rings from late and term pregnancy was less than in midpregnancy, and the presence of placental tissue did not influence the responses. The presence of placental tissue enhances inhibition of uterine contractility by agents that spontaneously release nitric oxide, such as diethylamine-nitric oxide, but not by nitroglycerin, which requires metabolic transformation for nitric oxide to be released. Refractoriness to nitric oxide near or at term does not depend on the presence or absence of placental tissue.


The electrophoresis of transferrins in urea/polyacrylamide gels.
The denaturation of transferrin by urea has been studied by (a) electrophoresis in polyacrylamide gels incorporating a urea gradient, (b) measurements of the loss of iron-binding capacity and (c) u.v. difference spectrometry. In human serum transferrin and hen ovotransferrin the N-terminal and C-terminal domains of the iron-free protein were found to denature at different urea concentrations.


Diagnostic value of sinus-tract cultures in chronic osteomyelitis.
Sinus-tract cultures were compared with cultures of operative specimens from 40 patients with chronic osteomyelitis. Thirty-five patients (87.5%) had a single pathogen isolated from their operative specimens. Only 44% of the sinus-tract cultures contained the operative pathogen. Isolation of Staphyloccus aureus from sinus tracts correlated with the presence of S aureus in the operative specimen. However, less than half of the sinus-tract cultures obtained from patients with S aureus osteomyelitis contained this organism. Isolation of bacteria other than S aureus from sinus tracts had a low likelihood of predicting the pathogen isolated from bone. A presumptive diagnosis of S aureus osteomyelitis is justified if S aureus is isolated from an associated sinus tract. A bacteriologic diagnosis of chronic osteomyelitis based on isolation of common pathogens other than S aureus from sinus tracts must be verified by an appropriate operative culture.


Comparison of the diagnostic accuracy of a vacuum-assisted percutaneous intact specimen sampling device to a vacuum-assisted core needle sampling device for breast biopsy: initial experience.
The objective of this research was to determine whether biopsy of the breast using a percutaneous intact specimen sampling device influences the underestimation rate of ductal carcinoma in situ (DCIS) compared to a vacuum-assisted core needle biopsy (VACNB) device. This study was a retrospective comparison of two series of 800 consecutive patients that underwent stereotactic biopsy of the breast for mammographic lesions presenting as microcalcifications classified by our institution as Breast Imaging Reporting and Data System (BI-RADS) 4 or 5. In the first series of patients (n = 800), a VACNB device was used; in the second series (n = 800), a vacuum-assisted percutaneous intact specimen biopsy (VAPIB) device was used. Initial diagnoses were made from the histopathologic examination of the tissue retrieved at biopsy. Lesions presenting as DCIS or atypical ductal hyperplasia (ADH) after percutaneous biopsy were then compared to the histopathologic analysis of specimens retrieved at surgical biopsy. DCIS upgrades were defined as cases in which the diagnosis of the stereotactic biopsy was DCIS and the diagnosis of the subsequent surgical excision was infiltrating ductal carcinoma (IDC). ADH upgrades were defined as cases in which the diagnosis of the stereotactic biopsy specimen was ADH and the diagnosis of the surgical excision was DCIS, lobular carcinoma in situ (LCIS), or IDC. The lesions retrieved by both biopsy techniques yielded a similar pathology distribution. Underestimation of DCIS occurred less frequently (p = 0.06) in the biopsy samples taken using the intact biopsy device (1/31, 3.2%) as compared to biopsy samples taken using the core needle biopsy device (7/36, 19.4%). No significant adverse events were reported. Breast biopsy can be performed safely and accurately using a vacuum-assisted percutaneous intact specimen sampling device. In this study, such a device trended toward fewer underestimations of DCIS at biopsy compared to the vacuum-assisted core needle sampling biopsy method.


Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.
Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.


Ontology Matching with Semantic Verification.
ASMOV (Automated Semantic Matching of Ontologies with Verification) is a novel algorithm that uses lexical and structural characteristics of two ontologies to iteratively calculate a similarity measure between them, derives an alignment, and then verifies it to ensure that it does not contain semantic inconsistencies. In this paper, we describe the ASMOV algorithm, and then present experimental results that measure its accuracy using the OAEI 2008 tests, and that evaluate its use with two different thesauri: WordNet, and the Unified Medical Language System (UMLS). These results show the increased accuracy obtained by combining lexical, structural and extensional matchers with semantic verification, and demonstrate the advantage of using a domain-specific thesaurus for the alignment of specialized ontologies.


High human renin hypertension in transgenic rats.
We developed a model of spontaneously high human renin hypertension in the rat by producing two transgenic strains, one for human angiotensinogen with the endogenous promoter and one for human renin with the endogenous promoter. Neither transgenic strain was hypertensive. These strains were then crossed, producing a double transgenic strain. The double transgenic rats, both males and females, developed severe hypertension (mean systolic pressure, 200 mm Hg) and died after a mean of 55 days if untreated. The rats had a human plasma renin concentration of 269 +/- 381 (+/-SD) ng angiotensin I (Ang I)/mL per hour, plasma renin activity of 177 +/- 176 ng Ang I/mL per hour, rat angiotensinogen concentration of 1.49 +/- 1 microgram Ang I/mL, and human angiotensinogen concentration of 78 +/- 39 micrograms Ang I/mL (n = 49). Control rats had plasma renin activity of 3.7 +/- 3.9 ng Ang I/mL per hour and rat angiotensinogen of 1.32 +/- 0.16 micrograms Ang I/mL. Angiotensinogen transgene expression by RNase protection assay was ubiquitously present but most prominent in liver. Renin transgene expression was high in kidney but absent in liver. The rats featured severe cardiac hypertrophy, with increased cross section of cardiomyocytes but little myocardial fibrosis. The kidneys showed atrophic tubules, thickened vessel walls, and increased interstitium. Both the angiotensin-converting enzyme inhibitor lisinopril and the specific human renin inhibitor remikiren lowered blood pressure to normal values. Double transgenic mice have been developed that exhibit features quite similar to those described here; their gene expressions are similar. The specificity of rodent and human renin is similarly documented. Although many elegant physiological studies can now be done in mice, rats nevertheless offer flexibility, particularly in terms of detailed cardiac and renal physiology and pharmacology. We conclude that this double transgenic strain will facilitate simultaneous investigation of genetic and pathophysiological aspects of renin-induced hypertension. The fact that human renin can be studied in the rat is a unique feature of this model.


Mitochondrial Subtype Identification and Characterization.
Healthy, functional mitochondria are central to many cellular and physiological phenomena, including aging, metabolism, and stress resistance. A key feature of healthy mitochondria is a high membrane potential (Δψ) or charge differential (i.e., proton gradient) between the matrix and inner mitochondrial membrane. Mitochondrial Δψ has been extensively characterized via flow cytometry of intact cells, which measures the average membrane potential within a cell. However, the characteristics of individual mitochondria differ dramatically even within a single cell, and thus interrogation of mitochondrial features at the organelle level is necessary to better understand and accurately measure heterogeneity. Here we describe a new flow cytometric methodology that enables the quantification and classification of mitochondrial subtypes (via their Δψ, size, and substructure) using the small animal model C. elegans. Future application of this methodology should allow research to discern the bioenergetic and mitochondrial component in a number of human disease and aging models, including, C. elegans, cultured cells, small animal models, and human biopsy samples. © 2018 by John Wiley & Sons, Inc.


Phosph-Akt1 expression is associated with a favourable prognosis in pancreatic cancer.
Akt, a serine/threonine protein kinase, mediates growth factor-associated cell survival. In several human cancers, including pancreatic cancer, constitutive activation of Akt (phosphorylated Akt, p-Akt) has been observed and may be associated with chemotherapy and radiotherapy resistance. However, there are contradictory viewpoints in p-Akt in pancreatic cancer on prognosis, and the clinical relevance of p-Akt in pancreatic cancer is not well understood. This study aims to investigate the expressions and relevance of Akt and p-Akt1 in pancreatic cancer tissues and their clinical significance. The expressions of Akt and p-Akt in 74 surgically resected paraffin-embedded pancreatic ductal adenocarcinoma samples and 10 normal pancreatic tissue samples were examined by immunohistochemistry. The associations of their expression with clinicopathological and survival data were analysed. The positive expression rate of Akt and p-Akt1 were 87.8% and 83.8%, respectively, which were remarkably higher then those in normal pancreatic tissue (P <0.05). There was a positive correlation between the expression of Akt and p-Akt1. High p-Akt1 expression correlated with lower T stage (P = 0.004), while Akt was not associated with any clinicopathologic variables. Kaplan-Meier survival analysis revealed that higher expression of Akt, p-Akt1 were respectively correlated with favourable prognosis (16.0[4.7-27.3] vs 9.3[9.0-9.6] months, P = 0.007, and 23.0[12.2-33.8] vs 11.1[7.5-14.7] months, P = 0.004, respectively). Multivariate analysis identified p-Akt1 as a significant independent favourable prognostic factor (HR=0.421, P = 0.010). These results suggest that high p-Akt1 expression may be a favourable prognostic factor in pancreatic cancer.


A critical role for protein kinase C-theta-mediated T cell survival in cardiac allograft rejection.
Protein kinase C (PKC)-theta mediates the critical TCR signals required for T cell activation. Previously, we have shown that in response to TCR stimulation, PKC-theta-/- T cells undergo apoptosis due to greatly reduced levels of the anti-apoptotic molecule, Bcl-xL. In this study, we demonstrate that PKC-theta-regulated expression of Bcl-xL is essential for T cell-mediated cardiac allograft rejection. Rag1-/- mice reconstituted with wild-type T cells readily rejected fully mismatched cardiac allografts, whereas Rag1-/- mice reconstituted with PKC-theta-/- T cells failed to promote rejection. Transgenic expression of Bcl-xL in PKC-theta-/- T cells was sufficient to restore cardiac allograft rejection, suggesting that PKC-theta-regulated survival is required for T cell-mediated cardiac allograft rejection in this adoptive transfer model. In contrast to adoptive transfer experiments, intact PKC-theta-/- mice displayed delayed, but successful cardiac allograft rejection, suggesting the potential compensation for PKC-theta function. Finally, a subtherapeutic dose of anti-CD154 Ab or CTLA4-Ig, which was not sufficient to prevent cardiac allograft rejection in the wild-type mice, prevented heart rejection in the PKC-theta-/- mice. Thus, in combination with other treatments, inhibition of PKC-theta may facilitate achieving long-term survival of allografts.


[Otoacoustic emissions in sudden deafness].
The idiopathic type of sudden deafness installed in few hours become evident in audiometry as deafness perceptive of loud tones, neurosensorial deafness of loud tones and completely of treble sounds or cofosis. The otoacoustic emissions are modificated in sudden deafness. To know and describe how are the otoacoustic emissions and the audition in sudden deafness. To analyse a possible relationship between audition, otovestibular and clinic participation with the parameters of the graphoelements of the otoacoustic emissions. We study 52 patients with diagnostic of sudden deafness with a backward, observational and descriptive and analytic design of the results. Patients with ORL diagnostic were selectioned and audiometric, vestibular test and otoacoustic emissions were made. In our research we find quantitative and qualitative variations statistically significative in the otoacoustic emissions design. Its presence in the different frequencies is altered or is missing in any case of sudden deafness in which there are damages of the inner ear. There is not associative correlation between the alterations of otoacoustic emissions and the kind of sudden deafness, neither its provoking factors, anigiohematical, viral or traumatic. There are modifications of the otoacoustic emissions but not specificals or the kinds of sudden deafness and its provoking factors. Another publications agree and underwrite our discoveries. We thought that our aportation with this study is fundamental for the clinic application of the otoacoustic emissions in the processes of sudden deafness.


Impact of bacterial and fungal donor organ contamination in lung, heart-lung, heart and liver transplantation.
We investigated to which extent bacterial and fungal donor organ contamination (DOC) caused posttransplant nosocomial infections (NI) in solid organ transplant (Tx) recipients. Between January 2002 to December 2003 (lung and heart Tx) and October 2003 to September 2004 (liver Tx), NIs were determined according to modified CDC criteria for NIs for all transplantations performed at Hannover Medical School. Organisms of the same species cultured from donor organs and infected transplantees were genotyped if available. Out of 282 solid organ recipients (140 lung-Tx, 16 heart-lung-Tx, 51 heart-Tx, 75 liver-Tx), 150 recipients (53.2%) received contaminated donor organs. Incidences of NIs were 33.7% in lung, 68.8% in heart-lung, 21.6% in heart, and 28% in liver recipients. In 11 out of 282 transplantees (3.9%, CI (95%) 2.0-6.9%) organisms of NIs and of contamination of the donor organ were of the same species. Even if assuming five missing pairs of organisms as genetically identical, incidences of DOC-related posttransplant infections were only between 1.3% (CI(95%) 0.0; 7.2) in liver-Tx and 18.8% (CI(95%) 4; 45.6) in heart-lung Tx, and DOC related mortality was 0.4% (CI(95%) 0.0;1.9). Despite high DOC rates, posttransplant infections due to DOC were rare under the condition of adequate preoperative antibiotic prophylaxis and aseptic organ retrievement.


Nirsevimab Immunization to Prevent Respiratory Syncytial Virus-Associated Lower Respiratory Tract Infections in Infants and Children up to 24 Months of Age.
Respiratory syncytial virus (RSV) infects nearly all infants in their first year of life and is the leading cause of hospitalization for infants younger than 1 year of age in the United States. Historically, the only option for RSV prevention was palivizumab. However, not all infants are eligible for palivizumab, it requires multiple doses per RSV season, and it is costly. In July 2023, the U.S. Food and Drug Administration approved nirsevimab for the prevention of RSV-associated lower respiratory tract infections for all infants. Nirsevimab inhibits RSV from fusing to cellular membranes and thereby neutralizes the virus in the body. Nirsevimab is expected to significantly reduce the health and economic burdens of RSV. This article provides an overview of nirsevimab, potential adverse effects, and implications for nursing practice.


Understory Dwarf Bamboo Affects Microbial Community Structures and Soil Properties in a Betula ermanii Forest in Northern Japan.
In order to understand the relationships between understory bamboo and soil properties, we compared microbial community structures in the soil of a Betula ermanii boreal forest with Sasa kurilensis present and removed using high-throughput DNA sequencing. The presence of understory S. kurilensis strongly affected soil properties, including total carbon, total nitrogen, nitrate, and the C:N ratio as well as relative soil moisture. Marked differences were also noted in fungal and bacterial communities between plots. The relative abundance of the fungal phylum Ascomycota was 13.9% in the Sasa-intact plot and only 0.54% in the Sasa-removed plot. Among the Ascomycota fungi identified, the most prevalent were members of the family Pezizaceae. We found that the abundance of Pezizaceae, known to act as mycorrhizal fungi, was related to the amount of total carbon in the Sasa-intact plot. The relative abundance of Proteobacteria was significantly higher, whereas those of Planctomycetes and Actinobacteria were lower in the Sasa-intact plot than in the Sasa-removed plot. Furthermore, the results obtained suggest that some species of the phylum Planctomycetes are more likely to occur in the presence of S. kurilensis. Collectively, these results indicate that the presence of S. kurilensis affects microbial communities and soil properties in a B. ermanii boreal forest.


Hyperbaric oxygen in epidural fibrosis: is there a potential for treatment?
To investigate the effects of hyperbaric oxygen treatment on epidural fibrosis formation in an experimental laminectomy model. Twenty-four Wistar rats underwent L5-L6 total laminectomy and divided into three groups. Animals in the control group received no further treatment while animals in short and long term groups received 2,5 ATM ABS of hyperbaric oxygen for 3 and 7 days, respectively. The amount of epidural fibrosis was analyzed histologically at the end of 42 days of follow up. The ratio of severe fibrosis was 57% in the control, 29% in the short HBOT, and 14% in the long HBOT groups. Although there was a clear trend towards having less fibrosis in the HBOT groups, the difference did not reach to the level of statistical significance (p=0.242), probably due to small number of animals used in this preliminary study. Our findings suggest that hyperbaric oxygen treatment may have favorable effects on epidural fibrosis. Further studies with larger cohorts are required to prove our results.


Natriuretic Peptides in the Cardiovascular System: Multifaceted Roles in Physiology, Pathology and Therapeutics.
The natriuretic peptides (NPs) family includes a class of hormones and their receptors needed for the physiological control of cardiovascular functions. The discovery of NPs provided a fundamental contribution into our understanding of the physiological regulation of blood pressure, and of heart and kidney functions. NPs have also been implicated in the pathogenesis of several cardiovascular diseases (CVDs), including hypertension, atherosclerosis, heart failure, and stroke. A fine comprehension of the molecular mechanisms dependent from NPs and underlying the promotion of cardiovascular damage has contributed to improve our understanding of the molecular basis of all major CVDs. Finally, the opportunity to target NPs in order to develop new therapeutic tools for a better treatment of CVDs has been developed over the years. The current Special Issue of the Journal covers all major aspects of the molecular implications of NPs in physiology and pathology of the cardiovascular system, including NP-based therapeutic approaches.


Application of predictive QSAR models to database mining: identification and experimental validation of novel anticonvulsant compounds.
We have developed a drug discovery strategy that employs variable selection quantitative structure-activity relationship (QSAR) models for chemical database mining. The approach starts with the development of rigorously validated QSAR models obtained with the variable selection k nearest neighbor (kNN) method (or, in principle, with any other robust model-building technique). Model validation is based on several statistical criteria, including the randomization of the target property (Y-randomization), independent assessment of the training set model's predictive power using external test sets, and the establishment of the model's applicability domain. All successful models are employed in database mining concurrently; in each case, only variables selected as a result of model building (termed descriptor pharmacophore) are used in chemical similarity searches comparing active compounds of the training set (queries) with those in chemical databases. Specific biological activity (characteristic of the training set compounds) of external database entries found to be within a predefined similarity threshold of the training set molecules is predicted on the basis of the validated QSAR models using the applicability domain criteria. Compounds judged to have high predicted activities by all or the majority of all models are considered as consensus hits. We report on the application of this computational strategy for the first time for the discovery of anticonvulsant agents in the Maybridge and National Cancer Institute (NCI) databases containing ca. 250,000 compounds combined. Forty-eight anticonvulsant agents of the functionalized amino acid (FAA) series were used to build kNN variable selection QSAR models. The 10 best models were applied to mining chemical databases, and 22 compounds were selected as consensus hits. Nine compounds were synthesized and tested at the NIH Epilepsy Branch, Rockville, MD using the same biological test that was employed to assess the anticonvulsant activity of the training set compounds; of these nine, four were exact database hits and five were derived from the hits by minor chemical modifications. Seven of these nine compounds were confirmed to be active, indicating an exceptionally high hit rate. The approach described in this report can be used as a general rational drug discovery tool.


Mindfulness Intervention Improves Coping and Perceptions of Children's Behavior among Families with Elevated Risk.
Mindfulness-informed interventions (MIIs) are increasingly common but have not been extensively studied among families with elevated levels of risk (e.g., those involved in child protective services and/or receiving financial assistance). These families often experience high rates of stressors that can impact coping strategies, interpersonal dynamics, and relationships. Given that mindfulness has been shown to promote health and wellbeing, this study used a sample from two pilot randomized controlled trials to test the extent to which a mindfulness-informed intervention improved coping strategies and perceptions of children's behavior among 53 families with elevated risk. A principal components analysis with a direct oblimin rotation revealed that cognitive-emotion coping strategies could be characterized by three factors: positive adaptation, negative adaptation, and positive refocusing. Intention-to-treat analysis indicated significant group by time differences, with intervention participants demonstrating improvements in positive refocusing coping, positive adaptation coping, and perceptions of children's behavior problems compared to participants in the waitlist control group. No significant differences were found for negative adaptation coping strategies. Findings provide preliminary support for the benefits of mindfulness training in a sample generally underrepresented in the mindfulness intervention literature.


Functional disorders of the biliary tract and pancreas.
The term "dysfunction" defines the motor disorders of the gall bladder and the sphincter of Oddi (SO) without note of the potential etiologic factors for the difficulty to differentiate purely functional alterations from subtle structural changes. Dysfunction of the gall bladder and/or SO produces similar patterns of biliopancreatic pain and SO dysfunction may occur in the presence of the gall bladder. The symptom-based diagnostic criteria of gall bladder and SO dysfunction are episodes of severe steady pain located in the epigastrium and right upper abdominal quadrant which last at least 30 minutes. Gall bladder and SO dysfunctions can cause significant clinical symptoms but do not explain many instances of biliopancreatic type of pain. The syndrome of functional abdominal pain should be differentiated from gall bladder and SO dysfunction. In the diagnostic workup, invasive investigations should be performed only in the presence of compelling clinical evidence and after non-invasive testing has yielded negative findings. Gall bladder dysfunction is suspected when laboratory, ultrasonographic, and microscopic bile examination have excluded the presence of gallstones and other structural abnormalities. The finding of decreased gall bladder emptying at cholecystokinin-cholescintigraphy is the only objective characteristic of gall bladder dysfunction. Symptomatic manifestation of SO dysfunction may be accompanied by features of biliary obstruction (biliary-type SO dysfunction) or significant elevation of pancreatic enzymes and pancreatitis (pancreatic-type SO dysfunction). Biliary-type SO dysfunction occurs more frequently in postcholecystectomy patients who are categorized into three types. Types I and II, but not type III, have biochemical and cholangiographic features of biliary obstruction. Pancreatic-type SO dysfunction is less well classified into types. When non-invasive investigations and endoscopic retrograde cholangiopanreatography show no structural abnormality, manometry of both biliary and pancreatic sphincter may be considered.


Health status and use of health services among recently arrived men with refugee backgrounds: a comparative analysis of urban and regional settlement in South-east Queensland.
Approximately one-third of refugee and humanitarian entrants to Australia are adult men. Many of these men and their families settle in regional areas. Little is known about the health status of refugee men and the use of health services, and whether or not there are differences between those living in urban and regional areas. This paper reports on the cross-sectional differences in health status and use of health services among a group of 233 recently arrived refugee men living in urban and regional areas of South-east Queensland. Overall, participants reported good levels of subjective health status, moderate to good levels of well-being, and low prevalence of mental illness. Men living in urban areas were more likely to have a long-standing illness and report poorer health status than those settled in regional areas. In contrast, men living in regional areas reported poorer levels of well-being in the environment domain and were more likely to visit hospital emergency departments. Targeted health promotion programs will ensure that refugee men remain healthy and develop their full potential as members of the Australian community. Programs that facilitate refugees' access to primary health care in regional areas may promote more appropriate use of hospital emergency departments by these communities.


Effect of intra-amniotic lipopolysaccharide on nephron number in preterm fetal sheep.
Chorioamnionitis is an antecedent of preterm birth. We aimed to determine the effect of experimental chorioamnionitis in fetal sheep during late gestation on 1) nephron number, 2) renal corpuscle volume, and 3) renal inflammation. We hypothesized that exposure to chorioamnionitis would lead to inflammation in fetal kidneys and adversely impact on the development of nephrons, leading to a reduction in nephron number. At ∼121 days of gestation (term ∼147 days), pregnant ewes bearing twin or singleton fetuses received a single intra-amniotic injection of lipopolysaccharide (n = 6; 3 singletons, 3 twins); controls were either untreated or received an intra-amniotic injection of saline (n = 8; 4 singletons, 4 twins). One twin was used from each twin-bearing ewe. At ∼128 days of gestation, fetuses were delivered via Caesarean section. Kidneys were collected and stereologically analyzed to determine nephron number and renal corpuscle volume. Renal inflammation was assessed using immunohistochemistry. Experimental chorioamnionitis did not affect body weight or relative kidney weight. There was a significant reduction in nephron number but no change in renal corpuscle volume in LPS-exposed fetuses relative to controls. On average, nephron number was significantly reduced by 23 and 18% in singleton and twin LPS-exposed fetuses, respectively. The degree of renal inflammation did not differ between groups. Importantly, this study demonstrates that exposure to experimental chorioamnionitis adversely impacts on nephron number in the developing fetus.


Intestinal Escherichia coli colonization in a mallard duck population over four consecutive winter seasons.
We report the population structure and dynamics of one Escherichia coli population of wild mallard ducks in their natural environment over four winter seasons, following the characterization of 100 isolates each consecutive season. Macro-restriction analysis was used to define isolates variously as multi- or 1-year pulsed-field gel electrophoresis (PFGE) types. Isolates were characterized genotypically based on virulence-associated genes (VAGs), phylogenetic markers, and phenotypically based on haemolytic activity, antimicrobial resistance, adhesion to epithelial cells, microcin production, motility and carbohydrate metabolism. Only 12 out of 220 PFGE types were detectable over more than one winter, and classified as multi-year PFGE types. There was a dramatic change of PFGE types within two winter seasons. Nevertheless, the genetic pool (VAGs) and antimicrobial resistance pattern remained remarkably stable. The high diversity and dynamics of this E. coli population were also demonstrated by the occurrence of PFGE subtypes and differences between isolates of one PFGE type (based on VAGs, antimicrobial resistance and adhesion rates). Multi- and 1-year PFGE types differed in antimicrobial resistance, VAGs and adhesion. Other parameters were not prominent colonization factors. In conclusion, the high diversity, dynamics and stable genetic pool of an E. coli population seem to enable their successful colonization of host animal population over time.


STBase: one million species trees for comparative biology.
Comprehensively sampled phylogenetic trees provide the most compelling foundations for strong inferences in comparative evolutionary biology. Mismatches are common, however, between the taxa for which comparative data are available and the taxa sampled by published phylogenetic analyses. Moreover, many published phylogenies are gene trees, which cannot always be adapted immediately for species level comparisons because of discordance, gene duplication, and other confounding biological processes. A new database, STBase, lets comparative biologists quickly retrieve species level phylogenetic hypotheses in response to a query list of species names. The database consists of 1 million single- and multi-locus data sets, each with a confidence set of 1000 putative species trees, computed from GenBank sequence data for 413,000 eukaryotic taxa. Two bodies of theoretical work are leveraged to aid in the assembly of multi-locus concatenated data sets for species tree construction. First, multiply labeled gene trees are pruned to conflict-free singly-labeled species-level trees that can be combined between loci. Second, impacts of missing data in multi-locus data sets are ameliorated by assembling only decisive data sets. Data sets overlapping with the user's query are ranked using a scheme that depends on user-provided weights for tree quality and for taxonomic overlap of the tree with the query. Retrieval times are independent of the size of the database, typically a few seconds. Tree quality is assessed by a real-time evaluation of bootstrap support on just the overlapping subtree. Associated sequence alignments, tree files and metadata can be downloaded for subsequent analysis. STBase provides a tool for comparative biologists interested in exploiting the most relevant sequence data available for the taxa of interest. It may also serve as a prototype for future species tree oriented databases and as a resource for assembly of larger species phylogenies from precomputed trees.


A game theoretical approach to optimal control of dual drug delivery for HIV infection treatment.
For human immunodeficiency virus (HIV) infection treatment, the host immune system and antiviral drugs form a coalition to fight against HIV. Evidence suggests that drug therapy with Highly Active Antiretroviral Therapy can effectively prolong the life of the patient because it can reduce the replication of HIV while, at the same time, protecting the CD4+ T cells. The dosages of different drugs, however, are important in determining the success of the treatment. In addition, drug therapy for HIV is complicated by the fact that viruses can mutate, thereby effectively escaping from the attack of the drugs. This paper models HIV drug therapy by considering a game between HIV and a coalition consisting of both antiviral drugs and the host immune system. The Nash equilibrium (NE) is calculated as the solution of the game. The simulation results show that an NE exists in which both T cells and viruses remain and coexist after several generations. This brings a new drug therapy during HIV infection to prolong the life of the patient with HIV coexistence.


Influence of paraquat, glyphosate, and cadmium on the activity of some serum enzymes and protein electrophoretic behavior (in vitro).
In vitro study for the determination of the toxicity of some pesticides (glyphospate and paraquat) and cadmium chloride (CdCl2) on the activities of serum acetylcholinesterase (AChE), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AlP), and acid phosphatase (AcP) is described. Changes in electrophoretic patterns of serum proteins were also tested. Results revealed that glyphosate was effective on all enzymes except AcP. Its IC50 values (the concentration of compound that inhibits 50% of the enzyme activity in 1 h at 37 degrees C) were 714.3, 750, 54.2, 270.8, and 71.4 mM for AChE, LDH, AST, ALT, and AlP, respectively. The inhibitory effect of paraquat varied markedly among all enzymes. The IC50 values of paraquat were 321.4 and 750 mM for AST and ALT, respectively. It had mild effect on AChE and LDH; and no effect on the activities of AlP and AcP. The effect of CdCl2 was pronounced with AChE, ALT, AlP, and AcP, and no effect on LDH and AST was found. The corresponding IC50 values were 77.7, 22.2, 33.3, and 83.3 mM for AChE, ALT, AlP, and AcP, respectively. Polyacrylamide gel electrophoretic patterns of serum proteins showed marked differences with glyphosate and CdCl2 but not with paraquat. The results suggest that the in vitro enzyme-activity test seems to have a potential for the assessment of pesticide and heavy metal toxicity.


The synergistic regulatory effect of Runx2 and MEF transcription factors on osteoblast differentiation markers.
Bone tissues for clinical application can be improved by studies on osteoblast differentiation. Runx2 is known to be an important transcription factor for osteoblast differentiation. However, bone morphogenetic protein (BMP)-2 treatment to stimulate Runx2 is not sufficient to acquire enough bone formation in osteoblasts. Therefore, it is necessary to find other regulatory factors which can improve the transcriptional activity of Runx2. The erythroblast transformation-specific (ETS) transcription factor family is reported to be involved in various aspects of cellular proliferation and differentiation. We have noticed that the promoters of osteoblast differentiation markers such as alkaline phosphatase (Alp), osteopontin (Opn), and osteocalcin (Oc) contain Ets binding sequences which are also close to Runx2 binding elements. Luciferase assays were performed to measure the promoter activities of these osteoblast differentiation markers after the transfection of Runx2, myeloid Elf-1-like factor (MEF), and Runxs+MEF. Reverse-transcription polymerase chain reaction was also done to check the mRNA levels of Opn after Runx2 and MEF transfection into rat osteoblast (ROS) cells. We have found that MEF, an Ets transcription factor, increased the transcriptional activities of Alp, Opn, and Oc. The addition of Runx2 resulted in the 2- to 6-fold increase of the activities. This means that these two transcription factors have a synergistic effect on the osteoblast differentiation markers. Furthermore, early introduction of these two Runx2 and MEF factors significantly elevated the expression of the Opn mRNA levels in ROS cells. We also showed that Runx2 and MEF proteins physically interact with each other. Runx2 interacts with MEF proteins and binds to the promoters of the osteoblast markers such as Opn nearby MEF to increase its transcriptional activity. Our results also imply that osteoblast differentiation and bone formation can be increased by activating MEF to elicit the synergistic effect of Runx2 and MEF.


NMR and computational studies of stereoisomeric equine estrogen-derived DNA cytidine adducts in oligonucleotide duplexes: opposite orientations of diastereomeric forms.
The equine estrogens equilin (EQ) and equilenin (EN) are the active components in the widely prescribed hormone replacement therapy formulation Premarin. Metabolic activation of EQ and EN generates the catechol 4-hydroxyequilenin (4-OHEN) that autoxidizes to the reactive o-quinone form in aerated aqueous solutions. The o-quinones react predominantly with C, and to a lesser extent with A and G, to form premutagenic cyclic covalent DNA adducts in vitro and in vivo. To obtain insights into the structural properties of these biologically important DNA lesions, we have synthesized site-specifically modified oligonucleotides containing the stereoisomeric 1'S,2'R,3'R-4-OHEN-C3 and 1'R,2'S,3'S-4-OHEN-C4 adducts derived from the reaction of 4-OHEN with the C in the oligonucleotide 5'-GGTAGCGATGG in aqueous solution. A combined NMR and computational approach was utilized to determine the conformational characteristics of the two major 4-OHEN-C3 and 4-OHEN-C4 stereoisomeric adducts formed in this oligonucleotide hybridized with its complementary strand. In both cases, the modified C adopts an anti glycosidic bond conformation; the equilenin distal ring protrudes into the minor groove while its two proximal hydroxyl groups are exposed on the major groove side of the DNA duplex. The bulky 4-OHEN-C adduct distorts the duplex within the central GC*G portion, but Watson-Crick pairing is maintained adjacent to C* in both stereoisomeric adducts. For the 4-OHEN-C3 adduct, the equilenin rings are oriented toward the 5'-end of the modified strand, while in 4-OHEN-C4 the equilenin is 3'-directed. Correspondingly, the distortions of the double-helical structures are more pronounced on the 5'- or the 3'-side of the lesion, respectively. These differences in stereoisomeric adduct conformations may play a role in the processing of these lesions in cellular environments.


Mitochondrial permeability transition in CNS trauma: cause or effect of neuronal cell death?
Experimental traumatic brain injury (TBI) and spinal cord injury (SCI) result in a rapid and significant necrosis of neuronal tissue at the site of injury. In the ensuing hours and days, secondary injury exacerbates the primary damage, resulting in significant neurologic dysfunction. It is believed that alterations in excitatory amino acids (EAA), increased reactive oxygen species (ROS), and the disruption of Ca(2+) homeostasis are major factors contributing to the ensuing neuropathology. Mitochondria serve as the powerhouse of the cell by maintaining ratios of ATP:ADP that thermodynamically favor the hydrolysis of ATP to ADP + P(i), yet a byproduct of this process is the generation of ROS. Proton-pumping by components of the electron transport system (ETS) generates a membrane potential (DeltaPsi) that can then be used to phosphorylate ADP or sequester Ca(2+) out of the cytosol into the mitochondrial matrix. This allows mitochondria to act as cellular Ca(2+) sinks and to be in phase with changes in cytosolic Ca(2+) levels. Under extreme loads of Ca(2+), however, opening of the mitochondrial permeability transition pore (mPTP) results in the extrusion of mitochondrial Ca(2+) and other high- and low-molecular weight components. This catastrophic event discharges DeltaPsi and uncouples the ETS from ATP production. Cyclosporin A (CsA), a potent immunosuppressive drug, inhibits mitochondrial permeability transition (mPT) by binding to matrix cyclophilin D and blocking its binding to the adenine nucleotide translocator. Peripherally administered CsA attenuates mitochondrial dysfunction and neuronal damage in an experimental rodent model of TBI, in a dose-dependent manner. The underlying mechanism of neuroprotection afforded by CsA is most likely via interaction with the mPTP because the immunosuppressant FK506, which has no effect on the mPT, was not neuroprotective. When CsA was administrated after experimental SCI at the same dosage and regimen used TBI paradigms, however, it had no beneficial neuroprotective effects. This review takes a comprehensive and critical look at the evidence supporting the role for mPT in central nervous system (CNS) trauma and highlights the differential responses of CNS mitochondria to mPT induction and the implications this has for therapeutically targeting the mPT in TBI and SCI.


Copper-free Sonogashira cross-coupling reactions: an overview.
The Sonogashira reaction is a cross-coupling reaction of a vinyl or aryl halide with a terminal alkyne to form a C-C bond. In its original form, the Sonogashira reaction is performed with a palladium species as a catalyst while co-catalyzed by a copper species and a phosphine or amine. The reaction is conducted under mild conditions, i.e., room temperature, aqueous solutions, and the presence of mild bases. Undeniably, the Sonogashira reaction is among the most competent and efficient reactions widely used in organic synthesis. This named reaction has proved useful in many organic synthesis areas, including the synthesis of pharmaceuticals, heterocycles, natural products, organic compounds, complex molecules having biological activities, nanomaterials, and many more materials that we use in our daily lives. The presence of transition metals as a catalyst was indeed essential in the Sonogashira reaction. However, recently, the reaction has been successfully conducted without copper as a co-catalyst and phosphines or amines as bases. In this critical review, we have focused on developments in the Sonogashira reaction successfully performed in the absence of copper complexes, phosphines or amines, which could be of particular advantage in implementing green chemistry principles and making the reactions more achievable from an economic viewpoint.


Comparison of different busulfan analogues for depletion of hematopoietic stem cells and promotion of donor-type chimerism in murine bone marrow transplant recipients.
Busulfan (1,4-butanediol dimethanesulfonate, BU) is relatively unique among other standard chemotherapy compounds in its ability to deplete noncycling primitive stem cells in the host and consequently to allow for high levels of long-term, donor-type engraftment after bone marrow transplantation (BMT). Such a property explains why this drug can be used as an alternative to total body irradiation in preparative regimes for BMT. However, as with radiation, BU conditioning is still troubled by severe toxicities that limit its applications to suboptimal drug doses. These problems stress the need for other BMT-conditioning drugs that are better tolerated and more selectively targeted toward normal and malignant hematopoietic stem cells. We have therefore compared the effects of various novel dimethanesulfonate compounds (related to BU) in terms of their toxicity to different stem cell subsets in vivo and in vitro and their ability to provide for long-term donor bone marrow engraftment using the congenic glucose-6-phosphate isomerase type 1 marker. Introduction of a benzene or cyclohexane ring in some of these drugs affords rigidity to the molecule and restricts the spatial positioning of the alkylating groups. Among 25 different compounds thus far tested at single doses, PL63 [cis-1,2-(2-hydroxyethyl) cyclohexane dimethanesulfonate] proved to be the most effective in providing for hematopoietic engraftment. The transisomer of the same compound gave significantly less engraftment and was comparable with the effects of dimethylbusulfan and Hepsulfam. The engraftment data correlated well with the depletion of different bone marrow stem cell subsets in the host as measured using the cobblestone area forming cell assay. The extent of stem cell depletion could not be explained on the basis of the distance and orientation of the two alkylating groups. Pharmacokinetic data, however, indicate that there is a correlation between biological activity and plasma levels reached. The diverse cytotoxic effects shown by these novel analogues of BU have provided a basis for relating biological activity with pharmacokinetic properties rather than with structural properties such as distance and orientation of the two alkylating groups. The identification of highly active compounds such as PL63 offers an opportunity for further developing other closely related drugs for potential application in clinical BMT conditioning therapy.


Molecular Evolution of Human Coronavirus 229E in Hong Kong and a Fatal COVID-19 Case Involving Coinfection with a Novel Human Coronavirus 229E Genogroup.
Compared to other human coronaviruses, the genetic diversity and evolution of human coronavirus 229E (HCoV-229E) are relatively understudied. We report a fatal case of COVID-19 pneumonia coinfected with HCoV-229E in Hong Kong. Genome sequencing of SARS-CoV-2 and HCoV-229E from a nasopharyngeal sample of the patient showed that the SARS-CoV-2 strain HK13 was most closely related to SARS-CoV-2 type strain Wuhan-Hu-1 (99.99% nucleotide identity), compatible with his recent history of travel to Wuhan. The HCoV-229E strain HK20-42 was most closely related to HCoV-229E strain SC0865 from the United States (99.86% nucleotide identity). To investigate if it may represent a newly emerged HCoV-229E genotype in Hong Kong, we retrieved 41 archived respiratory samples that tested positive for HCoV-229E from 2004 to 2019. Pneumonia and exacerbations of chronic airway diseases were common among infected patients. Complete RdRp, S, and N gene sequencing of the 41 HCoV-229E strains revealed that our contemporary HCoV-229E strains have undergone significant genetic drift with clustering of strains in chronological order. Two novel genogroups were identified, in addition to previously described genogroups 1 to 4, with recent circulating strains including strain HK20-42 belonging to novel genogroup 6. Positive selection was detected in the spike protein and receptor-binding domain, which may be important for viral evolution at the receptor-binding interphase. Molecular dating analysis showed that HCoV-229E shared the most recent common ancestor with bat and camel/alpaca 229E-related viruses at ∼1884, while camel/alpaca viruses had a relatively recent common ancestor at ∼1999. Further studies are required to ascertain the evolutionary origin and path of HCoV-229E.IMPORTANCE Since its first appearance in the 1960s, the genetic diversity and evolution of human coronavirus 229E (HCoV-229E) have been relatively understudied. In this study, we report a fatal case of COVID-19 coinfected with HCoV-229E in Hong Kong. Genome sequencing revealed that our SARS-CoV-2 strain is highly identical to the SARS-CoV-2 strain from Wuhan, compatible with the patient's recent travel history, whereas our HCoV-229E strain in this study is highly identical to a recent strain in the United States. We also retrieved 41 archived HCoV-229E strains from 2004 to 2019 in Hong Kong for sequence analysis. Pneumonia and exacerbations of chronic airway diseases were common diagnoses among the 41 patients. The results showed that HCoV-229E was evolving in chronological order. Two novel genogroups were identified in addition to the four preexisting HCoV-229E genogroups, with recent circulating strains belonging to novel genogroup 6. Molecular clock analysis dated bat-to-human and bat-to-camelid transmission to as early as 1884.


HDAC6 Suppresses Age-Dependent Ectopic Fat Accumulation by Maintaining the Proteostasis of PLIN2 in Drosophila.
Age-dependent ectopic fat accumulation (EFA) in animals contributes to the progression of tissue aging and diseases such as obesity, diabetes, and cancer. However, the primary causes of age-dependent EFA remain largely elusive. Here, we characterize the occurrence of age-dependent EFA in Drosophila and identify HDAC6, a cytosolic histone deacetylase, as a suppressor of EFA. Loss of HDAC6 leads to significant age-dependent EFA, lipid composition imbalance, and reduced animal longevity on a high-fat diet. The EFA and longevity phenotypes are ameliorated by a reduction of the lipid-droplet-resident protein PLIN2. We show that HDAC6 is associated physically with the chaperone protein dHsc4/Hsc70 to maintain the proteostasis of PLIN2. These findings indicate that proteostasis collapse serves as an intrinsic cue to cause age-dependent EFA. Our study suggests that manipulation of proteostasis could be an alternative approach to the treatment of age-related metabolic diseases such as obesity and diabetes.


Age-adjusted limits of fluoride intake to minimize the prevalence of fluorosis.
The range of optimal fluoride intake for adults, 1.5 to 4 mg per day, was adjusted for children and adolescents aged 1 to 19 by relating these limits to body weight and energy intake. Limits related to weight agreed well with the usually recommended ranges for supplemented fluorides. However, for children up to 6 years of age limits related to energy intake were twice as high as those related to body weight. These differences diminished with increasing age and were small between 16 and 19 years of age. New conservative limits were based on an interval for adults ranging from 1.45 to 2.9 mg fluoride per day. The new age-adjusted limits were compatible with most current recommendations.


Mesenchymal Stem Cell Therapy in Ischemic Stroke: A Meta-analysis of Preclinical Studies.
Numerous preclinical studies have been carried out using mesenchymal stem cells (MSCs) therapy for ischemic stroke. The purpose of the present meta-analysis is to review the quality of preclinical studies. In all, 4,361 articles were identified, out of which 64 studies were included (excluding in vitro studies). The results were obtained across species, route, and time of administration, immunogenicity, and doses. The median quality score 4.90/10, confidence interval 95%, and large effect size were observed, which strongly supports the translation potential of MSC therapy for ischemic stroke.


Comments and illustrations of the WFUMB CEUS liver guidelines: Rare benign focal liver lesion, part I.
Improved detection and characterization of common focal liver lesions (FLL) are the main topics of the World Federation for Ultrasound in Medicine and Biology (WFUMB) guidelines on the use of contrast-enhanced ultrasound (CEUS). On stateof-the-art CEUS imaging, to create a library of rare FLL, especially concerning their atypical imaging characteristics, might be helpful for improving clinical diagnostic efficiency. In this review, we aim to summarize the ultrasound and CEUS features of rare benign FLL. Currently there are limited reports and images published.


[Mainstream medicine versus complementary medicine (homeopathic) intervention: a critical methodology study of care in pregnancy].
This meticulously evaluated study investigated two fundamental questions. The first dealt with the usefulness and adequacy of the instruments (questionnaires and case report forms) presently available in mainstream clinical research when trying to evaluate two dissimilar therapeutic systems such as main stream medicine and homeopathy. The second question dealt with the comparability of the two populations of patients in terms of individual personality characteristics as well as regarding the progress of the pregnancies and the course of the deliveries under the two systems of care and control. It turned out that a study of that kind is feasible in principle but is very demanding and time consuming. In addition the study showed clearly that the instruments presently available in mainstream medicine do not cover essential aspects of homeopathy and, therefore, impede a comparison of the two therapeutic systems. In the homeopathic group the frequency of situations requiring a Cesarean was remarkably low. However, the number of cases is too small to draw qualifying conclusions.


The Prognostic Value of 18F-FDG PET Imaging at Staging in Patients with Malignant Pleural Mesothelioma: A Literature Review.
Malignant pleural mesothelioma (MPM) is an aggressive malignancy, frequently diagnosed at locally-advanced/metastatic stages. Due to a very poor prognosis and limited treatment options, the need to identify new prognostic markers represents a great clinical challenge. The prognostic role of metabolic information derived from Positron Emission Tomography (PET) with 18F-Fluoro-deoxy-glucose (18F-FDG) has been investigated in different MPM settings, however with no definitive consensus. In this comprehensive review, the prognostic value of FDG-PET imaging exclusively performed at staging in MPM patients was evaluated, conducting a literature search on PubMed/MEDLINE from 2010 to 2020. From the 19 selected studies, despite heterogeneity in several aspects, staging FDG-PET imaging emerges as a valuable prognostic biomarker, with higher tumor uptake predictive of worse prognosis, and with volumetric metabolic parameters like Metabolic Tumor Volume, (MTV) and Total Lesion Glycolisis (TLG) performing better than SUVmax. However, PET uptake parameters were not always confirmed as independent prognostic factors, especially in patients previously treated with pleurodesis and with a non-epithelioid histotype. Future prospective studies in larger and clinically homogeneous populations, and using more standardized methods of PET images analysis, are needed to further validate the value of staging FDG-PET in the prognostic MPM stratification, with a potential impact on better patient-tailored treatment planning, in the perspective of personalized medicine.


Can Psychophysics Be Fun? Exploring the Feasibility of a Gamified Contrast Sensitivity Function Measure in Amblyopic Children Aged 4-9 Years.
Routine assessments of the Contrast Sensitivity Function [CSF] could be useful for the diagnosis and monitoring of amblyopia. However, current CSF measures are not clinically practical, as they are too slow, too boring, and too uncomfortable to sustain a young child's interest. Here we assess the feasibility of a more gamified approach to CSF testing, in which a maximum likelihood psychophysical algorithm (QUEST+) is combined with a largely unconstrained user interface (no fixation target, head restraints, or discrete trials). Twenty-five amblyopes (strabismic, anisometropic, or mixed) aged 4.0-9.2 years performed the gamified CSF assessment monocularly (once per eye). The test required the child to "pop" (press) grating stimuli as they "bounced" around a tablet screen. Head tracking via the tablet's front-facing camera was used to adjust for variations in viewing distance post hoc. CSFs were fitted for each eye, and Area Under the CSF (AUCSF) computed as a summary measure of sensitivity. The results showed that AUCSF measurements were able to separate moderately and severely amblyopic eyes from fellow eyes (case-control effect), and to distinguish individuals with varying degrees of vision loss (dose effect). Even the youngest children exhibited no difficulties completing the test or comprehending what to do, and most children appeared to find the test genuinely enjoyable. Informal feedback from a focus group of older children was also positive, although potential shortcomings with the present design were identified. This feasibility study indicates that gamified, child-friendly vision assessments have promise as a future means of pediatric clinical assessment. Such measures could be particularly valuable for assessing children outside of conventional eye-care facilities (e.g., home-monitoring, school screening).


Prophylactic corticosteroid use prevents engraftment syndrome in patients after autologous stem cell transplantation.
Engraftment syndrome (ES) following autologous stem cell transplantation (ASCT) at the time of neutrophil recovery may comprise fever, rash, pulmonary edema, or diarrhea. Usually, ES is easily manageable using corticosteroids but may prolong hospitalization. In two consecutive cohorts of subsequent patients with myeloma, lymphomas, and testicular/germ cell cancer, we assessed the benefit of corticosteroid use to prevent incidence and severity of ES following ASCT. Whereas Cohort A (82 patients) received no prophylactic corticosteroids, corticosteroids (4 mg dexamethasone oral daily) were started in Cohort B (60 patients) at day +9 until day +13 following ASCT. Steroid prophylaxis significantly reduced the incidence of ES (6/60; 10% vs. 33/82; 40%; p < 0.001). Hospitalization duration was longer in patients with ES than in patients without ES within both cohorts (in Cohort A: p = 0.007; and B: p = 0.011), but did not differ significantly between cohorts A and B. Finally, in Cohort A, there was a trend to an inferior 2-year overall survival rate in patients without ES compared to patients with ES (p = 0.067), but definite conclusions are not yet allowed. Our results suggest that corticosteroid prophylaxis from days +9 to +13 following ASCT significantly reduces the risk of ES and shortens hospitalization duration.


The central lip flap and nasal mucosal rotation advancement: important aspects of composite correction of the bilateral cleft lip nose deformity.
The columella, nasal tip, lip relationship in the secondary bilateral cleft deformity remains an enigma and a great challenge for the cleft surgeon. A subset of patients with bilateral cleft lip still require columellar lengthening and nasal correction, despite the advances in preoperative orthopedics and primary nasal corrections. An approach to correct this deformity is described. This consists of (1) lengthening the columella by a central lip advancement flap; (2) open rhinoplasty, allowing definitive repositioning of lower lateral cartilages, ear cartilage grafting to the tip and columella when necessary; (3) nasal mucosal advancement; (4) alar base narrowing; and (5) reconstruction of the orbicularis oris as required. Depending on the individual assessment of the patients, some of these steps were not performed, leaving the nasal mucosal advancement the most important aspect of the reconstruction. In a consecutive series of 72 patients with repaired bilateral cleft lip and palate, 17 patients have been treated with nasal mucosal rotation advancement and followed up for a maximum period of 10 years. With the use of this technique, the secondary bilateral cleft lip nose deformity has been successfully corrected.


Metabolite monitoring concept for the biometric identification of individuals from the skin surface.
This study aims at proof of concept that constant monitoring of the concentrations of metabolites in three individuals' sweat over time can differentiate one from another at any given time, providing investigators and analysts with increased ability and means to individualize this bountiful biological sample. A technique was developed to collect and extract authentic sweat samples from three female volunteers for the analysis of lactate, urea, and L-alanine levels. These samples were collected 21 times over a 40-day period and quantified using a series of bioaffinity-based enzymatic assays with UV-vis spectrophotometric detection. Sweat samples were simultaneously dried, derivatized, and analyzed by a GC-MS technique for comparison. Both UV-vis and GC-MS analysis methods provided a statistically significant MANOVA result, demonstrating that the sum of the three metabolites could differentiate each individual at any given day of the time interval. Expanding upon previous studies, this experiment aims to establish a method of metabolite monitoring as opposed to single-point analyses for application to biometric identification from the skin surface.


Fabrication and study of microstructured optical fibers with elliptical holes.
We report the fabrication of what are believed to be the first microstructured optical fibers with uniformly oriented elliptical holes. A high degree of hole ellipticity is achieved with a simple technique that relies on hole deformation during fiber draw. Both form and stress-optic birefringence are characterized over a broad wavelength range. These measurements are in excellent agreement with numerical modeling and demonstrate a birefringence as high as 1.0 x 10(-4) at a wavelength of 850 nm.


Impact of acquisition and modeling parameters on the test-retest reproducibility of edited GABA.
Literature values vary widely for within-subject test-retest reproducibility of gamma-aminobutyric acid (GABA) measured with edited magnetic resonance spectroscopy (MRS). Reasons for this variation remain unclear. Here, we tested whether three acquisition parameters-(1) sequence complexity (two-experiment MEscher-GArwood Point RESolved Spectroscopy [MEGA-PRESS] vs. four-experiment Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy [HERMES]); (2) editing pulse duration (14 vs. 20 ms); and (3) scanner frequency drift (interleaved water referencing [IWR] turned ON vs. OFF)-and two linear combination modeling variations-(1) three different coedited macromolecule models (called "1to1GABA", "1to1GABAsoft", and "3to2MM" in the Osprey software package); and (2) 0.55- versus 0.4-ppm spline baseline knot spacing-affected the within-subject coefficient of variation of GABA + macromolecules (GABA+). We collected edited MRS data from the dorsal anterior cingulate cortex from 20 participants (mean age: 30.8 ± 9.5 years; 10 males). Test and retest scans were separated by removing the participant from the scanner for 5-10 min. Each acquisition consisted of two MEGA-PRESS and two HERMES sequences with editing pulse durations of 14 and 20 ms (referred to here as MEGA-14, MEGA-20, HERMES-14, and HERMES-20; all TE = 80 ms, 224 averages). We identified the best test-retest reproducibility following postprocessing with a composite model of the 0.9- and 3-ppm macromolecules ("3to2MM"); this model performed particularly well for the HERMES data. Furthermore, sparser (0.55- compared with 0.4-ppm) spline baseline knot spacing yielded generally better test-retest reproducibility for GABA+. Replicating our prior results, linear combination modeling in Osprey compared with simple peak fitting in Gannet resulted in substantially better test-retest reproducibility. However, reproducibility did not consistently differ for MEGA-PRESS compared with HERMES, for 14- compared with 20-ms editing pulses, or for IWR-ON versus IWR-OFF. These results highlight the importance of model selection for edited MRS studies of GABA+, particularly for clinical studies that focus on individual patient differences in GABA+ or changes following an intervention.


Proposed consensus for definitions and endpoints for clinical trials of acute kidney transplant rejection.
Progress in transplantation therapeutics requires validation from multicenter trials in which enrollment criteria and endpoint definitions have been standardized. A database of acute rejection was established from 19 North American, European, and Australian transplant centers and included parameters on rejection diagnosis and treatment of 50 consecutive rejection episodes from each center. Patient demographics, induction and maintenance immunosuppressive therapies, antirejection agents (drug, dose, duration), clinical signs (decrease in urine volume, presence of fever of > or =38.5 degrees C), serum creatinine concentration (nadir, at rejection, daily during antirejection therapy to 15 days, and days 30, 90, 180, and 365 after rejection date), rejection biopsy findings, morbidity, recurrence of rejection, and renal function at 1 year were recorded for 953 rejection episodes. From these data, three definitions were proposed. Acute rejection was defined as an immunologic process resulting in a serum creatinine increase of > or =0.4 mg/dL, with or without clinical signs, and should include a biopsy confirmation that has been standardized to the Banff criteria. Corticosteroid-resistant rejection was defined as a rejection episode in which a minimum of 250 to 1000 mg of methylprednisolone administered as initial therapy fails to result in stabilization or reduction of the serum creatinine after 3 days of corticosteroid treatment. Successful response to therapy was defined as a serum creatinine level < or =110% of the serum creatinine on the day of the rejection diagnosis and a return of the serum creatinine to or below the rejection creatinine level by 5 days of therapy with maintenance of this response for a minimum of 30 days. The work represented in the Efficacy Endpoints Database provides a step toward improving definitions in clinical trials. Continuity in clinical trial design should lead to improvements in evaluation of outcomes and, thereby have an effect on clinical practice.


Multifocal visual evoked potentials are influenced by variable contrast stimulation in MS.
To test the hypothesis that patients with multiple sclerosis (MS) with intereye asymmetry on low contrast letter acuity, and thickness of the retinal nerve fiber layer (RNFL), would exhibit corresponding changes in cortical timing and amplitude responses on pattern reversal multifocal visual evoked potentials (mfVEP), contingent upon variable stimulus contrast. In a cross-sectional study, we investigated a cohort of 11 normal subjects and 40 patients with MS, 21 of whom had a history of acute optic neuritis (MS-AON) with an intereye asymmetry with respect to RNFL thickness, and on low contrast letter acuity performance. Pattern reversal mfVEP was performed at high (100%), low (33.3%), and very low (14.2%) Michelson-contrast levels. Compared to baseline measures at 100% contrast, the mean amplitude of the mfVEP was reduced in MS-AON eyes, upon pattern-reversal stimulation at the 2 lower contrast levels (p < 0.0001). With respect to changes in timing responses, the intereye asymmetry was increased in the MS-AON patients upon lower contrast pattern-reversal stimulation (p < 0.0001 for 33.3% compared to 100%, and p < 0.001 for 14.2% compared to 100%). The fellow eye in 12 (57%; p < 0.001) of the patients with an abnormal eye, and a history of AON, revealed abnormal amplitude and timing responses upon low contrast stimulation (signifying unmasking of occult damage). Our findings support the hypothesis that mfVEP metric abnormalities are contingent upon contrast magnitude during pattern reversal stimulation. Further, this paradigm was capable of unmasking occult abnormalities in a significant number of apparently unaffected eyes.


Lack of effect of bromocriptine and domperidone on arginine-vasopressin response to insulin-induced hypoglycemia in normal men.
In order to establish whether the arginine-vasopressin (AVP) increase evoked by insulin-induced hypoglycemia is mediated by a dopaminergic pathway, 16 normal men were given an insulin tolerance test (ITT) under basal conditions and after treatment with the dopamine agonist bromocriptine (2.5 mg by mouth) (eight subjects) or the dopamine antagonist domperidone (10 mg i.v.) (eight subjects). In addition, five out of eight subjects in each group were treated with higher doses of bromocriptine (5 mg by mouth) or domperidone (20 mg i.v.). Basal and ITT-stimulated AVP secretion was not modified by the drug treatments, suggesting that dopamine is not involved in the regulation of AVP secretion in response to insulin-induced hypoglycemia.


Efficient limitation of intracellular edema and sodium accumulation by cardioplegia is dissociated from recovery of rat hearts from cold ischemic storage.
Energy deficiency and disturbances of sodium and water homeostasis are considered as mechanisms of injury during hypothermic preservation of cardiac muscle. The present study attempts to characterize the effect of potassium (K+) and magnesium (Mg2+) cardioplegia on these mechanisms. Cellular parameters were measured by multinuclear NMR spectroscopy in isolated rat hearts during 12 h of ischemia at 4 degrees C and 2 h of normothermic reperfusion with an isoosmotic Krebs-Henseleit (KH) solution. Potassium and magnesium cardioplegia (a) reduced the rate of ATP hydrolysis and cellular acidification during early stages of ischemia; (b) caused an early cessation of the phase of fast sodium influx after 40 min (P<0.001 vs 120 min with KH); (c) reduced intracellular sodium accumulation to 148-165 micromol/gdw after 12 h (P<0.01 vs 268+/-15 micromol/gdw with KH); (d) decreased ischemic volumes to 2.7+/-0.1 and 2.8+/-0.1 ml/gdw after 8 and 12 h of storage, respectively (P<0.005 v 3.0 and 3.3 ml/gdw with KH). Quantitative analysis of these parameters showed that both hypothermia and cardioplegia increased the relative contribution of sodium to intracellular water accumulation by a factor of 2-2.5. In view of the marked reduction in absolute sodium and water contents, the data indicate that cold cardioplegia limits the increase in intracellular osmolarity. Myocardial mechanical and metabolic recoveries, and cellular viability deteriorated during prolongation of the ischemic period from 8 to 12 h in all experimental groups (P<0.005). Reperfusion was efficient in reversing intracellular sodium and water accumulation in hearts stored with cardioplegia, in contrast to hearts stored in KH. Magnesium, but not potassium cardioplegia, lowered interstitial water contents (P<0.01 v KH), increased intracellular magnesium concentrations (P<0.001), improved mechanical and metabolic recoveries (P<0.01) and cellular viability (P<0.001). These results indicate (a) cardioplegia reduces intracellular sodium (by approximately 46%) and water accumulation (by 66%) during cold ischemia; (b) both hypothermia and cardioplegia limit the rise in intracellular osmolarity and increase the contribution of sodium to cellular swelling; (c) intracellular sodium and water contents were dissociated from myocardial viability and recovery from cold ischemia in potassium and magnesium cardioplegic solutions. It is concluded that intracellular sodium and water accumulation are not dominant factors in determination of cardiac outcome from ischemia.


[Study of the effectiveness of artificial oxygen carrier on the hemoglobin base in blood loss replacement in dogs].
The effectiveness of modified polyhemoglobin proposed as an artificial oxygen carrier (AOC) was evaluated in experiments on dogs with acute fatal hemorrhage. It was shown that total oxygen consumption, arterial blood pressure and circulating blood volume were maintained at the normal physiological levels during 4 h after infusion of 10% solution of polyhemoglobin. AOC infusion provided 100% survival of the animals. It has been concluded that hemoglobin polymer modified with pyridoxal-5'-phosphate can be used as the basis for the production of the medicinal form of AOC.


Incidence of Salmonella Enteritidis in chicken layer flocks in Turkey: results by real-time polymerase chain reaction and International Organization for Standardization culture methods.
This study presents Salmonella Enteritidis incidence in chicken layer flocks in Turkey determined by real-time PCR (rPCR) and by International Organization for Standardization (ISO) method 6579:2002/Amd 1:2007. A total of 259 samples, composed of 1,036 individual samples each pooled into 4, including 175 cloacal swab, 14 intestine, 35 gizzard swab, and 35 cecal swab samples, belonging to 6 major companies, were collected from 50 layer flocks and tested by rPCR and ISO culture methods. Overall incidence of Salmonella in layer flocks by rPCR and culture was 61.0 and 55.6%, respectively, where 70.1% of these Salmonella isolates were determined as Salmonella Enteritidis. Incidences of Salmonella Enteritidis in culture-positive samples were 65.3% in cloacal swabs, 50.0% in intestines, 73.9% in gizzard swabs, and 87.5% in cecal swabs. The rPCR results were in 100% agreement (100% sensitivity and specificity) with culture results when cecal swabs were selected as the sample type. The relative accuracy of rPCR was 92.4, 91.4, and 84% for intestine, gizzard, and cloacal swab samples, respectively. As a result, by using rPCR and ISO culture, we determined that the Salmonella Enteritidis incidence in layer flocks in Turkey was high and that the use of cecal swab and intestine samples in Salmonella detection would yield reliable results. To reduce this high Salmonella Enteritidis incidence in layer flocks, Salmonella Enteritidis-specific vaccination should be implemented properly in conjunction with a well-designed biosecurity plan, including verifiable corrective actions.


[Assessing fall risk and preventing falls in the elderly].
Assessment of fall risk in the elderly is clearly documented in the literature. However, intervention preventive strategies are not well identified. Two types of methods can be discussed: on the one hand, classical techniques using different tests and exercises in balance with materials and/or sensitization by dual task; on the other hand, rhythmic exercises. Their results and value are not quite established and further studies are needed to assess their prospective benefit, even if they seem interesting in some Parkinson's population. Physical activity and global fall management allow a better outcome in different gait parameters of the elderly.


Why patients attend emergency departments for conditions potentially appropriate for primary care: reasons given by patients and clinicians differ.
To compare reasons identified by clinical staff for potential primary care attendances to the ED with those previously identified by patients. Survey of staff and primary care patients in five ED in New South Wales, Australia using questionnaire based on reasons identified in published studies. Clinicians in the survey identify a broader spectrum of reasons for potential primary care cases presenting to the ED than the patients themselves report. Doctors reported on average 4.1 very important reasons and nurses 4.8 compared with patients 2.4 very important reasons. The main reasons identified by both doctors and nurses were similar and quite different to those identified by patients. Clinicians were more likely to emphasize cost and access issues rather than acuity and complexity issues. There was no difference within the clinician group between doctors and nurses nor by varying levels of experience. Furthermore doctors with significant experience in both primary care and emergency medicine did not differ from the overall clinicians' pattern. These data confirm that clinician perspectives on reasons for potential primary care patients' use of ED differ quite markedly from the perspectives of patients themselves. Those differences do not necessarily represent a punitive or blaming philosophy but will stem from the very different paradigms from which the two protagonists approach the interactions, reflecting the standard tension in a provider - consumer relationship. If policy is to be developed to improve system use and access, it must take both perspectives into account with respect to redesign, expectations and education.


Modulation of Immune Tolerance via Siglec-Sialic Acid Interactions.
One of the key features of the immune system is its extraordinary capacity to discriminate between self and non-self and to respond accordingly. Several molecular interactions allow the induction of acquired immune responses when a foreign antigen is recognized, while others regulate the resolution of inflammation, or the induction of tolerance to self-antigens. Post-translational signatures, such as glycans that are part of proteins (glycoproteins) and lipids (glycolipids) of host cells or pathogens, are increasingly appreciated as key molecules in regulating immunity vs. tolerance. Glycans are sensed by glycan binding receptors expressed on immune cells, such as C-type lectin receptors (CLRs) and Sialic acid binding immunoglobulin type lectins (Siglecs), that respond to specific glycan signatures by triggering tolerogenic or immunogenic signaling pathways. Glycan signatures present on healthy tissue, inflamed and malignant tissue or pathogens provide signals for "self" or "non-self" recognition. In this review we will focus on sialic acids that serve as "self" molecular pattern ligands for Siglecs. We will emphasize on the function of Siglec-expressing mononuclear phagocytes as sensors for sialic acids in tissue homeostasis and describe how the sialic acid-Siglec axis is exploited by tumors and pathogens for the induction of immune tolerance. Furthermore, we highlight how the sialic acid-Siglec axis can be utilized for clinical applications to induce or inhibit immune tolerance.


EFFECTS OF A LIGHTER DISCUS ON SHOULDER MUSCLE ACTIVITY IN ELITE THROWERS, IMPLICATIONS FOR INJURY PREVENTION.
Performance in the discus throw requires high forces and torques generated from the shoulder of the throwing arm, making shoulder muscles at risk of overuse injury. Little is known on muscle activation patterns in elite discus throw. The purpose of this study was to compare the body kinematics and muscle activation patterns of arm and shoulder muscles involved in discus throwing when using discs of different mass (1.7 kg vs 2.0 kg). It was hypothesized that the use of a lighter discus would modify the activation of the shoulder musculature compared to a standard discus. Case-control laboratory study. Seven male elite discus throwers performed five throws using a standard discus (STD, 2.0 kg) and five throws using a lighter weight discus (LGT, 1.7 kg). Surface EMG was recorded for the biceps brachii (BB), deltoideus anterior (DA), deltoideus medialis (DM), clavicular head of the pectoralis major (PM), latissimus dorsi (LD), and trapezius medialis (TM). Three-dimensional high-speed video analysis was utilized to record discus speed and identify the different temporal phases of each throw from the preparation phase (P1) to the delivery phase (P5). The EMG activation of LD lasted longer (p < 0.01) in P1 and was initiated later in P5 with the LGT discus compared to STD. In P5, the EMG intensity of BB decreased (p = 0.02) with LGT (%EMGmax = 50.4 ± 49.6%) compared to STD (64.8 ± 77.9%) and the activation of PM increased (p < 0.01) with LGT (86.2 ± 40.3%) compared to STD (66.2 ± 26.9%). The discus speed at release was increased (p = 0.04) by using the LGT discus (20.62 ± 0.75m.s-1) compared to STD (19.61 ± 0.57m.s-1). The throwing distance was also increased (P < 0.01) with the LGT (43.1 ± 4.3m) discus compared to STD (39.4 ± 3.4m). /Clinical relevance: A lighter discus could be used by elite athletes in training to add variability in muscle solicitation and thus limit the overload on certain muscles of the shoulder region. These results may have implications regarding lowering the risk of injury in discus throw. Level 3.