An injectable cellulose-based hydrogel for the transfer of autologous nasal chondrocytes in articular cartilage defects.
Articular cartilage has a low capacity for spontaneous repair. To promote the repair of this tissue, the transfer of autologous chondrocytes using a three-dimensional matrix appears promising. In this context, the aim of the present work was to investigate the potential use of autologous rabbit nasal chondrocytes (RNC) associated with an injectable self-setting cellulose-based hydrogel (Si-HPMC). Firstly, the influence of Si-HPMC on chondrocytic phenotype was investigated by real-time PCR for specific chondrocyte markers (type II collagen and aggrecan) and type I collagen. Thereafter, autologous RNC were amplified in vitro for 4 weeks before transplantation with Si-HPMC into a rabbit articular cartilage defect followed by analysis 6 weeks later. Implants were histologically characterized for the presence of sulfated GAG and type II collagen. Transcripts analysis indicated that dedifferentiated RNC recovered expression of the main chondrocytic markers after in vitro three-dimensional culture within Si-HPMC. Histological analysis of autologous RNC transplanted in an articular cartilage defect revealed the formation of repair tissue with a histological organization similar to that of healthy articular cartilage. In addition, immunohistological analysis of type II collagen suggested that the repair tissue was a hyaline-like cartilage. Si-HPMC hydrogel associated with nasal chondrocytes therefore appears a promising injectable tissue engineering device for the repair of articular cartilage.


Stressed-Out Endoplasmic Reticulum Inflames the Mitochondria.
Bacterial infection induces inflammasome activation and release of interleukin-1 (IL-1) cytokines. Bronner et al. (2015) show that during Brucella abortus infection, an endoplasmic reticulum stress sensor, IRE1α, initiates NLRP3- and caspase-2-mediated mitochondrial damage that potentiates NLRP3 inflammasome assembly.


Incidence and prevalence of dermatitis herpetiformis in a country in central Sweden, with comments on the course of the disease and IgA deposits as diagnostic criterion.
In a defined area of 273 000 inhabitants in Central Sweden a total number of 125 patients with dermatitis herpetiformis (DH) were observed during the years 1974-1982. The incidence was calculated for the years 1943-1982 and was found to be 0.86-1.45 patients/100 000 inhabitants/year, which is in agreement with a report from Finland. However, the prevalence of DH in the area was 39.2 patients/100 000 inhabitants, which is much higher than previously reported. Spontaneous transient remissions of more than half a year duration were seen in 20% of the patients. At the end of the study, 16 out of 37 patients (43%) on normal diet used no dapsone because of no or minimal rash. Immunohistochemical demonstration of IgA-deposits at the dermoepidermal junction was found to be a good diagnostic criterion. Granular deposits were seen in all except one patient, also in those needing no dapsone. Five out of 6 patients with a granular-linear pattern were still alive at the end of the study, and all of them needed dapsone for control of the rash.


Proteomic approaches in the analysis of hypertension.
The completion of the genomic sequence and the definition of the genes provide a wealth of data to interpret cellular protein expression patterns and relate them to protein function. Proteomics is the large-scale study of proteins in the post-genomic era, aimed at identifying and characterizing protein expression, function, posttranslational modification, regulation, trafficking, interaction and structure, and their perturbation by disease and drug action. The multigenetic background and essentially unknown etiology of hypertension, makes this main killer a prime candidate for proteomic analysis. The classical proteomic approaches are based on two-dimensional gel electrophoretic protein separation and their subsequent identification and characterization by mass spectrometry analysis. However, expression level analysis may not reflect the functional state of proteins and is biased towards long-lived abundant proteins. This review describes a variety of techniques that can be used to identify low-abundance proteins that may be of more functional interest. The modification of classical two-dimensional electrophoresis in order to study post-translational modifications, e.g., phosphorylation, is also discussed.


Decolorization of complex dyes and textile effluent by extracellular enzymes of Cyathus bulleri cultivated on agro-residues/domestic wastes and proposed pathway of degradation of Kiton blue A and reactive orange 16.
In this study, the white-rot fungus Cyathus bulleri was cultivated on low-cost agro-residues, namely wheat bran (WB), wheat straw (WS), and domestic waste orange peel (OP) for production of ligninolytic enzymes. Of the three substrates, WB and OP served as good materials for the production of laccase with no requirement of additional carbon or nitrogen source. Specific laccase activity of 94.4 U mg-1 extracellular protein and 21.01 U mg-1 protein was obtained on WB and OP, respectively. Maximum decolorization rate of 13.6 μmol h-1 U-1 laccase for reactive black 5 and 22.68 μmol h-1 U-1 laccase for reactive orange 16 (RO) was obtained with the WB culture filtrate, and 11.7 μmol h-1 U-1 laccase for reactive violet 5 was observed with OP culture filtrate. Importantly, Kiton blue A (KB), reported not to be amenable to enzymatic degradation, was degraded by culture filtrate borne activities. Products of degradation of KB and RO were identified by mass spectrometry, and a pathway of degradation proposed. WB-grown culture filtrate decolorized and detoxified real and simulated textile effluents by about 40%. The study highlights the use of inexpensive materials for the production of enzymes effective on dyes and effluents.


Systematic Review of Racial, Socioeconomic, and Insurance Status Disparities in Neurosurgical Care for Intracranial Tumors.
The impact of race, socioeconomic status (SES), insurance status, and other social metrics on the outcomes of patients with intracranial tumors has been reported in several studies. However, these findings have not been comprehensively summarized. We conducted a PRISMA systematic review of all published articles between 1990 and 2020 that analyzed intracranial tumor disparities, including race, SES, insurance status, and safety-net hospital status. Outcomes measured include access, standards of care, receipt of surgery, extent of resection, mortality, complications, length of stay (LOS), discharge disposition, readmission rate, and hospital charges. Fifty-five studies were included. Disparities in mortality were reported in 27 studies (47%), showing minority status and lower SES associated with poorer survival outcomes in 14 studies (52%). Twenty-seven studies showed that African American patients had worse outcomes across all included metrics including mortality, rates of surgical intervention, extent of resection, LOS, discharge disposition, and complication rates. Thirty studies showed that privately insured patients and patients with higher SES had better outcomes, including lower mortality, complication, and readmission rates. Six studies showed that worse outcomes were associated with treatment at safety-net and/or low-volume hospitals. The influence of Medicare or Medicaid status, or inequities affecting other minorities, was less clearly delineated. Ten studies (18%) were negative for evidence of disparities. Significant disparities exist among patients with intracranial tumors, particularly affecting patients of African American race and lower SES. Efforts at the hospital, state, and national level must be undertaken to identify root causes of these issues.


Plasmodium vivax: in vitro growth and reinvasion in red blood cells of Aotus nancymai.
Plasmodium vivax was maintained in experimentally infected Aotus nancymai. Positive monkeys were used as donors for culture material. After leucocyte removal with two different methods, including the classic CF11 method and a commercially available filter, parasites were grown under continuous shaking conditions in standard RPMI 1640, containing 20% human AB + serum. When mature schizonts were present, artificially induced reticulocytes from monkeys pretreated with the hemolytic drug phenylhydrazine HCl were added. Addition of reticulocytes and shaking were both necessary to realize a significant reinvasion under in vitro conditions. A strong positive correlation between the percentage of reticulocytes and in vitro invasion was demonstrated, and a preferential invasion into reticulocytes was demonstrated in vivo and in vitro using blood films stained with brilliant cresyl blue and counterstained with Giemsa.


Patterns of cellular gene expression in cells infected with cytopathic or non-cytopathic bovine viral diarrhea virus.
Bovine viral diarrhea virus (BVDV) infection in cattle is responsible for mucosal disease; an invariably fatal syndrome characterized by the recovery of two BVDV strains: cytopathic (cp) or noncytopathic (ncp). To understand the cellular responses to cp BVDV infection, we carried out differential display-polymerase chain reaction (DD-PCR) analysis of gene expression in infected cells. Altered expression of 14 genes involved in several functions was observed in cells infected with cp BVDV: (1) immune regulation, such as CD46, FKBP-12, and osteopontin (OPN); (2) apoptosis-related cysteine proteases like calpain; (3) signaling plasma membrane proteins such as integrin beta1, and prion protein; and (4) unknown function genes. Northern blot analysis of the expression of these genes in ncp BVDV infected cells revealed that while the expression of some genes was affected as in cp BVDV infected cells, others show a clearly contrary change. We postulate that a cause-effect relationship may exist between the differential gene expression alterations that characterize cp and ncp BVDV infections and the unique diseases associated with each BVDV biotype.


Use of reverse phase protein microarrays to study protein expression in leukemia: technical and methodological lessons learned.
Leukemias are well suited to proteomic profiling by RPPA due to the ready accessibility of blasts from the blood or marrow. In this review, we review methodological and procedural issues that affect the quality of RPPA data. We recommend contact printers that minimize sample quantities and evaporation and maximize sample per slide. The impact of sample selection and handling is reviewed as well. Protein is best prepared fresh on the date of acquisition as cryopreservation changes protein expression levels in some diseases. Rapid processing is also required to avoid changes in phosphorylation over time. Sample source, blood vs. marrow does not seem to affect results as long as leukemic blast enrichment procedures are utilized. The choice of the correct "normal" control is important for comparing diseased to "normal" expression. Various means of normalizing the data are discussed.


[Effect of zixoryn on diuresis and renal transport of xenobiotics].
A new inducer of the monooxygenase system zixoryn (oral dose--100 mg/kg, for 4 days) increased the excretion and maximum tubular transport of cardiotrast (diodrast) in rats. Zixoryn had no effect on daily and water diuresis and renal excretion of sodium, potassium and creatinine.


Ruptured femoral pseudoaneurysm presenting as a lateral abdominal wall hematoma.
Lateral abdominal wall hematomas are rare. We describe a patient with a delayed rupture of a femoral artery pseudoaneurysm, who presented with such a hematoma. In contrast to other types of abdominal wall hematomas, which are often managed conservatively, a ruptured femoral artery pseudoaneurysm frequently requires emergent surgical intervention. Rupture of a pseudoaneurysm can be catastrophic. Due to the rising incidence of femoral artery pseudoaneurysms and shorter hospital stays, it is useful for the emergency physician to be familiar with the diagnosis and management of femoral artery pseudoaneurysms and their potentially life-threatening complications.


Structural insights into CYP107G1 from rapamycin-producing Streptomyces rapamycinicus.
Rapamycin is a clinically important macrolide agent with immunosuppressant and antiproliferative properties, produced by the actinobacterium, Streptomyces rapamycinicus. Two cytochrome P450 enzymes are involved in the biosynthesis of rapamycin. CYP107G1 and CYP122A2 catalyze the oxidation reactions of C27 and C9 of pre-rapamycin, respectively. To understand the structural and biochemical features of P450 enzymes in rapamycin biosynthesis, the CYP107G1 and CYP122A2 genes were cloned, their recombinant proteins were expressed in Escherichia coli, and the purified enzymes were characterized. Both enzymes displayed low spin states in the absolute spectra of ferric forms, and the titrations with rapamycin induced type I spectral changes with Kd values of 4.4 ± 0.4 and 3.0 ± 0.3 μM for CYP107G1 and CYP122A2, respectively. The X-ray crystal structures of CYP107G1 and its co-crystal complex with everolimus, a clinical rapamycin derivative, were determined at resolutions of 2.9 and 3.0 Å, respectively. The overall structure of CYP107G1 adopts the canonical scaffold of cytochrome P450 and possesses large substrate pocket. The distal face of the heme group is exposed to solvents to accommodate macrolide access. When the structure of the everolimus-bound CYP107G1 complex (CYP107G1-Eve) was compared to that of the ligand-free CYP107G1 form, no significant conformational change was observed. Hence, CYP107G1 has a relatively rigid structure with versatile loops to accommodate a bulky substrate. The everolimus molecule is bound to the substrate-binding pocket in the shape of a squeezed donut, and its elongated structure is bound perpendicular to a planar heme plane and I-helix.


Proton T1 study of coverage parameter changes in tissues from tumor-bearing mice.
measurements of water proton spin-lattice relaxation time, T1, at 20 and -15 degrees C have been performed in spleen, kidney, liver, and muscle tissues from tumor-bearing mice, as well as in tumors grown in their dorsal subcutaneous tissues. All mice used were either from the C3H/HeJ or BALB/c strain. At - 15 degrees C the T1's of tissues of a given type from tumor-bearing and healthy mice are essentially the same. It is shown that in spleen the increased T1 from tumor-bearing mice can only be explained in terms of a large change in the water coverage parameter of macromolecules. In liver, muscle, and tumors the increased water content accounts for the changes in T1, while kidney represents an intermediate case.


[Antiphospholipid antibodies, antiphospholipid syndrome and viral infections].
Since the association between antiphospholipid antibodies and syphilis was first described, many other viral, bacterial and parasitic infections have been shown to induce antiphospholipid antibodies, notably anticardiolipin antibodies. These aPL are usually associated neither with anti-beta2 glycoprotein I antibodies (anti-beta2-GPI) nor with thrombotic events, even if cases of arterial and deep venous thrombosis have been reported in such circumstances. A literature review shows that anticardiolipin antibodies occur frequently in viral infections, particularly in HIV (49.8%), HBV (24%) and HCV (20%). The prevalence of anti-beta2 glycoprotein I antibodies (anti-beta2GPI) is lower (HCV: 1.7%, HIV: 5.6%, HBV: 3.3%) and there is no demonstrated association with a risk of thrombotic events or hematological manifestations defining antiphospholipid syndrome (APS). Regarding other viral infections, including viral hepatitis A, herpes virus (CMV, EBV, VZV), parvovirus B19 and HTLV-1 infections, only a few studies are available but data confirm the high prevalence of antiphospholipid antibodies at the acute phase. Finally, antiphospholipid antibodies, mainly anticardiolipin, are frequently associated with viral infections. Their presence may probably reflect an intense or chronic antigenic stimulation of the immune system. However, their evolution under antiviral therapy and correlation with the quality of the virological control and/or the immune restoration remain to be determined.


Apraxia in a patient with atypical cerebral dominance.
Liepmann postulated that the left hemisphere of right-handed persons contains the "movement formulas" that control purposeful skilled movements of the limbs on both sides of the body. Accordingly, in right-handers apraxia should follow damage to the left hemisphere, whereas right hemisphere damage should not lead to apraxia. Although this is generally true, we recently examined a right-handed man who after a right hemispheric stroke became aphasic and apraxic with his nonparalyzed right hand. Our observations suggest that the right hemisphere of this right-handed man made a critical contribution to the planning and execution of skilled movements. This case provides evidence that right-handers should not be considered a homogeneous group in terms of cerebral motor dominance and that contrary to Liepmann's postulate, hemispheric dominance for the control of skilled movements does not entirely determine handedness.


Cortical involvement in anticipatory postural reactions in man.
All movements are accompanied by postural reactions which ensure that the balance of the body is maintained. It has not been resolved that to what extent the primary motor cortex and corticospinal tract are involved in the control of these reactions. Here, we investigated the contribution of the corticospinal tract to the activation of the soleus (SOL) muscle in standing human subjects (n=10) in relation to voluntary heel raise, anticipatory postural activation of the soleus muscle when the subject pulled a handle and to reflex activation of the soleus muscle when the subject was suddenly pulled forward by an external perturbation. SOL motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) increased significantly in relation to rest -75 ms prior to the onset of EMG in the heel-raise and handle-pull tasks. The short-latency facilitation of the soleus H-reflex evoked by TMS increased similarly, suggesting that the increased MEP size prior to movement was caused at least partly by increased excitability of corticospinal tract cells with monosynaptic projections to SOL motoneurones. Changes in spinal motoneuronal excitability could be ruled out since there was no significant increase of the SOL H-reflex until immediately prior to EMG onset for any of the tasks. Tibialis anterior MEPs were unaltered prior to the onset of SOL EMG activity in the handle-pull task, suggesting that the MEP facilitation was specific for the SOL muscle. No significant increase of the MEPs was observed prior to EMG onset for the external perturbation. These data suggest that the primary motor cortex is involved in activating the SOL muscle as part of an anticipatory postural reaction.


27-Hydroxylation of 7- and 8-dehydrocholesterol in Smith-Lemli-Opitz syndrome: a novel metabolic pathway.
Smith-Lemli-Opitz syndrome (SLOS) is attributable to mutations in the gene coding for 7-dehydrocholesterol reductase. Low to absent enzyme activity accounts for the accumulation of both 7-dehydrocholesterol and 8-dehydrocholesterol in plasma and other tissues. Since oxysterols can participate in the regulation of cholesterol homeostasis, we examined the possibility that they are formed from these dehydrocholesterol intermediates. In patients with SLOS, we found serum levels of 27-hydroxy-7-dehydrocholesterol ranging from 0.1 to 0.25micro M and evidence for circulating levels of 27-hydroxy-8-dehydrocholesterol (0.04-0.51 micro M). Picomolar quantities of 27-hydroxy-7-dehydrocholesterol were identified in normal individuals. Biologic activities of 27-hydroxy-7-dehydrocholesterol were found to include inhibition of sterol synthesis and the activation of nuclear receptor LXRalpha but not that of LXRbeta. These activities occurred at concentrations found in plasma and presumably at those existing in tissues. Thus, patients with SLOS have increased levels of metabolites derived from intermediates in cholesterol synthesis that are biologically active and may contribute to the regulation of cholesterol synthesis in vivo.


Non-Toxigenic Penicillin and Cephalosporin-Resistant Corynebacterium diphtheriae Endocarditis in a Child: A Case Report and Review of the Literature.
Reports of invasive disease caused by non-toxigenic Corynebacterium diphtheriae are increasing; however, medical management has not been extensively studied. We describe what we believe is the first documented case of penicillin and cephalosporin-resistant C diphtheriae endocarditis in a child successfully treated with vancomycin, meropenem, and valvular replacement surgery.


What is the accident waiting to happen?
Working on an MHA subcommittee has many benefits. The benefit I value the most is the opportunity to build relationships with people from hospitals across the state and share ideas that work. Recently, at an MHA patient safety committee meeting, I shared an initiative that Allan Franke, MD, from Partners Health Care System in Boston, presented at the Institute for Health Care Improvement in San Francisco.


Control mechanisms mediating shifts of attention in auditory and visual space: a spatio-temporal ERP analysis.
The neural systems that mediate voluntary shifts of attention to visual and auditory stimuli were investigated by examining the patterns of human brain electricity elicited by attention-directing cues in auditory and visual tasks. Several lateralized event-related potential (ERP) components were observed when participants shifted attention in expectation of visual targets (experiment 1). One component was focused over frontal cortex and a second was focused primarily over the occipital-temporal cortex but also spread to parietal regions of the scalp. Previous work has indicated that the frontal component reflects supramodal processes involved in the executive control of attention and that the posterior component reflects either spatial attentional control processes in the posterior parietal lobe or modulation of processes in visual cortex. Here, the posterior component was observed when participants shifted attention in expectation of auditory targets (experiments 2-4), but the frontal component was found only in the visual task. The posterior component seemed to be generated in parietal and occipital areas even when there was no visual information about the to-be-attended locations. These results are consistent with the view that voluntary shifts of attention are mediated by supramodal processes in the parietal lobe and that the spatial coordinates of the to-be-attended location are based on visual representations of space.


A journey with no roadmap-The need for validated criteria of the MS prodrome.
A growing body of compelling evidence has emerged to validate a set of signs and symptoms that indicates the onset of disease before more typical signs and symptoms present to fulfill a diagnosis of MS. On 24 June 2021, a group of international researchers, patient advocates, and Society representatives led by Professors Helen Tremlett (University of British Columbia) and Ruth Ann Marrie (University of Manitoba) convened virtually for a workshop. Identify key gaps in knowledge, opportunities, and research priorities regarding the prodromal stage of MS. The group developed a new framework for MS that includes the stage of early signs and symptoms of MS-and outlined a roadmap to guide future research, with the "goal of preventing the progression to onset of typical symptoms of MS in those who present during the prodromal stage of MS". If high-risk individuals in the early stages of MS can be identified with a high degree of certainty, there is an opportunity to intervene and minimize the risk of progressing to typical MS symptoms and a diagnosis of MS. Standardized criteria must be developed, validated, and point of intervention found to better recognize, better diagnose, and better treat MS.


Dynamic harmonization of source-oriented and receptor models for source apportionment.
Millions of premature mortalities are caused by the air pollution of fine particulate matter with aerodynamic diameters less than 2.5 μm (PM2.5) globally per year. To effectively control the dominant emission sources and abate air pollution, source apportionment of PM2.5 is normally conducted to quantify the contributions of various sources, but the results of different methods might be inconsistent. In this study, we dynamically harmonized the results from the two dominant source apportionment methods, the source-oriented and receptor models, by updating the emission inventories of primary PM2.5 from the major sectors based on the Bayesian Inference. An adjoint model was developed to efficiently construct the source-receptor sensitivity matrix, which was the critical information for the updates, and depicted the response of measurements to the changes in the emissions of various sources in different regions. The harmonized method was applied to a measurement campaign in Beijing from January to February 2021. The results suggested a significant reduction of primary PM2.5 emissions in Beijing. Compared with the baseline emission inventory of 2017, the primary PM2.5 emissions from the local residential combustion and industry in Beijing had significantly declined by about 90 % during the investigated period of the year, and the traffic emission decreased by about 50 %. The proposed methods successfully identified the temporally dynamic changes in the emissions induced by the Spring Festival. The methods could be a promising pathway for the harmonization of source-oriented and receptor source apportionment models.


Protein synthesis inhibition induced by dimethylnitrosamine and diethylnitrosamine on isolated rat hepatocytes.
Time- and dose-dependent protein synthesis inhibition takes place following exposure to high doses of dimethylnitrosamine (DMN) or diethylnitrosamine (DENA) in isolated rat hepatocytes. The ability of DENA to depress protein synthesis is 5-fold higher than that of DMN. Cells inhibited by 60 min exposure to DMN or DENA, and then incubated in a nitrosamine-free medium, regain their initial rate of protein synthesis. This recovery is faster and more complete for DENA-treated cells.


Diagnostic and management plan concordance across advanced audiologists, paediatric audiologists and non-specialist ENT doctors.
To compare the concordance of advanced audiologists (AA), junior doctors (JD) and paediatric audiologists (PA) with an Ear, Nose and Throat (ENT) specialist on the diagnosis and management of children with middle ear or hearing concerns. A clinical equivalence (concordance) study. Three AAs, five JDs, three PAs and one ENT specialist asynchronously reported diagnoses and management plans for ten, online paediatric cases consisting of video-otoscopic images and clinical findings. For medical diagnosis, significant agreement with the ENT specialist was observed at moderate and near-perfect levels for two AAs (k = 0.561 and 0.815), moderate levels for four JDs (k = 0.5 to 0.603) and near-perfect level for one PA (k = 0.815). For management decisions, significant agreement with the ENT specialist was observed at substantial (k = 0.636) and near-perfect (k = 0.818) levels for two AAs, and at a moderate level (k = 0.538) for one PA. Within group inter-rater agreement for management plans was substantial for AAs and JDs, and moderate for PAs. For children with middle ear disease or hearing concerns, AAs, JDs and PAs showed similar levels of agreement with an ENT specialist on diagnosis, but AAs were more likely than JDs or PAs to agree with an ENT specialist on management.


Stimulus parameters affecting paired-pulse depression of dentate granule cell field potentials. II. Low-frequency stimulation.
Low frequency (1 Hz) stimulation of the perforant path produces a depression in the population spike (PS) of dentate granule cell field potentials and also may affect the strength of paired pulse depression. The effects of 1 Hz stimulation (30 s train) on paired pulse depression (20 and 200 ms interpulse intervals, IPI) were evaluated in the unanesthetized rat under two conditions: (i) when the stimulus intensity of both pulses was increased simultaneously (5-100%); and (ii) when the stimulus intensity of the first (conditioning) pulse was increased (5-100%), while the stimulus intensity of the second (test) pulse was held constant (50%). The test PS amplitude was predicted based upon either the conditioning PS amplitude at the end of the 1 Hz train or upon the additive effects of paired pulse depression and 1 Hz stimulation. These predicted values then were assessed for the best fit to observed values following 1 Hz trains. Under both stimulus conditions, the 1 Hz depression in the conditioning PS amplitude exhibited characteristics that were identical to late paired pulse depression recorded before the train. A decrease in the test PS amplitude also was observed following 1 Hz stimulation at the 20 and 200 ms IPIs. The best fit to observed values of the test PS at the end of 1 Hz trains was provided by estimates based upon the additive effects of 1 Hz stimulation and paired pulse depression. These results indicate that the strength of paired pulse depression in the unanesthetized rat is unchanged following 1 Hz stimulation, and further, that the 1 Hz depression in dentate granule cell field potentials most likely reflects the cumulative influence of late paired pulse depression.


Factors affecting ED length-of-stay in surgical critical care patients.
To determine what patient characteristics are associated with prolonged emergency department (ED) length-of-stay (LOS) for surgical critical care patients, the charts of 169 patients admitted from the ED directly to the operating room (OR) or intensive care unit (ICU) during a 6-week period in 1993 were reviewed. The ED record was reviewed for documentation of factors that might be associated with prolonged ED LOS, such as use of computed tomographic (CT), radiology special procedures, and the number of plain radiographs and consultants. ED LOS was considered to be the time from triage until a decision was made to admit the patient. Using a Cox proportional hazards model, use of CT and special procedures were the strongest independent predictors of prolonged ED length-of-stay. The number of plain radiographs and consultants had only a minimal effect. Use of a protocol-driven trauma evaluation system was associated with a shorter ED LOS. In addition to external factors that affect ED overcrowding, ED patient management decisions may also be associated with prolonged ED length-of-stay. Such ED-based factors may be more important in surgical critical care patients, whose overall ED LOS is affected more by the length of the ED work-up rather than the time spent waiting for a ICU bed or operating suite.


Propulsive appliance stimulates the synthesis of insulin-like growth factors I and II in the mandibular condylar cartilage of young rats.
Functional orthopedic appliances correct dental malocclusion partially by exerting indirect mechanical stimulus on the condylar cartilage, modulating growth and the adaptation of orofacial structures. However, the exact nature of the biological responses to this therapy is not well understood. Insulin-like growth factors I and II (IGF-I and IGF-II) are important local factors during growth and differentiation of several tissues, including cartilage. The aim of this study was to verify the mRNA and protein expression of IGF-I and IGF-II in the condylar cartilage of young male Wistar rats that used a mandibular propulsive appliance for 3, 5, 7, 9, 11, 13 or 15 days. For this purpose, sagittal sections of decalcified and paraffin-embedded condyles were submitted to immunohistochemistry and in situ hybridization. IGF-I and IGF-II expression increased with developmental age in the control and treated rats. After 9 days of treatment the positivity for both peptides in the animals that wore the propulsive appliance increased even more, expressively different from the age-matched controls. The expression patterns of both IGFs were similar, although IGF-I labelling was stronger. Furthermore, the enhanced expression of both peptides was in parallel with the proliferating cell nuclear antigen (PCNA) positivity, a proliferation cell marker. The modulation of IGF-I and IGF-II expression in the condylar cartilage in response to the propulsive appliance suggests that both peptides are involved in the mandibular adaptation during this therapy.


[Concentration in bone and haematoma of the aminoglycoside antibiotic tobramycin (author's transl)].
Tobramycin concentrations were assayed in the rabbit in serum during surgery and in serum, haematoma and bone tissue of the condyle of the femur in the absence of surgery. After a single i. m. injection serum levels were found to be 30% higher initially than in humans, but then dropped at a faster rate to zero. The hardening haematoma appeared to slow penetration of the antibiotic. The concentration in bone tissue was dependent on vascular supply. Surgery did not show any influence on the level of the concentrations.


Hexavalent Vaccines in India: Current Status.
Hexavalent vaccines containing diphtheria, tetanus, pertussis, Haemophilus influenzae type b, poliomyelitis, and hepatitis B virus antigens have the potential to be used for the primary series in India (6, 10, 14 weeks of age) and the toddler booster dose. Three hexavalent vaccines are available in India: DTwP-Hib/HepB-IPV (wP-hexa), DTaP-IPV-HB-PRP~T(2aP-hexa), and DTaP-HBV-IPV/Hib (3aP-hexa). In the three published phase-3 Indian studies, pertussis 'vaccine response' rates 1 month after a 6-10-14-week primary series were 68.4-75.7% for wP-hexa, 93.8-99.3% for 2aP-hexa, and 97.0-100% for 3aP-hexa; seroprotection rates for the other five antigens were 88.2-100%, 49.6-100%, and 98.6-100%, respectively. Studies outside India show: good immunogenicity/safety after boosting dosing; immune persistence to age 4.5 years (2aP-hexa), 7-9 years (3aP-hexa) (all antigens), and 9-10 and 14-15 years, respectively (hepatitis B); and successful co-administration with other vaccines. Hexavalent vaccines could reduce the number of injections, simplify vaccination schedules, and improve compliance.


Cytotoxic effects of a leukocidin from Fusobacterium necrophorum on bovine hepatic cells.
Cytotoxic effects of a leukocidin from Fusobacterium necrophorum were demonstrated on bovine hepatic cells. The cytotoxic response was dose-dependent and could be inhibited by homologous antiserum. Scanning electron microscopy revealed damaged hepatic cell surface. These findings indicated a pathogenic role of the leukocidin in F. necrophorum infections.


Surgical repair of the injured spleen.
Fatal sepsis has been reported with increasing frequency following splenectomy for trauma. Efforts to save the spleen were made in 17 children with blunt abdominal trauma. Two patients required splenectomy, but 15 were managed successfully by splenic repair. No patient required reoperation, and there were no complications. Follow-up scans were remarkably normal. It is concluded that splenic lacerations are usually amenable to suture repair, and splenorrhaphy, not splenectomy, is the treatment of choice for splenic injury.


Manifestations of esophageal disease on plain chest radiographs.
The chest film appearances of various esophageal abnormalities are illustrated. Inability to recognize these abnormalities on chest radiographs can result in confusion and misinterpretation. This pictorial essay should assist the radiologist in recognizing esophageal abnormalities on chest films and in recognizing their place in the spectrum of chest film abnormalities.


Newer antidepressants. Beyond selective serotonin reuptake inhibitor antidepressants.
This article outlines the use of alternative agents to TCAs and SSRIs. Features of the more commonly used alternative antidepressant agents are outlined. In addition, antidepressant agents that are currently either under development or used in other countries are indicated for completeness because it seems likely that many of these will be introduced in the United States within the next few years. Many of these agents will be used by pediatricians and child psychiatrists for treatment of depression in children, and although much further research is needed, the future for alternative antidepressants and augmenting strategies is extremely promising.


[Impact of thoracic epidural analgesia on revenue for G-DRG M01B, OPS-301 5-604.0 (radical retropubic prostatectomy)].
Using the surgical procedure OPS 5-604.0 (radical retropubic prostatectomy) as an example, our study identifies revenue-relevant patient characteristics and describes the impact of the perioperative application of thoracic epidural analgesia (TEA). Factors affecting duration of stay were determined in 460 patients undergoing OPS 5-604.0 in the year 2001 and 2002 using multifactorial regression analysis. Preoperative parameters served as factors for matched-pair analysis of the effects of TEA. Characteristics significantly affecting length of postoperative hospital stay were ASA status, age, preoperative haemoglobin concentration, postoperative tachycardia, number of transfused packed red cells, wound infection and surgical revision. Based on identical matching criteria 27 pairs (with/without TEA) could be formed. While the induction time in the TEA group was 8+/-18 min longer (p=0.04), emergence was briefer by 3+/-9 min (p=0.045). Neither anaesthesia presence time nor anaesthesia costs or total costs of surgery differed significantly between the pairs. However, duration of epidural postoperative pain therapy was longer with TEA but in contrast, the postoperative length of hospital stay after TEA was reduced. Assuming a continuous demand for OPS 5-604.0 procedures, TEA enables 32 more procedures to be carried out per year with an increased yield on turnover of 2.7%. At first sight combined anaesthesia procedures require more human resources and material, however, as a result of shortened hospital stay and optimized pain therapy patient satisfaction increases and a substantial potential for increased revenue is gained.


Let's Get This Party Started: The Effects of Descriptive and Injunctive Norms on Preparty Behavior in College Students.
Participants (N = 202) were students at a college in the northeastern United States who participated in the 2010 Core Alcohol and Drug survey. Data were collected on prepartying behavior, preparty social norms, and individual-difference variables. Using multivariate logistic and least-squares regression, it was found that descriptive social norms were associated with prepartying in women and injunctive social norms were associated with prepartying in men. Prepartying also was found to be negatively related to underage status and GPA in women and positively related to Greek membership and athlete status in men. Implications for social-norms interventions and suggestions for future social-norms research are discussed.


Efficiency of the revised Bethesda guidelines (2003) for the detection of mutations in mismatch repair genes in Austrian HNPCC patients.
The clinical diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) is based on the Amsterdam II criteria (ACII). The purpose of using the Bethesda guidelines (BG) is to select tumours for microsatellite analysis. Recently, the modified Amsterdam criteria (ACmod) and Bethesda guidelines (BGmod) were proposed to simplify definitions. We evaluated the efficiency of the ACmod and BGmod to identify patients with germ-line mutations in MLH1 and MSH2 in 81 unrelated Austrian HNPCC families. Microsatellite (MS) analysis was performed in 55 tumours. The new criteria included more families than the old ones: BGmod, n = 81; BG, n = 72; ACmod, n = 52 and ACII, n = 35. The more stringent old criteria tended to show greater positive predictive value for association with a germ-line mutation than the corresponding new criteria: BGmod, 23%; BG, 26%; ACmod, 31% and ACII, 37%. The larger number of patients analysed in the ACmod group resulted in greater sensitivity compared to the ACII. The increased workload for BGmod was not associated with greater sensitivity. Microsatellite instability (MSI) significantly enhanced specificity in all subgroups. We recommend the use of the ACmod criteria to select patients for primary sequence analysis, when microsatellite analysis is not possible. If the BG are used, we suggest that BG be given preference over BGmod, as the former signify a lesser workload.


A convenient, unified scheme for the differential extraction of conjugated and unconjugated serum C19 steroids on Sep-Pak C18-cartridges.
In order to conveniently and rapidly isolate by group both conjugated and unconjugated serum androgens, a scheme has been devised for their differential extraction from commercially available, disposable octadecylsilane cartridges (Sep-Pak C18). Using added radioactive steroid standards and detection of endogenous serum steroids by group-specific enzymatic assays, the quantitative recovery of steroid glucuronides and sulfates in the 47% methanol fraction and of unconjugated steroids in the 100% methanol fraction was observed. Maximum recovery of serum protein-bound steroids (e.g. testosterone) was achieved with serum denatured by urea and heat. In order to separate glucuronides from sulfates, sequential hydrolysis of the conjugated fraction (47% methanol) by enzymatic hydrolysis and then organic solvolysis as well as an additional Sep-Pak cartridge extraction step was required. Groups of extracted steroids may be further separated and assayed by any appropriate method(s). An application is given which employs HPLC and an enzymatic assay for 17 beta-hydroxy- and 17-oxo-steroids to provide separate profiles of unconjugated, glucuronidated, and sulfated androgens in human, male serum.


Beyond height and weight: a programme of school nurse assessed skinfold measurements from white British and South Asian origin children aged 4-5 years within the Born in Bradford cohort study.
To describe the feasibility, reliability and additional information gained from collecting additional body fatness measures (beyond height and weight) from UK reception year children. Prospective cohort study. Bradford, UK. 2458 reception year children participating in the Born in Bradford (BiB) cohort study. The feasibility and reliability of subscapular and triceps skinfold measurements and differences in adiposity between ethnic groups. Of those children who were matched to their school, 91% had a subscapular skinfold measurement and 92% had a triceps skinfold measurement recorded. Reliability was generally over 90% for all measurers and both measurements. Pakistani children were slightly taller but weighed less and had lower triceps skinfold thickness (mean difference -1.8 mm, 95% CI -2.1 to -1.4 mm) but higher subscapular (mean difference 0.1 mm, 95% CI -0.1 to 0.4 mm) than white British children. We have shown that it is feasible for school nurses to collect skinfold measurements in a similar way to the height and weight measurements collected from reception year children for the National Child Measurement Programme (NCMP), and that these measurements are reliable. It is important for healthcare practice to acknowledge ethnic-specific risk and these additional measurements can provide important information to examine population-level risk in populations with large proportions of South Asian children.


Prevalence of coronary artery disease risk factors in Iran: a population based survey.
Coronary artery disease (CAD) is a leading cause of mortality, morbidity, and disability with high health care cost in Iran. It accounts for nearly 50 percent of all deaths per year. Yet little is known about CAD and CAD risk factors in the Iranian population. We aimed to assess the prevalence of different CAD risk factors in an Iranian population. A descriptive cross sectional survey was conducted involving 3000 healthy adults at 18 years of age or above who were recruited with cluster random sampling. Demographic data and risk factors were determined by taking history, physical examination and laboratory tests. The average age was 36.23 +/- 15.26. There was 1381 female (46%) and 1619 male (54%) out of which 6.3% were diabetic, 21.6% were smoker, and 15% had positive familial heart disease history. 61% had total cholesterol level > 200 mg/dL, 32% triglyceride > 200 mg/dl, 47.5% LDL-c > 130 mg/dl, 5.4% HDL-c < 35 mg/dl, 13.7% systolic blood pressure > 140 mmHg, 9.1% diastolic blood pressure > 90 mmHg and 87% of them were physically inactive. Clinical and Para-clinical data indicated that Iranian adult population are of a high level of CAD risk factors, which may require urgent decision making to address national control measures regarding CAD.


Effect of Viagra on the foveolar choroidal circulation of AMD patients.
To investigate the effects of sildenafil citrate (Viagra) on foveolar choroidal circulation in patients with age related macular degeneration (AMD). Double-blinded, randomized, placebo-controlled, crossover study. Fifteen male AMD patients received a dose of 100 mg of sildenafil or matching placebo on two separate days. Laser Doppler flowmetry was performed to assess relative choroidal blood velocity (ChB(Vel)), volume (ChB(Vol)) and flow (ChB(Flow)) in the study eye prior to administration of the drug at baseline and 30, 90, 180, 300 min after dosing. Best corrected visual acuity (BCVA), contrast sensitivity (CS), mean arterial blood pressure (BPm), heart rate (HR), intraocular pressure (IOP) and ocular perfusion pressure (PP) were determined. In comparison to placebo, sildenafil did not cause any statistically significant changes in mean ChB(Vel) (ANOVA, P=0.12), ChB(Vol) (ANOVA, P=0.24) or ChB(Flow) (ANOVA, P=0.46). There were no statistically significant changes in CS (ANOVA, P=0.59), BCVA (P=0.58), IOP (P=0.81) or HR (P=0.07) throughout the study. Significant decreases in BPm (P=0.006) and PP (P=0.006) were observed at 30 min after sildenafil. Administration of sildenafil citrate didn't cause any statistically significant changes in the foveolar choroidal circulation of AMD patients.


Deep phenotyping the cervical spine: automatic characterization of cervical degenerative phenotypes based on T2-weighted MRI.
Radiological degenerative phenotypes provide insight into a patient's overall extent of disease and can be predictive for future pathological developments as well as surgical outcomes and complications. The objective of this study was to develop a reliable method for automatically classifying sagittal MRI image stacks of cervical spinal segments with respect to these degenerative phenotypes. We manually evaluated sagittal image data of the cervical spine of 873 patients (5182 motion segments) with respect to 5 radiological phenotypes. We then used this data set as ground truth for training a range of multi-class multi-label deep learning-based models to classify each motion segment automatically, on which we then performed hyper-parameter optimization. The ground truth evaluations turned out to be relatively balanced for the labels disc displacement posterior, osteophyte anterior superior, osteophyte posterior superior, and osteophyte posterior inferior. Although we could not identify a single model that worked equally well across all the labels, the 3D-convolutional approach turned out to be preferable for classifying all labels. Class imbalance in the training data and label noise made it difficult to achieve high predictive power for underrepresented classes. This shortcoming will be mitigated in the future versions by extending the training data set accordingly. Nevertheless, the classification performance rivals and in some cases surpasses that of human raters, while speeding up the evaluation process to only require a few seconds.


Antibody response after third dose of COVID-19 mRNA vaccination in allogeneic hematopoietic stem cell transplant recipients is comparable to that in healthy counterparts.
To determine the efficacy of SARS-CoV-2 mRNA vaccination for allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, we measured antibody titer serially in 92 allo-HSCT patients. Among the evaluable 87 patients, median age at vaccination was 53 years (range, 18-75). The average time between allo-HSCT and vaccination was 3.3 years (range, 0.5-15.7). One month after the second dose, 70 patients (80.5%) had a positive response, whereas 17 patients (19.5%) had a negative response (< 20 U/mL). Only patients older than 44 years had a negative response. Low IgM level was the only significant predictor of vaccine failure in elderly patients. When antibody response before and after the third vaccination was examined in 47 patients, antibodies increased significantly from a median of 18.3 U/mL to 312.6 U/mL (P < 0.01). The median antibody titer after the third vaccination of healthy individuals (n = 203) was 426.4 U/mL, which was comparable to that of patients (P = 0.2). The antibody titer after the third mRNA vaccination increased even in patients whose first two mRNA vaccinations failed. These findings suggest that allo-HSCT recipients should receive the mRNA vaccine regularly.


Stabilization of parameter estimates from multiexponential decay through extension into higher dimensions.
Analysis of multiexponential decay has remained a topic of active research for over 200 years. This attests to the widespread importance of this problem and to the profound difficulties in characterizing the underlying monoexponential decays. Here, we demonstrate the fundamental improvement in stability and conditioning of this classic problem through extension to a second dimension; we present statistical analysis, Monte-Carlo simulations, and experimental magnetic resonance relaxometry data to support this remarkable fact. Our results are readily generalizable to higher dimensions and provide a potential means of circumventing conventional limits on multiexponential parameter estimation.


Separation of Enantiomers of a Phospholipid in Langmuir Monolayers by a New Selector.
Chiral discrimination in a racemic mixture of dipalmitoylphosphatidylcholine (DPPC) is induced by a new selector at the water-air interface: L-DPPC is segregated in the condensed phase of a Langmuir monolayer upon interactions with an enantiopure amphiphilic compound.


The effect of aging on cognate function and development of immune memory.
Immunological memory is one of the central features of the immune system and can be described as the ability of the immune system to respond more efficiently to a second encounter with the same pathogen. The immune system is dramatically affected by age-related changes and it is becoming apparent that immune memory exhibits significant defects as a result of aging. Although immune memory generated during youth functions well into old age, that generated later in life functions poorly. Importantly, age-related defects in the cognate helper function of CD4(+) T cells can potentially influence the development of both humoral and cell-mediated immune memory. These defects ultimately result in aged individuals who exhibit reduced responses to both infections and vaccinations.


Histone demethylase Utx regulates differentiation and mineralization in osteoblasts.
Alteration of methylation status of lysine 27 on histone H3 (H3K27) associates with dramatic changes in gene expression in response to various differentiation signals. Demethylation of H3K27 is controlled by specific histone demethylases including ubiquitously transcribed tetratricopeptide repeat X chromosome (Utx). However, the role of Utx in osteoblast differentiation remains unknown. In this study, we examined whether Utx should be involved in osteoblast differentiation. Expression of Utx increased during osteoblast differentiation in MC3T3-E1 cells and primary osteoblasts. GSK-J1, a potent inhibitor of H3K27 demethylase, increased the levels of trimethylated H3K27 (H3K27me3) and decreased the expressions of Runx2 and Osterix and ALP activity in MC3T3-E1 cells. Stable knockdown of Utx by shRNA attenuated osteoblast differentiation and decreased ALP activity, calcium content, and bone-related gene expressions. Silencing of Utx increased the level of H3K27me3 on the promoter regions of Runx2 and Osterix and decreased the promoter activities of Runx2 and Osterix. Taken together, our present results propose that Utx plays important roles in osteoblast differentiation by controlling the expressions of Runx2 and Osterix.


A relationship between diffusional transport in lipid membranes and a lipophilic-eutectic parameter.
A theoretical model has been developed to relate passive diffusional transport with a parameter termed the lipophilic-eutectic coefficient, Le. Based on this parameter it is proposed that the lipophilicity of a substance can be estimated. The method is based on the melting point lowering of a pure substance in the presence of an impurity of similar structure. Cholesterol was chosen as a model biological lipid because it is a neutral lipid that is found in relatively high concentrations in a variety of membranes. Transdermal absorption in humans and intestinal absorption in the rat both show a high degree of correlation with respect to Le. For our studies, Le appears to be as satisfactory as the partition coefficient for estimating lipophilicity and its determination is less demanding analytically.


Direct observation of valence band splitting using room temperature photoluminescence of CdS hollow submicrospheres.
The room-temperature photoluminescence spectra of CdS hollow submicrospheres prepared via employing silica hard templates and microwave irradiation present a profound insight into the quantum confinement-induced splitting of electron and hole states in the valence band.


Oligonucleotide and plasmid DNA packaging into polyoma VP1 virus-like particles expressed in Escherichia coli.
The drug delivery system described here is based on the properties of the capsoid or capsid-like structure resulting from the assembly of polyoma virus capsid protein VP1 expressed in Escherichia coli. The capsid protein VP1 was expressed as a fusion protein with a completely removable N-terminal His6 affinity tag. The pentameric morphology of the recombinant VP1 protein was confirmed by electron microscopy after affinity chromatography and factor Xa cleavage under conditions of low ionic strength. The self-assembly of VP1 capsoids can be induced from purified VP1 pentamers by increasing the ionic strength with (NH4)2SO4. These VP1 capsoid particles were packed in vitro with anti-sense oligonucleotides and plasmid DNA. The loading with DNA was pH-dependent. We observed the highest efficiency at pH 5. DNase I treatment of particles with encapsidated material showed that 37-55% of the bound oligonucleotides and fragments of 1.5-1.8 kb double-stranded DNA were protected against degradation.


Relationship of QRS amplitude to left ventricular dimensions after acute blood volume reduction in normal subjects.
The relationship between the acute reduction in left ventricular dimensions induced by intravenous frusemide and scalar electrocardiographic QRS amplitude was studied in 14 normal subjects. The major electrocardiographic change was a significant increase in QRS voltages inversely proportional to the changes in left ventricular dimensions. This effect was opposite to the change predicted by the Brody effect. Surface electrocardiographic voltages are greatly influenced by myocardial cell orientation and the effective dipoles of the wave of activation are parallel to the long axes of cardiac fibres. As in the normal ventricle the arrangement of fibres is mainly circumferential, the body surface potentials are strongly affected by longitudinal wave front voltages. We suggest that during acute reduction of blood volume the inverse relationship of left ventricular volume and QRS amplitude can be explained by a reduced short-circuiting effect of blood mass on a longitudinally directed wave of activation.


Recalcitrant hypocalcemia after thyroidectomy in patients with previous Roux-en-Y gastric bypass.
Hypocalcemia is a potential complication after thyroidectomy. Patients with previous roux-en-Y gastric bypass (RYGBP) may be at increased risk for recalcitrant symptomatic hypocalcemia after thyroidectomy. This complication is poorly described and there is no current consensus on optimal management in this unique population. All patients from 2000 to 2012 who underwent thyroidectomy with history of preceding RYGBP were identified retrospectively. Each of the 19 patients meeting inclusion criteria were matched 2:1 for age, gender, and body mass index (BMI) to a cohort who underwent thyroidectomy without previous RYGBP. The study cohort and matched controls were compared for incidence of symptomatic postoperative hypocalcemia, requirement of intravenous (IV) calcium supplementation, and duration of hospital stay. Age, proportion of female patients, and BMI were equivalent between cases (n = 19) and controls (n = 38). Comparison of primary outcomes demonstrated that the study group had a significantly higher incidence of symptomatic hypocalcemia (42% vs. 0%; P < .01), administration of IV calcium (21% vs. 0%; P < .01), and duration of hospital stay (2.2 vs. 1.2 days, P = .02). Patients with previous RYGBP have a greater incidence of recalcitrant symptomatic hypocalcemia after thyroidectomy, resulting in prolonged duration of hospital stay. In this patient population, calcium levels should be closely monitored and early calcium and vitamin D supplementation initiated preemptively.


Prognostic significance of clinical grading of patients envenomed by Bothrops lanceolatus in Martinique. Members of the Research Group on Snake Bite in Martinique.
The correlation between clinical grading of patients bitten by Bothrops lanceolatus and the subsequent development of their envenoming was examined. Severity of envenoming was graded using a 1-4 scale (minor to major). Patients were classified into 2 groups according to the time elapsed between bite and treatment with a specific purified equine F(ab')2 antivenom. The late/no treatment group (n = 33) was characterized by a systemic thrombotic complication rate of 14/33 (42.4%) leading to 4 deaths, which increased with the maximum severity assessed on the first day following the bite (P = 0.003). However, infarctions could develop in patients who presented initially with signs of moderate envenoming, normal blood clotting and low serum levels of venom antigens. No such complication of fatality occurred in the early (0.5-6 h) treatment group (n = 70). Multiple regression analysis showed that duration of stay in hospital in this group increased with the length of the snake (P = 0.017), venom antigenaemia (P = 0.016), initial grading (P < 0.001), and with the need for surgical debridement (n = 10/70, P < 0.001). Outcome was correlated with initial severity of envenoming. However, the only factor with a positive prognostic significance for the individual envenomed patient was the early infusion of specific antivenom, which led to 100% recovery in our series.


[Primary hyperparathyroidism: parathyroid scintigraphy and ultrasound in problem patients].
In a retrospective study, the sensitivity of parathyroid scintigraphy and ultrasound was investigated in patients with primary hyperparathyroidism (HPT) with prior histories of surgery of the thyroid or parathyroid (unsuccessful or recidive). Preoperative ultrasound and parathyroid scintigraphy were performed on 65 patients who had had successful surgery and on 12 who had had unsuccessful surgery. The scintigraphy was carried out using a combined double phase/double nuclide technique with 300-600 MBq 99mTc-sestamibi for parathyroid imaging and 80-100 MBq 99mTc-pertechnetate for thyroid imaging. The sensitivity of parathyroid scintigraphy was 86% in patients with normal thyroid glands, 77% in those with recurrent goiter, and 62% in those with recurrent or persistent HPT. The ultrasound sensitivity was 86%, 50%, and 57% respectively. The sensitivity of parathyroid scintigraphy and ultrasound decreases considerably after surgery. That of parathyroid scintigraphy lay significantly below results published to date. However, parathyroid scintigraphy should be performed precisely in these cases, because the number of alternative parathyroid imaging methods aside from ultrasound are limited.


High-performance liquid chromatographic method for stability and pharmacokinetic studies of nicorandil.
Nicorandil is a unique vasodilator that combines the actions of a potassium channel activator and a nitrovasodilator. Little literature is available on its chemical stability and pharmacokinetics in animals. We developed a simple, specific, sensitive, and precise high-performance liquid chromatographic method for the determination of nicorandil in aqueous solution and rat plasma, achieving a detection limit of 0.3 microgram/ml with 180-microliters samples. Nicorandil was found to be relatively stable between pH 2 and 10 at 37 degrees C (half-life = 461-84 h) and it is subjected to specific base catalysis above pH 10. Both chemical degradation and in vivo metabolism produced N-(2-hydroxyethyl)nicotinamide, the denitrated product. Preliminary pharmacokinetic investigations showed that the assay is capable of quantitating nicorandil in rat plasma over a range of 0.3-100 micrograms/ml. These studies also suggested that the pharmacokinetics of nicorandil are dose-dependent.


Detection of cocaine and its polar transformation products and metabolites in human urine.
This paper describes a method for the analysis of thermal degradation compounds generated from cocaine during the smoking process, together with chemical and enzymatic biotransformation products which, by virtue of their polarity, are not recovered by existing analytical procedures. The method employs cation exchange solid phase extraction coupled with gas chromatography/mass spectrometry. Compounds identified in urine from subjects of cocaine-related death included cocaine, benzoylecgonine, ecgonine methyl ester and ecgonine, which were measured quantitatively, and ecgonidine, ecgonidine methyl ester, ecgonine ethyl ester, ethyl benzoylecgonine, norcocaine, benzoylnorecgonine, cinnamoylcocaine, and cinnamoylecgonine. The concentrations of ecgonine (0-104 micrograms/ml) and ecgonine methyl ester (0-177 micrograms/ml) were substantial and averaged about one tenth the concentrations of benzoylecgonine (0-1074 micrograms/ml) and cocaine (0-1221 micrograms/ml). These and several of the other compounds identified will be valuable markers for cocaine use, in degraded samples and for indicating the route of administration.


Effect of Creatine Supplementation Dosing Strategies on Aging Muscle Performance.
This study compared the effects of different creatine supplementation dosages, independent of resistance training, on aging muscle performance and functionality. Using a double-blind, repeated measures design, participants were randomized to one of three groups: Creatine-High (CR-H; n=11; 0.3 g/kg/day of creatine + 0.1 g/kg/day of maltodextrin), Creatine-Moderate (CR-M: n=11; 0.1 g/kg/day of creatine + 0.3 g/kg/day of maltodextrin) or Placebo (PLA; n=11; 0.4 g/kg/day of maltodextrin) for 10 consecutive days. The primary dependent variables measured at baseline and after supplementation included muscle strength (1-repetition maximum leg press, chest press, hand-grip), muscle endurance (leg press and chest press; maximal number of repetitions performed for 1 set at 80% and 70% baseline 1-repetition maximum respectively), and physical performance (dynamic balance). There was a significant increase over time for muscle strength (Leg press: CR-H pre 161.5 ± 55.1 kg, post 169.2 ± 59.2 kg; CR-M pre 145.2 ± 47.7 kg, post 151.7 ± 45.0 kg; PLA pre 163.7 ± 51.5 kg, post 178.2 ± 65.6 kg, p = 0.001; Chest press: CR-H pre 57.0 ± 26.2 kg, post 58.8 ± 28.0 kg; CR-M pre 54.5 ± 27.9 kg, post 56.8 ± 30.1 kg; PLA pre 55.1 ± 26.9 kg, post 58.5 ± 30.1 kg, p = 0.001) and endurance (Leg press: CR-H pre 17.1 ± 6.0 reps, post 21.0 ± 7.2 reps; CR-M pre 24.1 ± 11.6 reps, post 29.1 ± 17.0 reps; PLA pre 23.8 ± 9.7 reps, post 29.5 ± 11.9 reps, p = 0. 001; Chest press: CR-H pre 15.6 ± 2.7 reps, post 18.9 ± 2.7 reps; CR-M pre 18.0 ± 5.0 reps, post 19.9 ± 7.1 reps; PLA pre 20.5 ± 6.2 reps, post 21.6 ± 5.5 reps, p = 0. 001), with no other differences. Short-term creatine supplementation, independent of dosage and resistance training, has no effect on aging muscle performance.


Surgical Resection of the Primary Tumor in Stage IV Colorectal Cancer Without Metastasectomy is Associated With Improved Overall Survival Compared With Chemotherapy/Radiation Therapy Alone.
Controversy exists over whether resection of the primary tumor in stage IV colorectal cancer with inoperable metastases improves patient outcomes. The purpose of this study was to evaluate whether resection of the primary tumor without metastasectomy in patients with stage IV colorectal cancer is associated with improved overall survival compared with patients undergoing chemotherapy and/or radiation therapy alone. This was a retrospective review of a multi-institutional dataset. This study was conducted in all participating commission on cancer (CoC)-accredited facilities. The 2003-2006 National Cancer Data Base was reviewed to identify patients with stage IV adenocarcinoma of the colon or rectum who underwent palliative treatment without curative intent, either in the form of surgical resection of the primary tumor without metastasectomy consisting of a colectomy or rectal resection with or without chemotherapy and/or radiation or chemotherapy and/or radiation alone. Groups were compared for baseline characteristics. Overall survival was compared using Kaplan-Meier analysis before and after propensity matching with a 1:1 nearest-neighbor algorithm. Of the 1446 patients included in the analysis, 231 (16%) underwent surgical resection of the primary tumor without metastasectomy. Surgical resection was associated with a significant survival benefit on unadjusted analysis (median survival, 9.2 vs. 7.6 months; p < 0.01). After propensity matching to adjust for nonrandom treatment selection, surgical resection continued to be associated with a significant survival benefit (median survival, 9.2 vs. 7.3 months; p < 0.01). This study was limited by the potential for selection bias regarding which patients received surgical resection. There was also a lack of data regarding the indication for operation, specifically whether a patient was symptomatic or asymptomatic before resection. The inability to account for tumor size or grade among patients who did not receive surgical resection was another limitation. Surgical resection of the primary tumor without metastasectomy in patients with metastatic colorectal cancer is associated with improved survival as compared with chemotherapy/radiation therapy alone. Additional research is necessary to determine which patients may benefit from this intervention.


Perivascular epithelioid tumor of urinary bladder and vagina.
Perivascular epithelioid cell tumors are recently characterized neoplasms composed of large clear HMB-45-positive epithelioid cells arranged in an organoid pattern. The histogenesis of these neoplasms remain obscure. We report here 2 such tumors in young female patients aged 19 and 16 years involving the urinary bladder and vagina, respectively (in the absence of the tuberous sclerosis complex) . Microscopically, both tumors were composed of perivascularly arranged cells with granular eosinophilic fluffy cytoplasm, round-to-oval nuclei, and prominent nucleoli. Melanin pigmentation was present in the vaginal tumor. Immunohistochemically, both tumors strongly expressed HMB-45. They were negative for cytokeratin, vimentin, and S-100. The vaginal tumor recurred 10 months after resection and chemotherapy. The patient with the bladder tumor was lost to follow-up.


Astrocyte endfoot formation controls the termination of oligodendrocyte precursor cell perivascular migration during development.
Oligodendrocyte precursor cells (OPCs) undergo an extensive and coordinated migration in the developing CNS, using the pre-formed scaffold of developed blood vessels as their physical substrate for migration. While OPC association with vasculature is critical for dispersal, equally important for permitting differentiation and proper myelination of target axons is their appropriate and timely detachment, but regulation of this process remains unclear. Here we demonstrate a correlation between the developmental formation of astrocytic endfeet on vessels and the termination of OPC perivascular migration. Ex vivo and in vivo live imaging shows that astrocyte endfeet physically displace OPCs from vasculature, and genetic abrogation of endfoot formation hinders both OPC detachment from vessels and subsequent differentiation. Astrocyte-derived semaphorins 3a and 6a act to repel OPCs from blood vessels at the cessation of their perivascular migration and, in so doing, permit subsequent OPC differentiation by insulating them from a maturation inhibitory endothelial niche.


In vitro assessment of the upper gastrointestinal tolerance of potential probiotic dairy propionibacteria.
This study aimed to assess the transit tolerance of potential probiotic dairy propionibacteria strains in human upper gastrointestinal tract in vitro, and to evaluate the effect of food addition on viability of these strains in simulated pH 2.0 gastric juices. The transit tolerance of 13 dairy propionibacteria strains was determined at 37 degrees C by exposing washed cell suspensions to simulated gastric juices at pH values at 2.0, 3.0, and 4.0, and simulated small intestinal juices (pH 8.0) with or without 0.3% bile salts. The viability of dairy propionibacteria in pH 2.0 simulated gastric juice with So-Good original soymilk or Up & Go liquid breakfast was also determined. The simulated gastric transit tolerance of dairy propionibacteria was strain-dependent and pH-dependent. All tested strains were tolerant to simulated small intestinal transit. The addition of So-Good original soymilk or Up & Go liquid breakfast greatly enhanced the survival of dairy propionibacteria strains in pH 2.0 simulated gastric juices. Dairy propionibacteria strains demonstrate high tolerance to simulated human upper gastrointestinal tract conditions and offer a relatively overlooked, yet alternative source for novel probiotics besides Lactobacillus and Bifidobacterium.


FAR gene enables the brown planthopper to walk and jump on water in paddy field.
Many insects can live on water and survive being caught in the rain. Current research has shown that insect cuticular hydrocarbons (CHC) confer desiccation resistance to maintain water balance. In this study, we identified a fatty acyl-CoA reductase gene (NlFAR) of the rice brown planthopper, Nilaparvata lugens that is essential for the production of CHCs, and found that NlFAR is essential for N. lugens to walk and jump on water when moving from one rice plant to another in paddy fields. NlFAR was mainly expressed in the integument at the beginning of each molt. Cuticular surface analysis by scanning electron microscopy and characterization of CHC extracts indicated that N. lugens with knockdown of NlFAR using RNA inference (RNAi) had a neater epicuticle layer and a significant decrease in CHC contents. Knockdown of NlFAR did not influence the desiccation resistance of N. lugens, but the dsNlFAR-treated insects were easily adhered and moistened by water droplets or their own secreted honeydew and unable to walk or jump on water. These results suggested that NlFAR is a crucial enzyme for CHC biosynthesis and cuticle waterproofing, but not for water retention of N. lugens, which may provide a potential strategy for pest management.


Intensity difference thresholds assessed with eighth nerve and auditory cortex potentials: compared values from cochlear and vascular responses.
In normal guinea pigs the eighth nerve compound action potential shows a latency of about 1 ms and the evoked early potential at the auditory cortex occurs after about 10 ms. Determination of auditory sensitivity with both responses using tone-bursts of variable rise/fall time and plateau duration showed they are responses to the onset of the stimulus since the existence of a plateau has no effect. Increases in stimulus rise time diminish the synchrony of both responses, the limits were found to be 2 ms for eighth nerve responses and 10 ms for cortical potentials. Amplitude modulation of continuous tones using these time values evokes clear responses at levels which apparently correspond to intensity difference thresholds measured behaviorally by other authors. Similar measures were performed on saccular acoustic responses, using the model of selective cochlear destruction. Evoked responses could also be observed at levels of amplitude modulation similar to those of normal animals. This fine sensitivity reinforces the idea of a functionality of the saccular acoustic reception.


Naloxone-sensitive potentiation at granule cell synapses in the ventral dentate gyrus and stress ulcers.
Continuous perfusion of the granule cells in the ventral dentate gyrus with naloxone blocked the long-term potentiation (LTP) induced by high-frequency electrical stimulation of the posterolateral amygdala in freely-moving rats. This treatment also aggravated the stomach ulceration produced by cold restraint. LTP, on the other hand, attenuated the gastric stress pathology. It was suggested that a naloxone-sensitive granule cell gate modulates the impact of environmental stressors.


Menopause transition: Physiology and symptoms.
With life expectancy for women on the rise, most women will experience menopausal transition and spend a significant number of years of their life in the menopausal phase. Menopausal transition involves a myriad of physical, endocrine, and psychological changes which are influenced by ethnic, psychological, and socio-cultural factors. Every woman's experience of the menopausal transition is unique, and a one-size-fits-all approach to the management of symptoms does not work. An understanding of the pathophysiology and severity of menopausal symptoms and the benefits and risks associated with both hormonal and non-hormonal treatments is important when individualising treatment options for menopausal symptoms.


Correlation between in vitro growth rate and in vivo virulence in Aspergillus fumigatus.
We describe a kinetic microbroth method of measuring the growth rate of Aspergillus fumigatus spectrophotometrically. Using this method, growth rates were determined for nine A. fumigatus isolates for which an LD90 value in immunosuppressed CD-1 mice had previously been obtained. Comparison of the growth rates and LD90 values of these isolates suggests that a correlation exists between the two parameters.


Improved prediction of protein-protein interactions using novel negative samples, features, and an ensemble classifier.
Computational methods are employed in bioinformatics to predict protein-protein interactions (PPIs). PPIs and protein-protein non-interactions (PPNIs) display different levels of development, and the number of PPIs is considerably greater than that of PPNIs. This significant difference in the number of PPIs and PPNIs increases the cost of constructing a balanced dataset. PPIs can be classified as either physical or genetic. However, ready-made PPNI databases were proven only to have no physical interactions and were not proven to have no genetic interactions. Hence, ready-made PPNI databases contain false negative non-interactions. In this study, two PPNI datasets were artificially generated from a PPI database. In contrast to various traditional PPI feature extraction methods based on sequential information, two types of novel feature extraction methods were proposed. One is based on secondary structure information, and the other is based on the physicochemical properties of proteins. The experimental results of the RandomPairs dataset validate the efficiency and effectiveness of the proposed prediction model. These results reveal the potential of constructing a PPI negative dataset to reduce false negatives. Related datasets, tools, and source codes are accessible at http://lab.malab.cn/soft/PPIPre/PPIPre.html.


Evaluation of health-care utilization among adult patients with epilepsy in Germany.
This study evaluated the resource use of patients with epilepsy in the German district of Marburg-Biedenkopf. A cross-sectional cohort of consecutive adults with epilepsy, irrespective of seizure severity, duration of illness and epilepsy syndrome, was investigated in all health-care sectors. Costs of inpatient and outpatient treatment were derived from billing data of participating hospitals and office-based physicians. Data on socioeconomic status, course of epilepsy and further direct and indirect costs were recorded using patient questionnaires. We enrolled 366 patients from the district of Marburg-Biedenkopf and calculated annual epilepsy-specific costs of €7738 per patient. Direct costs contributed 31.1% (€2406) and indirect costs 68.9% (€5332) of the total costs. Direct medical costs were mainly due to hospitalization (33.2% of total direct costs) and anticonvulsants (26.7%). Costs of admissions were due to status epilepticus (24.4%), video-EEG monitoring (14.8%), newly diagnosed patients (14.4%) and seizure-related injuries (8.8%). Indirect costs were mainly due to early retirement (38.0%), unemployment (35.9%) and days off due to seizures (26.2%). The mean costs of epilepsy found in our study were lower than those found in studies conducted at European epilepsy centers due to the inclusion of patients in all health-care sectors.


Shunt-based interventions: Why, how, and when to place a shunt.
The broad categories of surgical fetal therapy can be separated into either open surgical techniques or minimally invasive endoscopic/ultrasound-guided techniques that require only puncture of the uterus with single or multiple small ports. Benefits of fetoscopic or ultrasound-guided fetal intervention include decreased uterine irritability, decreased incidence of preterm labor, and avoidance of risks associated with hysterotomy and commitment to cesarean delivery for future pregnancies. Fetal abnormalities potentially amenable to ultrasound-guided drainage techniques include thoracic fluid-filled lesions and lower urinary tract obstruction.


Frontotemporal dementia and mitochondrial DNA transitions.
Frontotemporal dementia (FTD) is the second most common type of primary degenerative dementia. Some patients present an overlap between Alzheimer's disease (AD) and FTD both in neuropathological and clinical aspects. This may suggest a similar overlap in physiopathology, namely an involvement of mitochondrial DNA (mtDNA) in FTD, as it has been associated to AD. To determine if mtDNA is involved in FTD, we performed a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis, specific to mtDNA NADH Dehydrogenase subunit 1 (ND1) nucleotides 3337-3340, searching for mutations previously described in Parkinson's and AD patients. We could identify one FTD patient with two mtDNA transitions: one already known (3316 G-to-A) and another unreported (3337 G-to-A). Additionally, mitochondrial respiratory chain complex I activity was reduced in leukocytes of this patient (36% of the control mean activity). To our knowledge, this is the first report of mtDNA variants in FTD patients.


Incomplete expression of the MOPC 460 idiotype in the sera of BALB/c mice immunized either with DNP antigen or with anti-idiotypic antibodies.
The MOPC 460 idiotype, as defined by polyclonal probes, has been described as a recurrent marker among the anti-DNP antibodies synthetized by IghCa mice. In this paper, we demonstrate, using syngeneic monoclonal anti-idiotypic probes, that only a part of the idiotopes of this idiotype are indeed recurrently expressed in BALB/c mice (IghCa) after immunization with DNP antigen. We will also show that the immunization of BALB/c mice with monoclonal anti-idiotypic antibody specific for the recurrent determinant results firstly in the synthesis of anti-DNP antibodies and secondly in the expression of the same recurrent M460 idiotope present on a part of induced anti-DNP molecules. Contrary to this, the immunization with the monoclonal anti-idiotypic antibody specific for the private idiotope never resulted in the synthesis of anti-DNP antibodies. These results clearly suggest that, after DNP or anti-idiotypic immunization, the M460 idiotype is not expressed in its entirety.


Fluoroscopy Learning Curve in Hip Arthroscopy-A Single Surgeon's Experience.
To determine if (1) absorbed radiation dose and (2) fluoroscopy time decreased with experience over the first 100 cases of a single surgeon's hip arthroscopy practice. Subjects who underwent hip arthroscopy for symptomatic femoroacetabular impingement and labral injury were eligible for analysis. Inclusion criteria included the first 100 subjects who underwent hip arthroscopy by a single surgeon (December 2013 to December 2014). Subject demographics, procedure details, fluoroscopy absorbed dose (milligray [mGy]), and time were recorded. Subjects were categorized by date of surgery to one of 4 possible groups (25 per group). One-way analysis of variance was used to determine if a significant difference in dose (mGy) or time was present between groups. Simple linear regression analysis was performed to determine the relation between case number and both radiation dose and fluoroscopy time. Subjects underwent labral repair (n = 93), cam osteoplasty (n = 90), and pincer acetabuloplasty (n = 65). There was a significant (P < .001 for both) linear regression between case number and both radiation dose and fluoroscopy time. A significant difference in mGy was observed between groups, group 1 the highest and group 4 the lowest amounts of radiation (P = .003). Comparing individual groups, group 4 was found to have a significantly lower amount of radiation than group 1 (P = .002), though it was not significantly lower than that of group 2 (P = .09) or group 3 (P = .08). A significant difference in fluoroscopy time was observed between groups, group 1 the highest and group 4 the lowest times (P = .05). Comparing individual groups, group 4 was found to have a significantly lower fluoroscopy time than group 1 (P = .039). Correction for weight, height, and body mass index all revealed the same findings: significant (P < .05) differences in both dose and time across groups. The absorbed dose of radiation and fluoroscopy time decreased significantly over the first 100 cases of a single surgeon's hip arthroscopy practice learning curve. Level IV, therapeutic, retrospective, noncomparative case series.


The Longitude-Latitude-Loop Used for Complex Bankart Lesion Repair: An All-Arthroscopic Technique.
The most frequent operation for anterior shoulder instability is the arthroscopic Bankart repair, which has a positive outcome and a low rate of complications. A variety of restoration procedures have been reported to reconstruct labral height and reproduce a dynamic concavity-compression reaction. The longitude-latitude loop is a knotless high-strength suture method that simultaneously tightens the joint capsule in the warp and weft direction and resists tearing. The suture method is safe and reproducible. This study aimed to present a longitude-latitude loop suture for joint capsule labral complex repair during Bankart arthroscopy surgery.


Evaluation of Intermittent Hemodialysis in Critically Ill Cancer Patients with Acute Kidney Injury Using Single-Pass Batch Equipment.
Data on renal replacement therapy (RRT) in cancer patients with acute kidney injury (AKI) in the intensive care unit (ICU) is scarce. The aim of this study was to assess the safety and the adequacy of intermittent hemodialysis (IHD) in critically ill cancer patients with AKI. In this observational prospective cohort study, 149 ICU cancer patients with AKI were treated with 448 single-pass batch IHD procedures and evaluated from June 2010 to June 2012. Primary outcomes were IHD complications (hypotension and clotting) and adequacy. A multiple logistic regression was performed in order to identify factors associated with IHD complications (hypotension and clotting). Patients were 62.2 ± 14.3 years old, 86.6% had a solid cancer, sepsis was the main AKI cause (51%) and in-hospital mortality was 59.7%. RRT session time was 240 (180-300) min, blood/dialysate flow was 250 (200-300) mL/min and UF was 1000 (0-2000) ml. Hypotension occurred in 25% of the sessions. Independent risk factors (RF) for hypotension were dialysate conductivity (each ms/cm, OR 0.81, CI 0.69-0.95), initial mean arterial pressure (each 10 mmHg, OR 0.49, CI 0.40-0.61) and SOFA score (OR 1.16, CI 1.03-1.30). Clotting and malfunctioning catheters (MC) occurred in 23.8% and 29.2% of the procedures, respectively. Independent RF for clotting were heparin use (OR 0.57, CI 0.33-0.99), MC (OR 3.59, CI 2.24-5.77) and RRT system pressure increase over 25% (OR 2.15, CI 1.61-4.17). Post RRT blood tests were urea 71 (49-104) mg/dL, creatinine 2.71 (2.10-3.8) mg/dL, bicarbonate 24.1 (22.5-25.5) mEq/L and K 3.8 (3.5-4.1) mEq/L. IHD for critically ill patients with cancer and AKI offered acceptable hemodynamic stability and provided adequate metabolic control.


Theogallin and L-theanine as active ingredients in decaffeinated green tea extract: I. electrophysiological characterization in the rat hippocampus in-vitro.
The in-vitro hippocampus slice preparation was used to mimic a physiological situation where nervous tissue is exposed directly to the water soluble extract of green tea and some of its constituents. This investigation provides evidence that L-theanine- and theogallin-enriched decaffeinated green tea extract is able to change the physiological pattern of electrical hippocampus activity in a concentration dependent manner (EC50 3 mg L(-1)). Of the seven fractions or single components tested (fraction containing all amino acids without L-theanine, fractions containing all amino acids plus L-theanine, glutamic acid, theogallin, its metabolites quinic acid and gallic acid, and L-theanine alone), glutamic acid produced the strongest changes in terms of increased population spike amplitude after single stimuli and increased long-term potentiation, commonly taken as representative for enhancement of spatial and time dependent memory. The presence of theogallin alone shifted the activity in the same direction. Similar results as with theogallin were obtained in the presence of quinic acid. No effect was seen with gallic acid. Opposite changes (decrease of population spike amplitude and attenuated long-term potentiation) were observed in the presence of L-theanine alone. No effects were detected during the addition of the amino acid mixture unless L-theanine was added, leading to a decrease of the responses as observed for the action of L-theanine alone. The results provide evidence for the involvement of several active principles in the action of enriched green tea extract on electrical brain activity. The overall enhancement of hippocampal pyramidal cell responses as observed for the crude extract seems to be due to the combined action of glutamic acid and theogallin (or its presumable metabolite quinic acid), whereas L-theanine seems to have an opposite effect. However, this action was not strong enough to antagonize the effects of glutamic acid and theogallin. The results are in line with the observation that the tested green tea extract improves cognition at concomitant mental relaxation in man.


The relationship between land cover and microbial community composition in European lakes.
Microbes are essential for element cycling and ecosystem functioning. However, many questions central to understanding the role of microbes in ecology are still open. Here, we analyze the relationship between lake microbiomes and the lakes' land cover. By applying machine learning methods, we quantify the covariance between land cover categories and the microbial community composition recorded in the largest amplicon sequencing dataset of European lakes available to date. Our results show that the aggregation of environmental features or microbial taxa before analysis can obscure ecologically relevant patterns. We observe a comparatively high covariation of the lakes' microbial community with herbaceous and open spaces surrounding the lake; nevertheless, the microbial covariation with land cover categories is generally lower than the covariation with physico-chemical parameters. Combining land cover and physico-chemical bioindicators identified from the same amplicon sequencing dataset, we develop analytical data structures that facilitate insights into the ecology of the lake microbiome. Among these, a list of the environmental parameters sorted by the number of microbial bioindicators we have identified for them points towards apparent environmental drivers of the lake microbial community composition, such as the altitude, conductivity, and area covered herbaceous vegetation surrounding the lake. Furthermore, the response map, a similarity matrix calculated from the Jaccard similarity of the environmental parameters' lists of bioindicators, allows us to study the ecosystem's structure from the standpoint of the microbiome. More specifically, we identify multiple clusters of highly similar and possibly functionally linked ecological parameters, including one that highlights the importance of the calcium-bicarbonate equilibrium for lake ecology. Taken together, we demonstrate the use of machine learning approaches in studying the interplay between microbial diversity and environmental factors and introduce novel approaches to integrate environmental molecular diversity into monitoring and water quality assessments.


Role of radiation therapy in the management of malignant chondroid syringoma.
Malignant sweat gland neoplasms are exceedingly rare tumors. Malignant chondroid syringoma (MCS) is one of the rarest subtypes, and as such, still poorly understood. It lacks distinctive clinical features, often delaying initial diagnosis and therapeutic management. A current case and the available literature are reviewed to determine the overall clinical course of the MCS and the potential role of adjuvant therapy. A case of MCS was studied by light microscope, immunohistochemistry, and electron microscopy. The clinical data of this case and of other reported cases are summarized and compared. This tumor recurred locally after initial local excision. Subsequent re-excision and radiation therapy rendered the patient without evidence of disease. This case study and the literature review of the 20 reported cases indicate that MCS is highly recurrent with tendency toward metastasis. MCS appears to behave in an aggressive manner. An initial treatment modality is aggressive surgery. Adjuvant radiation therapy with or without chemotherapy should be tried in future cases.


Real-time measurement of transmitter release from single synaptic vesicles.
Neurotransmitter release is mediated by Ca2+ dependent exocytosis of synaptic vesicles. Neither the amount of transmitter released from individual synaptic vesicles nor the kinetics of this process have yet been directly determined. Using carbon fibres as electrochemical detectors, we have measured release of the neurotransmitter serotonin from cultured neurons of the leech. This technique allowed us to monitor transmitter discharge from single synaptic vesicles as spike-like oxidation currents at high time resolution, providing new insight into the mechanism of neuronal exocytosis. Two types of signals were characterized, corresponding to exocytosis of small clear and large dense core vesicles present in these cells. A small vesicle discharges about 4,700 transmitter molecules with a time constant in the region of 260 microseconds, whereas large vesicles release their content of approximately 80,000 molecules with a time constant of about 1.3 ms. Release from both vesicle types is initiated rapidly, with a rise time of less than 60 microseconds, suggesting an abrupt opening of a preassembled fusion pore.


Cathepsins D and L reduce the toxicity of advanced glycation end products.
Advanced glycation end product-modified proteins are known for accumulating during aging and in several pathological conditions such as diabetes, renal failure, and neurodegenerative disorders. There is little information about the intracellular fate of endocytosed advanced glycation end products (AGEs) and their influence on proteolytic systems. However, it is known that the lysosomal system is impaired during aging. Therefore, undegraded material may accumulate and play a considerable role in the development of diverse diseases. To investigate if AGEs can be degraded and to test whether they accumulate because of impaired lysosomal proteases we studied the effects of advanced glycation end products on the endosomal-lysosomal system. Five different types of AGEs were generated by bovine serum albumin incubation with glyoxal, methylglyoxal, glucose, fructose, and ribose. The first experiments revealed the uptake of AGEs by the macrophage cell line RAW 264.7. Further investigations demonstrated an increase in cathepsin D and L activity and an increase in mature cathepsins D and L. Increased activities were accompanied by the presence of more lysosomes, measured by staining with LysoTracker blue. To specify the roles of cathepsins D and L we used knockout cells to test the roles of both cathepsins on the toxicity of advanced glycation end products. In summary we conclude that both cathepsins are required for a reduction in advanced glycation end product-induced cytotoxicity.


Clarification of type material for Bornean species of the genus Osteochilus (Cyprinidae).
Two species and one subspecies of the genus Osteochilus (Cypriniformes: Cyprinidae) were described from Borneo in a revision of the group by Karnasuta in 1993. Examination of type material has illuminated points of conflict regarding some of the type specimens listed in original descriptions. Based on archived correspondence and the author's original thesis, we were able to determine the disposition of specimens and revise collection information for type material accordingly.


Functional characterization of chicken TLR5 reveals species-specific recognition of flagellin.
Mammalian Toll-like receptor 5 (TLR5) senses flagellin of several bacterial species and activates the innate immune system. The avian TLR repertoire exhibits considerable functional diversity compared to mammalian TLRs and evidence of a functional TLR5 in the avian species is lacking. In the present study we cloned and successfully expressed chicken TLR5 (chTLR5) in HeLa cells, as indicated by laser confocal microscopy. Infection of chTLR5 transfected cells with Salmonella enterica serovar Enteritidis activated NF-kappaB in a dose- and flagellin-dependent fashion. Similar NF-kappaB activation was observed with recombinant bacterial flagellin. Targeted mutagenesis of the proline residue at position 737 in the chTLR5-TIR domain was detrimental to chTLR5 function, confirming that the observed effects were conferred via chTLR5 and the MyD88 signaling pathway. Comparison of human, mouse and chicken TLR5 activation by flagellin of S. enterica serovar Typhimurium revealed that chTLR5 consistently yielded stronger responses than human but not mouse TLR5. This species-specific reactivity was not observed with flagellin of serovar Enteritidis. The species-specific TLR5 response was nullified after targeted mutagenesis of a single amino acid (Q89A) in serovar Typhimurium flagellin, while L415A and N100A substitutions had no effect. These results show that chickens express a functional TLR5 albeit with different flagellin sensing qualities compared to human TLR5. The finding that single amino acid substitutions in bacterial flagellin can alter the species-specific TLR5 response may influence the host range and susceptibility of infection.


Leptotrichia endocarditis: report of two cases from the International Collaboration on Endocarditis (ICE) database and review of previous cases.
Leptotrichia species typically colonize the oral cavity and genitourinary tract. We report the first two cases of endocarditis secondary to L. goodfellowii sp. nov. Both cases were identified using 16S rRNA gene sequencing. Review of the English literature revealed only two other cases of Leptotrichia sp. endocarditis.


Significance of blood urea nitrogen as an index of renal function in mice infected with Plasmodium berghei.
Parameters of renal function were evaluated in severe malarial infection, using mice infected with Plasmodium berghei. When 7-week-old male BALB/c mice were inoculated with 1 x 10(7) P. berghei NK65-infected red blood cells, the rodents died an average of 7.4 days after inoculation. Anemia developed on day 5 after inoculation and progressed markedly on days 6 and 7. Plasma urea nitrogen increased rapidly on day 6 or 7, after which death occurred within 24 h. In contrast, urinary urea nitrogen excretion decreased on the same day. Urinary beta-N-acetyl-D-glucosaminidase (NAG) activity increased from day 3 to day 5, then decreased to normal levels on day 7. Renal ATP concentration and energy charge decreased markedly on day 7. These data indicate that the blood oxygen supply to the tissues began to decrease on day 6 and that renal insufficiency developed in the terminal stage of infection. We concluded that even a moderate increase in the level of plasma urea nitrogen could be a useful index of renal insufficiency in this infection system.