Production and purification of Escherichia coli hemolysin.
Eight strains of Escherichia coli, isolated from patients with a urinary tract infection were investigated for production of hemolysin. Six of these produced hemolysin and one revealed maximum hemolytic activity. Three urinary and two faecal isolates were positive for mannose-resistant hemagglutination. One isolate positive for hemagglutination and giving maximum hemolytic activity was then used. Hemolysin was present in the supernatant broth and the medium of choice to obtain the optimum yield was the alkaline meat extract broth followed by brain heart infusion broth. The highest yield appeared in the exponential phase of growth. Hemolysin is a heat-labile protein, being produced optimally at pH 8. A three-stage procedure was the best method for its purification.


Treatment of central nervous system metastases: parenchymal, epidural, and leptomeningeal.
With prolonged survival from systemic therapies in the adjuvant and salvage setting, and because these agents cannot cross the intact blood-brain barrier, central nervous system metastases are becoming a therapeutic challenge in oncology. Recent therapeutic achievements include an extended use of surgery and radiosurgery. Although each of these treatment modalities has its own indications, in patients eligible for both treatments the upfront comparison of these two techniques has not been performed yet. Systemic chemotherapies and biotherapies may be effective in the management of central nervous system metastases as they may act on both neurologic and extra-central nervous system lesions. In the treatment of epidural metastases, a surgical procedure providing immediate direct circumferential decompression of the spinal cord followed by local irradiation has been demonstrated in a prospective randomized trial. The management of leptomeningeal metastases remains controversial and of limited efficacy especially in chemoresistant tumours and still relies on the combination of chemotherapy (intrathecal and intravenous) and focal radiotherapy. Aggressive treatments in patients with early diagnosis and in whom central nervous system metastases are the life-threatening location may provide a substantial increase in survival and favourably affect quality of life.


Increase diagnostic accuracy in differentiating focal type autoimmune pancreatitis from pancreatic cancer with combined serum IgG4 and CA19-9 levels.
To distinguish autoimmune pancreatitis (AIP), especially focal type, from pancreatic cancer, is a greatest challenge for clinician. The aim of the study is to compare the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of combined serum IgG4 and CA19-9 levels to differentiate AIP from pancreatic cancer by HISORt, Asian and international consensus diagnostic criteria. We measured serum IgG4, CEA, and CA19-9 levels in 188 AIP patients, 86 non-AIP chronic pancreatitis patients, and 130 pancreatic cancer patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were compared with different diagnostic criteria. We also compared the diagnostic performance in patients with or without jaundice. The serum level of IgG4 was significantly higher in AIP than those in non-AIP chronic pancreatitis and pancreatic cancer. The optimal cutoffs of IgG4 and CA19-9 to differentiate AIP from pancreatic cancer were 175 mg/dL and 85.0 U/ml based on ROC analysis. Combining IgG4 level over 280 mg/dL and CA19-9 below 85.0 U/ml could yield a best diagnostic accuracy (85.6%) to distinguishing AIP from pancreatic cancer in all of the HISORt, Asian and international consensus diagnostic criteria. With the combination of serological test, focal type AIP could be diagnosed with comparable accuracy as diffuse type AIP. Our study demonstrated that combined use of serum IgG4 (over 280 mg/dL) and CA19-9 9 (below 85.0 U/ml) together increases the diagnostic accuracy to distinguish AIP from pancreatic cancer non-invasively, especially in focal type autoimmune pancreatitis.


[Reevaluation of melancholic depression].
15 operational definitions for melancholic depression and their validation studies are reviewed. None of these definitions have yet been conclusively validated. Using a different approach, we attempt to validate melancholic symptoms rather than operational definitions for melancholia. The aim is to define, by means of a review of genetic, biological and therapeutical studies, a "biological symptomatic profile" that responds to somatic therapies. Psychomotor and appetite disturbances, early awakening, anhedonia and psychotic symptoms seem more likely to reflect this biological dysfunction in melancholia. Confounding variables such as symptom stability, severity of depression and possible subtypes of melancholia are also discussed.


Metal-bound claMP Tag inhibits proteolytic cleavage.
Biologics can be an improvement to small molecule drugs, providing high specificity for an identified target, lowering toxicity and limiting side effects. To achieve effective delivery, the biologic must have sufficient time to reach the target tissue. A prolonged half-life in the circulating environment is desired, but often serum stability is limited by proteases. Proteolysis in the serum causes degradation and inactivation as the biologic is fragmented and more rapidly cleared from the body. To improve the circulating half-life, large, hydrophilic polymers may be conjugated or stable fusion tags may be engineered to increase the effective size of the peptide and to hinder degradation by proteases. Improved resistance to proteases is essential for effective delivery. Here, a proof of concept study is presented using a metal-binding tripeptide tag known as the claMP Tag to create an inline conjugate and the ability of the tag to inhibit proteolysis was examined.


Good statistical practice in utilizing real-world data in a comparative study for premarket evaluation of medical devices.
Observational (non-randomized) comparative studies have been adopted in the pre-market safety/effectiveness evaluation of medical devices. There has been an increased interest in utilizing this design with the growing available real-world data. However, in such studies, biases that are introduced in every stage and aspect of study need to be addressed. Otherwise, the objectivity of study design and validity of study results will be compromised. In this paper, challenges and opportunities are discussed from the regulatory perspective. Considerations and good statistical practice to mitigate the potential bias are presented.


Metal-Induced Planar Chirality of Soft-Bridged Binuclear Platinum(II) Complexes: 100 % Phosphorescence Quantum Yields, Chiral Self-Sorting, and Circularly Polarized Luminescence.
PtII complexes have attracted a great deal of interest due to their rich phosphorescent properties. However, these square-planar PtII complexes are far more likely to encounter the problems of lack of metal-induced chirality and emission "aggregation-caused quenching". Herein, soft-bridged binuclear PtII complexes bearing metal-induced planar chirality were synthesized and characterized. These soft bridging ligands with smaller conjugated system would help to not only improve solubility for synthesis and enantioseparation but also introduce point chirality from amino acid for highly efficient diastereoselectivity. Furthermore, the intramolecular Pt-Pt distances could be well regulated by soft bridging ligands, and consequently the phosphorescence quantum yield up to 100 % could be achieved by shortening intramolecular Pt-Pt distance for first time. These complexes can be used as emitters in highly efficient solution-processed organic light-emitting diodes.


[Mucin histochemistry of the digestive tract in the human fetus].
Mucin secretion was studied in the gastric, intestinal, left colic and/or rectal mucosa of 42 human fetuses ranging in age from 10 to 41 weeks of gestation (menstrual age). Several histochemical techniques were used at different pH to demonstrate neutral mucins, sialomucins and sulphomucins (Periodic Acid Shiff (PAS) with and without amylase, Alcian Blue (BA) pH 2.5, pH 1 with and without hyaluronidase, BA/PAS pH 2.5 and High Iron Diamine (HID)/BA). The gastric mucosa showed mixed neutral/acid secretions during the second term. The neutral mucins increased during the 3rd term when acid mucins fell and represented only 20 percent of the secretions by the end of gestation, as during the neonatal period. These mixed secretions closely reassembled the intestinal metaplasia described in inflammatory or tumoral lesions of the stomach. The intestinal mucosa secreted mucins as early as 10 weeks before the gastric and rectal mucosa. There were neutral and acid mucins, but unlike in adults, the sulphomucins were secreted by the goblet cells of the villous and crypt epithelia. The secretions of the rectal mucosa were acid and the sulphomucins increased in quantity from 14 to 26 weeks of gestation. The HID positive sulphomucins diffused into the meconium, and probably modified the physical and chemical properties of meconium and influenced anal continence.


Targeting MET and vascular endothelial growth factor receptor signaling in castration-resistant prostate cancer.
Effective management of bone metastases in men with castration-resistant prostate cancer (CRPC) remains an important unmet medical need. MET and vascular endothelial growth factor receptor (VEGFR) are rational targets for intervention in CRPC. Clinical trials involving agents that inhibit one but not both pathways have reported modest activity and no improvement in overall survival. Cabozantinib is an oral multitargeted tyrosine kinase inhibitor that inhibits both MET and VEGFR-2. A phase II randomized discontinuation study involving subjects with CRPC demonstrated that cabozantinib therapy is associated with improvement in bone scans, bone turnover markers, and pain response, but with significant adverse events leading to dose reduction and treatment discontinuation. Lower doses of cabozantinib retain high levels of activity with less toxicity. Ongoing phase III clinical trials will define the role of cabozantinib in CRPC. We summarize the rationale for targeting MET and VEGFR pathways in CRPC and the clinical data available to date.


Dietary silymarin suppresses 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats.
The modifying effect of dietary administration of a polyphenolic antioxidant flavonoid silymarin isolated milk thistle [Silybum marianum (L.) Gaertneri] on 4-nitroquinoline 1-oxide (4-NQO)-induced tongue tumorigenesis was investigated in male F344 rats. Based on the results in pilot studies showing that silymarin treatment together with 4-NQO significantly reduced the occurrence of tongue dysplasia and gavaged with silymarin significantly elevated the phase II detoxifying enzymes' activities in the liver and tongue, the effects of dietary feeding of silymarin on tongue carcinogenesis were investigated in a long-term experiment, where rats were initiated with 4-NQO and fed silymarin containing diets during or after 4-NQO exposure. At 5 weeks of age, all animals except those treated with silymarin alone and untreated rats were given 20 p.p.m. 4-NQO in drinking water for 8 weeks to induce tongue neoplasms. Starting 1 week before 4-NQO administration, animals were fed the experimental diets containing silymarin (100 and 500 p.p.m.) for 10 weeks, and then maintained on a basal diet for 24 weeks. Starting 1 week after the cessation of 4-NQO exposure, the experimental groups given 4-NQO and a basal diet were fed the experimental diets containing 100 or 500 p.p.m. silymarin for 24 weeks. At week 34, feeding of 500 p.p.m. silymarin during the promotion phase significantly inhibited the incidence of tongue carcinoma, when compared with 4-NQO alone group (20% versus 64%, P = 0.019). Dietary silymarin decreased the cell proliferating activity and increased apoptotic index of tongue carcinoma. The treatment with silymarin decreased the polyamine content and prostaglandin (PG) E(2) level in the tongue mucosa. Thus, the results indicate that feeding of silymarin (500 p.p.m.) during the promotion phase of 4-NQO-induced rat tumorigenesis exerts chemopreventive ability against tongue squamous cell carcinoma through modification of phase II enzymes activity, cell proliferation, and/or PGE(2) content.


The complexity of assessing overall severity of suicidality: a case study.
This paper investigates the relationship between total scale scores and some other measures used to assess global severity of suicidality in order to determine if "global assessment" can be accomplished with one metric or if is it necessary to judge severity of suicidality in a multidimensional fashion. For over a year, one subject with daily suicidality self-rated a global severity of suicidality score, the time spent in suicidality over 31,183 events of suicidality, the Sheehan-Suicidality Tracking Scale, Hopelessness Spectrum measure, and the Suicide Plan Tracking Scale. Relying on only one or two metrics to assess global severity of suicidality appears to have significant limitations. As with all single case reports, the findings may not be generalizable to other cases of suicidality. At the middle to high end of the suicidality spectrum, it is necessary to rely on multiple metrics, not just a global severity of suicidality rating, to properly assess the overall severity of suicidality.


Molecular simulation of the confined crystallization of ice in cement nanopore.
Freezing of water under nanoconfinement exhibits physical peculiarities with respect to the bulk water. However, experimental observations are extremely challenging at this scale, which limits our understanding of the effect of confinement on water properties upon freezing. In this study, we use molecular dynamic simulations to investigate how confinement affects the kinetics of growth of ice and the thermodynamic equilibrium of ice-liquid coexistence. TIP4P/Ice water model and CSH-FF model were applied to simulate ice crystallization in a confined cement system at temperatures down to 220 K. We adapted an interface detection algorithm and reparameterized the CHILL/CHILL+ algorithm to capture ice growth. The confinement leads to a shift of the maximum growth rate of ice to a higher temperature than for bulk water. Both the confinement and surface impurities contribute to slowing down the ice growth. For the ice-liquid coexistence at equilibrium, we derive a formulation of Thomson's equation adapted to statistical physics quantities accessible by molecular simulation, and we show that this adapted equation predicts accurately the melting line of bulk and confined ice Ih as a function of pressure. The confinement decreases systematically the melting temperature of ice of about 5 K compared with bulk ice Ih. A premelted water film about 1 nm thick is observed between the solid wall and ice, and its thickness is found to decrease continuously as temperature is lowered. We note that the surface impurities are key to the formation of the premelted water nanofilm when the temperature is lower than 250 K.


Non-Nutritive Polyol Sweeteners Differ in Insecticidal Activity When Ingested by Adult Drosophila melanogaster (Diptera: Drosophilidae).
Previous work showed the non-nutritive polyol sweetener Erythritol was toxic when ingested by Drosophila melanogaster (Meigen, 1930). This study assessed whether insect toxicity is a general property of polyols. Among tested compounds, toxicity was highest for erythritol. Adult fruit flies (D. melanogaster) fed erythritol had reduced longevity relative to controls. Other polyols did not reduce longevity; the only exception was a weaker but significant reduction of female (but not male) longevity when flies were fed D-mannitol. We conclude at least some non-nutritive polyols are not toxic to adult D. melanogaster when ingested for 17 days. The longer time course (relative to erythritol) and female specificity of D-mannitol mortality suggests different mechanisms for D-mannitol and erythritol toxicity to D. melanogaster.


Antibiotic sensitivity profile of bacterial isolates from stool samples among children below five years in Murang'a County, Kenya.
the discovery of antibiotics led to the optimistic belief of completely eradicating infectious diseases during the golden era following their discovery. Countries are grappling with the burden of microbial resistance bringing a near paralysis of all facets of mankind. Enterobacteriaceae and other hard-to-treat Gram-negative bacteria have become resistant to nearly all antibiotic options available, and this is a bad taste in the fight against microbial resistance. during the months of April-October 2017, 163 children below five years presenting with diarrhea were randomly selected in Murang´a and Muriranja´s Hospitals. Bacterial agents were identified and antibiotic susceptibility profile was determined. Design: a cross-sectional study approach was used. Statistical analyses were performed using STATA v. 13. a total of 188 bacteria belonging to 11 genera were isolated, and identified and their antibiotic susceptibility profiles were determined. Susceptibility testing showed that almost all the Enterotoxigenic Escherichia coli (ETEC), Enteropathogenic Escherichia coli (EPEC), Enteroaggregative Escherichia coli (EAEC), Salmonella, Klebsiella, Shigella, Vibrio, Enterobacter, Proteus, Pseudomonas, Aeromonas, Citrobacter and Yersinia species were resistant to the following antibiotics: ampicillin, amoxicillin, chloramphenicol, ciprofloxacin, ceftriaxone and kanamycin. Other than ETEC (90.9%), all the rest of the isolates were resistant to nalidixic acid. Other than ETEC (9.1%), EAEC (33.3%) and Salmonella species (95.2%), all the rest of the isolates were resistant to gentamicin. Other than V. cholerae, all the other isolates were resistant to trimethoprim-sulfamethoxazole. Isolates were sporadically resistant to erythromycin, streptomycin, doxycycline, and ofloxacin. the high resistance rate of enteric Gram-negative bacterial pathogens in Murang´a County is alarming. The need for urgent, efficient, and sustainable actions and interventions, such as culture and susceptibility testing, is needed and must be taken into account to minimize and prevent the establishment and spread of enteric pathogenic bacteria.


Adverse drug reactions reported in Indira Gandhi Government Medical College and Hospital, Nagpur.
To detect the adverse drug reactions (ADRs) through spontaneous reporting system in IGGMC&H, Nagpur and analyze them using World Health Organization (WHO) assessment scales. An observational, prospective study was conducted based on ADRs reported between 1st June '05 to 31st May '09 to the ADR reporting unit of the hospital. The ADRs reported by spontaneous reporting system were from patients attending outpatient department (OPD), in-patient department (IPD) and casualty of IGGMC&H Nagpur. Evaluation of the data was done for various parameters which included patient demographics, drug and reaction characteristics, and outcome of the reactions. Assessment was also done for causality and severity. Total 2639 ADRs were reported with in the period from 1st June '05 to 31st May '09. Antimicrobial agents (AMA) were the drug class most commonly involved and Non Steroidal Anti-inflammatory Drugs (NSAIDs) were next to AMA. Cotrimoxazole a well established agent was the individual drug most frequently reported in this study. Upon causality assessment, majority of the reports were rated as probable (55.89%). The pattern of ADRs reported in our hospital is comparable with the results of studies conducted in hospital set up elsewhere. AMAs were causing maximum ADRs. This study provides a database of ADRs due to common drugs used in our hospital, which will help clinicians for optimum and safe use of these drugs. Hence strict vigilance is required for the use of these likely drugs and their safety assessment.


Thrombotic microangiopathy following aortic surgery with hypothermic circulatory arrest: a single-centre experience of an underestimated cause of acute renal failure.
Acute kidney injury (AKI) following surgery involving the heart-lung-machine is associated with high mortality and morbidity. In addition to the known mechanisms, thrombotic microangiopathy (TMA) triggered by the dysregulation of complement activation was recently described as another pathophysiological pathway for AKI following aortic surgery. The aim of this retrospective study was to analyse incidence, predictors and outcome in these patients. Between January 2018 and September 2019, consecutive patients undergoing aortic surgery requiring hypothermic circulatory arrest were retrospectively reviewed. If suspected, diagnostic algorithm was initiated to identify a TMA and its risk factors, and postoperative outcome parameters were comparably investigated. The incidence of TMA in the analysed cohort (n = 247) was 4.5%. Multivariable logistic regression indicated female gender {odds ratio (OR) 4.905 [95% confidence interval (CI) 1.234-19.495], P = 0.024} and aortic valve replacement [OR 8.886 (95% CI 1.030-76.660), P = 0.047] as independent predictors of TMA, while cardiopulmonary bypass, X-clamp and hypothermic circulatory arrest times showed no statistically significance. TMA resulted in postoperative AKI (82%), neurological disorders (73%) and thrombocytopaenia [31 (interquartile range 25-42) G/l], corresponding to the diagnostic criteria. Operative mortality and morbidity were equal to patients without postoperative TMA, despite a higher incidence of re-exploration for bleeding (27 vs 6%; P = 0.027). After 6 months, survival, laboratory parameters and need for dialysis were comparable between the groups. TMA is a potential differential diagnosis for the cause of AKI following aortic surgery regardless of the hypothermic circulatory arrest time. Timely diagnosis and appropriate treatment resulted in a comparable outcome concerning mortality and renal function.


Effects of hydrolysis on the delta13C values of individual amino acids derived from polypeptides and proteins.
This study investigates the effects of hydrolysis on the delta13C values of individual amino acids (IAAs) derived from polypeptide standards, and modern and ancient bone collagen. All IAAs were derivatised to their trifluoroacetyl/isopropyl (TFA/IP) esters for delta13C determination using gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). Firstly, authentic single poly amino acid standards (SPAAs; n = 5) were hydrolysed for 4, 10, 24 and 48 h. As expected, IAA yields increased as a function of hydrolysis time. Significantly, it was only after 24 h of hydrolysis that IAA delta13C values were statistically identical to bulk SPAA values for all five standards. The accuracy of IAA delta13C values was thus shown to be a function of yield; however, poly phenylalanine demonstrated accurate IAA delta13C values with yields of only 1.4 and 4.3%, after 24 and 48 h of hydrolysis time, respectively. Authentic mixed poly amino acid standards (MPAAs; n = 5) comprising two different amino acids were then hydrolysed for 24 h. Percentage recoveries ranged from 36-95%. Estimates of bulk MPAA delta13C values calculated from measured IAA delta13C values agreed within experimental error with measured bulk MPAA values for three out of the five standards. Finally, the experimental procedure was applied to modern rat (MBCs; n = 20) and ancient ovi-caprine and bovine (ABCs; n = 27) bone collagen samples where the delta13C values of 12 out of its 18 constituent amino acids were determined. Estimated bulk MBC and ABC delta13C values were calculated from constituent amino acid delta13C values using mass balance. With the exclusion of three ABC samples, calculated bulk bone collagen delta13C values (delta13C(BCcal)) were shown to correlate extremely well with measured bone collagen values (delta13C(BCmes)) for both modern and ancient samples, where R2 = 0.91 and 0.84, respectively. Significantly, the variation between calculated and measured bone collagen values (Delta13C(BCcal-BCmes)) exhibited similar ranges for both MBC (from -2.6 to +1.2 per thousand ) and ABC (from -2.7 to +2.2 per thousand ) samples, providing evidence for the preservation of intact collagen in the ancient samples. These results demonstrate that the experimental procedures employed in the acid hydrolytic cleavage of peptides or proteins to their constituent amino acids does not involve significant isotopic fractionation.


Comparison of the LLNL and JAERI torso phantoms using Ge detectors and phoswich detectors.
The Human Monitoring Laboratory has compared the LLNL and JAERI torso phantoms using its germanium detector lung counting system by measuring the counting efficiencies for radioactive materials in the phantoms at photon energies of 17.7 keV, 59.5 keV, 121.8 keV, and 344 keV to assess the similarity (or differences) in performance characteristics. The counting efficiencies obtained from the two phantoms were compared by converting the Chest Wall Thickness data and Adipose Mass Fractions of the phantoms to Muscle Equivalent Chest Wall Thicknesses. The counting efficiencies for the two phantoms were found to be within a factor of 1.44 of each other at 17.7 keV, 1.30 at 59.5 keV, 1.25 at 121.8 keV, and 1.17 at 344 keV when using a four detector array (JAERI efficiency divided by LLNL efficiency). However, individual detector responses show that the counting efficiencies from the two phantoms differ considerably in the region of the heart (up to a factor of 6 at 17 keV). Other areas above the lungs give counting efficiencies that are similar to each other. A routine intercomparison exercise with Cameco Corporation has shown that the counting efficiencies derived from the LLNL and JAERI phantoms were found to be within a factor of 1.18 (JAERI/LLNL) when a natural uranium lung set was used to calibrate a lung counter consisting of phoswich detectors. This work has also shown that over the energy range 63 keV-185 keV the LLNL phantom can be used to calibrate phoswich detector systems that are positioned on the back of the subject.


Genetic hypervariability of telomere-related sequences is associated with meiosis in Plasmodium falciparum.
Sequences related to those near chromosome telomeres in the human malaria parasite, Plasmodium falciparum, were extremely unstable during a genetic cross between two different clonal genotypes. Many progeny of the heterologous cross displayed telomere-homologous restriction fragments found in neither parent. A significant number of the new fragments resulted from rearrangements at chromosome-internal locations which were bounded by more complex tracts of DNA sequence. The same instability was not seen to arise during an inbreeding cross, nor during mitotic replication of parasites. Thus, a form of genetic hypervariability results from molecular events which occur during meiotic reduction and is apparent only in a cross between heterologous strains of parasite. Since other sequences were entirely stable under the same conditions, it appears that chromosome-internal blocks of telomeric sequences in the P. falciparum genome may designate conditionally unstable chromosomal domains. We discuss some potential implications of these findings for the population biology of P. falciparum.


Grade I diastolic dysfunction and elevated left ventricular end-diastolic pressure: Mitral Doppler inflow, pulmonary vein atrial reversal, and the M-mode mitral B-bump.
Grade I diastolic dysfunction (DD) is generally associated with a normal mean left atrial pressure (LAP) and normal left ventricular end-diastolic pressure (LVEDP). The first hemodynamic alteration seen in DD, however, is the development of an elevated LVEDP with a persistent normal LAP. This is manifested by echocardiography as a continued mitral pulsed wave (PW) E/A <0.8 (Grade I DD), but with evidence of an elevated LVEDP. Such findings include alterations in PV flow, mitral PW inflow response to Valsalva maneuver, and also the presence of a B-bump on the mitral M-mode tracing. When assessing diastolic function, it may be clinically helpful to assess for this early hemodynamic manifestation of DD.


Time course of polyglutamine aggregate body formation and cell death: enhanced growth in nucleus and an interval for cell death.
Polyglutamine (polyQ) aggregate bodies are a hallmark of dentatorubral-pallidoluysian atrophy and related neurodegenerative disorders, although the relationship between aggregate body formation and cell death is not clear. We analyzed the kinetics of polyQ aggregate formation and the time intervals for cell death, tracking individual cells using fluorescence video microscopy, for the first time. Expanded polyQ tracts of atrophin-1 with or without nuclear localization signal (NLS) labeled with green fluorescent protein (GFP) were constructed, Q57NLS/GFP and Q56/GFP, respectively. All of the Q57NLS/GFP aggregate bodies were in nuclei, and all of the Q56/GFP aggregate bodies were in cytoplasm. Aggregates of Q56/GFP were larger than those of Q57NLS/GFP. Surprisingly, a kinetic analysis showed that the latter grew 5.37 times faster than the former. The time interval between transfection and cell death was shorter in Q57NLS/GFP, but the time between the end of the rapid growing phase of aggregation and the start of the cell death process did not show a significant difference. Aggregate growth was confirmed to correspond to the accumulated free polyQ by the time of starting aggregation. These findings suggest that aggregate body formation induced by expanded polyQ stretches is a self-limiting process and is enhanced by factor(s) in nuclei, whereas it is not tightly bound to the cell death process.


Does prehabilitation improve outcomes in cardiac surgical patients?
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: does prehabilitation improve outcomes in cardiac surgical patients? Altogether more than 483 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Four meta-analyses concluded that prehabilitation reduced postoperative pulmonary complications (PPCs). The 6 randomized controlled trials (RCT) included, differed significantly in the type of prehabilitation delivered. There was replication of some RCTs across the meta-analyses. The consensus across the meta-analyses was a reduction in PPCs and 3 of 4 meta-analyses finding a reduction in length of stay (LOS). There were no adverse events or difference in mortality found. Two small RCTs showed feasibility and modest improvements in physiological parameters. Three RCTs demonstrated a reduction in LOS and a reduction in PPCs. One RCT found no difference in quality of life scores, LOS or postoperative atrial fibrillation. None of the RCTs found negative evidence of prehabilitation interventions. We conclude that the prehabilitation is a positive preoperative intervention, most favourably in older patients and in those who are at risk of PPCs. Specifically inspiratory muscle training is the intervention with most favourable evidence.


Magnetic resonance identification of hydrogen at a zinc vacancy in ZnO.
Hydrogen (H) at a zinc vacancy (VZn) in ZnO is identified by electron paramagnetic resonance (EPR) and electron spin echo envelope modulation (ESEEM). In ZnO irradiated by 2 MeV electrons, a doublet EPR spectrum, labelled S1, is observed. The doublet structure and the accompanying weak satellites are shown to be the allowed and forbidden lines of the hyperfine structure due to the dipolar interaction between an electron spin S = 1/2 and a nuclear spin I = 1/2 of (1)H located at a VZn. The involvement of a single H atom in the S1 defect is further confirmed by the observation of the nuclear Zeeman frequency of (1)H in ESEEM experiments. We show that at a VZn, H prefers to make a short O-H bond with one O neighbour and is off the substitutional site, forming a low symmetry C1 defect. In this partly H passivated VZn, the unpaired electron localizes on the p orbital of another O neighbour of VZn, and not on the H.


Daily bilateral pudendal nerve electrical stimulation improves recovery from stress urinary incontinence.
Stress urinary incontinence (SUI) in women is strongly associated with childbirth which injures the pudendal nerve (PN) and the external urethral sphincter (EUS) during delivery. Electrical stimulation (ES) can increase brain-derived neurotrophic factor (BDNF) expression in injured neurons, activate Schwann cells and promote neuroregeneration after nerve injury. The aim of this study was to determine if more frequent ES would increase recovery from SUI in a rat model. Forty female Sprague-Dawley rats underwent either sham injury or pudendal nerve crush (PNC) and vaginal distention (VD) to establish SUI. Immediately after injury, electrodes were implanted at the pudendal nerve bilaterally. Each injured animal underwent sham ES, twice per week ES (2/week), or daily ES of 1 h duration for two weeks. Urethral and nerve function were assessed with leak point pressure (LPP), EUS electromyography and pudendal nerve sensory branch potential (PNSBP) recordings two weeks after injury. LPP was significantly increased after daily ES compared to 2/week ES. EUS neuromuscular junction innervation was decreased after injury with sham ES, but improved after 2/week or daily ES. This study demonstrates that daily bilateral ES to the pudendal nerve can accelerate recovery from SUI. Daily ES improved urethral function more than 2/week ES.


Efficient testing of the RET gene by DHPLC analysis for MEN 2 syndrome in a cohort of patients.
Multiple Endocrine Neoplasia type 2 (MEN 2) is an autosomal dominant inherited syndrome characterized by a strong predisposition for developing endocrine tumors. MEN 2 is caused by germline mutations in the ret proto-oncogene. We investigated the feasibility of using the DHPLC technique in mutation detection of the ret gene in members of MTC families. We compared DHPLC analysis with direct sequencing with regard to sensitivity, reliability, cost and time. Exons 10 and 11 were amplified with PCR from forty-three samples in seventeen unrelated Greek families and were analyzed for mutations by DHPLC and DNA sequencing. Eight PCR amplicons showed a distinct non-wild-type DHPLC profile. Sequence analysis confirmed different nucleotide variations: six of them were localized in exon 10 and two in exon 11. Mutations were detected in five out of seventeen families tested (29%). None of the alterations detected by direct sequencing was missed by DHPLC. We conclude that DHPLC is a fast, sensitive, cost-efficient and reliable method for the scanning of ret germline mutations.


[Laparoscopic ureterolithotomy for ureteral calculi: three case reports].
With the development of extracorporeal shock wave lithotripsy (ESWL), improved endourologic instrumentation, and medical dissolution therapy, the need for open ureterolithotomy has become less common. Open operation is occasionally necessary when less invasive techniques fail. As in many of the surgical specialties, laparoscopy has become more common in urologic surgery. We recently experienced three cases of ureteral stones, which were treated by laparoscopic ureterolithotomy. The stones were all large and impacted stones. The patients were a 73-year-old man and two 34-year-old men. All procedures were performed by a retroperitoneal approach. We used Roticulator endo mini-shears resourcefully, when we incised the ureteral wall. After surgery, all three patients were stone-free, and hydronephrosis was improved.


Repair of calvarial defects in rabbits with platelet-rich plasma as the scaffold for carrying bone marrow stromal cells.
Platelet-rich plasma (PRP) is becoming a new application in tissue engineering and a developing area for clinicians and researchers because it is a natural source of growth factors, many of which can accelerate and promote bone regeneration. However, few studies have reported the potentiality of using PRP as a scaffold in bone tissue engineering. The present study investigated the feasibility of using PRP as a scaffold to carry bone marrow stromal cells (BMSCs) to repair calvarial defects in a rabbit model. The primary cultured BMSCs were divided into 2 groups. One group was induced with dexamethasone and the other was not induced. Full-thickness bone defects of 5-mm diameter (4 defects per calvarium) were created on the calvaria of 10 New Zealand white rabbits. PRP or whole blood was used, respectively to incorporate the induced or uninduced BMSCs. Then, the composites were activated and applied to repair the defects. The samples were harvested 8 weeks later and bone regeneration was assessed grossly and analyzed by radiographic or histologic examination. Eight weeks after the implantation of the materials, substantial bone regeneration was observed at the calvarial defect restored with PRP incorporating the induced BMSCs. Less new bone formation was observed at the defect implanted with PRP incorporating the uninduced BMSCs. In contrast, no bone regeneration was detected at the defects implanted with the whole blood incorporating BMSCs, whether the BMSCs were induced or not. PRP can be used as a scaffold to carry in vitro expanded BMSCs to repair a rabbit's calvarial defect, but its inductive ability to BMSCs was limited.


A role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses.
Members of the tumor necrosis factor (TNF) receptor (TNFR) superfamily are potent regulators of apoptosis, a process that is important for the maintenance of immune homeostasis. Recent evidence suggests that TNFR-1 and Fas and TRAIL receptors can also trigger an alternative form of cell death that is morphologically distinct from apoptosis. Because distinct molecular components including the serine/threonine protein kinase receptor-interacting protein (RIP) are required, we have referred to this alternative form of cell death as "programmed necrosis." We show that TNFR-2 signaling can potentiate programmed necrosis via TNFR-1. When cells were pre-stimulated through TNFR-2 prior to subsequent activation of TNFR-1, enhanced cell death and recruitment of RIP to the TNFR-1 complex were observed. However, TNF-induced programmed necrosis was normally inhibited by caspase-8 cleavage of RIP. To ascertain the physiological significance of RIP and programmed necrosis, we infected Jurkat cells with vaccinia virus (VV) and found that VV-infected cells underwent programmed necrosis in response to TNF, but deficiency of RIP rescued the infected cells from TNF-induced cytotoxicity. Moreover, TNFR-2-/- mice exhibited reduced inflammation in the liver and defective viral clearance during VV infection. Interestingly, death effector domain-containing proteins such as MC159, E8, K13, and cellular FLIP, but not the apoptosis inhibitors Bcl-xL, p35, and XIAP, potently suppressed programmed necrosis. Thus, TNF-induced programmed necrosis is facilitated by TNFR-2 signaling and caspase inhibition and may play a role in controlling viral infection.


Imbuing medical professionalism in relation to safety: a study protocol for a mixed-methods intervention focused on trialling an embedded learning approach that centres on the use of a custom designed board game.
Healthcare organisations have a responsibility for ensuring that the governance of workplace settings creates a culture that supports good professional practice. Encouraging such a culture needs to start from an understanding of the factors that make it difficult for health professionals to raise issues of concern in relation to patient safety. The focus of this study is to determine whether a customised education intervention, developed as part of the study, with interns and senior house officers (SHOs) can imbue a culture of medical professionalism in relation to patient safety and support junior doctors to raise issues of concern, while shaping a culture of responsiveness and learning. We will use quantitative and qualitative methods to collect data. The sample size will be approximately 200 interns and SHOs across the two hospital sites. Two surveys will be included with one measuring leadership inclusiveness and psychological safety and a second capturing information on safety concerns that participants may have witnessed in their places of work. The PlayDecide embedded learning intervention will be developed with key stakeholders. This will be trialled in the middle stage of data collection for both interns and SHOs. A detailed content analysis will be conducted on the surveys to assess any changes in reporting following the PlayDecide intervention. This will be compared with the incident reporting levels and the results of the preintervention and postintervention leadership inclusiveness and psychological safety survey. Statistical analysis will be conducted using SPSS. Differences will be considered statistically significant at p<0.05. Semistructured interviews using a critical incident technique will be used for the ongoing analysis and evaluation of the project. These will be transcribed, de-identified and coded into themes. The study has been granted ethics approval from University College Dublin (Ref. LS-15-19-Ward-McAuliffe: Imbuing Medical Professionalism in Relation to Safety). The study results will be disseminated through peer-reviewed publications.


Extended wavelength anisotropy resolved multidimensional emission spectroscopy (ARMES) measurements: better filters, validation standards, and Rayleigh scatter removal methods.
Anisotropy resolved multidimensional emission spectroscopy (ARMES) provides valuable insights into multi-fluorophore proteins (Groza et al 2015 Anal. Chim. Acta 886 133-42). Fluorescence anisotropy adds to the multidimensional fluorescence dataset information about the physical size of the fluorophores and/or the rigidity of the surrounding micro-environment. The first ARMES studies used standard thin film polarizers (TFP) that had negligible transmission between 250 and 290 nm, preventing accurate measurement of intrinsic protein fluorescence from tyrosine and tryptophan. Replacing TFP with pairs of broadband wire grid polarizers enabled standard fluorescence spectrometers to accurately measure anisotropies between 250 and 300 nm, which was validated with solutions of perylene in the UV and Erythrosin B and Phloxine B in the visible. In all cases, anisotropies were accurate to better than ±1% when compared to literature measurements made with Glan Thompson or TFP polarizers. Better dual wire grid polarizer UV transmittance and the use of excitation-emission matrix measurements for ARMES required complete Rayleigh scatter elimination. This was achieved by chemometric modelling rather than classical interpolation, which enabled the acquisition of pure anisotropy patterns over wider spectral ranges. In combination, these three improvements permit the accurate implementation of ARMES for studying intrinsic protein fluorescence.


Childhood trauma and women's health outcomes in a California prison population.
We sought to describe the prevalence of childhood traumatic events among incarcerated women in substance abuse treatment and to assess the relation between cumulative childhood traumatic events and adult physical and mental health problems. The study was modeled after the Adverse Childhood Events study's findings. In-depth baseline interview data for 500 women participating in the Female Offender Treatment and Employment Program evaluation were analyzed. Hypotheses were supported, and regression results showed that the impact of childhood traumatic events on health outcomes is strong and cumulative (greater exposure to childhood traumatic events increased the likelihood of 12 of 18 health-related outcomes, ranging from a 15% increase in the odds of reporting fair/poor health to a 40% increase in the odds of mental health treatment in adulthood). Our findings suggest a need for early prevention and intervention, and appropriate trauma treatment, within correctional treatment settings.


Intravitreal injection of Tacrolimus (FK506) suppresses ongoing experimental autoimmune uveoretinitis in Rats.
To determine whether intravitreal injection of tacrolimus suppresses ongoing experimental autoimmune uveoretinitis (EAU) in rats. Rats were immunised with interphotoreceptor retinoid-binding protein peptide (R14) and given an intravitreal injection of tacrolimus on day 12 after immunisation. Intraocular inflammation was assessed by slit-lamp biomicroscopy and histopathological examination. Interferon gamma and tumour necrosis factor alpha protein levels in the ocular tissues were measured. Gene expression of chemokines was determined in ocular tissues by reverse transcription-polymerase chain reaction. To evaluate the systemic effect of intravitreal injection of tacrolimus, delayed-type hypersensitivity was measured by ear swelling. Clinical and pathological scores showed that ocular inflammation of tacrolimus-treated eyes was markedly less than that of vehicle-treated eyes. The amount of interferon gamma and tumour necrosis factor alpha was considerably inhibited in tacrolimus-treated eyes. The gene expression of monocyte chemattractant protein-1 (MCP-1) and regulated upon activation, normal T cell expressed and secreted (RANTES) was markedly reduced in tacrolimus-treated eyes. Delayed-type hypersensitivity responses were not impaired in tacrolimus-treated rats. Intravitreal injection of tacrolimus was highly effective in suppressing the ongoing process of EAU without any side effects on systemic cellular immunity. This treatment may be useful in the management of patients with severe uveitis.


Comparative evaluation of the isolation and quantification of stem cells derived from dental pulp and periodontal ligament of a permanent tooth and to assess their viability and proliferation on a platelet-rich fibrin scaffold.
The present study aims to comparatively evaluate the isolation and quantification of stem cells derived from dental pulp and periodontal ligament of a permanent tooth and to assess their viability and proliferation on a platelet-rich fibrin (PRF) scaffold. A total of 15 systemically healthy individuals between the age group of 15-25 years requiring third molar or orthodontic premolar extractions. Teeth were extracted atraumatically and transported to the laboratory. Stem cells were isolated from dental pulp and periodontal ligament. After attaining more than 90% confluency by the 7th day, these cells were tested for their viability and characterization. Stem cells were also incubated with PRF and viability was assessed on the 7th day. The mean number of cell for dental pulp stem cells (DPSCs) and periodontal ligament stem cell (PDLSC) was statistically insignificant (P > 0.05). The mean live cell viability was compared between DPSC (98.07%) and PDLSC (98%). Both DPSC and PDLSC showed a high percentage of expression of CD73 markers, 30.40% and 29.80%, respectively. However, DPSCs and PDLSCs lacked expression of CD34 expressing only 3.47% and 3.53%, respectively. PRF membrane as a scaffold exhibited no cytotoxic effects on DPCS's or PDLSC's. The cell viability of cells cultured with PRF was statistically insignificant (P > 0.05) when compared to the cells cultured with culture media. The study thus indicates that dental pulp and periodontal ligament are both rich sources of mesenchymal stem cells and can be successfully used for obtaining stem cells. PRF exhibits no cytotoxic effects on the cells and can be used in conjunction with dental stem cells.


Two-Dimensional Magnesium Phosphate Nanosheets Form Highly Thixotropic Gels That Up-Regulate Bone Formation.
Hydrogels composed of two-dimensional (2D) nanomaterials have become an important alternative to replace traditional inorganic scaffolds for tissue engineering. Here, we describe a novel nanocrystalline material with 2D morphology that was synthesized by tuning the crystallization of the sodium-magnesium-phosphate system. We discovered that the sodium ion can regulate the precipitation of magnesium phosphate by interacting with the crystal's surface causing a preferential crystal growth that results in 2D morphology. The 2D nanomaterial gave rise to a physical hydrogel that presented extreme thixotropy, injectability, biocompatibility, bioresorption, and long-term stability. The nanocrystalline material was characterized in vitro and in vivo and we discovered that it presented unique biological properties. Magnesium phosphate nanosheets accelerated bone healing and osseointegration by enhancing collagen formation, osteoblasts differentiation, and osteoclasts proliferation through up-regulation of COL1A1, RunX2, ALP, OCN, and OPN. In summary, the 2D magnesium phosphate nanosheets could bring a paradigm shift in the field of minimally invasive orthopedic and craniofacial interventions because it is the only material available that can be injected through high gauge needles into bone defects in order to accelerate bone healing and osseointegration.


A Statistical Analysis of the Relationship between Harmonic Surprise and Preference in Popular Music.
Studies have shown that some musical pieces may preferentially activate reward centers in the brain. Less is known, however, about the structural aspects of music that are associated with this activation. Based on the music cognition literature, we propose two hypotheses for why some musical pieces are preferred over others. The first, the Absolute-Surprise Hypothesis, states that unexpected events in music directly lead to pleasure. The second, the Contrastive-Surprise Hypothesis, proposes that the juxtaposition of unexpected events and subsequent expected events leads to an overall rewarding response. We tested these hypotheses within the framework of information theory, using the measure of "surprise." This information-theoretic variable mathematically describes how improbable an event is given a known distribution. We performed a statistical investigation of surprise in the harmonic structure of songs within a representative corpus of Western popular music, namely, the McGill Billboard Project corpus. We found that chords of songs in the top quartile of the Billboard chart showed greater average surprise than those in the bottom quartile. We also found that the different sections within top-quartile songs varied more in their average surprise than the sections within bottom-quartile songs. The results of this study are consistent with both the Absolute- and Contrastive-Surprise Hypotheses. Although these hypotheses seem contradictory to one another, we cannot yet discard the possibility that both absolute and contrastive types of surprise play roles in the enjoyment of popular music. We call this possibility the Hybrid-Surprise Hypothesis. The results of this statistical investigation have implications for both music cognition and the human neural mechanisms of esthetic judgments.


Characterization and open windrow composting of MSW in Jodhpur City, Rajasthan, India.
Solid waste is sometimes not suitable for direct land application. Processing solid waste through composting converts it to a humus-containing organic material advantageous for agriculture/horticulture use. Major advantages of composting are stabilization of the wastes; substantially reduced C/N ratio and gas formation, and virtually elimination of odors and pathogens. Composting is accomplished under aerobic conditions developing temperatures of 55 degrees C or above. The windrow technique is simple and accomplished easily with standard equipments. The open windrow composting of municipal solid waste (MSW) in windrows was analyzed in this study for six weeks. The raw MSW was introduced to active composting without any source segregations. The moisture content of the MSW dropped from 58.88% to 48.06% and windrow attained a thermophillic temperature for about two weeks. It was observed that the pH, C/N ratio and temperature variations were comparable to that of traditional windrow composting. The peak temperature recorded was 68 degrees C and temperature remained above 60 degrees C for more than three weeks. The volume reduction was obtained by using one-cu.m. cage. The results indicate that the bulk composting could reduce by about 29% the total mass of the waste.


Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia.
Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE. Serum samples were collected at 32-36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16) and pregnant controls (n = 32). The effect of oxygen tension on placental cells was assessed by incubation JEG-3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6) were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels). Aromatase content and estrogens and androgens concentrations were measured. The protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG-3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be associated with chronic placental ischemia and hypoxia later in gestation. Placental aromatase expression and functionality are diminished in pregnancies complicated by preeclampsia in comparison with healthy pregnant controls.


Humulus lupulus L. Strobilus In Situ Photosynthesis and Respiration Temperature Responses.
The primary metabolism and respiration of the hop strobilus has not been quantified in response to daily temperature fluctuations. The objective of this study was to assess strobilus gas exchange, specifically the response to temperature fluctuations. Hop strobilus were measured under controlled environment conditions to assess the organ's contribution to carbon assimilation and respiration during the maturation phase. Strobilus-specific daily carbon budgets were estimated in response to temperature fluctuation. The optimal temperature for net carbon gain occurred at 15.7 °C. Estimated strobilus carbon uptake decreased approximately 41% per 5 °C increase in temperature above 20 °C. Daily temperatures within 10-27 °C resulted in a net positive strobilus daily carbon balance, whereas temperature increases beyond 27 °C increasingly exhaust strobilus carbon reserves. The Q10 temperature coefficient (the rate respiration increases every 10 °C rise in temperature) approximately doubled per 10 °C rise in temperature from 7-40 °C (1.94-2) with slightly reduced values at lower temperatures. In conclusion, we show that photosynthetically active bracts maintain a positive strobilus carbon balance at moderate temperatures and as mean daily temperatures progressively exceed 27 °C, strobilus net carbon reserves are precipitously exhausted due to ever-increasing respiration rates.


Transcriptome wide identification and characterization of starch branching enzyme in finger millet.
Starch-branching enzymes (SBEs) are one of the four major enzyme classes involved in starch biosynthesis in plants and play an important role in determining the structure and physical properties of starch granules. Multiple SBEs are involved in starch biosynthesis in plants. Finger millet is calcium rich important serial crop belongs to grass family and the transcriptome data of developing spikes is available on NCBI. In this study it was try to find out the gene sequence of starch branching enzyme and annotate the sequence and submit the sequence for further use. Rice SBE sequence was taken as reference and for characterization of the sequence different in silico tools were used. Four domains were found in the finger millet Starch branching enzyme like alpha amylase catalytic domain from 925 to2172 with E value 0, N-terminal Early set domain from 634 to 915 with E value 1.62 e-42, Alpha amylase, C-terminal all-beta domain from 2224 to 2511 with E value 5.80e-24 and 1,4-alpha-glucan-branching enzyme from 421 to 2517 with E value 0. Major binding interactions with the GLC (alpha-d-glucose), CA (calcium ion), GOL (glycerol), TRS (2-amino-2-hydroxymethylpropane- 1, 3-diol), MG (magnesium ion) and FLC (citrate anion) are fond with different residues. It was found in the phylogenetic study of the finger millet SBE with the 6 species of grass family that two clusters were form A and B. In cluster A, finger millet showed closeness with Oryzasativa and Setariaitalica, Sorghum bicolour and Zea mays while cluster B was formed with Triticumaestivum and Brachypodium distachyon. The nucleotide sequence of Finger millet SBE was submitted to NCBI with the accession no KY648913 and protein structure of SBE of finger millet was also submitted in PMDB with the PMDB id - PM0080938. This research presents a comparative overview of Finger millet SBE and includes their properties, structural and functional characteristics, and recent developments on their post-translational regulation.


Enrichment of IL-17A+ IFN-γ+ and IL-22+ IFN-γ+ T cell subsets is associated with reduction of NKp44+ ILC3s in the terminal ileum of Crohn's disease patients.
Crohn's disease (CD) is a chronic inflammatory condition of the human gastrointestinal tract whose aetiology remains largely unknown. Dysregulated adaptive immune responses and defective innate immunity both contribute to this process. In this study, we demonstrated that the interleukin (IL)-17A+ interferon (IFN)-γ+ and IL-22+ IFN-γ+ T cell subsets accumulated specifically in the inflamed terminal ileum of CD patients. These cells had higher expression of Ki-67 and were active cytokine producers. In addition, their proportions within both the IL-17A-producer and IL-22-producer populations were increased significantly. These data suggest that IL-17A+ IFN-γ+ and IL-22+ IFN-γ+ T cell subsets might represent the pathogenic T helper type 17 (Th17) population in the context of intestinal inflammation for CD patients. In the innate immunity compartment we detected a dramatic alteration of both phenotype and function of the intestinal innate lymphoid cells (ILCs), that play an important role in the maintenance of mucosal homeostasis. In the inflamed gut the frequency of the NKp44- CD117- ILC1s subset was increased significantly, while the frequency of NKp44+ ILC3s was reduced. Furthermore, the frequency of human leucocyte antigen D-related (HLA-DR)-expressing-NKp44+ ILC3s was also reduced significantly. Interestingly, the decrease in the NKp44+ ILC3s population was associated with an increase of pathogenic IL-17A+ IFN-γ+ and IL-22+ IFN-γ+ T cell subsets in the adaptive compartment. This might suggest a potential link between NKp44+ ILC3s and the IL-17A+ IFN-γ+ and IL-22+ IFN-γ+ T cell subsets in the terminal ileum of CD patients.


On the Probability Density of the Nuclei in a Vibrationally Excited Molecule.
For localized and oriented vibrationally excited molecules, the qualitative features of the one-body probability density of the nuclei (one-nucleus density) are investigated. Like the familiar and widely used one-electron density that represents the probability of finding an electron at a given location in space, the one-nucleus density represents the probability of finding a nucleus at a given position in space independent of the location of the other nuclei and independent of their type. In contrast to the electrons, however, the nuclei are comparably localized. Due to this localization of the individual nuclei, the one-nucleus density provides a quantum-mechanical representation of the "chemical picture" of the molecule as an object that can largely be understood in a three-dimensional space, even though its full nuclear probability density is defined on the high-dimensional configuration space of all the nuclei. We study how the nodal structure of the wavefunctions of vibrationally excited states translates to the one-nucleus density. It is found that nodes do not necessarily lead to visible changes in the one-nucleus density: Already for relatively small molecules, only certain vibrational excitations change the one-nucleus density qualitatively compared to the ground state. It turns out that there are simple rules for predicting the shape of the one-nucleus density from the normal mode coordinates. A Python module for the computation of the one-nucleus density is provided at https://gitlab.com/axelschild/mQNMc.


Prediction of drug disposition on the basis of its chemical structure.
The chemical structure of any drug determines its pharmacokinetics and pharmacodynamics. Detailed understanding of relationships between the drug chemical structure and individual disposition pathways (i.e., distribution and elimination) is required for efficient use of existing drugs and effective development of new drugs. Different approaches have been developed for this purpose, ranging from statistics-based quantitative structure-property (or structure-pharmacokinetic) relationships (QSPR) analysis to physiologically based pharmacokinetic (PBPK) models. This review critically analyzes currently available approaches for analysis and prediction of drug disposition on the basis of chemical structure. Models that can be used to predict different aspects of disposition are presented, including: (a) value of the individual pharmacokinetic parameter (e.g., clearance or volume of distribution), (b) efficiency of the specific disposition pathway (e.g., biliary drug excretion or cytochrome P450 3A4 metabolism), (c) accumulation in a specific organ or tissue (e.g., permeability of the placenta or accumulation in the brain), and (d) the whole-body disposition in the individual patients. Examples of presented pharmacological agents include "classical" low-molecular-weight compounds, biopharmaceuticals, and drugs encapsulated in specialized drug-delivery systems. The clinical efficiency of agents from all these groups can be suboptimal, because of inefficient permeability of the drug to the site of action and/or excessive accumulation in other organs and tissues. Therefore, robust and reliable approaches for chemical structure-based prediction of drug disposition are required to overcome these limitations. PBPK models are increasingly being used for prediction of drug disposition. These models can reflect the complex interplay of factors that determine drug disposition in a mechanistically correct fashion and can be combined with other approaches, for example QSPR-based prediction of drug permeability and metabolism, pharmacogenomic data and tools, pharmacokinetic-pharmacodynamic modeling approaches, etc. Moreover, the PBPK models enable detailed analysis of clinically relevant scenarios, for example the effect of the specific conditions on the time course of the analyzed drug in the individual organs and tissues, including the site of action. It is expected that further development of such combined approaches will increase their precision, enhance the effectiveness of drugs, and lead to individualized drug therapy for different patient populations (geriatric, pediatric, specific diseases, etc.).


HIV seronegative eosinophilic pustular folliculitis successfully treated with metronidazole.
We describe a patient with eosinophilic pustular folliculitis (EPF) who initially responded to oral indomethacin, the most often-used therapy for EPF, but eventually became refractory to continuous administrations. Treatment with metronidazole resulted in complete clearance of the lesion.


Knowledge and attitudes about vitamin D, and behaviors related to vitamin D in adults with and without coronary heart disease in Saudi Arabia.
Vitamin D deficiency is prevailing in Saudi Arabia. Recent national data indicated an inverse association between vitamin D status and coronary heart disease (CHD), which increases concerns about vitamin D deficiency as a serious public health problem. Therefore, the current study aimed to investigate whether knowledge, attitudes and behaviors related to vitamin D contribute to the prevalence of vitamin D deficiency among adults with and without CHD in Saudi Arabia. This case-control study consisted of 130 CHD cases and 195 matched controls. The study subjects were recruited from three hospitals in Saudi Arabia. Structured interviews were completed to collect data on participants' socio-demographics, knowledge about vitamin D, attitudes toward sun exposure, and behaviors related to vitamin D. Also, serum vitamin D levels were measured. Severe vitamin D deficiency [serum 25(OH)D < 10 ng/mL] was more prevalent in the CHD cases than in the controls (46% and 3%, respectively). The total knowledge score was higher in the controls than in the cases [2.5 (±1.8) and 1.6 (±2.2), respectively]. The cases had better attitudes toward sun exposure compared to the controls (p = 0.001); however, the controls had better attitudes toward vitamin D compared to the cases (p = 0.001). The controls had a higher consumption of multivitamin supplements than the cases (6.7% and 0.8%, respectively; p = 0.010). Similarly, the controls had a higher consumption of butter (p = 0.001), oily fish (p = 0.004), and liver (p = 0.003) than the cases; however, the cases had a significantly higher intake of milk (p = 0.001). A multivariate logistic regression showed that vitamin D deficiency [25(OH)D < 20 ng/mL] was associated with low levels of knowledge about vitamin D, with an odds ratio of 1.82 (95% CI: 1.08-3.06, P = 0.024). Vitamin D deficiency was also associated with low intake of vitamin supplements, with an odds ratio of 4.35 (95% CI: 2.12-8.92, P < 0.001). The present study revealed that low levels of knowledge about vitamin D and low consumption of vitamin supplementation, including vitamin D, calcium, multivitamin, and calcium supplements with vitamin D, may have contributed to the higher prevalence of vitamin D deficiency among the CHD cases than among the controls. Further studies using a qualitative approach are crucial to explore the underlying reasons for low knowledge about vitamin D and behaviors related to vitamin D including the intake of vitamin supplementation that may contribute to the high burden of vitamin D deficiency in the country.


[Risk management in anesthesia and critical care medicine].
Throughout its history, anesthesia and critical care medicine has experienced vast improvements to increase patient safety. Consequently, anesthesia has never been performed on such a high level as it is being performed today. As a result, we do not always fully perceive the risks involved in our daily activity. A survey performed in Swiss hospitals identified a total of 169 hot spots which endanger patient safety. It turned out that there is a complex variety of possible errors that can only be tackled through consistent implementation of a safety culture. The key elements to reduce complications are continuing staff education, algorithms and standard operating procedures (SOP), working according to the principles of crisis resource management (CRM) and last but not least the continuous work-up of mistakes identified by critical incident reporting systems.


Biomedical research brings mTBI biomarkers a step closer to the bedside - implementation in clinical practice.
Research in the field of TBI (traumatic brain injury) has long been focused on severe brain injury, while the number of mild injuries far overweigh severe injuries. Mild head injuries constitute up to 95% of all traumatic head injuries. The purpose of this work is to identify mTBI (mild traumatic brain injury) patients who are unlikely to benefit from CT (computed tomography) scanning. Biomarkers capable of clearly discriminating between CT-positive and CT-negative subjects are needed. Biomarkers hold the potential to document whether a concussion occurred, especially when the history is unclear and neurocognitive sequelae persist. Recently, following advances in proteomics analysis, investigators have introduced ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) as two promising brain injury biomarkers. The authors provide an update on the current knowledge of TBI biomarkers, especially protein biomarkers for neuronal cell body injury (UCH-L1) and astroglial injury (GFAP, S100B), and a focused literature review dealing with implementation of mTBI biomarkers in clinical practice.


Using the TIME model in Spectrum to estimate tuberculosis-HIV incidence and mortality.
Reliable estimates of the joint burden of HIV and tuberculosis epidemics are crucial to planning strategic global and national tuberculosis responses. Prior to the Global Tuberculosis Report 2013, the Global Tuberculosis Programme (GTB) released estimates for tuberculosis-HIV incidence at the global level only. Neither GTB nor United Nations Programme on HIV/AIDS (UNAIDS) published country specific estimates for tuberculosis-HIV mortality. We used a regression approach that combined all available data from GTB and UNAIDS in order to estimate tuberculosis-HIV incidence and mortality at country level. A regression method was devised to relate CD4 dynamics (based on national Spectrum files) to an increased relative risk (RR) of tuberculosis disease. The objective function is based on least squares and incorporates all available country-level estimates of tuberculosis-HIV incidence. Global regression parameters, obtained from averaging results over countries with population survey estimates for tuberculosis-HIV burden, were applied to countries with no survey tuberculosis-HIV incidence estimates. The method produced results that are in reasonably close agreement with existing GTB estimates for global tuberculosis-HIV burden. It estimated that tuberculosis-HIV accounts for 12.6% of global tuberculosis incidence, 21.3% of all tuberculosis deaths, and 20% of all HIV deaths as estimated by the Spectrum AIDS Impact Module (AIM). Regional estimates show the highest absolute incidence burden in East and Southeast Asia, and the highest per capita burden in sub-Saharan Africa, where between 12.5% (Central sub-Saharan Africa) and 60.6% (Southern sub-Saharan Africa) of all tuberculosis disease occurs in people living with HIV (PLWH). Tuberculosis mortality follows a similar pattern, except that a disproportionate percentage of global tuberculosis deaths (12.1%) relative to global incidence (8.7%) occurred in Southern sub-Saharan Africa. The disaggregation of tuberculosis incidence using a regression method on RR of tuberculosis disease and all available data on HIV burden (from UNAIDS) and tuberculosis-HIV testing (survey, sentinel and routine surveillance data) produces results that closely match GTB estimates for 2011. The tuberculosis-HIV incidence and mortality results were published in the Global Tuberculosis Report 2013. Several limitations of and potential improvements to the process are suggested.


Biodistributions and Imaging of Poly(ethylene glycol)-Conjugated Silicon Quantum Dot Nanoparticles in Osteosarcoma Models via Intravenous and Intratumoral Injections.
Osteosarcoma is a malignant tumor with relatively high mortality rates in children and adolescents. While nanoparticles have been widely used in assisting the diagnosis and treatment of cancers, the biodistributions of nanoparticles in osteosarcoma models have not been well studied. Herein, we synthesize biocompatible and highly photoluminescent silicon quantum dot nanoparticles (SiQDNPs) and investigate their biodistributions in osteosarcoma mouse models after intravenous and intratumoral injections by fluorescence imaging. The bovine serum albumin (BSA)-coated and poly(ethylene glycol) (PEG)-conjugated SiQDNPs, when dispersed in phosphate-buffered saline (PBS), can emit red photoluminescence with the photoluminescence quantum yield more than 30% and have very low in vitro and in vivo toxicity. The biodistributions after intravenous injections reveal that the SiQDNPs are mainly metabolized through the livers in mice, while only slight accumulation in the osteosarcoma tumor is observed. Furthermore, the PEG conjugation can effectively extend the circulation time. Finally, a mixture of SiQDNPs and indocyanine green (ICG), which complement each other in the spectral range and diffusion length, is directly injected into the tumor for imaging. After the injection, the SiQDNPs with relatively large particle sizes stay around the injection site, while the ICG molecules diffuse over a broad range, especially in the muscular tissue. By taking advantage of this property, the difference between the osteosarcoma tumor and normal muscular tissue is demonstrated.


Molecular cloning and sequencing of the cDNA and gene for a novel elastinolytic metalloproteinase from Aspergillus fumigatus and its expression in Escherichia coli.
An extracellular elastinolytic metalloproteinase, purified from Aspergillus fumigatus isolated from an aspergillosis and patient/and an internal peptide derived from it were subjected to N-terminal sequencing. Oligonucleotide primers based on these sequences were used to PCR amplify a segment of the metalloproteinase cDNA, which was used as a probe to isolate the cDNA and gene for this enzyme. The gene sequence matched exactly with the cDNA sequence except for the four introns that interrupted the open reading frame. According to the deduced amino acid sequence, the metalloproteinase has a signal sequence and 227 additional amino acids preceding the sequence for the mature protein of 389 amino acids with a calculated molecular mass of 42 kDa, which is close to the size of the purified mature fungal proteinase. This sequence contains segments that matched both the N terminus of the mature protein and the internal peptide. A. fumigatus metalloproteinase contains some of the conserved zinc-binding and active-site motifs characteristic of metalloproteinases but shows no overall homology with known metalloproteinases. The cDNA of the mature protein when introduced into Escherichia coli directed the expression of a protein with a size, N-terminal sequence, and immunological cross-reactivity identical to those of the native fungal enzyme. Although the enzyme in the inclusion bodies could not be renatured, expression at 30 degrees C yielded soluble enzyme that showed chromatographic behavior identical to that of the native fungal enzyme and catalyzed hydrolysis of elastin. The metalloproteinase gene described here was not found in Aspergillus flavus.


Control of Circularly Polarized Electroluminescence in Induced Twist Structure of Conjugate Polymer.
An extremely high degree of circularly polarized photoluminescence (CPPL) and electroluminescence (CPEL) (dissymmetry factor values: |gPL | = 0.72 and |gEL | = 1.13) are generated from twisted stacking of achiral conjugated polymer induced by nonemitting chiral dopant of high helical twisting power for the first time. Using a theoretical analysis incorporating the Stokes parameter, the twisting angle and birefringence of the aligned conjugated polymer, and the degree of linear polarization in the emitted light are found to make a roughly equal contribution to the degree of CPEL as to the degree of CPPL. Moreover, it is also found that the location of the recombination zone within the emitting layer is a crucial parameter for determining the difference in the dissymmetry factor between CPEL and CPPL. This result is applied to an organic light-emitting display to improve the luminous efficiency by 60%.


Hibiscus sabdariffa Meal Improves Iron Status of Childbearing Age Women and Prevents Stunting in Their Toddlers in Northern Ghana.
Globally, iron deficiency (ID) is the most common form of nutritional deficiency, particularly in young children and childbearing age women. ID can lead to stunting and impaired cognitive development in children, as well as adverse maternal health and birth outcomes. In this study, the efficacy of an alternative food-to-food fortification utilizing indigenous iron-rich food sources was investigated in a quasi-experimental study. Childbearing age women (15⁻49 years, intervention-Kassena Nankana West district: n = 60; control-Builsa North district: n = 60) and their toddlers (6⁻24 months) consumed Hibiscus sabdariffa leaf meals (HSM, 1.71 mg Fe/100 g meal) three times a week for 12 weeks during the dry/lean season in Northern Ghana. We found that feeding the HSM (1.9 kg/day) improved iron status of women of childbearing age with time (p = 0.011), and protected stunting among toddlers during the dry/lean season (p = 0.024), which is the period with the worst food and nutrition insecurity. Compared with the control group, the number of stunted toddlers declined in the intervention group.


Mapping the metabolic characteristics of probiotic-fermented Ganoderma lucidum and its protective mechanism against Cd-induced nephrotoxicity.
An animal model of Cd-induced kidney damage was designed to investigate the nephroprotective potential of the probiotic-fermented Ganoderma lucidum (FGL) via metabonomic analysis. The results showed that FGL enhanced sugar and amino acid metabolism. The interaction of Ganoderma lucidum (GL) and probiotics efficiently elevated short-chain fatty acid production following gut microbiota fermentation. The current data revealed that the FGL intervention alleviated Cd-induced nephrotoxicity via elevating the activity of antioxidant enzymes and decreasing the levels of pro-inflammatory and apoptotic factors. Based on transcriptome analysis, FGL intervention mediated renal dysfunction via decreasing the expressions of Nos2, Tnfsf14, S100a9, Map3k6 and Hk3, which were involved in oxidative stress, inflammatory response and the apoptosis process. The current study highlights a new approach for achieving positive nephroprotection via natural product intervention.


Efficacy and Safety of IncobotulinumtoxinA in the Treatment of Lower Limb Spasticity in Japanese Subjects.
To confirm the efficacy and safety of incobotulinumtoxinA (Xeomin®, Merz Pharmaceuticals GmbH; total dose 400 U) in Japanese subjects with lower limb (LL) poststroke spasticity using the Modified Ashworth Scale spasticity score for the plantar flexors (MAS-PF). This phase III study (Japic clinical study database No. CTI-153030, 7 October 2015) included a double-blind, 12-week main period (MP) in which 208 subjects were randomized to receive one injection cycle of incobotulinumtoxinA 400 U (n = 104) or placebo (n = 104) in the pes equinus muscles, and an open-label extension (OLEX) that enrolled 202 subjects who received three injection cycles, 10-14 weeks in duration (the last cycle was fixed at 12 weeks). Changes in MAS-PF for incobotulinumtoxinA vs. placebo from baseline to Week 4 of the MP and to the end-of-cycle visits in the OLEX were evaluated. The area under the curve for the change in MAS-PF was statistically significantly greater with incobotulinumtoxinA vs. placebo in the MP (mean: -7.74 vs. -4.76; least squares mean: -8.40 vs. -5.81 [p = 0.0041]). In the OLEX, mean changes in MAS-PF from baseline to end-of-study showed continued improvement with repeated injections. No new safety concerns were observed with the incobotulinumtoxinA treatment. Its efficacy and safety were consistent regardless of the length of the injection cycle interval in the OLEX. This study demonstrated that incobotulinumtoxinA (total dose 400 U) is an effective and a well-tolerated treatment for LL spasticity in Japanese subjects using flexible injection intervals of 10-14 weeks.


Influence of myocardial mechanical activity and coronary blood flow on myocardial digoxin uptake.
The myocardial content of digoxin 60 min after intravenous administration in open-chest dogs correlated with heart rate controlled in individual dogs between 64 and 215 beats/min. In other dogs, increasing right ventricular mechanical work by constriction of the pulmonary artery resulted in greater right ventricular digoxin uptake. Increase in myocardial blood flow per se could not explain these findings since, in further dogs, increasing regional myocardial blood flow by adenosine infusion did not much affect digoxin uptake. Active uptake of cardiac glycosides is probably influenced by myocardial mechanical and metabolic activity.


Polymorphism of erythromycin studied by differential thermal analysis.
The polymorphism of erythromycin has been studied by differential thermal analysis. Three main forms, two crystalline (I and SI) and one amorphous have been characterized. Solvation and imbibition water can be differentiated. Solvates from 2-propanol (SII), trichloromethane (SIII) and tetrachloromethane (SIV) have been characterized. The physical stability of the various forms both in the dry state and in aqueous suspension are discussed.


Effect of Major Depressive Disorder on Stroke Risk and Mortality: A Systematic Review.
This study aimed to systematically review the available data on major depressive disorder (MDD) and provide insight into how it may affect stroke risk and mortality. We conducted this systematic review drawing upon research published between July 2002 and July 2022 from the following databases: PubMed, ScienceDirect, and Google Scholar. After eliminating duplicates, screening the title and abstract, determining eligibility, and quality assessment, eight articles were left for utilization in this systematic review (one meta-analysis and seven non-randomized studies). There was a potentially significant association between MDD and stroke risk and mortality. The apparent connection between MDD and stroke has medical and public health relevance, given the high incidence, prevalence, and financial burden of MDD and stroke in the general populace. Therefore, it is imperative that further studies are conducted to confirm and validate this association between MDD and stroke while also elucidating the mechanism involved, investigating potential variables influencing this association, and contrasting MDD with conventional stroke risk factors to determine its predictive usefulness in comparison to traditional risk factors. This will have a significant effect on clinical practice since the information provided by such research will help guide essential targets for stroke prevention.


The production of tumour necrosis factor, tissue thromboplastin, lactoferrin and cathepsin C during lipopolysaccharide stimulation in whole blood.
The release of tumour necrosis factor (TNF), lactoferrin (LF) and cathepsin C (CC) into plasma and production of thromboplastin (TPL) in monocytes were studied in lipopolysaccharide (LPS) stimulated heparinized whole blood from 10 healthy donors. The influence of dextran 70, haemaccel and methylprednisolone on levels of these parameters were examined. TNF concentration in plasma 5 min after the addition of LPS (0 h) was 250 pg/ml (median), 520 pg/ml after 1 h and 1300 pg/ml after 3 h. The addition of dextran 70 to the blood in addition to LPS at the same intervals gave significantly higher values of 740 pg/ml and 1800 pg/ml after 1 h and 3 h respectively. Unstimulated cells had no TPL but after 1 h with LPS, the TPL activity in incubated cells was 2.3 mU/10(6) monocytes and after 3 h, 2.7 mU/10(6) monocytes. LPS induced the secretion of LF from granulocytes (PMN) and the levels 5 min after the addition of LPS (0 h) were 2.1 mg/l (control 0.2 mg/l) and after 1 h, 5.3 mg/l (control 1.3 mg/l) in plasma after LPS stimulation. Haemaccel enhanced the LPS-induced generation of TPL in monocytes and production of CC. The LPS-induced secretion of LF was, to a small extent, influenced by the three reagents tested. Methylprednisolone (1 mmol/l) reduced the production and appearance of TNF in plasma and the generation of TPL activity in monocytes. This model for stimulating heparinized whole blood is suitable for examination of the production and appearance of cellular factors and the influence of drugs on this production.


Determination of trans Fat in Selected Fast Food Products and Hydrogenated Fats of India Using Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) Spectroscopy.
This paper reports the application of a simple and rapid method for the determination of trans fatty acid (TFA) content in some of the selected Indian fast food products and hydrogenated fats using Fourier transform infrared (FTIR) spectroscopy in conjunction with second derivative procedure. FTIR spectroscopy has been successfully applied to trans measurement using the absorbance bands at or near 966 cm-1 in the FTIR spectra. It was found from the analysis that TFA content of fast food product was ranging from 1.57% to 3.83% of the total fat while for hydrogenated fats, comparatively large quantity of TFA was detected in the range of 3.31% to 4.73%. Since GC-FID is most widely used method for the determination of fatty acid (FA) composition, this method was used for the sake of comparison. Value of regression coefficient was found very close to one (0.99503) with standard deviation of 0.10247 showing a good agreement between GC-FID and proposed ATR-FTIR method.


Disc and nerve root findings on lumbar MRI with straightened v s flexed hips and knees-pilot study.
To compare disc and nerve root findings, image quality, and pain between supine lumbar MRI positions with straightened v s flexed hips and knees. In this prospective pilot study, 14 adults with sciatica or suspected lumbar radiculopathy underwent MRI supine with their hips and knees flexed and then straightened. For each position, two experienced radiologists assessed disc contour, location/size of disc herniation, nerve root affection, image quality, image evaluation difficulty, and sagittal angles between the vertebral bodies at each disc level L3-S1. Patients scored pain (0-10) after MRI in each position. We compared MRI assessments and mean pain scores (t-test, log-transformation) between the two positions. We found no clear difference in disc bulges, disc herniation, nerve root affection, image quality, or image evaluation difficulty between MRI with straightened v s flexed knees/hips. Herniation size differed ≤ 0.6 mm between the two positions. Sagittal angles between neighboring vertebral bodies differed ≤3.8°. Mean pain score after MRI with straightened v s flexed knees/hips was 4.64 v s 3.29 (p = 0.005). In this pilot study, supine lumbar MRI with straightened vs flexed hips/knees showed similar disc and nerve root findings. The straightened position appeared more painful. In previous studies, spondylolisthesis increased on supine MRI with straightened v s flexed lower limbs, but corresponding data on disc findings were lacking. In this pilot study, supine lumbar MRI with straightened rather than flexed hips and knees was more painful and did not improve the diagnosis of disc or nerve root findings.


Comparing Antibody Responses in Chickens Against Plasmodium falciparum Lactate Dehydrogenase and Glyceraldehyde-3-phosphate Dehydrogenase with Freund's and Pheroid® Adjuvants.
Pheroid® technology was assessed as an alternative to Freund's adjuvant to raise antibodies in experimental animals. Chickens were immunized with two recombinantly expressed Plasmodium falciparum proteins, lactate dehydrogenase (PfLDH) and glyceraldehyde-3-phosphate dehydrogenase (PfGAPDH), alone or in combination with Freund's adjuvant or Pheroid®. Chicken egg yolk antibodies (IgY) were isolated and compared for specificity, sensitivity and yield. Freund's adjuvant and Pheroid® stimulated prolonged antibody responses in chickens against both antigens. Affinity purified antibodies had specificity for the recombinant and the native proteins on Western blots. Antibodies generated in the presence of Freund's adjuvant had high sensitivity for both antigens. Pheroid® generated antibodies that detected the lowest concentration of recombinant PfLDH. Freund's adjuvant and Pheroid® both improved chicken IgY yields, with Pheroid® showing a 2-fold increase relative to controls. Pheroid® was well-tolerated in chickens and has potential for development as a safe adjuvant for testing alternative stimulatory factors to improve adjuvant formulations.


Exacerbation of underlying pulmonary disease in pregnancy.
The presence of underlying pulmonary disease in women of childbearing potential can present a significant challenge during pregnancy and the postpartum period. Management of the underlying disease, recognizing and preventing disease progression, and, most important, managing and minimizing toxic side effects of various therapies require the expertise of an interdisciplinary team. This team must involve close collaboration between intensive care physicians, pulmonary physicians, and high-risk obstetricians familiar with these disease states in an effort to minimize fetal and maternal morbidity and mortality. We will review the impact of the pregnant state in lung transplant recipients, patients with pulmonary arterial hypertension, and patients with underlying cystic fibrosis. Review of the literature in regards to pregnancy outcomes and issues for patients with cystic fibrosis, pulmonary hypertension, and lung transplants. A review of the epidemiology, pathophysiology, risk factors, classification, clinical features, and outcomes for pregnant patients with underlying pulmonary diseases. Safety of pregnancy in the female lung transplant recipient concerns three outcomes: maternal outcome, fetal outcome, and transplanted graft outcome.


Enhanced norepinephrine release in hypothalamus from locus coeruleus in SHR.
The hypothesis that a functional projection from the locus coeruleus (LC) to the posterior hypothalamus contributes to the development of hypertension in SHR, was tested by measuring norepinephrine (NE) in the posterior hypothalamus by brain dialysis after injections of L-glutamate (L-glu) into LC. L-glu elicited a prolonged elevation of blood pressure in both SHR and WKY. Pressor effects were significantly larger in SHR than in WKY. Extracellular NE in the posterior hypothalamus increased after LC stimulation; NE release was significantly higher in SHR than in WKY. Injections of 6-hydroxydopamine (6-OHDA) into posterior hypothalamus lowered the resting blood pressure and attenuated the pressor responses to L-glu injections into the LC in SHR. These findings suggest that the LC projects functionally to the posterior hypothalamus and that the projection can contribute to the development of hypertension in SHR.


Prescriber Implementation of STOPP/START Recommendations for Hospitalised Older Adults: A Comparison of a Pharmacist Approach and a Physician Approach.
Two randomised controlled trials (RCTs) conducted simultaneously in the same Irish university teaching hospital have shown that provision of Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert doctors to Right Treatment (START) recommendations to attending prescribers by a physician or a pharmacist can reduce in-hospital adverse drug reactions (ADRs) in older adults (≥ 65 years). The aims of this study were to compare the prescriber implementation rates of STOPP/START recommendations between the physician approach and the pharmacist approach in these two RCTs and to provide a narrative summary of the comparable clinical outcomes. Data were extracted from the two RCT published papers and their associated computerised databases to calculate the percentage prescriber implementation rates for the STOPP/START recommendations. The Chi-square test was used to quantify the differences in prescriber implementation rates, with differences considered statistically significant where p < 0.05. Prescriber implementation rates of the STOPP and START recommendations made by the physician were 81.2% and 87.4% respectively, significantly higher than those made by the pharmacist (39.2% and 29.5% respectively), p < 0.0001. A greater absolute risk reduction in patients with ADRs was shown with the physician's intervention compared to the pharmacist's intervention (9.3% vs 6.8%). This study shows that the methods of communication and the medium through which the STOPP/START recommendations are delivered significantly affect their implementation. Non-implementation of some pharmacist-delivered recommendations may be contributing to preventable ADRs in older adults. Thus, future research should aim to identify the factors influencing prescriber implementation of pharmacist recommendations in order to inform the design of more effective pharmacist interventions in optimising older patients' pharmacotherapy.


Prognostic relevance of PCI-related myocardial infarction.
Procedure-related myocardial infarction (pMI) is directly associated with a coronary revascularization procedure, such as percutaneous coronary intervention (PCI) or CABG surgery. In contrast to spontaneous myocardial infarction (MI), the prognostic relevance of pMI is the subject of ongoing debate. Data from retrospective analyses of large, randomized clinical trials, and large, contemporary cohort studies have several shortcomings that limit their extrapolation to clinical practice. In our opinion, the currently available evidence is insufficient to conclude that pMI during PCI, as currently defined, always has important prognostic implications. Until further evidence is available, we recommend adopting the definition for MI given in the third universal definition of MI, which differentiates between pMI and spontaneous MI. This is important not only for clinical decision-making but also for the interpretation of pMI as a surrogate end point in clinical trials. Further studies are essential to understand the pathophysiology and consequences of pMI.


Physical principles of ultrasonic dissection and clinical application of BERCHTOLD SONO-CUT reusable ultrasonic scissors.
Technical principles and physical action mechanisms of ultrasonic dissection are introduced. We list various indications for using the BERCHTOLD SONO-CUT scissors and describe early clinical experiences, e.g. in pediatric laparoscopic surgery.


High tau levels in cerebrospinal fluid predict nursing home placement and rapid progression in Alzheimer's disease.
Increased concentrations of cerebrospinal fluid (CSF) total tau (t-tau) and phosphorylated tau, as well as decreased amyloid-β 42 peptide, are biomarkers of Alzheimer's disease (AD) pathology, but few studies have shown an association with AD progression rate. We hypothesized that high CSF tau, as a marker of ongoing neurodegeneration, would predict a more aggressive course of AD, using time to nursing home placement (NHP) as the main outcome. Our sample inlcuded 234 patients with mild cognitive impairment (MCI) due to AD (n = 134) or mild to moderate AD (n = 100) who underwent lumbar puncture at a memory clinic and were followed for 2-11 years (median 4.9 years). Individuals with CSF t-tau in the highest quartile (≥900 ng/L) had a higher ratio of NHP, both in the total cohort and in patients with MCI only (adjusted HR 2.17 [95% CI 1.24-3.80]; HR 2.37 [95% CI 1.10-5.09], respectively), than the lowest quartile. The association between high t-tau levels and future steep deterioration was confirmed in analyses with conversion to moderate dementia (HR 1.66; 95% CI 1.08-2.56), rapid decline in Mini Mental State Examination score (≥4-point drop/12 months), and dying in severe dementia as outcomes. To our knowledge, this is the first study to show that high CSF t-tau levels predict early NHP and conversion to moderate dementia in an AD cohort. Selecting patients with high CSF t-tau, indicating more aggressive neurodegeneration and steeper decline, for AD immunotherapy trials might increase the possibility of showing contrast between active treatment and placebo.


Passage of Time Judgments Is Relative to Temporal Expectation.
Time seems to pass quickly sometimes or slowly at other times. While this belief is prevalent, the psychological bases of such judgments on speed of time have remained unclear. In this study, we tested following two hypotheses: (1) the passage of time judgment (POTJ) is a function of the discrepancy between felt duration and temporal expectation of events and (2) POTJ is based on two distinct components: post hoc comparison of expected and felt durations and online anticipation of the end of an event. In four experiments, participants engaged in N-back tasks for several minutes and rated their POTJ during the tasks. Their temporal expectations were manipulated by providing them with false instructions on task durations. The results consistently supported the hypotheses and confirmed the idea that temporal expectation plays an important role in POTJ. In addition, the current findings might explain our daily temporal experiences such as "time flies when you are having fun."