Ultrastructure of the body wall of Cystidicoloides ephemeridarum (Nematoda, Cystidicolidae) in relation to the histopathology of this nematode in salmonids.
Light, scanning and transmission electron microscope examinations of adult Cystidicoloides ephemeridarum nematodes, parasitic in the stomach of brown trout (Salmo trutta fario L.), revealed that the body wall is composed of a cuticle, a hypodermis and longitudinally oriented somatic musculature. The body cuticle is composed of a trilaminated epicuticle, an outer and inner cortical zone, a median zone with globular bodies and a basal zone consisting of three subzones. Massive cuticle in the three zones and an osmiophilic lining is present in the buccal capsule. Armament is absent both from the buccal capsule and the head end. The surface of the body is transversely striated with cortical annuli. The only specialized attachment devices of C. ephemeridarum are the flexible overlapping margins of the annuli which are elongated in the first third of the body. Together with the sucking pressure of the oesophagus, they seem to play a role in the penetration and mechanical damage of the host's tissue. The hypodermis appears to be syncytial. Up to 300 worms were present in the bolus of food consumed by the host, or attached by their head ends in the lamina epithelialis, which resulted in localized disruptions of the mucosal epithelium with no inflammation. Infection with C. ephemeridarum seems to be a temporary, season-dependent event of mild pathogenicity.


Effects of biological nitrification inhibitor in regulating NH3 volatilization and fertilizer nitrogen recovery efficiency in soils under rice cropping.
Biological nitrification inhibitors are exudates from plant roots that can inhibit nitrification, and have advantages over traditional synthetic nitrification inhibitors. However, our understanding of the effects of biological nitrification inhibitors on nitrogen (N) loss and fertilizer N recovery efficiency in staple food crops is limited. In this study, acidic and calcareous soils were selected, and rice growth pot experiments were conducted to investigate the effects of the biological nitrification inhibitor, methyl 3-(4-hydroxyphenyl) propionate (MHPP) and/or a urease inhibitor (N-[n-butyl], thiophosphoric triamide [NBPT]) on NH3 volatilization, N leaching, fertilizer N recovery efficiency under a 20% reduction of the conventional N application rate. Our results show that rice yield and fertilizer N recovery efficiency were more sensitive to reduced N application in the calcareous soil than in the acidic soil. MHPP stimulated NH3 volatilization by 13.2% in acidic soil and 9.06% in calcareous soil but these results were not significant. In the calcareous soil, fertilizer N recovery efficiency significantly increased by 19.3% and 44.4% in the MHPP and NBPT+MHPP groups, respectively, relative to the reduced N treatment, and the rice yield increased by 16.7% in the NBPT+MHPP treatment (P < 0.05). However, such effects were not significant in the acidic soil. MHPP exerted a significant effect on soil ammonia oxidizers, and the response of abundance and community structure of ammonia-oxidizing archaea, ammonia-oxidizing bacteria, and total bacteria to MHPP depended on the soil type. MHPP+NBPT reduced NH3 volatilization, N leaching, and maintaining rice yield for a 20% reduction in conventional N fertilizer application rate. This could represent a viable strategy for more sustainable rice production, despite the inevitable increase in cost for famers.


Hepatocytic p62 suppresses ductular reaction and tumorigenesis in mouse livers with mTORC1 activation and defective autophagy.
Either activation of mTORC1 due to loss of Tsc1 (tuberous sclerosis complex 1) or defective hepatic autophagy due to loss of Atg5 leads to spontaneous liver tumorigenesis in mice. The purpose of this study was to investigate the mechanisms by which autophagy contributes to the hepatic metabolic changes and tumorigenesis mediated by mTORC1 activation. Atg5 Flox/Flox (Atg5F/F) and Tsc1F/F mice were crossed with albumin-Cre mice to generate liver-specific Atg5 knockout (L-Atg5 KO), L-Tsc1 KO and L-Atg5/Tsc1 double KO (DKO) mice. These mice were crossed with p62/Sqstm1F/F (p62) and whole body Nrf2 KO mice to generate L-Atg5/Tsc1/p62 and L-Atg5/Tsc1-Nrf2 triple KO mice. These mice were housed for various periods up to 12 months, and blood and liver tissues were harvested for biochemical and histological analysis RESULTS: Deletion of Atg5 in L-Tsc1 KO mice inhibited liver tumorigenesis but increased mortality and was accompanied by drastically enhanced hepatic ductular reaction (DR), hepatocyte degeneration and metabolic reprogramming. Deletion of p62 reversed DR, hepatocyte degeneration and metabolic reprogramming as well as the mortality of L-Atg5/Tsc1 DKO mice, but unexpectedly promoted liver tumorigenesis via activation of a group of oncogenic signaling pathways. Nrf2 ablation markedly improved DR with increased hepatocyte population and improved metabolic reprogramming and survival of the L-Atg5/Tsc1 DKO mice without tumor formation. Decreased p62 and increased mTOR activity were also observed in a subset of human hepatocellular carcinomas. These results reveal previously undescribed functions of hepatic p62 in suppressing tumorigenesis and regulating liver cell repopulation and metabolic reprogramming resulting from persistent mTORC1 activation and defective autophagy. Metabolic liver disease and viral hepatitis are common chronic liver diseases and risk factors of hepatocellular carcinoma, which are often associated with impaired hepatic autophagy and increased mTOR activation. Using multiple genetically engineered mouse models of defective hepatic autophagy and persistent mTOR activation, we dissected the complex mechanisms behind this observation. Our results uncovered an unexpected novel tumor suppressor function of p62/Sqstm1, which regulated liver cell repopulation, ductular reaction and metabolic reprogramming in liver tumorigenesis.


High Yes-associated protein 1 with concomitant negative LATS1/2 expression is associated with poor prognosis of advanced gastric cancer.
The Hippo pathway is a tumour-suppressive pathway and its inactivation is known to be associated with progression and metastasis of various cancers. LATS1/2 (large tumour suppressor homolog 1 and 2), YAP1 (Yes-associated protein 1), and TEAD4 (TEA domain-containing sequence-specific transcription factors 4) are core components of the Hippo pathway, and their prognostic roles have not yet been studied in advanced gastric cancers (AGCs). A total of 318 surgically resected AGCs were retrieved. Immunolabelling for LATS1/2, YAP1 and TEAD4 was compared with clinicopathological factors including patients' survival. High expression of YAP1 and TEAD4 was identified in 108 (34.0%) and 131 (41.2%) cases, respectively, and 223 (70.1%) cases were negative for LATS1/2 expression. High YAP1 expression was significantly correlated with the presence of perineural invasion (p=0.032). High YAP1 and high TEAD4 expressions were significantly associated with poor overall survival (p<0.001 and p=0.003, respectively), and negative LATS1/2 expression was also associated with poor overall survival (p=0.002). Combined expression of YAP1highLATS1/2neg showed the worst overall survival (p<0.001). Expression of YAP1high (HR=2.938; 95% CI 1.726-4.998; p<0.001), LATS1/2neg (HR=0.371; 95% CI 0.181-0.758; p=0.007), and combined YAP1highLATS1/2neg (HR=13.785; 95% CI 3.245-58.554; p<0.001) were independent poor prognostic factors of AGC patients. Combined or individual expression of YAP1, LATS1/2, and TEAD4 can be used as prognostic markers of AGC patients.


Changes in pulmonary surfactant function and composition in bleomycin-induced pneumonitis and fibrosis.
Bleomycin is a widely accepted cancer drug but may induce life-threatening interstitial lung disease in a subset of patients. We evaluated the effect of bleomycin administration on pulmonary surfactant function and composition in rabbit lungs. In order to obtain a uniform response to bleomycin, aerosol technology was employed for bronchoalveolar delivery of 1.8 U/kg b.w. bleomycin. On days 4, 8, 16, 24, 32, and 64 after challenge, bronchoalveolar lavages were performed. Sham-aerosolized rabbits served as controls. In the early acute respiratory distress syndrome (ARDS)-like post-bleomycin period (4-16 days), marked loss of surface activity of the large surfactant aggregate (LA) fraction of surfactant was noted. In parallel, reduced percentages of LA, but only minor changes in surfactant apoproteins (SP)-A, SP-B, and SP-C, were encountered. Analysis of the surfactant lipid profile showed impressively enhanced cholesterol and significantly decreased phosphatidylglycerol (PG) levels. The relative content of dipalmitoyl-PC (DPPC) was slightly increased, and a several-fold increase within the 1-O-alkyl-2-acyl subclass of PC was observed. During the prolonged fibroproliferative period, a highly significant downregulation of SP-B and SP-C levels was observed. This was paralleled by an upregulation of the total extracellular phospholipid pool, with a far-reaching normalization of the (phospho)-lipid profile. The biophysical surfactant function never fully normalized within the 64-day observation period. In conclusion, bleomycin caused marked abnormalities of pulmonary surfactant, with the profile of changes being different between the early ARDS and the late fibrotic phase.


Neurodegeneration, oxidative stress and lipid metabolism plasma biomarkers to differentiate Parkinson's disease from atypical parkinsonian syndromes.
The identification of blood biomarkers appears to be a means of improving diagnosis accuracy in Parkinson's disease (PD) and atypical parkinsonian syndromes (APS). We, therefore, evaluate the performance of neurodegeneration, oxidative stress and lipid metabolism plasma biomarkers to distinguish PD from APS. This was a monocentric study with a cross-sectional design. Plasma levels and discriminating power of neurofilament light chain (NFL), malondialdehyde (MDA) and 24S-Hydroxycholesterol (24S-HC) were assessed in patients with clinical diagnoses of PD or APS. In total, 32 PD cases and 15 APS cases were included. Mean disease durations were 4.75 years in PD group and 4.2 years in APS group. Plasma levels of NFL, MDA and 24S-HC differed significantly between the APS and PD groups (P=0.003; P=0.009; P=0.032, respectively). NFL, MDA and 24S-HC discriminated between PD and APS (AUC=0.76688; AUC=0.7375; AUC=0.6958, respectively). APS diagnosis significantly increased with MDA level≥23.628nmol/mL (OR: 8.67, P=0.001), NFL level≥47.2pg/mL (OR: 11.92, P<0.001) or 24S-HC level≤33.4pmol/mL (OR: 6.17, P=0.008). APS diagnosis considerably increased with the combination of NFL and MDA levels beyond cutoff values (OR: 30.67, P<0.001). Finally, the combination of NFL and 24S-HC levels, or MDA and 24S-HC levels, or all three biomarkers' levels beyond cutoff values systematically classified patients in the APS group. Our results suggest that 24S-HC and especially MDA and NFL could be helpful for differentiating PD from APS. Further studies will be needed to reproduce our findings on larger, prospective cohorts of patients with parkinsonism evolving for less than 3 years.


Characterization of a strain of Mycoplasma hominis lacking 120 kDa membrane protein isolated from Vero cell culture.
A strain of Mycoplasma hominis lacking a major membrane protein of 120 kDa was isolated from a Vero cell culture. This strain showed very slow growth rate and formed nipple-less colonies on agar medium.


Increased expression of the ATP-gated P2X7 receptor reduces responsiveness to anti-convulsants during status epilepticus in mice.
Refractory status epilepticus is a clinical emergency associated with high mortality and morbidity. Increasing evidence suggests neuroinflammation contributes to the development of drug-refractoriness during status epilepticus. Here, we have determined the contribution of the ATP-gated P2X7 receptor, previously linked to inflammation and increased hyperexcitability, to drug-refractory status epilepticus and its therapeutic potential. Status epilepticus was induced via a unilateral microinjection of kainic acid into the amygdala in adult mice. Severity of status epilepticus was compared in animals with overexpressing or knock-out of the P2X7 receptor, after inflammatory priming by pre-injection of bacterial lipopolysaccharide (LPS) and in mice treated with P2X7 receptor-targeting and anti-inflammatory drugs. Mice overexpressing P2X7 receptors were unresponsive to several anticonvulsants (lorazepam, midazolam, phenytoin and carbamazepine) during status epilepticus. P2X7 receptor expression increased in microglia during status epilepticus, at times when responses to anticonvulsants were reduced. Overexpression of P2X7 receptors induced a pro-inflammatory phenotype in microglia during status epilepticus and the anti-inflammatory drug minocycline restored normal responses to anticonvulsants in mice overexpressing P2X7 receptors. Pretreatment of wild-type mice with LPS increased P2X7 receptor levels in the brain and reduced responsiveness to anticonvulsants during status epilepticus, which was overcome by either genetic deletion of P2X7 receptors or treatment with the P2X7 receptor antagonists, AFC-5128 or ITH15004. Our results demonstrate that P2X7 receptor-induced pro-inflammatory effects contribute to resistance to pharmacotherapy during status epilepticus. Therapies targeting P2X7 receptors could be novel adjunctive treatments for drug-refractory status epilepticus.


Assessment of human brain water content by cerebral bioelectrical impedance analysis: a new technique and its application to cerebral pathological conditions.
Total brain water content changes in several cerebral pathological conditions and the measurement of brain water content are important for the selection of appropriate therapeutic procedures. We present a quantitative, in vivo, bioelectrical impedance analysis (BIA) method and propose its use for the accurate assessment of brain water content among human subjects. Cerebral BIA is based on the conduction of an applied current in the brain parenchyma. Application of an excitatory current of 800 microA at 50 kHz, via two electrodes placed on the eyelids with the eyes closed, and detection of the voltage drop with two electrodes placed in the suboccipital region allow brain resistance and reactance to be measured. By means of an equation that considers cranial circumference and resistance, it is possible to quantify the total brain water content, expressed as the bioelectrical volume. Cerebral BIA was performed with a series of healthy volunteers (n = 100), for determination of average brain water content values. The method was then applied to 50 patients with brain tumors (n = 20), intracranial hemorrhage (n = 16), or hydrocephalus (n = 14), for assessment of changes in global brain water contents. Data were compared with those obtained for healthy volunteers. Statistically significant differences (P < 0.001) were observed between the two groups. Mean brain water content values (expressed as bioelectrical volume values) were 38.2 +/- 3.9 cm2/Omega for healthy volunteers and 67.7 +/- 13.1 cm2/Omega for patients with cerebral pathological conditions. Statistically significant differences (P < 0.05) were also observed among patients with cerebral pathological conditions. The results of this study suggest that BIA, applied to the cerebral parenchyma, is a valid method for the prediction of brain water contents under both normal and pathological conditions. However, further studies are needed to establish whether it is sensitive and reliable enough for future clinical applications.


IL-7R signaling in regulatory T cells maintains peripheral and allograft tolerance in mice.
Foxp3(+)CD4(+) regulatory T cells (Treg) have a crucial role in controlling CD4(+) T-cell activation, proliferation, and effector function. However, the molecular mechanisms regulating Treg function remain poorly understood. Here we assessed the role of IL-7, a key cytokine regulating T-cell homeostasis, in suppressor capacity of Treg. Using a skin allograft model in which transplant acceptance is controlled by the number of transferred Treg, we find that Treg impair the proliferation of allogeneic CD4(+) T cells, decrease production of IFNγ by effector T cells, and prevent early and increase late IL-7 induction by lymph node stromal cells. Increased IL-7 availability enhanced Treg survival, stabilized Treg molecular signature, enhanced surface IL-2Rα expression, and improved IL-2 binding of Treg, which diminished proliferation of alloreactive CD4(+) T cells. Sequestration of IL-7 or impairment of IL-7R signaling after allograft transplantation abolished Treg-mediated tolerance by limiting their suppressive capacity. Aged Il7rα-ΔTreg mice displayed mild symptoms of autoimmunity correlating with impaired expansion of effector Treg in response to IL-2. Thus, IL-7R signaling on Treg supports the functional activity of effector Treg by increasing their IL-2 sensitivity in the lymph node during peripheral and allograft tolerance.


Clinical, laboratory, and pacing predictors of CRT response.
A decade of research has established the role of cardiac resynchronization therapy (CRT) in medically refractory, moderate to severe systolic heart failure (HF) with intraventricular conduction delay. CRT is an electrical therapy instituted to reestablish ventricular synchronization in order to improve cardiac function and favorably modulate the neurohormonal system. CRT confers a mortality benefit, improved HF hospitalizations, and functional outcome in this population, but not all patients consistently demonstrate a positive CRT response. The nonresponder rate varies from 20% to 40%, depending on the defined response criteria. Efforts to improve response to CRT have focused on a number of fronts. Methods to optimize the correction of electrical and mechanical dyssynchrony, which is the primary target of CRT, has been the focus of research, in addition to improving patient selection and optimizing post-implant care. However, a major issue in dealing with improving nonresponse rates has been finding an accurate and generally accepted definition of "response" itself. The availability of a standard consensus definition of CRT response would enable the estimation of nonresponder burden accurately and permit the development of strategies to improve CRT response. In this review, we define various aspects of "response" to CRT and outline variability in the definition criteria and the problems with its inconsistencies. We describe clinical, laboratory, and pacing predictors that influence CRT response and outcome and how to optimize response.


Protective predictors of alcohol use trajectories among Canadian Aboriginal youth.
Some Aboriginal youth are at disproportionate risk of using substances and developing abuse and dependence disorders. However, not all Aboriginal youth misuse substances and limited research has examined the protective factors conferring against substance use among these youth. The present study aimed to identify protective factors related to the alcohol use trajectories from early adolescence to emerging adulthood among off-reserve Canadian Aboriginal youth. Participants (N = 330; 50.3% male) aged 12-23 were selected from cycles 2-7 of Statistics Canada's NLSCY. Multilevel modeling was employed to identify protective factors for two constructs of alcohol use. Participation in weekly activities and optimism were found to be protective for both the frequency of alcohol use and heavy drinking trajectories. Attendance of religious services was also found to be protective for heavy drinking behaviors. In contrast, positive peer relationships were a risk factor for frequency of alcohol use, but not heavy drinking. The results provide preliminary evidence of important developmental factors to integrate into substance use intervention programs targeting Aboriginal youth.


Safety and efficacy of lomefloxacin versus cefaclor in the treatment of acute exacerbations of chronic bronchitis.
In two multicenter trials, lomefloxacin and cefaclor were compared as treatments for acute bacterial exacerbations of chronic bronchitis. In total, 522 adult outpatients were enrolled at 50 centers in the United States. Patients were randomized to treatment groups receiving either 400 mg lomefloxacin orally once daily (n = 259) or 250 mg cefaclor every 8 hours (n = 263) for 7-10 days. Both groups were comparable in terms of age, severity of exacerbation, smoking history, theophylline use, and baseline pathogens. The most common baseline pathogens were Haemophilus influenzae, found in 32% of patients in the lomefloxacin group and in 29% in the cefaclor group, Pseudomonas aeruginosa (13% and 16%, respectively), Moraxella (Branhamella) catarrhalis (12% and 13%), and Streptococcus pneumoniae (10% in both groups). Bacterial eradication rates 1-4 days after the completion of treatment for all patients with baseline pathogens were 81.8% in the lomefloxacin group and 62.7% in the cefaclor group (p less than 0.001). Clinical success (disappearance or improvement of presenting signs and symptoms) was noted in 80.0% of patients in the lomefloxacin group and 64.7% in the cefaclor group (p = 0.002). Eradication rates for the subgroup of patients who had pathogens susceptible in vitro to both study drugs and who completed treatment were 97.1% for lomefloxacin and 84.6% for cefaclor (p = 0.002). Clinical success rates in this subgroup were 92.4% for lomefloxacin and 90.1 for cefaclor (p = 0.585). Treatment-related adverse events were reported for 7% of patients in the lomefloxacin group and 5% in the cefaclor group. The most common adverse events in both groups were nausea and diarrhea. Six patients were withdrawn from treatment with lomefloxacin and four from the cefaclor group because of adverse events. There was no clinical or laboratory evidence of theophylline interaction with either treatment. Once-daily oral administration of 400 mg lomefloxacin was an effective, well-tolerated alternative to 250 mg of cefaclor three times daily in the treatment of acute exacerbations of chronic bronchitis.


The role of MRI and CT in diagnosis and treatment planning of cherubism: a 13-year follow-up case report.
Cherubism is characterised by mesenchymal alterations during the development of the jaws secondary to perivascular fibrosis. According to the ALARA (As Low As Reasonably Achievable) principle, it is important to avoid conditions where the amount of radiation used is more than that needed for the procedure, because there is no benefit from unnecessary radiation. However, the use of MRI has been poorly studied in cherubism. The patient underwent head and neck MRI and 3D CT for imaging assessment. MRI is necessary to evaluate the extension of dysplastic tissue and the cystic part of the lesions. Bone window CT only allows evaluation of strong densitometric alterations of cherubism lesions. Moreover, on radiographic film it is not always possible to distinguish fibrous tissue from mucous pseudocystic tissue. By contrast, these differences are readily evident on MRI. MRI, in addition to other traditional radiographs and CT, could be useful in helping the clinician in the diagnosis and treatment of cherubism.


Outdoor Air Quality Awareness, Perceptions, and Behaviors Among U.S. Children Aged 12-17 Years, 2015-2018.
This study aimed to assess U.S. adolescents' perceptions and knowledge about air quality and their behaviors aimed to reduce air pollution exposure and whether they vary by demographic characteristics. We analyzed data from the Porter Novelli Public Services YouthStyles survey, a nationally representative survey of U.S. adolescents aged 12-17 years. In survey years 2015-2018, a total of 3,547 adolescents self-reported awareness, perceptions, and behaviors related to air pollution. We calculated weighted percentages of respondents reporting each aspect of air quality awareness, perception, and behaviors overall and by categories of age, gender, parental education, metropolitan status, region, and survey year. Overall, an estimated 81% of U.S. adolescents thought outdoor air pollution could impact health, 52% thought there were things they could do to limit their or their family's exposure, 19% were aware of air quality alerts, 46% of those who thought or were informed air quality was bad did something differently, and 19% always or usually avoided busy roads to reduce air pollution exposure; differences were reported by some demographic variables. Among U.S. adolescents, awareness that air pollution could impact health was relatively high. However, gaps were found in the awareness of the potential impacts and other aspects of awareness and perceptions related to air pollution and the engagement in behaviors to reduce exposure, some of which varied by demographic characteristics. These results can be used to inform interventions that increase awareness and behaviors to reduce air pollution exposures among U.S. adolescents.


Assessing the role of ¹⁸F-FDG PET and ¹⁸F-FDG PET/CT in the diagnosis of soft tissue musculoskeletal malignancies: a systematic review and meta-analysis.
Twelve years ago a meta-analysis evaluated the diagnostic performance of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in assessing musculoskeletal soft tissue lesions (MsSTL). Currently, PET/CT has substituted PET imaging; however, there has not been any published meta-analysis on the use of PET/CT or a comparison of PET/CT with PET in the diagnosis of MsSTL. Therefore, we conducted a meta-analysis to identify the current diagnostic performance of (18)F-FDG PET/CT and determine if there is added value when compared to PET. A systematic review of English articles was conducted, and MEDLINE PubMed, the Cochrane Library, and Embase were searched from 1996 to March 2015. Studies exploring the diagnostic accuracy of (18)F-FDG PET/CT (or dedicated PET) compared to histopathology in patients with MsSTL undergoing investigation for malignancy were included. Our meta-analysis included 14 articles composed of 755 patients with 757 soft tissue lesions. There were 451 (60 %) malignant tumors and 306 benign lesions. The (18)F-FDG PET/CT (and dedicated PET) mean sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for diagnosing MsSTL were 0.96 (0.90, 1.00), 0.77 (0.67, 0.86), 0.88 (0.85, 0.91), 0.86 (0.78, 0.94), and 0.91 (0.83, 0.99), respectively. The posterior mean (95 % highest posterior density interval) for the AUC was 0.92 (0.88, 0.96). PET/CT had higher specificity, accuracy, and positive predictive value when compared to a dedicated PET (0.85, 0.89, and 0.91 vs 0.71, 0.85, and 0.82, respectively). (18)F-FDG PET/CT and dedicated PET are both highly accurate in the diagnosis of MsSTL. PET/CT is more accurate and specific and has a higher positive predictive value than PET.


Early protein synthesis in activated human peripheral blood mononuclear cells.
Though B-cell division and Ig synthesis in response to pokeweed mitogen (PWM) require interaction with T-cells and monocytes, it is not clear which earlier events in B-cell activation share this requirement, and which are the result of direct interaction of mitogen with the B-cell. Having previously shown that the acceleration of lecithin synthesis in human B-cells at 16-20 hr requires both T-cells and monocytes, we now examine whether B-cells require similar interactions to increase their protein synthetic rate, another important activation event. At 21-24 hr of PWM stimulation, the stimulation index (SI) for incorporation of [35S]methionine into protein was 2.1 +/- 0.4 for unfractionated cells, 1.7 +/- 0.1 for B-cells, 2.5 +/- 0.1 for T-cells, and 3.4 +/- 0.5 for monocytes. Thus monocytes contributed substantially to early mitogen-induced protein synthesis by human peripheral blood mononuclear cells. When the monocyte/B-cell fraction (MB) and T-cell fraction (T) were mixed at various ratios in PWM-stimulated cultures, synergy was apparent at MB:T ratios of 1:1 and 1:2, indicating cell interactions augmented early mitogen-driven protein synthesis in at least one of these cell types. However, much or all of this synergy could be attributed to T-cells, whose protein synthetic response was augmented by B-cells and monocytes. In contrast, the early increase in B-cell protein synthesis appeared to be independent of cell interactions, since their SI of 1.7 was not influenced by varying the proportion of M- or T-cells over a 50-fold range. These contrasting results between two contemporary events fits the hypothesis that one (accelerated phospholipid synthesis) requires a first signal plus one or more cell interaction signals, whereas the other (accelerated protein synthesis) requires only the first signal.


[Severe epigastric pain in a 59-year-old patient].
Abdominal pain is a frequent cause of consultation to doctors' offices and emergency rooms. The most common differential diagnoses can be confirmed with readily available, cost-effective, and low-risk diagnostic tools such as laboratory tests, ultrasound, or gastroscopy. Additional diagnostic tests are required to exclude rare causes such as small, solid, or hematological malignancies, metabolic disorders, or polyneuropathies of varying origin. In the following, we present the case of a patient with severe epigastric pain due to neuroborreliosis, and recapitulate the diagnostic steps for clarifying abdominal pain using this example.


The natural history of epiphora in childhood.
To investigate the incidence and aetiology of epiphora in a population of 7-year-old children and determine whether a conservative management policy for congenital nasolacrimal duct obstruction (CNLDO) results in excess lacrimal dysfunction in later childhood. A postal questionnaire was sent to the parents of a large cohort of 7-year-old children previously investigated to determine the incidence and natural progression of CNLDO. They were asked about the presence of epiphora, and its relationship to atopic disease and the presence of upper respiratory tract infections (URTI). Information on epiphora had also been gathered from the same cohort at age 3 1/2 years at a routine examination. Data were compared with those for epiphora in infancy in the same cohort. The incidence of epiphora at 3 1/2 years was 5.5%, and 7 years 7.7%. At age 7 years 70% of cases were related to atopic disease or URTI. CNLDO was not significantly related to epiphora in later childhood (p = 0.000032). A policy of delaying nasolacrimal probing in CNLDO until after the age of 1 year does not result in a detectable excess of lacrimal dysfunction in later childhood, when epiphora is more likely to be related to atopic disease or upper respiratory tract infection.


Clinical and molecular characterization of the BRCA2 p.Asn3124Ile variant reveals substantial evidence for pathogenic significance.
Variants of uncertain clinical significance (VUS) in the high-penetrance breast cancer susceptibility genes BRCA1 and BRCA2 represent a major obstacle in genetic counseling of high-risk breast cancer families. We analyzed a missense VUS located in BRCA2 (p.Asn3124Ile; HGVS: BRCA2 c.9371A > T) present in seven independent high-risk breast cancer families that were counseled and genetically tested in South-West Germany. The VUS was identified by DNA sequencing. We analyzed co-occurrence with deleterious BRCA1/2 mutations, segregation, evolutionary conservation, in silico impact prediction, and prevalence in the general population. All carriers of the VUS suffered from breast or ovarian cancer. In two families, an additional high burden of other cancers such as pancreatic, prostate, and gastric cancers was reported, one further family included two cases of male breast cancer. The VUS did not co-occur with deleterious BRCA1/2 mutations and segregated in two affected individuals of one family. In contrast to the 7/1,347 (0,5 %) tested high-risk BC families without clearly pathogenic mutations in BRCA1/2, none of 3,126 healthy population controls sharing the same ethnic and geographical background were found to carry this VUS (p = 0.0002). In-silico prediction revealed strong evolutionary conservation of the asparagine residue, residing in the C-terminal oligonucleotide-binding-fold-3 region, and a most likely damaging impact of this exchange on the protein structure. The BRCA2 p.Asn3124Ile (BRCA2 c.9371A > T) variant is a rare mutation with a damaging effect on the BRCA2 protein that is strongly associated with familial breast and ovarian cancer risk, indicating its most likely pathogenic nature and clinical relevance.


The association of arterial blood pressure waveform-derived area duty cycle with intra-arrest hemodynamics and cardiac arrest outcomes.
Develop a novel, physiology-based measurement of duty cycle (Arterial Blood Pressure-Area Duty Cycle [ABP-ADC]) and evaluate the association of ABP-ADC with intra-arrest hemodynamics and patient outcomes. This was a secondary retrospective study of prospectively collected data from the ICU-RESUS trial (NCT02837497). Invasive arterial waveform data were used to derive ABP-ADC. The primary exposure was ABP-ADC group (<30%; 30-35%; >35%). The primary outcome was systolic blood pressure (sBP). Secondary outcomes included intra-arrest physiologic goals, CPR quality targets, and patient outcomes. In an exploratory analysis, adjusted splines and receiver operating characteristic (ROC) curves were used to determine an optimal ABP-ADC associated with improved hemodynamics and outcomes using a multivariable model. Of 1129 CPR events, 273 had evaluable arterial waveform data. Mean age is 2.9 years + 4.9 months. Mean ABP-ADC was 32.5% + 5.0%. In univariable analysis, higher ABP-ADC was associated with lower sBP (p < 0.01) and failing to achieve sBP targets (p < 0.01). Other intra-arrest physiologic parameters, quality metrics, and patient outcomes were similar across ABP-ADC groups. Using spline/ROC analysis and clinical judgement, the optimal ABP-ADC cut point was set at 33%. On multivariable analysis, sBP was significantly higher (point estimate 13.18 mmHg, CI95 5.30-21.07, p < 0.01) among patients with ABP-ADC < 33%. Other intra-arrest physiologic and patient outcomes were similar. In this multicenter cohort, a lower ABP-ADC was associated with higher sBPs during CPR. Although ABP-ADC was not associated with outcomes, further studies are needed to define the interactions between CPR mechanics and intra arrest patient physiology.


Vein occlusion by upper versus forearm tourniquets in humans.
To determine the optimal location for a tourniquet applied to the arm during cannulation of a hand vein. Experimental study. Operating room of a university hospital. 15 volunteers, 6 men and 9 women. A vein on the dorsum of the hand was cannulated and attached to a pressure transducer. A blood pressure cuff was applied to the forearm or upper arm and inflated in graded steps. Vein pressure was recorded when it became steady. Studies were carried out in random order with the cuff on both the forearm and upper arm of both arms of each subject. Vein pressure averaged 70% to 80% of cuff pressure and was higher when the cuff was located on the forearm at cuff pressures of 20 to 40 mmHg. Time to reach a steady pressure was longer with the cuff on the upper arm (average 109 +/- 58 s) than on the forearm (75 +/- 52 s; P < 0.005). A tourniquet on the forearm effectively distends hand veins and does so more quickly than a tourniquet on the upper arm.


Dewatering of phosphorus extracted from liquid swine waste.
Phosphorus (P) recovery from liquid swine manure is an attractive technology when on-farm application of liquid swine manure is not an option. We developed a technology that enables separation of this P, but its high moisture content makes transportation difficult. In this work, we investigated dewatering procedures to concentrate the P product. Sludge rich in calcium phosphate (> 20% P2O5) was obtained using a field prototype, and it was further dewatered using a combination of polymer treatment and filter bags. Anionic polyacrylamide polymer treatment (> or = 20 mg/L) was effective to flocculate the P-rich sludge, which enhanced filtration and dewatering. Without polymer, filtration was incomplete due to clogging of filters. Non-woven polypropylene and monofilament filter bag fabrics with mesh size < or = 200 microm retained > 99% of suspended solids and total P. Solids content dramatically increased from about 1.5% to > 90%. These dewatered solids can be transported more economically off the farm for use as a valuable fertilizer material.


Repeated automated assessment of abstinent male alcoholics: essential fatty acid supplementation and age effects.
A double-blind trial carried out with alcohol-dependent males randomly allocated to n-6 essential fatty acid (EFA) supplementation or placebo capsules over a 6-month period incorporated a battery of automated neuropsychological tests. Results from problem-solving and perceptual motor speed tests are used. The effect that EFA supplementation had on recovery over 6 months of abstinence is shown, as well as the tests in which younger (aged 20-39) alcohol-dependent males differ from the older (aged 40-59) subjects.


[Evaluation of vinyl chloride toxicity based on its metabolism].
Discussed in the paper are the processes of absorption, distribution and metabolization of vinyl chloride in the living organism. The latest views on the occurrence and excretion of vinyl chloride metabolites, possible indices of occupational exposure to this compound, have been presented.


Wastewater remediation of heavy metals and pesticides using rice straw and/or zeolite as bioadsorbents and assessment of treated wastewater reuse in the culture of Nile tilapia (Oreochromis niloticus).
The remediation of wastewater (WW) is a promising solution for limited water sources. This study aimed to evaluate rice straw (RS) and zeolite (Z) as bioadsorbents for the removal of pollutants, including heavy metals (HMs) (cadmium [Cd], nickel [Ni], and lead [Pb]) and malathion (PC), from WW and to assess the suitability of reusing remediated WW in fish rearing units. A total of 11 treatment groups with 3 replicates each were designed with different combinations of RS and/or Z for the treatment of real WW contaminated with HMs and malathion, where the WW remained in contact with the adsorbents for 24 h. Different remediated WWs were used for rearing Nile tilapia (Oreochromis niloticus), which were randomly allocated into 33 glass aquaria representing 11 treatments with 3 replicates each for 30 days. The best remediation efficiency was achieved using a mixture of whole RS (WRS), chopped RS (CRS), and Z (HM-PC-WRS-CRS-Z group), with removal percentages of 92%, 95%, 96%, and 99% for Cd, Ni, Pb, and malathion, respectively. The health status of the aquatic ecosystems was assessed through blood tests to characterize biochemical parameters and through pathological changes of cultured O. niloticus reared in treated WW. A significant (P ˂ 0.05) effect on the blood biochemistry of fish reared in treated WW was found and better biochemical and histologic architecture was observed than that of fish reared in untreated WW. A novel mixture of WRS, CRS, and Z could possibly be a promising low-cost adsorbent for wastewater treatment. Graphical abstract.


Paget's disease of bone: benefits of neridonate as a first treatment and in cases of relapse after clodronate.
This study assessed the efficacy of 200 mg of aminohexane bisphosphonate (neridronate) administered by intravenous infusion in a single dose or in two separate doses on consecutive days in 32 patients (16 males and 16 females, average age 66 years) affected by active Paget's disease of bone. Fifteen patients had never been treated with any antiresorptive agent and 17 had had unsatisfactory results from a prior clodronate treatment. All of the latter patients had failed to enter a remission stage (i.e., normalization of bone turnover was not reported at any time during treatment) and had had a full relapse within 6 months after clodronate infusion. In the present study bone-specific alkaline phosphatase (bAp), deoxypyridinoline (dPyr), and N- and C-terminal polypeptide of collagen type 1 (Ntx, Ctx) were determined before neridronate administration and at 1, 3, 6, and 12 months thereafter. Basal values of bAp were 51.7 +/- 2.3 microg/L, range 31.7-92.5 (normal range 6.2-23.6). No statistical differences in markers of bone turnover were evident in the basal state between new pagetic patients (bAp = 55.1 +/- 4.1) and those suffering a relapse after clodronate (bAp = 48.8 +/- 2.6). Neridronate induced an average percent change from baseline in excess bAp of 68.0 +/- 4.3 and in excess dPyr, Ntx, and Ctx of 68.1 +/- 11, 60.6 +/- 8.5, and 86.7 +/- 7.8, respectively. Markers of bone resorption declined more slowly in patients treated previously with clodronate, although the average change in percent decrement from baseline in excess bAp as well as in excess of bone resorption markers was not different from that registered in untreated pagetic patients. Response to treatment, defined as a percent decrement from baseline in excess bAp of 50% or more at any time during the 12-month follow-up, was observed in 27 patients (84.4%). Remission (a drop in bAp to within normal range) was achieved in 21 patients (65.6%) and was maintained in 12 at 12-month follow-up, with no significant differences between either 1- or 2-day infusions, or between new pagetic patients and those relapsing after clodronate. In 15 of 21 patients requiring analgesics to alleviate bone pain, pain was reduced or completely alleviated in 8. A slight, short-lived acute phase reaction (fever and/or arthromyalgia) occurred in 6 patients. To summarize, 200 mg of intravenous neridronate, in one or two doses, significantly reduced the biochemical indices of disease activity in the majority of patients, showing a normalization of bAp in more than 60%. We conclude that neridronate can be used safely in the treatment of patients with Paget's disease of bone either as a first bisphosphonate treatment or as retreatment for patients relapsing after clodronate.


Carbamazepine and carbamazepine-10,11-epoxide clearance measurements during continuous venovenous hemofiltration in a massive overdose.
Carbamazepine (CBZ) overdose can result in significant neurologic and cardiovascular toxicity, and is compounded by the presence of an active metabolite, carbamazepine-10,11-epoxide (CBZE). Existing publications describing continuous venovenous hemofiltration (CVVH) in CBZ overdose are limited in their ability to calculate accurate clearances. We report a case of CBZ overdose treated with CVVH with detailed measurement of CBZ, CBZE and their respective clearances calculated utilizing serial effluent measurements. This was coupled with serum level determinations comparing two analytical methodologies, time-of-flight mass spectroscopy and an immunoassay. A 41-year-old woman presented unresponsive after an overdose of CBZ. Initial CBZ serum levels were markedly elevated (57.8 μg/mL) and continued to rise. Due to continued hemodynamic instability, extracorporeal removal was initiated using CVVH. During the first 30 h of CVVH, interval serum samples and all ultrafiltrate bags were collected and analyzed. Serum and effluent levels of CBZ and CBZE were measured using an Agilent 6230 time-of-flight high-resolution mass spectrometer (TOF-MS). CBZ levels were also obtained utilizing the Microgenics CEDIA Carbamazepine Immunoassay (Thermo Fisher, Waltham, MA) for serum and effluent samples. Immunoassay analysis was performed using Siemens ADVIA 1800 instrument. The clearances achieved for CBZE (mean = 25.2, range 17.7-42.6 mL/min) exceeded that for CBZ (mean = 18.1, range 12.7-28.7 mL/min). CVVH removed a total of 1293 and 1261 mg of CBZ and CBZE, respectively. Serum levels of CBZ measured by immunoassay when compared with TOF-MS indicated cross reactivity of CBZE with the immunoassay. CVVH removed CBZE with higher clearances than CBZ. However, CVVH clearance rates for both CBZ and CBZE were lower than published clearances of CBZ and CBZE by intermittent hemodialysis. Our methodology allowed for a precise pharmacokinetic assessment of clearance based on total quantity of parent drug and active metabolite removed. Use of an immunoassay to determine CBZ serum levels reflects both parent compound and active metabolite due to cross-reactivity with CBZE.


Programmed cell death: Past, present and future.
It is known that all living organisms are mortal. For many decades, the main interest of researchers has been focused on the investigation of proliferation, differentiation and other fundamental cellular processes, completely ignoring the understanding of the mechanisms of cell elimination. Since the 60s-70s of the last century, a systematic study of cell death began, which is currently one of the most rapidly developing areas of biomedicine. Since this field of research is very wide, in these short notes we tried to discuss the hottest, but not all, topics that are of interest to many of our colleagues.


Longitudinal effects of SafeTalk, a motivational interviewing-based program to improve safer sex practices among people living with HIV/AIDS.
Programs to help people living with HIV/AIDS practice safer sex are needed to prevent transmission of HIV and other sexually transmitted infections. We sought to assess the impact of SafeTalk, a multicomponent motivational interviewing-based safer sex program, on HIV-infected patients' risky sexual behavior. We enrolled sexually active adult HIV-infected patients from one of three clinical sites in North Carolina and randomized them to receive the 4-session SafeTalk intervention versus a hearthealthy attention-control. There was no significant difference in the proportion of people having unprotected sex between the two arms at enrollment. SafeTalk significantly reduced the number of unprotected sex acts with at-risk partners from baseline, while in controls the number of unprotected sex acts increased. Motivational interviewing can provide an effective, flexible prevention intervention for a heterogeneous group of people living with HIV.


Olfactory performance during childhood. II. Developing a discrimination task for children.
(1) To create a match-to-sample odorant discrimination task (MODT) for children and adolescents; (2) to assess whether nonolfactory factors affect olfactory performance more on an identification task than on the MODT; (3) to evaluate subjects with olfactory dysfunction; and (4) to create age-appropriate sets of odorants for use in the MODT format to test children of different ages. We tested 75 normal children, aged 2 to 18 years, and 17 other subjects, aged 7 to 53 years, with known or suspected olfactory dysfunction, with the MODT. We compared the age trends in variability of scores on the MODT with those on an odorant identification task, using a weighted linear regression analysis. The MODT was useful in children aged 5 years and older, but not generally in the 2- to 4-year-old children. There was an appreciable age trend in the variability of the scores on the identification task but not on the MODT. Mean MODT scores for subjects with suspected or known olfactory dysfunction were far below average. Finally, we created four sets of odorants that will likely be sensitive to age-specific changes in olfactory performance. The MODT appears to be a suitable test instrument to assess olfaction in children aged 5 and older and is less likely to be influenced by nonolfactory factors than an identification task. According to our preliminary results, it is likely that the MODT will allow us to detect olfactory deficits in children of many ages.


Prestin, a new type of motor protein.
Prestin, a transmembrane protein found in the outer hair cells of the cochlea, represents a new type of molecular motor, which is likely to be of great interest to molecular cell biologists. In contrast to enzymatic-activity-based motors, prestin is a direct voltage-to-force converter, which uses cytoplasmic anions as extrinsic voltage sensors and can operate at microsecond rates. As prestin mediates changes in outer hair cell length in response to membrane potential variations, it might be responsible for sound amplification in the mammalian hearing organ.


Investigation of antitumor potential of Ni(II) complexes with tridentate PNO acylhydrazones of 2-(diphenylphosphino)benzaldehyde and monodentate pseudohalides.
Square-planar azido Ni(II) complex with condensation product of 2-(diphenylphosphino)benzaldehyde and Girard's T reagent was synthesized and its crystal structure was determined. Cytotoxic activity of the azido complex and previously synthesized isothiocyanato, cyanato and chlorido Ni(II) complexes with this ligand was examined on six tumor cell lines (HeLa, A549, K562, MDA-MB-453, MDA-MB-361 and LS-174) and two normal cell line (MRC-5 and BEAS-2B). All the investigated nickel(II) complexes were cytotoxic against all tumor cell lines. The newly synthesized azido complex showed selectivity to HeLa and A549 tumor cell lines compared to the normal cells (for A549 IC50 was similar to that of cisplatin). Azido complex interferes with cell cycle phase distribution of A549 and HeLa cells and possesses nuclease activity towards supercoiled DNA. The observed selectivity of the azido complex for some tumor cell lines can be connected with its strong DNA damaging activity.


Capillary reversed-phase high-performance liquid chromatographic determination of acetyl-methylprednisolone in feline spinal cord.
Capillary reversed-phase high-performance liquid chromatography (RP-HPLC) was used to determine acetylmethylprednisolone (A-MP) that had been administered to feline spinal cord tissue. The method used a 300 mm x 0.32 mm I.D. packed capillary octadecylsilyl (ODS) column and an isocratic mobile phase of 40 mM triethylamine formate (TEAF, pH 3.2)-acetonitrile (50:50, v:v). The chromatographic behavior of A-MP was evaluated with respect to peak-area and peak-height by varying the A-MP concentration (12-190 microM) with a fixed injection volume (1 microliter), and by varying the injection volume (1-10 microliter) with a fixed concentration (12 microM) of A-MP. The limit of detection (signal-to-noise ratio, 3:1) was 250 pg (600 fmol) of synthetic A-MP. Various amounts of A-MP directly spiked into feline spinal cord segments were solvent extracted, separated, and plotted against peak-area (r2 = 1.00). Background tissue without A-MP gives minimal (< 1%) interference at 243 nm. The method also detects exogenous A-MP that was administered into feline spinal cord via an intrathecal injection. Furthermore, the presence of A-MP was confirmed via its molecular ion and corresponding product ions that were obtained by fast-atom bombardment tandem mass spectrometry (FAB-MS-MS).


Long noncoding RNAs in regulating adipogenesis: new RNAs shed lights on obesity.
Long noncoding RNAs (lncRNAs) are an emerging class of regulators involved in a myriad of biological processes. Recent studies have revealed that many lncRNAs play pivotal roles in regulating adipocyte development. Due to the prevalence of obesity and the serious effects of adiposity on human health and society development, it is necessary to summarize functions and recent advances of lncRNAs in adipogenesis. In this review, we highlight functional lncRNAs contributed to the regulation of adipogenesis, discussing their potential use as therapeutic targets to combat human obesity.


Diffusion abnormalities in the corpus callosum in first episode schizophrenia: Associated with enlarged lateral ventricles and symptomatology.
Abnormalities in the corpus callosum (CC) and the lateral ventricles (LV) are hallmark features of schizophrenia. These abnormalities have been reported in chronic and in first episode schizophrenia (FESZ). Here we explore further associations between CC and LV in FESZ using diffusion tensor imaging (DTI). . Sixteen FESZ patients and 16 healthy controls (HC), matched on age, gender, and handedness participated in the study. Diffusion and structural imaging scans were acquired on a 3T GE Signa magnet. Volumetric measures for LV and DTI measures for five CC subdivisions were completed in both groups. In addition, two-tensor tractography, the latter corrected for free-water (FAt), was completed for CC. Correlations between LV and DTI measures of the CC were examined in both groups, while correlations between DTI and clinical measures were examined in only FESZ. Results from two-tensor tractography demonstrated decreased FAt and increased trace and radial diffusivity (RDt) in the five CC subdivisions in FESZ compared to HC. Central CC diffusion measures in FESZ were significantly correlated with volume of the LV, i.e., decreased FAt values were associated with larger LV volume, while increased RDt and trace values were associated with larger LV volume. In controls, correlations were also significant, but they were in the opposite direction from FESZ. In addition, decreased FAt in FESZ was associated with more positive symptoms. Partial volume corrected FAt, RDt, and trace abnormalities in the CC in FESZ suggest possible de- or dys-myelination, or changes in axonal diameters, all compatible with neurodevelopmental theories of schizophrenia. Correlational findings between the volume of LV and diffusion measures in FESZ reinforce the concept of a link between abnormalities in the LV and CC in early stages of schizophrenia and are also compatible with neurodevelopmental abnormalities in this population.


Effect of Protein Corona on the Specificity and Efficacy of Nanobioconjugates to Treat Intracellular Infections.
Encapsulating drugs into functionalized nanoparticles (NPs) is an alternative to reach the specific therapeutic target with lower doses. However, when the NPs are in contact with physiological media, proteins adsorb on their surfaces, forming a protein corona (PC) biomolecular layer, acquiring a distinct biological identity that alters their interactions with cells. Itraconazole (ITZ), an antifungal agent, is encapsulated into PEGylated and/or functionalized NPs with high specificity for macrophages. It is evaluated how the PC impacts their cell uptake and antifungal effect. The minimum inhibitory concentration and colony-forming unit assays demonstrate that encapsulated ITZ into poly(ethylene glycol) (PEG) NPs improves the antifungal effect compared with NPs lacking PEGylation. The improvement can be related to the synergistic effect of the encapsulated ITZ and NPs composition and the reduction of PC formation in PEG NPs. Functionalized NPs with anti-F4/80 and anti-MARCO antibodies, or mannose without PEG and treated with PC, show an improved uptake but, in the presence of PEG, significantly reduce the endocytosis, dominating the stealth effect from PEG. Therefore, the PC plays a crucial role in the nanosystem uptake and antifungal effects, which suggests the need for in vivo model studies to evaluate the effect of PC in the specificity and biodistribution.


Frequency of familial occurrence in 164 patients with allergic bronchopulmonary aspergillosis.
Asthma is known to run in families. Allergic bronchopulmonary aspergillosis (ABPA) occurs predominantly in patients with asthma. However, there are only 6 reports of familial occurrence over a period of 35 years. To determine the frequency of familial occurrence in 164 patients with ABPA diagnosed over a period of 22 years in one unit. The 164 patients with ABPA were reviewed for the occurrence of familial ABPA. Symptomatic family members were evaluated for the presence of ABPA as well as allergic Aspergillus sinusitis (AAS). Allergic bronchopulmonary aspergillosis and AAS were diagnosed as per criteria established. Of the 164 patients with ABPA, familial occurrence was detected in 4 pairs of first degree relatives, 2 of whom were parent-child while the other 2 were siblings. Familial ABPA was seen in 4.9% of the total patients. Of these 8 patients seven had symptoms of rhinitis while 4 had sinusitis confirmed on computed tomography of paranasal sinuses. Allergic Aspergillus sinusitis was detected in 3 of these 4 patients. The fourth patient with sinusitis did not consent to surgery required to confirm the diagnosis. Five of our 8 patients, prior to referral, had received antituberculous therapy. All patients responded favourably to oral prednisolone. Familial occurrence was documented in 4.9% of the 164 patients with ABPA.


Post-transplant food allergy in children is associated with liver and not with renal transplantation: a monocentric comparative study.
Food allergy is increasingly reported after paediatric liver transplantation. The underlying physiopathological mechanism remains incompletely understood. Therefore, we aimed to determine the incidence, clinical presentation, possible risk factors, and prognosis of post-transplant food allergy in children currently followed after liver and renal transplantation. The study population consists of 49 liver and 21 renal transplant patients transplanted between the age of 22 months and 15 years. Data were collected retrospectively from medical records and via a doctor's questionnaire taken from the parents in a monocentric setting. Post-transplant food allergy has developed in 13 liver transplant patients and in none of the renal transplant recipients. Within the liver transplant group, median age at liver transplantation is significantly lower in the food-allergic (10 months) versus non-food-allergic group (3.3 years; p = 0.002). The use of tacrolimus as primary maintenance immunosuppression is associated with food allergy (p = 0.032) and mean donor age is significantly lower in the food-allergic group (p = 0.009). Compared to the renal transplant group, median age at transplantation is significantly lower in the liver patients (p < 0.001). No significant differences are found in primary immunosuppressive regimens between renal and liver transplant patients. Post-transplant food allergy is an important clinical problem in children after liver transplantation which does not affect renal transplant patients despite similar immunosuppressive regimens. Within the group of liver transplant recipients, tacrolimus use, young age at time of transplant and younger donor age were associated with the development of food allergy.


Effects of near-infra-red laser irradiation on adenosine triphosphate and adenosine diphosphate contents of rat brain tissue.
Low-power, near-infra-red laser irradiation has been used to relieve patients from various kinds of pain, though the precise mechanisms of such biological actions of the laser have not yet been resolved. To investigate the cellular mechanisms by near-infra-red laser on the nervous system, we examined the effect of 830-nm laser irradiation on the energy metabolism of the rat brain. The diode laser was applied for 15 min with an irradiance of 4.8 W/cm(2). Tissue adenosine triphosphate (ATP) content of the irradiated area in the cerebral cortex was 19% higher than that of the non-treated area, whereas the adenosine diphosphate (ADP) content showed no significant difference. Laser irradiation at another wavelength (652 nm) had no effect on either ATP or ADP contents. The temperature of the tissue was increased by 4.4-4.7 degrees C during the irradiation of both wavelengths. These results suggest that the increase in tissue ATP content did not result from the thermal effect, but from a specific effect of the laser operated at the 830-nm wavelength.


Effects on tyrosinase activity by the extracts of Ganoderma lucidum and related mushrooms.
The inhibitory effects on tyrosinase activity by extracts of several mushrooms belonging to Basidiomycetes were evaluated. Among the tested mushrooms (Ganoderma lucidum, Antrodia camphorata, Agaricus brasiliensis, and Cordyceps militaris), G. lucidum exhibited significant inhibition of tyrosinase activity (IC(50) value 0.32 mg/ml), compared to those prepared from other Basidiomycetes. Tyrosinase inhibitors are effective components of skin-lightening compounds and other cosmetics; currently many of the facial mask cosmetics in the market contain Ganoderma extracts in their ingredients. The finding that mushroom extracts contain tyrosinase activity inhibition will contribute to better understanding of how their 'healing' properties in various Chinese traditional herbal on skin care products.


Functional responses to multiple sequential abiotic stress (waterlogging-drought) in three woody taxa with different root systems and stress tolerance.
There is generally a trade-off in the resistance to drought and to waterlogging. However, several species are sequentially subjected to both stressors in many environments. We evaluated the ecophysiological strategies to cope with multiple sequential stress of waterlogging and drought (W + D) of three taxa differing in stress resistance and root morphology: the phreatophic Eucalyptus camaldulensis (Ec) and two shallow-rooted willow clones: Salix matsudana x Salix alba (SmxSa) and Salix nigra (Sn4). Individuals of the three taxa were grown in pots and assigned to either of four treatments: Control (well-watered plants), well-watered followed by drought (C + D); waterlogged for 15 days followed by drought (W15d + D) and waterlogged for 30 days followed by drought (W30d + D). Biomass allocation, growth (diameter, height, length of leaves, and roots), specific leaf area, stomatal conductance, water potential, hydraulic conductivity of roots and branches, leaf C13 and root cortical aerenchyma formation were determined at different stages of the experiment. Ec growth was not affected by W + D, developing tolerance strategies at leaf and whole plant levels. Differential effects of W + D were observed in both Salix clones depending on the time of waterlogging. In Sn4 and SmxSa, the root biomass was affected in W15d + D treatment, but a root tolerance response (aerenchyma and adventitious root formation) was observed in W30d + D. In the three taxa, and contrary to expectations, the previous exposure to a waterlogging period did not increase the susceptibility of the plants to a subsequent drought event. On the contrary, we found tolerance, which depended on the time of waterlogging exposure.


Different chromosomal localization of the Clcn4 gene in Mus spretus and C57BL/6J mice.
We report the unprecedented finding of a gene with a different map position in two mouse strains. The Clcn4 gene was found to map to the X chromosome in the wild Mediterrean mouse, Mus spretus but to chromosome 7 in the inbred strain of laboratory mouse C57BL/6J. These data indicate that a recent evolutionary rearrangement occurred on the mouse sex chromosomes, very close to the pseudoautosomal region. Our data provide molecular evidence for a major divergence near the pseudoautosomal region, consistent with the hypothesis that hybrid sterility in these species results from abnormal pairing of sex chromosomes during male meiosis.


Ankle arthrodesis and tibial lengthening for congenital sensory neuropathy with anhidrosis.
This report describes a patient with congenital sensory neuropathy with anhidrosis (CSNA) with destructive arthropathy of the left ankle joint that was treated with ankle arthrodesis and tibial lengthening, using an Ilizarov external fixator. The fusion at the ankle joint was successful, but, at the lengthening site, loosening of the apparatus occurred and formation and maturation of the distracted callus were delayed. Intramedullary nailing was used after the removal of the external fixator, and a low-intensity ultrasound device was employed, after which the distracted callus matured gradually. During the maturation period, the patient's dysplastic right hip joint was destroyed, without the occurrence of any severe symptoms. Distraction osteogenesis in patients with CSNA may lead to good results if rigid fixation, nonweight-bearing (i.e., adequate rest), and appropriate biological stimulation can be employed.


Eosinophilic pancreatitis with serum IgG4-positivity, potentially associated with autoimmune pancreatitis.
A 70-year-old man presented with unprovoked weight loss and intermittent left upper quadrant tenderness for one-and-a-half month. Computed tomography revealed irregular cystic lesions in the pancreatic tail. Endoscopic ultrasonography (EUS) revealed pancreatic tail enlargement and giant, thick-walled cysts surrounding the pancreatic tail with no connection with the pancreatic duct. Endoscopic ultrasonography-guided fine-needle aspiration was performed on the enlarged pancreatic parenchyma and thickened cyst wall. Both biopsies showed hyper eosinophilia and few plasma cells. Endoscopic retrograde pancreatography revealed an irregular narrowing of the main pancreatic duct. Pancreatic juice cytology revealed substantial eosinophilia. Blood sampling showed an elevated eosinophil count and immunoglobulin G4 (IgG4) and immunoglobulin E (IgE) levels at the initial examination. We considered the patient to have eosinophilic pancreatitis (EP) with autoimmune pancreatitis, or alternately, EP with IgG4-related retroperitoneal fibrosis (RPF). Upon prednisolone administration, the abdominal pain improved, the peripheral blood eosinophil count decreased to zero, IgG4 and IgE levels decreased, pancreatic enlargement improved, and the cystic lesions disappeared. The condition did not recur within the following 3 years. Both EP and EP with IgG4-related RPF are rare etiologies of pancreatitis, and this case is very instructive.


Efficacy of silver-coated medical devices.
Silver coating of medical devices is believed to prevent device-associated infection. Several in-vitro and in-vivo studies, as well as clinical observations on silver-nylon, silver-intramedullary pins, silver oxide Foley catheters and silver-coated vascular prostheses have been performed during the past 30 years. Nevertheless, randomized clinical studies showing efficacy of such coated medical devices in high-risk patient populations are rare, have dealt with very small numbers of patients or are controversial. Physico-chemical, pharmacological and microbiological data explaining the antimicrobial efficacy of silver in prophylaxis of implants are presented here, as well as the scientific background for the established clinical benefits of silver-preparations in burns.


Mechanosensitivity of spinal accessory lobe neurons in the pigeon.
In the avian lumbosacral spinal cord there are segmentally organized accessory lobes which protrude into the vertebral canal. These lobes consist of neurons and of glycogen cells. The neurons have been suggested to function as mechanosensitive elements in an extra-labyrinthine sense organ of equilibrium. To test this view, extracellular electrophysiological recordings were done during vibratory stimuli applied to the whole body of anesthetized pigeons. Single unit activity was analyzed with regard to interval distribution (interval histograms) and entrainment to the frequency of the stimulus (autocorrelograms). Most neurons were driven by a 100 or 75 Hz stimulus and there was a tight coupling to the phase of the stimulus. Neurons in the adjacent spinal gray substance did not respond to this stimulus. This strongly supports a mechanosensitive function of the lobe neurons.


Probing whole cell currents in high-frequency electrical fields: identification of thermal effects.
An open-end coaxial probe is combined with a planar patch-clamp system to apply electric fields with GHz frequencies during conventional patch-clamp measurements. The combination of pulsed microwave irradiation and lock-in detection allows for the separation of fast and slow effects and hence facilitates the identification of thermal effects. The setup and the influence of radiation on the patch-clamp current are thoroughly characterized. For the independent optical verification of heating effects, a temperature microscopy technique is applied with high spatial, temporal and temperature resolution. It is shown that the effect of radiation at GHz frequencies on whole cell currents is predominantly thermal in nature in the case of RBL cells with an endogenous K(ir) 2.1 channel.


Specifics of Experimental Modeling 8-OH-DPAT-Induced Perseverative Behavior in Mice.
The effect of 5-HT1A receptor agonist 8-OH-DPAT (intraperitoneal injection in doses of 1, 2, and 4 mg/kg) on spontaneous alternation behavior of mice in Y-maze was studied without and with habituation procedure and food reward. In the first case, 8-OH-DPAT administration led to a decrease in spontaneous alternation and locomotor activity in mice. At the same time, 8-OH-DPAT treatment after habituation and food deprivation increased repeated choices of goal arms without affecting locomotor activity, which was consistent with perseverative behavior. 8-OH-DPAT-induced decrease in spontaneous alternation behavior in Y-maze in mice with habituation and food reward is the most suitable procedure for experimental modeling of the perseverative behavior and studying the anticompulsive activity of new substances.


Loss of immunoreactivity for human calmodulin-like protein is an early event in breast cancer development.
Cell proliferation requires calmodulin, a protein that regulates calcium-dependent enzymes involved in signal transduction pathways in eukaryotic cells. Calmodulin-like protein (CLP) is found in certain epithelial cell types, including normal breast epithelium, and, although it closely resembles calmodulin in amino acid sequence, CLP interacts with different proteins than does calmodulin. The observation that CLP mRNA expression is dramatically reduced in transformed breast epithelial cells led to two hypotheses: (1) CLP helps to maintain the differentiated state in epithelial cells; and (2) downregulation of CLP accompanies malignant transformation of breast epithelial cells. The objective of this study was to determine if the expression of CLP in human breast cancer specimens is reduced in comparison to its expression in normal breast tissue. Eighty human breast cancer biopsy specimens were analyzed immunohistochemically for CLP expression by using a polyclonal rabbit antihuman CLP antibody. CLP expression was reduced in 79% to 88% of the invasive ductal carcinoma and lobular carcinoma specimens and in a similar fraction of the ductal carcinoma in-situ specimens, compared with normal breast specimens. None of the breast cancer specimens showed an increase in CLP expression. These findings support the hypotheses that CLP behaves as a functional tumor suppressor protein and is downregulated early in breast cancer progression.


Acalculous Cholecystitis in a Seven-Year-Old Girl With Epstein-Barr Virus Infection.
Epstein-Barr virus (EBV) infection with associated acute acalculous cholecystitis (AAC) has been reported in 18 pediatric patients. Our case is that of a seven-year-old girl with acute EBV infection and associated AAC.


The role of various biomarkers in the evaluation of styrene genotoxicity.
We evaluated our data on the occupational exposure to styrene in lamination workers. The battery of parameters included markers of external and internal exposure and biomarkers of biological effects and susceptibility. DNA repair capacities have been determined in both exposed and control groups. Styrene workplace concentration significantly correlated with styrene concentration in blood, exhaled air and urinary mandelic acid. Haemoglobin and O(6)-styrene oxide (SO)-guanine DNA adducts were significantly higher in exposed subjects as compared to controls and correlated with exposure parameters. In styrene-exposed workers 1-SO-adenine DNA adducts were detected (2.6 per 10(9) dNp), while in controls these adducts were below the detection limit. 1-SO-adenine adduct levels were affected by both acute and cumulative exposure (P=0.001, F=86.0 and P=0.017, F=59.0, respectively) and associated with cytochrome P450 2E1 (CYP2E1) polymorphisms (R(2)=0.442). Mutant frequencies (MF) at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus appeared to accumulate with exposure over time and were associated with glutathione S-transferase P1 (GSTP1) polymorphism. DNA repair capacity increased with the exposure, except for the group exposed to the highest styrene concentration. In this particular group, increased DNA repair capacity to remove oxidative DNA damage was found.


Heating infiltration solutions used in tumescent liposuction: minimizing surgical risk.
Liposuction, one of the most common operations performed by plastic surgeons, is not free of complications. One of the most common factors is patient hypothermia, a factor little studied but one capable of producing severe arrhythmias and cardiac arrest. A comparative clinical study was conducted to determine what effect using tumescent infiltration solutions at room temperature and at body temperature has on vital signs. Two similar groups of 15 healthy female subjects were studied. In the first group (group A), subcutaneous solutions were infiltrated at room temperature (24 degrees C), and in the second group (group B), solutions were infiltrated at body temperature (37 degrees C). Vital signs (i.e., heart rate, respiratory rate, temperature, and blood pressure) were monitored every 15 minutes until the basal vital signs were attained. Variables such as age, body mass index, infiltrated and aspirated liquids, and surgery time were very similar for both groups. Although there were differences in heart rate, respiratory rate, and arterial pressure, they were not statistically significant. Nevertheless, the differences between groups A and B for body temperature (34.9 +/- 1.1 degrees C versus 35.7 +/- 1.3 degrees C, respectively) and for the time necessary to attain basal vital signs (120 +/- 8 minutes versus 69 +/- 4 minutes, respectively) were statistically significant (p < 0.05). Despite the existence of a significant change in the body temperature in healthy female subjects during manipulation of the temperature of the infiltration solution, this change had no important effect on the intraoperative hemodynamic values. Nevertheless, it could have a more significant effect on patients with greater surgical risk.


Squamous cell carcinoma of the buccal mucosa: analysis of prognostic factors.
Although the TNM system is the accepted standard for head and neck tumor classification, there are often discrepancies between tumor size and survival. This retrospective analysis of 89 patients with squamous cell carcinoma of the buccal mucosa was carried out to evaluate tumor thickness and depth of invasion as prognostic variables and to compare them to the standard parameters. Recurrence rates increased with tumor size, clinical stage, thickness, and depth of invasion. In univariate analysis, sex, clinical stage, thickness, and depth of invasion were significantly related to survival (p less than 0.10). Multivariate analysis revealed that only thickness was an independent variable (p less than 0.0001). Patients with tumors less than 6 mm in thickness had a significantly better survival rate compared with those patients with tumors greater than 6 mm in thickness, regardless of the tumor stage. Measurement of tumor thickness should be included in estimating prognosis, planning therapy, and comparing results in patients with squamous cell carcinoma of the buccal mucosa.


Sporadic endolymphatic sac tumor: its clinical, radiological, and histological features, management, and follow-up.
Sporadic endolymphatic sac tumor (ELST) is rare. We described the clinical, radiological, and histological features, treatment, and follow-up of ELST. This was a retrospective analysis of 7 cases of sporadic ELST that were managed between 1993 and 2010. Twenty-five to 75 years was the age range of the patients. Subjective hearing loss and tinnitus were the most common presenting features. Five patients had total deafness and 2 had severe sensorineural hearing loss. The most common radiological feature was temporal bone destruction with tumor extension to cerebellopontine angle and posterior cranial fossa. Cholesterol or hemosiderin cysts around the tumor could be a characteristic feature. Major skull base procedures were performed in all 7 cases, and complete tumor excision was achieved in 6 of them. One patient needed a second surgery after she was referred to us after an incomplete first surgery. Recurrences were detected in 2 patients during follow-up; 1 of them received irradiation without minimal change to the tumor size and the second refused any treatment for the recurrence. Both of them are alive with disease. Early detection and radical surgical excision at first attempt give best results. Radiotherapy could be considered only in unresectable recurrences.


Development of de novo prolapse in untreated vaginal compartments after prolapse repair with and without mesh: a secondary analysis of a randomised controlled trial.
To compare the de novo prolapse rate in the untreated vaginal compartments following conventional vaginal prolapse repair and tension-free vaginal mesh repair. Secondary analysis of a randomised controlled trial. Thirteen centres in the Netherlands. Women with recurrent pelvic organ prolapse stage II or higher. Random assignment to either conventional vaginal native tissue repair or vaginal mesh insertion. de novo pelvic organ prolapse stage II or higher in the untreated vaginal compartments at 12 months after surgery. de novo pelvic organ prolapse at and beyond the hymen, de novo prolapse beyond the hymen and prolapse domain scores of the Urogenital Distress Inventory. At 12 months ten of 59 women (17%) in the conventional group versus 29 of 62 women (47%) in the mesh group were diagnosed with a de novo pelvic organ prolapse stage II or higher in the untreated compartment (P < 0.001, odds ratio 4.3, 95% confidence interval 1.9-10.0). Additional apical support to a mesh-augmented anterior repair significantly reduced the de novo prolapse rate. Women with a de novo prolapse in the mesh-treated group demonstrated significantly higher mean bother scores on the domain genital prolapse of the Urogenital Distress Inventory score (13.1 ± 24.2) compared with those without de novo prolapse (2.9 ± 13.9) (P = 0.03). Mesh-augmented prolapse repair in only one vaginal compartment is associated with a higher de novo prolapse rate in the untreated compartments compared with conventional vaginal native tissue repair in women with recurrent pelvic organ prolapse.


Temporal relation between blood pressure and serum creatinine in young adults from a biracial community: the Bogalusa Heart Study.
It is well recognized that end-stage renal disease (ESRD) is associated with accelerated and malignant hypertension. The association of renal disease and what is considered as normal blood pressure is still not clear. The present study examined the temporal relation between blood pressure and renal function reflected by serum creatinine in a biracial (black-white) community-based population enrolled in the Bogalusa Heart Study. The study included 662 young adults aged 19 to 32 years, (white men, n = 188; white women, n = 289; black men, n = 67; and black women, n = 118) who were followed for an average of 7.4 years. In black men, partial correlation adjusted for age, body mass index, serum glucose, uric acid, and cigarette smoking showed that baseline systolic and diastolic blood pressure are not significantly related to baseline serum creatinine, but significantly related to serum creatinine at follow-up (r = 0.38, P = .008 and r = 0.42, P = .003, respectively). Multivariate regression analysis further showed a significant prediction of serum creatinine at follow-up by baseline systolic and diastolic blood pressure (0.031 mg/dL and 0.037 mg/dL rise in follow-up serum creatinine for every 10 mm Hg increase in systolic (P = .000) and diastolic (P = .001) blood pressure at baseline, but not the other way around. Other race and sex groups did not show such significant temporal relations. We conclude that in young black men, higher blood pressure levels within normal range precede and explain part of the increase in serum creatinine, a measure of decline in renal function. Thus, our results underscore the beneficial effect of maintaining blood pressure levels lower than what is considered as the upper normal limit, particularly in black men.


An Updated Meta-Analysis on the Clinical Outcomes of Percutaneous Left Atrial Appendage Closure Versus Direct Oral Anticoagulation in Patients With Atrial Fibrillation.
The availability of direct oral anticoagulants (DOACs) with known lower bleeding risk compared with warfarin have raised questions about the role of left atrial appendage closure (LAAC). We aimed to perform a meta-analysis to compare the clinical outcomes for LAAC versus DOACs. All studies directly comparing LAAC with DOACs up to January 2023 were included. The outcomes studied included the combined major adverse cardiovascular (CV) events outcomes, ischemic stroke and thromboembolic events, major bleeding, CV mortality, and all-cause mortality. Hazard ratios (HRs) and their 95% confidence interval were extracted or estimated from the data and pooled together with a random-effects model. A total of 7 studies (1 randomized controlled trial, 6 propensity-matched observational studies) were finally included, with a pooled population of 4,383 patients who underwent LAAC and 4,554 patients on DOACs. There were no significant differences between patients who underwent LAAC and patients on DOACs in terms of baseline age (75.0 vs 74.7, p = 0.27), CHA2DS2-VASc score (5.1 vs 5.1, p = 0.33), or HAS-BLED score (3.3 vs 3.3, p = 0.36). After a mean weighted follow-up of 22.0 months, LAAC was associated with significantly lower rates of combined major adverse CV event outcomes (HR 0.73 [0.56 to 0.95], p = 0.02), all-cause mortality (HR 0.68 [0.54 to 0.86], p = 0.02), and CV mortality (HR 0.55 [0.41 to 0.72], p<0.01). There were no significant differences in the rates of ischemic stroke or systemic embolism (HR 1.12 [0.92 to 1.35], p = 0.25), major bleeding (HR 0.94 [0.67 to 1.32], p = 0.71), or hemorrhagic stroke (HR 1.07 [0.74 to 1.54], p = 0.74) between LAAC and DOAC. In conclusion, percutaneous LAAC was found to be as efficacious as DOACs for stroke prevention, with lower all-cause and CV mortality. The rates of major bleeding and hemorrhagic stroke were similar. LAAC has a potential role to play in stroke prevention in patients with atrial fibrillation in the era of DOACs, but further randomized data are needed.


Multiple comedonal papule of the nose.
Two unique patients are described with a smooth papule on the nose containing comedones and being preceded by trauma.


Inhibition of Cdk5 increases osteoblast differentiation and bone mass and improves fracture healing.
Identification of regulators of osteoblastogenesis that can be pharmacologically targeted is a major goal in combating osteoporosis, a common disease of the elderly population. Here, unbiased kinome RNAi screening in primary murine osteoblasts identified cyclin-dependent kinase 5 (Cdk5) as a suppressor of osteoblast differentiation in both murine and human preosteoblastic cells. Cdk5 knockdown by siRNA, genetic deletion using the Cre-loxP system, or inhibition with the small molecule roscovitine enhanced osteoblastogenesis in vitro. Roscovitine treatment significantly enhanced bone mass by increasing osteoblastogenesis and improved fracture healing in mice. Mechanistically, downregulation of Cdk5 expression increased Erk phosphorylation, resulting in enhanced osteoblast-specific gene expression. Notably, simultaneous Cdk5 and Erk depletion abrogated the osteoblastogenesis conferred by Cdk5 depletion alone, suggesting that Cdk5 regulates osteoblast differentiation through MAPK pathway modulation. We conclude that Cdk5 is a potential therapeutic target to treat osteoporosis and improve fracture healing.


Pharmacokinetics of 10B-p-boronophenylalanine (BPA) in the blood and tumors in human patients: A critical review with special reference to tumor-to-blood (T/B) ratios using resected tumor samples.
We reviewed 10B concentration kinetics in the blood and tumors in human patients administered with BPA. The 10B concentration in the blood peaked at the end of intravenous infusion of BPA, followed by a biphasic-decreasing curve with half-lives for the first and second components of the curve being 0.7-3.7 and 7.2-12.0 h, respectively. The mean tumor-to-blood (T/B) ratio obtained from resected tumor samples was 3.40 ± 0.83 for melanoma and the ratio ranged from 1.4 to 4.7 for glioblastoma.


The advent of clinical standards for professional liability.
The development of clinically based written standards to reduce the frequency and severity of medical malpractice loss appears to be gaining in popularity among provider specialty groups and professional liability underwriters. To date, such standards have addressed problems in specialties such as obstetrics and anesthesia where dollar losses associated with malpractice claims have been high. Guidelines can be developed and used by providers on a purely voluntary basis or mandated on an involuntary basis by third parties such as malpractice insurance companies or legislators. Because the advent of risk-control standards is a relatively new phenomenon, formal scientific studies on the long-term benefits of such guidelines have not yet been published. However, it appears that sharp reductions of malpractice losses in specialties such as anesthesia have coincided with the implementation of formal written standards specifically designed for liability control. This has led some liability insurance carriers to decrease premiums associated with specialists following such standards. Many providers are understandably concerned about the potential use of written standards by plaintiff attorneys in medical malpractice suits. Although it is possible that such policies and guidelines could be admitted into evidence to show that a provider breached the legal duty or standard of care owed to a patient, it is uncertain whether these risk-control standards could ultimately pass the evidentiary rules of relevancy or materiality in a given lawsuit. It is clear, however, that the consensus-based process of creating clinical standards and guidelines specifically for controlling professional liability losses is itself a powerful and emerging standard for health care risk management programs.


Stability of the nonlinear dynamics of an optically injected VCSEL.
Automated protocols have been developed to characterize time series data in terms of stability. These techniques are applied to the output power time series of an optically injected vertical cavity surface emitting laser (VCSEL) subject to varying injection strength and optical frequency detuning between master and slave lasers. Dynamic maps, generated from high resolution, computer controlled experiments, identify regions of dynamic instability in the parameter space.


Base specificity in the binding of benzo[a]pyrene diol epoxide to simian virus 40 DNA.
[14C]Simian virus 40 (SV40) DNA was reacted with [3H]7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene to give 0.60 adducts per genome. The modified DNA was digested to completion with Hind III restriction endonuclease and the 6 fragments isolated by polyacrylamide gel electrophoresis. Hydrocarbon binding to the fragments was proportional to their guanine--cytosine (G--C) content, reflecting selective reaction of the hydrocarbon with deoxyguanosine residues. No sites unusually susceptible to alkylation were detected.


Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB(1) and CB(2) receptor binding.
The N-1 alkyl side chain of the aminoalkylindole analogues (AAI) has been implicated as one of a three-point interaction with the cannabinoid CB(1) receptor. In this study, the morpholinoethyl of WIN 55,212-2 was replaced with carbon chains of varying lengths ranging from a methyl to heptyl group. Additional groups were added to the naphthoyl and the C2 positions of the molecule. These structural changes revealed that high affinity binding to the CB(1) and CB(2) receptors requires an alkyl chain length of at least three carbons with optimum binding to both receptors occurring with a five carbon side chain. An alkyl chain of 3-6 carbons is sufficient for high affinity binding; however, extension of the chain to a heptyl group results in a dramatic decrease in binding at both receptors. The unique structure of the cannabimimetic indoles provides a useful tool to define the ligand-receptor interaction at both cannabinoid receptors and to refine proposed pharmacophore models.


Re-evaluation of histological findings after colocystoplasty and gastrocystoplasty.
The potential of malignant transformation and its risk factors after bladder augmentation performed in childhood are still unknown. The necessity of surveillance cystoscopies and biopsies has been questioned in the past decade. In a previous study, the authors did not detect any malignancy after colocystoplasty (CCP) or gastrocystoplasty (GCP) during the short-term follow-up, however, various alterations of the mucosa were found. A correlation between the nature of histological changes and the frequency of bacterial colonization after CCP were also found. The authors hypothesized that a longer-term follow-up of their patients would reveal an increase in pathological change or show stronger association between the histological alteration, bacterial colonization, and/or stone formation. Thirty-five patients (20 cases of colocystoplasties - CCPs; 15 cases of gastrocystoplasties - GCPs) participated in the study published in 2002. All patients were followed biannually with endoscopic assessment and biopsies. Two independent pathologists, evaluated regular biopsies from the native bladder, from the segment used for augmentation and from the anastomosis line. Etiology, frequency of positive urine cultures, and stone events were recorded and compared with histological findings between groups and with the previously published results. Continuous surveillance allowed the follow-up of 30 patients (CCP 19/20, GCP 11/15) for 20 and 15 years. No malignancies were identified. Results of biopsies showed significant difference between groups (summarized in the tables). Chronic inflammatory changes were found following both types of augmentations, but they were more common in the urothelium following GCP and more common in the colonic mucosa following CCP. The rate of metaplastic lesions was higher after gastrocystoplasty (GCP). Significant association was found between the etiologic factor and the nature of histological change after CCP, as metaplastic lesions occurred only in patients with bladder exstrophy. Stones occurred more frequently in exstrophy patients as well. The nature of the histological changes did not correlate with positive urine cultures in either of the groups. Significantly higher incidence of bacterial colonization and stone occurrence were found after CCP. Long-term follow-up of the patients failed to reveal an increase in pathological changes, and no malignancies were observed. According to the results of this study, etiology of bladder dysfunction and the type of augmentation might influence the histological alterations after augmentation cystoplasty. The efficiency of surveillance cystoscopies and biopsies are low. The present data suggest that surveillance cystoscopy and biopsy should not be routinely performed, and should be done only if the symptoms are suspicious for malignancy.


Tropical shrimp aquaculture farms harbour pathogenic Vibrio parahaemolyticus with high genetic diversity and Carbapenam resistance.
In characterization of food borne pathogens from the environment, assessment of virulence, genetic diversity and AMR are essential preludes to formulate preventive strategies and to combat the spread. This study aimed to identify and characterize pathogenic Vibrio parahaemolyticus in the coastal aquaculture farms of Kerala, India. Twenty-seven β-haemolytic V. parahaemolyticus were isolated from 7 out of 40 farms studied. Among the 27 isolates, 15 possessed the tdh gene and 4 had trh. ERIC PCR and PFGE illustrated the presence of pathogenic isolates that shared genetic similarity with clinical strains. One pathogenic isolate was identified to be multidrug resistant (MDR) and 59% exhibited a MAR index of 0.2 or above. Seventy four percent of the pathogenic isolates were ESBL producers and 3.7% of them were carbapenemase producers phenotypically. This asks for adoption of control measures during farming to prevent the transmission of pathogenic V. parahaemolyticus to the environment and food chain.


[Early motherhood: sociodemographic profiles of 220 teenage mothers in Seine-Saint-Denis].
As part of teenage pregnancies, it is often found vulnerability and pregnancy follow-up of poorer quality. This investigation aims to establish profiles of young women and to assess what followed. A retrospective study (2007-2011) of 220 births to women aged 12 to 17. The monitoring of these teenage pregnancies remains generally lower than France national averages, but significant differences are observed when one takes into account the socio-demographic factors. Three profiles appear: 66 teenagers (group A) reported a chaotic pregnancy monitoring, with a poorly enquired social, professional, familial situation. One hundred and two teenagers (group B) have a better follow-up but pregnancy is often unwanted with an unstable social situation. Finally, 52 teenagers (group C) have a rather good quality monitoring with a more assertive investment of pregnancy. To consider the lives of these young women is essential to study early motherhood and mitigate the vulnerabilities of this fragile population. An identification of factors favoring an optimal monitoring of pregnancy among young women is paralleled with reduced obstetric and social risks.


A risk assessment approach to use of antimicrobials in the home to prevent spread of infection.
Home and everyday life hygiene is a key part of the public health strategy to reduce infectious disease, but an effective code of practice is required. This short review summarizes the basic scientific principles of a risk-based approach to home hygiene where hygiene procedures are applied at critical points at appropriate times. It suggests that, although detergent-based cleaning can be used to break the chain of infection, in some cases an antimicrobial agent is required.


Granular epithelial keratopathy as an unusual manifestation of Pseudomonas keratitis associated with extended-wear soft contact lenses.
We describe four patients who, using extended-wear soft contact lenses for myopia, abruptly developed ocular irritation and injection associated with elevated granular opacities initially confined to the central corneal epithelium. Cultures of the granular epithelial lesions were positive for Pseudomonas aeruginosa in all patients. Cultures of the contact lenses and lens case solutions grew Pseudomonas species and other gram-negative organisms. All patients responded to discontinuation of lens wear and frequent topical antibiotics. All recovered baseline visual acuity, and three have successfully resumed contact lens wear. These cases document that Pseudomonas keratitis may be manifested as a granular epithelial keratopathy.


Assessment of a four hour delay for urine samples stored without preservatives at room temperature for urinalysis.
To determine whether urine storage at room temperature for up to 2h versus 4h changes urinalysis results. We compared the rejection rate at eight different hospital laboratories and concordance of urinalysis results (n=83; two laboratories) between urines analyzed within 2h and 4h after collection. The rejection rate at the two hour cutoff was significantly higher as compared to the four hour cutoff. The concordance between urinalysis results was 97-100% between the two and four hour analyses. Urine may be stored for up to 4h at room temperature without significant changes to the urinalysis results.


Designing the esthetic dental environment.
The esthetic dental environment requires a re-thinking of outdated concepts of office design. The design of the dental office must reflect the dentist's commitment to excellence. Each detail of the office design must be both functional and esthetic to mirror the type of work the esthetic patient expects and demands.


Effects of the incontinence dish pessary on urethral support and urodynamic parameters.
To evaluate the effects of the incontinence dish pessary (IDP) on urethral mobility and urodynamics. Prospective study of women with symptoms of stress incontinence. Q-tip test was performed recording the resting and straining angles with and without an IDP. Changes in resting and straining angles were calculated. Those with evidence of urodynamic stress incontinence had urodynamics with the IDP. Paired t-test was used to compare the difference in Q-tip angles with and without the pessary. Mean Q-tip straining angle without and with the pessary, respectively, was 57.8 (+19.5) and 34.4 (+29.7). Mean change was 23.5 (+18.5) P < .00001. Maximum urethral closure pressure (MUCP) was significantly increased by 19.7 cm H(2)0 P < .001. Overall, 60% of the subjects did not leak with the IDP. The IDP eliminates >60% of USI. The mechanism of action may be a combination of improved UVJ support and increased MUCP.


Phenylethanolamine-N-methyl transferase and catechol-O-methyl transferase activity in rat uterus. Cyclic and steroid-induced changes.
The activity of phenylethanolamine-N-methyl-transferase (PNMT) and catechol-O-methyl-transferase (COMT) was studied in uterine homogenates from adult female Wistar rats with normal cycles and that had been ovariectomized, adrenalectomized, and steroid-treated. Activities of the two enzymes changed significantly during the normal estrus cycle. Both peaked during metestrus, with COMT showing a secondary peak of activity at proestrus. Progesterone treatment significantly increased and estradiol decreased PNMT activity in comparison to untreated controls. Hydrocortisone administration had no effect on uterine PNMT activity. COMT activity was not affected significantly by any of the steroid treatments. The data confirm that uterine tissues possess the enzymatic machinery to synthesize epinephrine from norepinephrine, and suggest the activity of this pathway may be mediated by variations in the sex hormone environment of the uterus.