Results of single stage exchange arthroplasty with retention of well fixed cement-less femoral component in management of infected total hip arthroplasty.
To investigate success of one stage exchange with retention of fixed acetabular cup. Fifteen patients treated by single stage acetabular component exchange with retention of well-fixed femoral component in infected total hip arthroplasty (THA) were retrospectively reviewed. Inclusion criteria were patients with painful chronic infected total hip. The patient had radiologically well fixed femoral components, absence of major soft tissue or bone defect compromising, and infecting organism was not poly or virulent micro-organism. The organisms were identified preoperatively in 14 patients (93.3%), coagulase negative Staphylococcus was the infecting organism in 8 patients (53.3%). Mean age of the patients at surgery was 58.93 (± 10.67) years. Mean follow-up was 102.8 mo (36-217 mo, SD 56.4). Fourteen patients had no recurrence of the infection; one hip (6.7%) was revised for management of infection. Statistical analysis using Kaplan Meier curve showed 93.3% survival rate. One failure in our series; the infection recurred after 14 mo, the patient was treated successfully with surgical intervention by irrigation, and debridement and liner exchange. Two complications: The first patient had recurrent hip dislocation 12 years following the definitive procedure, which was managed by revision THA with abductor reconstruction and constrained acetabular liner; the second complication was aseptic loosening of the acetabular component 2 years following the definitive procedure. Successful in management of infected THA when following criteria are met; well-fixed stem, no draining sinuses, non-immune compromised patients, and infection with sensitive organisms.


[Vaskuläre Dyspnoe: Lungenembolie].
In clinical practice, the differentiation of pulmonary embolism from other entities often remains difficult. Of utmost importance is the estimation of the pretest probability of the disease: predictive scoring systems and the use of clinical gestalt are equally useful tools. Exclusion or confirmation of the disease requires the rationale use of additional investigations (laboratory, imaging). In this article, we provide clinical engrams and outline our diagnostic algorithm. Based on the latest recommendations, we summarize the therapeutic approach for patients with pulmonary embolism. The importance of follow-up visits after the initial event is discussed in the last part. The assessment of risk factors promoting the development of venous thromboembolism is crucial for estimating the risk of recurrence. Excessive screening (thrombophilia testing or tumor investigations) are of minor relevance.


Vaginal lesion as first manifestation of colorectal disease.
A 73-year-old woman presented at Gyneacology Consultation with vaginal sensation of a lump. Physical examination revealed a vaginal exophytic lesion with 3 cm located at the right inner lip. The lesion was biopsied and histologic examination revealed infiltration by a mucinous adenocarcinoma. Immunohistochemical study suggested the diagnosis of colorectal aetiology. A subsequent colonoscopy demonstrated an ulcerated circumferential lesion at 8 cm from the anal verge Additional staging examinations revealed pulmonary metastasis and the patient was diagnosed with colorectal cancer stage IV. She was evaluated for chemotherapy and radiotherapy. We present an exceedingly rare case of true vaginal metastasis identified before the diagnosis of colorectal primary lesion.


Evaluating the use of an Unmanned Aerial Vehicle (UAV)-based active AirCore system to quantify methane emissions from dairy cows.
Enteric fermentation and manure methane emissions from livestock are major anthropogenic greenhouse gas emissions. In general, direct measurements of farm-scale methane emissions are scarce due to the source complexity and the limitations of existing atmospheric sampling methods. Using an innovative UAV-based active AirCore system, we have performed accurate atmospheric measurements of CH4 mole fractions downwind of a dairy cow farm in the Netherlands on four individual days during the period from March 2017 to March 2019. The total CH4 emission rates from the farm were determined using the UAV-based mass balance approach to be 1.1-2.4 g/s. After subtracting estimated emission factors of manure onsite, we derived the enteric emission factors to be 0.20-0.51 kgCH4/AU/d (1 AU = 500 kg animal weight) of dairy cows. We show that the uncertainties of the estimates were dominated by the variabilities in the wind speed and the angle between the wind and the flight transect. Furthermore, nonsimultaneous sampling in the vertical direction of the plume is one of the main limiting factors to achieving accurate estimate of the CH4 emissions from the farm. In addition, a N2O tracer release experiment at the farm was performed when both a UAV and a mobile van were present to simultaneously sample the N2O tracer and the CH4 plumes from the farm, improving the source quantification with a correction factor of 1.04 and 1.22 for the inverse Gaussian approach and for the mass balance approach, respectively. The UAV-based active AirCore system is capable of providing useful estimates of CH4 emissions from dairy cow farms. The uncertainties of the estimates can be improved when combined with accurate measurements of local wind speed and direction or when combined with a tracer approach.


Limits of endoscopic endonasal surgery for III ventricle craniopharyngiomas.
Craniopharyngiomas represent one of the most challenging brain tumors for the neurosurgeon. For most of the 20th century, these parasellar lesions have been approached via the classic open approaches of neurosurgery such as pterional, frontobasal, interhemispheric, and transpetrosal craniotomies. The endoscopic endonasal approach to these tumors, rather than craniotomy, has risen in popularity over the last two decades. Regardless of approach, a detailed knowledge of surgical anatomy and careful preoperative surgical planning are essential to achieve good clinical results; iatrogenic morbidity can potentially be severe due to hypothalamus, optic apparatus, and/or vascular injuries. Especially challenging, and highlighting the limitations of endoscopic endonasal surgery, are the tumors that arise primarily from within the third ventricle and do not expand the pituitary stalk and suprasellar region or tumors that have projected to areas far from the parasellar region as such as the sylvian and ambient cisterns. Herein we review the published literature regarding endoscopic endonasal surgery for craniopharyngioma, and the anatomical and functional limitations therein. The benefits and drawbacks of each surgical approach to this deep-seated area are discussed, and a strategy for surgical decision-making proposed.


[Immunosorption method of urokinase determination].
An immunosorption procedure is developed for quantitative estimation of plasminogen activator of the urokinase type in human blood serum. The procedure involved sorption of urokinase from blood serum using polyclonal antibodies to the enzyme as a sorbent at the first step of the assay. Concentration of the immunoreactive urokinase in a preparation correlated with the absorbed fraction of standard urokinase added into the sample at the second step after washing of the sorbent. The residual fibrinolytic activity of the standard dose was detected in fibrin-agar gel. Results of the assay were not altered in presence of high molecular (bovine blood serum, soy bean inhibitor of trypsin) and low molecular inhibitors of urokinase (benzamidine, arginine, epsilon-aminocapronic acid). Sensitivity of the assay constituted 0.05 IU/sample (2.5 IU/ml, 0.25 ng/sample) and might be increased by a decimal order after addition of plasminogen into fibrin-agar gel. Content of urokinase in blood serum of healthy men (21-48 years old) was equal to 166 +/- 8.9 IU/ml with individual variations from 107 to 260 IU/ml.


Inorganic surface nanostructuring by atmospheric pressure plasma-induced graft polymerization.
Surface graft polymerization of 1-vinyl-2-pyrrolidone onto a silicon surface was accomplished by atmospheric pressure (AP) hydrogen plasma surface activation followed by graft polymerization in both N-methyl-2-pyrrolidone (NMP) and in an NMP/water solvent mixture. The formation of initiation sites was controlled by the plasma exposure period, radio frequency (rf) power, and adsorbed surface water. The surface number density of active sites was critically dependent on the presence of adsorbed surface water with a maximum observed at approximately a monolayer surface water coverage. The surface topology and morphology of the grafted polymer layer depended on the solvent mixture composition, initial monomer concentration, reaction temperature, and reaction time. Grafted polymer surfaces prepared in pure NMP resulted in a polymer feature spacing of as low as 5-10 nm (average feature diameter of about 17 nm), an rms surface roughness range of 0.18-0.72 nm, and a maximum grafted polymer layer thickness of 5.5 nm. Graft polymerization in an NMP/water solvent mixture, however, resulted in polymer feature sizes that increased up to a maximum average feature diameter of about 90 nm at [NMP] = 60% (v/v) with polymer feature spacing in the range of 10-50 nm. The surface topology of the polymer-modified silicon surfaces grafted in an NMP/water solvent mixture exhibited a bimodal feature height distribution. In constrast, graft polymerization in pure NMP resulted in a narrow feature height distribution of smaller-diameter surface features with smaller surface spacing. The results demonstrated that, with the present approach, the topology of the grafted polymer surface was tunable by adjusting the NMP/water ratio. The present surface graft polymerization method, which is carried out under AP conditions, is particularly advantageous for polymer surface structuring via radical polymerization and can, in principle, be scaled to large surfaces.


Molecular genetic studies of cognitive ability.
Given that the evidence of a substantial genetic contribution to cognitive ability is now convincing, the next challenge is to locate and identify the genes involved. It is likely that there are several genes, each of only small effect. Detection of such so-called quantitative trait loci contributing to polygenic traits in plants and animals is facilitated by the ability to carry out experimental crosses. However, in humans detection of quantitative trait loci depends on studies of siblings or other relative pairs or on allelic association studies aimed at detecting linkage disequilibrium in populations. The allelic association approach is currently being applied to investigate cognitive ability by using both candidate genes and DNA pooling methods that potentially allow rapid screening of the whole genome for quantitative trait loci.


The effect of trochleoplasty on patellar stability and kinematics: a biomechanical study in vitro.
Objective patellar instability has been correlated with dysplasia of the femoral trochlea. This in vitro study tested the hypothesis that trochleoplasty would increase patellar stability and normalise the kinematics of a knee with a dysplastic trochlea. Six fresh-frozen knees were loaded via the heads of the quadriceps. The patella was displaced 10 mm laterally and the displacing force was measured from 0 degrees to 90 degrees of flexion. Patellar tracking was measured from 0 degrees to 130 degrees of knee flexion using magnetic sensors. These tests were repeated after raising the central anterior trochlea to simulate dysplasia, and repeated again after performing a trochleoplasty on each specimen. The simulated dysplasia significantly reduced stability from that of the normal knee (p < 0.001). Trochleoplasty significantly increased the stability (p < 0.001), so that it did not then differ significantly from the normal knee (p = 0.244). There were small but statistically significant changes in patellar tracking (p< 0.001). This study has provided objective biomechanical data to support the use of trochleoplasty in the treatment of patellar instability associated with femoral trochlear dysplasia.


[A case of lobar atrophy with stereotypic unusual laughing].
We report a case of a Pick's disease (frontal predominant type) with unusual laughing. The patient was a 54-year-old, right handed, female. The patient began to show low activity and inappropriate laughing at about 51 years. She did not speak at all and showed weird laughing with a voice "hi hi hi hi hi hi" frequently at first presentation. When asked some questions, she sometimes answered with a nod. Almost all of her laughing did not match with the situation and seemed to lack a relationship between affective change and observed expressions. The laughing could be elicited by non specific and varied stimuli. She often interrupt laughing voluntarily unlike pathological laughing. Neurological examination revealed visual rooting reflex and forced grasping reflex but there was no signs of pseudobulbar palsy often observed in patients with pathological laughing. Her electromyogram of facial expression during the laughing showed that electric discharge of M. corrugator supercilii was over 4 times as much as that in normal laughing. And it showed also that the duration of her laughing was several seconds as normal laughing. CT and MRI scans demonstrated atrophy in the fronto-temporo-parietal lobe bilaterally (L > R), most prominent in the frontal lobe. SPECT scan showed a significant diminution of blood flow in the atrophic region. An EEG was normal. We consider that the laughing of the present case is not due to an emotional disturbance but rather a disorder of affective expression as pathological laughing.


Clostridium difficile multidisciplinary team root cause analysis: impact on clinical care and circumvention of financial penalties posed by clinical commissioning groups, but at what cost?
In Hampshire Hospitals NHS Foundation Trust, in addition to an on-the-spot investigation into hospital-onset Clostridium difficile infection (CDI) by the infection prevention team, a multidisciplinary team root cause analysis (MDT-RCA) forum has been developed. The MDT-RCA aims to deliver a more thorough investigation into individual cases and the recommendation of cases to the clinical commissioning groups (CCG) appeals panel against potential financial penalties (£10,000 per breached case). We mainly aimed to investigate the financial impact of MDT-RCAs to the Trust. Over two years, 84 cases of hospital-onset CDI cases were reviewed by the MDT-RCA forum. Among this cohort, no additional learning outcomes were identified by the MDT-RCAs over those that were found by on-the-spot investigations. In total, 543 staff members attended the MDT-RCAs at a potential cost to the Trust of £23,795.74-£51,670.10. The Trust appealed against financial penalties for 27 cases and 14 were successful, i.e. £140,000 would have been avoided had targets been breached by 14 cases. However, targets were only breached by two cases, meaning only £20,000 in fines was avoided. Deducting this from the total costs of the MDT-RCA meant the Trust lost £3,795.74-£31,670.10. Over the two years reviewed, the MDT-RCA proved to be costly to the Trust, with no additional learning or quality improvement measures identified.


Rotavirus vaccine effectiveness and case-control study on risk factors for breakthrough infections in Germany, 2010-2011.
In the German federal state Mecklenburg-Western Pomerania, routine rotavirus (RV) vaccination in infants has been recommended since 2009. The effectiveness of RV vaccination was investigated after an unexpectedly high number of RV infections in fully vaccinated children occurred. Intensified RV surveillance was performed in Mecklenburg-Western Pomerania between 2010 and 2011. The screening method was applied to assess vaccine effectiveness (VE) in children up to 24 months after vaccination. To identify risk factors for breakthrough infections, a case-control study and genotyping were conducted in vaccinated and unvaccinated RV-infected children. VE for the prevention of RV infection requiring medical attention or hospitalization was 68% (95% confidence interval [CI]: 61-71) and 80% (95% CI: 77-83), respectively. VE for preventing hospitalization but not medical attention remained stable over 2 years. Vaccinated were less often hospitalized (23%) than unvaccinated RV-infected children (61%; P < 0.001). Breastfeeding (odds ratio, 3.99; 95% CI: 1.92-8.27) and attending daycare (odds ratio, 3.42; 95% CI: 1.64-7.12) were independently associated with breakthrough infections. Genotype G1P[8] was detected more frequently in RotaTeq-vaccinated (44% versus 11%; P < 0.03) and G2P[4] in Rotarix-vaccinated children (42% versus 6%; P < 0.02). RV vaccination protects young children effectively from RV disease and can reduce disease severity. Breastfeeding might impair VE, but further research is needed to identify the critical time window for this interference and to develop appropriate recommendations.


White matter lesion progression: a surrogate endpoint for trials in cerebral small-vessel disease.
There is neuropathologic evidence that confluent MRI white matter lesions in the elderly reflect ischemic brain damage due to microangiopathy. The authors hypothesize that measuring changes in the progression of white matter lesions as shown by MRI may provide a surrogate marker in clinical trials on cerebral small-vessel disease in which the currently used primary outcomes are cognitive impairment and dementia. This hypothesis is based on evidence that confluent white matter lesions progress rapidly as shown in a recent follow-up study in community-dwelling subjects. The mean increase in lesion volume was 5.2 cm(3) after 3 years. Based on these data in a clinical trial, 195 subjects with confluent lesions would be required per treatment arm to demonstrate a 20% reduction in the rate of disease progression over a 3-year period. Like any other MRI metric, the change in white matter lesion volume cannot be considered preferable to clinical outcomes unless it has been demonstrated that it matters to the patient in terms of function.


Association between alcohol consumption and diabetes preventive practices.
Little is known about the effect of alcohol consumption on the quality of care among patients with diabetes. We evaluated the association between alcohol consumption and diabetes preventive practices. We analyzed data from the 2001 Behavioral Risk Factor Surveillance System. Based on self-reported alcohol consumption in the past 30 days, we categorized participants into the following groups: nondrinkers, moderate drinkers (average drinks/day: < or = one for women, < or = two for men), or heavy drinkers (average drinks/day: > one for women, > two for men). We then examined the association between alcohol consumption and participants' reports of diabetes preventive practices. Of 10,980 respondents with a self-reported diagnosis of diabetes, 70% were current nondrinkers, 28% moderate drinkers, and 2% heavy drinkers. Heavy drinkers compared with nondrinkers were more likely to report not performing daily glucose self monitoring and not having had an eye examination in the past year, adjusting for age, gender, race, education, income, marital status, health insurance, diabetes duration, health status, and insulin use. Moderate drinkers were more likely than nondrinkers to report not performing daily glucose self monitoring and not having had a provider visit for diabetes in the past year. Adults with diabetes who report moderate or heavy alcohol consumption may be at risk for adverse diabetes outcomes due to suboptimal preventive practices.


The Development and Acceptability of a Mobile Application for Tracking Symptoms of Heart Failure Among Older Adults.
Heart failure (HF) is common in older adults. With increases in technology use among older adults, mobile applications may provide a solution for older adults to self-manage symptoms of HF. This article discusses the development and acceptability of a HF symptom-tracking mobile application (HF app). The HF app was developed to allow patients to track their symptoms of HF. Thirty (N = 30) older adults completed an acceptability survey after using the mobile app. The survey used Likert items and open-ended feedback questions. Overall, the acceptability feedback from users was positive with participants indicating that the HF app was both easy to use and understand. Participants identified recommendations for improvement including additional symptoms to track and the inclusion of instructions and reminders. HF is common in older adults, and acceptability of mobile apps is of key importance. The HF app is an acceptable tool for older patients with HF to self-manage their symptoms, identify patterns, and changes in symptoms, and ultimately prevent HF readmission.


Isolation, characterization, and hepatoprotective effects of the raffinose family oligosaccharides from Rehmannia glutinosa Libosch.
This study was aimed to isolate and characterize the raffinose family oligosaccharides (RGOs) from a novel plant source of Rehmannia glutinosa Libosch, and further evaluate whether RGOs can attenuate CCl4-induced oxidative stress and hepatopathy in mice. HPLC analysis showed that RGOs were mainly composed of stachyose (61.7%, w/w), followed by 23.7% raffinose and 7.1% sucrose. Administration of RGOs orally daily in mice for 21 days significantly reduced the impact of CCl4 toxicity on the serum markers of liver damage, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total-cholesterol (TC), and triglycerides (TG). RGOs also increased antioxidant levels of hepatic glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC), and ameliorated the elevated hepatic formation of malonaldehyde (MDA) induced by CCl4 in mice, which coincided with the histological alteration. These findings exhibited the potential prospect of RGOs as functional ingredients to prevent ROS-related liver damage.


[Clinical assessment of the efficacy of early enteral nutrition with the help of "peptamen" nutriment in patients who underwent gastrectomy due to stomach cancer].
The protein-energetic insufficiency in cancer patients aggravates the course of the disease and leads to various complications in the post-operative period including lethal outcomes. The purpose of the study is to assess the efficiency of the use of the Peptamen compound in the early post-operative period in patients with moderate and serious degrees of protein-energetic insufficiency, who underwent gastrectomy due to stomach cancer. Two groups of patients were studied differing by the method of nutritional support. The use of the Peptamen compound in the early post-operative period leads to the improvement of the absorption of nutrients, increase in the functional activity of the intestine and immunomodulation, and as a result of this, to the reduction of post-operative complications and fast restoration of homeostasis.


Pregnancy outcomes in women with endometriosis.
The association between endometriosis and subfertility is well known and has been the object of intense research in the last decades. However, the potential association between endometriosis and adverse pregnancy outcome has not been studied until recently. The results from epidemiological studies suggest that endometriosis is associated with preterm birth, preeclampsia, antepartal hemorrhage, and an increase in cesarean delivery. These findings suggest that women with endometriosis may need special care during pregnancy. The underlying mechanisms for the observed associations are unknown, and further studies, both experimental and epidemiological, are necessary.


Synthesis of novel muramic acid derivatives and their interaction with lysozyme: Action of lysozyme revisited.
The interaction of lysozyme with the N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) unit of peptidoglycan (PGN) polymer of the bacterial cell wall is of immense importance to understand the mechanism of lysozyme on PGN. The synthesis of three novel NAM derivatives containing fused oxazinone ring to the NAM moiety has been achieved. The synthesized compounds were evaluated for their potential as a glycomimetic acceptor of lysozyme using different biophysical and computational methods such as 1H NMR, STD NMR, DOSY and Molecular docking. Novel modified muramic acid derivatives have been synthesized in excellent yield containing fused cyclooxazine ring embedded on the muramic acid moiety using a newly developed hydrazinolysis reaction condition. From various biophysical studies, it has been established that the compound containing endo modified muramic acid moiety (compound 1) shows significant binding property for the lysozyme while the other isomer (compound 2) did not bind to the lysozyme. The catalytic residues Glu35 and Asp52 were found to be in the close proximity for the active molecule which justifies the selectivity of this molecule in conjunction to lysozyme enzymatic activity.


The role of categorization and scale endpoint comparisons in numerical information processing: A two-process model.
We propose a two-process conceptualization of numerical information processing to describe how people form impressions of a score that is described along a bounded scale. According to the model, people spontaneously categorize a score as high or low. Furthermore, they compare the numerical discrepancy between the score and the endpoint of the scale to which it is closer, if they are not confident of their categorization, and use implications of this comparison as a basis for judgment. As a result, their evaluation of the score is less extreme when the range of numbers along the scale is large (e.g., from 0 to 100) than when it is small (from 0 to 10). Six experiments support this two-process model and demonstrate its generalizability. Specifically, the magnitude of numbers composing the scale has less impact on judgments (a) when the score being evaluated is extreme, (b) when individuals are unmotivated to engage in endpoint comparison processes (i.e., they are low in need for cognition), and (c) when they are unable to do so (i.e., they are under cognitive load). Moreover, the endpoint to which individuals compare the score can depend on their regulatory focus. (PsycINFO Database Record


Nonlocal nonlinear refraction in Hibiscus sabdariffa with large phase shifts.
In this work we present a study of nonlinear optical properties in organic materials (hibiscus sabdariffa). Our results demonstrate that the medium exhibits a highly nonlocal nonlinear response. We show preliminary numerical results of the transmittance as nonlocal response by considering, simultaneously, the nonlinear absorption and refraction in media. Numerical results are accord to measurement obtained by Z- scan technique where we observe large phase shifts. We also analyze the far field diffraction ring patterns of the sample.


Effects of neutral detergent fiber and roughage source on dry matter intake and milk yield and composition of dairy cows.
Data were from 20 experiments that utilized early to midlactation Holstein cows fed complete mixed diets or fed at constant forage:concentrate ratios. Within-cow diet comparisons (1688 cow-periods) were analyzed by least squares analysis of variance; mathematical model included experiment, cow in experiment, period, body weight, and source of roughage. Objectives were to determine relationships between neutral detergent fiber content of diet and milk yield and dry matter intake. Roughages and number of cow-periods were: sugarcane bagasse/silage (507), cottonseed hulls (504), corn silage (268), ground corrugated boxes (170), alfalfa/peanut hay (132), and others (107). Dry matter intake and estimated net energy intake had linear effects on milk yield and explained 21.6 and 24.0% of its residual variation; milk yield had curvilinear (quadratic) effect and explained 22.4% of dry matter intake residual variation. Interaction between neutral detergent fiber and source of roughage on milk yield, 4% fat-corrected milk, and dry matter intake resulted in reductions of 5.6, 5.6, and 13% in residual variations. Results suggest neutral detergent (% of dry matter) has greater effect on dry matter intake than on milk yield and its use in formulating diets for dairy cows will be within roughage source.


Neural Conduction Along Postretinal Visual Pathways in Glaucoma.
Purpose: This study was conducted in order to evaluate retinal ganglion cell (RCG) function and the neural conduction along the postretinal large and small axons and its correlation with retinal nerve fiber layer thickness (RNFL-T) in open-angle glaucoma (OAG) eyes. Methods: Thirty-seven OAG patients (mean age: 51.68 ± 9.83 years) with 24-2 Humphrey mean deviation (MD) between -2.5 and -20 dB and IOP <21 mmHg on pharmacological treatment (OAG group) and 20 age-matched controls (control group) were enrolled. In both groups, simultaneous pattern electroretinograms (PERG) and visual evoked potentials (VEP), in response to checks stimulating macular or extramacular areas (the check edge subtended 15' and 60' of visual arc, respectively), and RNFL-T (measured in superior, inferior, nasal, and temporal quadrants) were assessed. Results: In the OAG group, a significant (ANOVA, p < 0.01) reduction of 60' and 15' PERG P50-N95 and VEP N75-P100 amplitudes and of RNFL-T [overall (average of all quadrants) or temporal] with respect to controls was found; the values of 60' and 15' PERG P50 and VEP P100 implicit times and of retinocortical time (RCT; difference between VEP P100 and PERG P50 implicit times) were significantly (p < 0.01) increased with respect to control ones. The observed increased RCTs were significantly linearly correlated (Pearson's test, p < 0.01) with the reduced PERG amplitude and MD values, whereas no significant linear correlation (p < 0.01) with RNFL-T (overall or temporal) values was detected. Conclusions: In OAG, there is an impaired postretinal neural conduction along both large and small axons (increased 60' and 15' RCTs) that is related to RGC dysfunction, but independent from the RNFL morphology. This implies that, in OAG, the impairment of postretinal neural structures can be electrophysiologically identified and may contribute to the visual field defects, as suggested by the linear correlation between the increase of RCT and MD reduction.


Modification by KCNE1 variants of the hERG potassium channel response to premature stimulation and to pharmacological inhibition.
human Ether-à-go-go-Related Gene (hERG) encodes the pore-forming subunit of cardiac rapid delayed rectifier K(+) current (I Kr) channels, which play important roles in ventricular repolarization, in protecting the myocardium from unwanted premature stimuli, and in drug-induced Long QT Syndrome (LQTS). KCNE1, a small transmembrane protein, can coassemble with hERG. However, it is not known how KCNE1 variants influence the channel's response to premature stimuli or if they influence the sensitivity of hERG to pharmacological inhibition. Accordingly, whole-cell patch-clamp measurements of hERG current (I hERG) were made at 37°C from hERG channels coexpressed with either wild-type (WT) KCNE1 or with one of three KCNE1 variants (A8V, D76N, and D85N). Under both conventional voltage clamp and ventricular action potential (AP) clamp, the amplitude of I hERG was smaller for A8V, D76N, and D85N KCNE1 + hERG than for WT KCNE1 + hERG. Using paired AP commands, with the second AP waveform applied at varying time intervals following the first to mimic premature ventricular excitation, the response of I hERG carried by each KCNE1 variant was reduced compared to that with WT KCNE1 + hERG. The I hERG blocking potency of the antiarrhythmic drug quinidine was similar between WT KCNE1 and the three KCNE1 variants. However, the I hERG inhibitory potency of the antibiotic clarithromycin and of the prokinetic drug cisapride was altered by KCNE1 variants. These results demonstrate that naturally occurring KCNE1 variants can reduce the response of hERG channels to premature excitation and also alter the sensitivity of hERG channels to inhibition by some drugs linked to acquired LQTS.


[Value of colonoscopy in tumor after-care after colorectal carcinoma].
The significance of colonoscopic follow up is discussed controversially. Colonoscopy after resection of colorectal cancer offers the possibility of direct inspection and to take biopsies for the early detection of local recurrence or additional neoplasms. In a retrospective study we examined the benefit of regular colonoscopies. Between 1/1995 and 4/1996 237 colonoscopies were performed on 164 patients after resection of colorectal cancer. The evaluation was done due to the stage of the primary tumor, the age of the patients, the time after operation and the number of previous colonoscopies. 54 adenomas were found in 35 of 164 patients. 32% of the adenomas were diagnosed in the ascending colon or colon transversum. Additionally three carcinomas were found. There were two local recurrences and one metachronous neoplasm. Two patients were diagnosed without clinical symptoms and were able to undergo potential curative resection again. Because of the number and the localisation of diagnosed neoplasms colonoscopic surveillance should be performed every six months in the first two years after resection of colorectal cancer.


Genetic assessment of pathogenic germline alterations in lysosomal genes among Asian patients with pancreatic ductal adenocarcinoma.
Lysosomes are closely linked to autophagic activity, which plays a vital role in pancreatic ductal adenocarcinoma (PDAC) biology. The survival of PDAC patients is still poor, and the identification of novel genetic factors for prognosis and treatment is highly required to prevent PDAC-related deaths. This study investigated the germline variants related to lysosomal dysfunction in patients with PDAC and to analyze whether they contribute to the development of PDAC. The germline putative pathogenic variants (PPV) in genes involved in lysosomal storage disease (LSD) was compared between patients with PDAC (n = 418) and healthy controls (n = 845) using targeted panel and whole-exome sequencing. Furthermore, pancreatic organoids from wild-type and KrasG12D mice were used to evaluate the effect of lysosomal dysfunction on PDAC development. RNA sequencing (RNA-seq) analysis was performed with established PDAC patient-derived organoids (PDOs) according to the PPV status. The PPV in LSD-related genes was higher in patients with PDAC than in healthy controls (8.13 vs. 4.26%, Log2 OR = 1.65, P = 3.08 × 10-3). The PPV carriers of LSD-related genes with PDAC were significantly younger than the non-carriers (mean age 61.5 vs. 65.3 years, P = 0.031). We further studied a variant of the lysosomal enzyme, galactosylceramidase (GALC), which was the most frequently detected LSD variant in our cohort. Autophagolysosomal activity was hampered when GALC was downregulated, which was accompanied by paradoxically elevated autophagic flux. Furthermore, the number of proliferating Ki-67+ cells increased significantly in pancreatic organoids derived from Galc knockout KrasG12D mice. Moreover, GALC PPV carriers tended to show drug resistance in both PDAC cell line and PDAC PDO, and RNA-seq analysis revealed that various metabolism and gene repair pathways were upregulated in PDAC PDOs harboring a GALC variant. Genetically defined lysosomal dysfunction is frequently observed in patients with young-onset PDAC. This might contribute to PDAC development by altering metabolism and impairing autophagolysosomal activity, which could be potentially implicated in therapeutic applications for PDAC.


Blue-light induced accumulation of reactive oxygen species is a consequence of the Drosophila cryptochrome photocycle.
Cryptochromes are evolutionarily conserved blue-light absorbing flavoproteins which participate in many important cellular processes including in entrainment of the circadian clock in plants, Drosophila and humans. Drosophila melanogaster cryptochrome (DmCry) absorbs light through a flavin (FAD) cofactor that undergoes photoreduction to the anionic radical (FAD•-) redox state both in vitro and in vivo. However, recent efforts to link this photoconversion to the initiation of a biological response have remained controversial. Here, we show by kinetic modeling of the DmCry photocycle that the fluence dependence, quantum yield, and half-life of flavin redox state interconversion are consistent with the anionic radical (FAD•-) as the signaling state in vivo. We show by fluorescence detection techniques that illumination of purified DmCry results in enzymatic conversion of molecular oxygen (O2) to reactive oxygen species (ROS). We extend these observations in living cells to demonstrate transient formation of superoxide (O2•-), and accumulation of hydrogen peroxide (H2O2) in the nucleus of insect cell cultures upon DmCry illumination. These results define the kinetic parameters of the Drosophila cryptochrome photocycle and support light-driven electron transfer to the flavin in DmCry signaling. They furthermore raise the intriguing possibility that light-dependent formation of ROS as a byproduct of the cryptochrome photocycle may contribute to its signaling role.


Telling ecological networks apart by their structure: A computational challenge.
Ecologists have been compiling ecological networks for over a century, detailing the interactions between species in a variety of ecosystems. To this end, they have built networks for mutualistic (e.g., pollination, seed dispersal) as well as antagonistic (e.g., herbivory, parasitism) interactions. The type of interaction being represented is believed to be reflected in the structure of the network, which would differ substantially between mutualistic and antagonistic networks. Here, we put this notion to the test by attempting to determine the type of interaction represented in a network based solely on its structure. We find that, although it is easy to separate different kinds of nonecological networks, ecological networks display much structural variation, making it difficult to distinguish between mutualistic and antagonistic interactions. We therefore frame the problem as a challenge for the community of scientists interested in computational biology and machine learning. We discuss the features a good solution to this problem should possess and the obstacles that need to be overcome to achieve this goal.


Stimulation of glucose transport by thyroid hormone in ARL 15 cells: increased abundance of glucose transporter protein and messenger ribonucleic acid.
We have studied regulation of the glucose transporter by thyroid hormone in ARL 15 cells, a thyroid hormone-responsive cell line derived from rat liver, T3 treatment (5 x 10(-8) M for 48 h) of confluent cell monolayers grown in thyroid hormone-deficient medium increased the rate of uptake of [3H] 2-deoxyglucose by 2.3 +/- 0.2-fold; this effect was half-maximal at a T3 concentration of 5 nM. The uptake of the nonmetabolizable hexose [3H]3-O-methylglucose was comparably increased, confirming a stimulation of glucose transport by thyroid hormone in these cells. In addition to enhancing glucose transporter activity, T3 increased the utilization of medium glucose to a similar degree. To elucidate the mechanism of the stimulation of glucose transport by T3, the number of glucose transporter units in crude membrane preparations was quantitated by measuring the glucose-inhibitable binding of [3H]cytochalasin-B. The Kd for specific (glucose-inhibitable) binding of [3H]cytochalasin-B was 50-60 nM, a value typical for nonhepatic glucose transporters. T3 treatment caused an increase in the glucose-inhibitable binding of this ligand that was similar in magnitude to the stimulation of [3H]2-deoxyglucose uptake (2.5 +/- 0.6-fold). Northern blot analysis of total cellular RNA using a cDNA probe for the rat brain glucose transporter showed a strong 2.9-kilobase hybridization signal after stringent washing, indicating that ARL 15 cells express the specific mRNA for this type of glucose transporter. T3 treatment increased the abundance of this mRNA by 2.3 +/- 0.2-fold. It is concluded that thyroid hormone stimulates glucose transport in ARL 15 cells, which express the brain type of glucose transporter. This effect is attributable at least in part, if not entirely, to an increase in the level of glucose transporter mRNA and an accompanying increase in the number of glucose transporter units. These findings suggest that thyroid hormone may be an important regulator of glucose transporter gene expression.


Variations in the experiences and expressions of depression among ethnic minorities.
The purpose of this paper is to examine the ethnic differences in the experiences and expressions of depressive symptoms. Also, a discussion is presented regarding the effects that depression has on the individual and consequently the adverse impact it will have on society. Because the expressions of depression are so varied, appropriate measures are required to account for the differences of these expressions in individuals in order to facilitate appropriate diagnosing Both in the United States and throughout the world, depression accounts for a significant proportion of psychiatric disorders, with women and the poor experiencing a disproportionate burden of morbidity. It is essential to remember that clinical depression is never normal and should not be accepted as a normal part of life for any individual, regardless of race, age, or life situation. Depression is a chronic, often relapsing illness, especially if initially under-treated. With depression, it is also essential to identify the role that certain biological variations and particularly the role that ethnicity and gender may play. In other words, because of environmental and certain biological variations, there may be diferences in not only the life experiences but also the mode of expression that depression takes, particularly in women and ethnic people of color. It is essential to identify these significant differences. Certainly, minimizing the risk of psychiatric misdiagnosis is critical to achieving optimal health.


Exploring the Psoriatic Arthritis Proteome in Search of Novel Biomarkers.
Psoriatic arthritis (PsA) is an inflammatory arthritis which develops in up to one-third of patients suffering from the cutaneous disorder, psoriasis. The complex and heterogeneous nature of PsA renders it difficult to diagnose, leading to poor outcomes and, therefore, warrants an examination into soluble biomarkers, which may facilitate early detection of the disease. Protein biomarkers are a dynamic resource of pathophysiological information able to provide an immediate reflection of pathological changes caused by disease. Investigations of the serum and synovial fluid of PsA patients has provided new insights into the molecular basis of this disease and led to the identification of sensitive diagnostic and prognostic biomarkers. The collection of novel PsA biomarkers identified through proteomic studies has been reviewed below.


Connections of the corticomedial amygdala in the golden hamster. I. Efferents of the "vomeronasal amygdala".
The medial (M) an posteromedial cortical (C3) amygdaloid nuclei and the nucleus of the accessory olfactory tract (NAOT) are designated the "vomeronasal amygdala" because they are the only components of the amygdala to receive a direct projection from the accessory olfactory bulb (AOB). The efferents of M and C3 were traced after injections of 3H-proline into the amygdala in male golden hamsters. Frozen sections of the brains were processed for autoradiography. The efferents of the "vomeronasal amygdala" are largely to areas which are primary and secondary terminal areas along the vomeronasal pathway, although the efferents from C3 and M terminate in different layers in these areas than do the projections from the vomeronasal nerve or the AOB. Specifically, C3 projects ipsilaterally to the internal granule cell layer of the AOB, the cellular layer of NAOT, and layer Ib of M. Additional fibers from C3 terminate in a retrocommissural component of the bed nucleus of the strain terminalis (BNST) bilaterally, and in the cellular layers of the contralateral C3. The medial nucleus projects to the cellular layer of the ipsilateral NAOT, layer Ib of C3, and bilaterally to the medial component of BNST. Projections from M to non-vomeronasal areas terminate in the medial preoptic area-anterior hypothalamic junction, ventromedial nucleus of the hypothalamus, ventral premammillary nucleus and possibly in the ventral subiculum. These results demonstrate reciprocal connections between primary and secondary vomeronasal areas between the secondary areas themselves. They suggest that M, but not C3, projects to areas outside this vomeronasal network. The medial amygdaloid nucleus is therefore an important link between the vomeronasal organ and areas of the brain not receiving direct vomeronasal input.


Serotonergic activation rescues reproductive function in fasted mice: does serotonin mediate the metabolic effects of leptin on reproduction?
Negative energy balance inhibits reproduction by restraining GnRH secretion. Leptin is a permissive metabolic signal for reproduction, but GnRH neurons do not appear to express leptin receptors, suggesting that interneurons transmit leptin signals to these cells. Serotonin (5HT) has satiety effects similar to those of leptin and alters LH release, and serotonergic neurons, which have been shown to express leptin receptors, terminate on GnRH neurons. We hypothesized that serotonergic neurons convey leptin signals to the reproductive neuroendocrine axis. To test this, mice were fasted for 48 h beginning on Diestrous Day 1. While fasting, mice received saline or leptin every 12 h or the 5HT-selective reuptake-inhibitor fluoxetine once at the start of the fast. Estrous cycles of fasted mice were longer (mean +/- SEM, 10.2 +/- 0.5 days; P < 0.0001) than those of fed mice (4.5 +/- 0.2 days). As previously reported, leptin prevented fasting-induced cycle lengthening (4.6 +/- 0.7 days). Fluoxetine also rescued estrous cycles in fasted mice (4.7 +/- 0.6 days), suggesting that 5HT and leptin have similar positive effects on reproduction. Coadministration of the 5HT 1/2/7 receptor-antagonist metergoline blocked rescue of cycle length by fluoxetine and by leptin. Treating leptin-deficient ob/ob and leptin receptor-deficient db/db mice with fluoxetine did not normalize body weight or rescue fertility, perhaps due to altered serotonergic tone in these animals. Together, these data demonstrate a permissive role for serotonergic systems in the metabolic control of reproduction and are consistent with the hypothesis that serotonergic neurons convey leptin signals to GnRH neurons.


Psychological distress and milk volume in lactating mothers.
The purpose of this article is twofold: (a) to compare psychological distress as measured via self-reported perceived stress, sleep, and fatigue levels in lactating mothers of a term infant and mothers of a preterm infant and(b) to determine whether the addition of psychological distress to a previous model predicts milk volume at Postpartum Week 6 by gestation group. The convenience sample of 95 mothers of a preterm infant (31 weeks) and 98 mothers of a term infant completed the Perceived Stress Visual Analogue Scale, Richards-Campbell Sleep Questionnaire, and the Fatigue Visual Analog Scale. Stress, sleep difficulty, and fatigue levels decreased during the 6-week study period for mothers of a term but not for mothers of a preterm infant. Perceived stress, sleep difficulty, and fatigue during the first 6 weeks postpartum were not related to milk volume; thus, the mother's perceived psychological distress had no apparent effect on lactation.


Prevalence of oral mucosal lesions among fishermen of Kutch coast, Gujarat, India.
The aim of the study was to assess the prevalence of oral mucosal lesions among fishermen population in the coastal region of Kutch, Gujarat, India. A descriptive cross-sectional survey was conducted to assess the prevalence of oral mucosal lesions among the 979 fishermen of Kutch District, Gujarat, India. The proforma included information on demographic details, habits (tobacco and alcohol), oral hygiene practices and presence and location of oral mucosal lesions according to World Health Organisation, 2013. Chi-square test was used for comparisons. Confidence level and p-value were set at 95% and 5%, respectively. The majority of study population consumed tobacco and alcohol (88.1%) in some or the other form and used chewsticks (42.9%) for cleaning their teeth. Amongst all, 30.03% of the study subjects suffered from oral mucosal lesions. Leukoplakia (13.8%) was found to be the most prevalent lesion. The most affected sites were lips and vermillion border. The prevalence of oral mucosal lesions was found to be significantly associated with age, gender, oral hygiene practices and adverse habits. Oral mucosal lesions were prevalent among 30.03% of the study population. More detailed studies probing this issue should be conducted and efforts should be directed towards primordial prevention of the conditions.


GhSTOP1, a C2H2 type zinc finger transcription factor is essential for aluminum and proton stress tolerance and lateral root initiation in cotton.
Aluminum (Al) and proton (H+ ) ions are major acid soil stress factors deleteriously affecting plant root growth and crop yield. In our preliminary studies, cotton (Gossypium hirsutum L.) seedlings displayed very sensitive phenotypes to Al and H+ rhizotoxicities. Based on previous Arabidopsis results, we aimed to characterise the Al stress responsive Sensitive to Proton rhizotoxicity 1 (GhSTOP1) transcription system in cotton using RNAi-mediated down-regulation. With the help of seed embryo apex explants, we developed transgenic cotton plants overexpressing a GhSTOP1-RNAi cassette with NPTII selection. Kanamycin-tolerant T1 seedlings were further considered for Al and H+ stress tolerance studies. Down-regulation of the GhSTOP1 increased sensitivity to Al and proton rhizotoxicities, and root growth was significantly reduced in RNAi lines. The expression profile of GhALMT1 (Aluminum-activated Malate Transporter 1), GhMATE (Multidrug and Toxic Compound Extrusion), GhALS3 (Aluminium Sensitive 3) and key genes involved in the GABA shunt were down-regulated in the transgenic RNAi lines. Additionally, the lateral root initiation process was delayed and expression of GhNAC1, which is involved in lateral roots, was also suppressed in transgenic lines. Besides, overexpression of GhSTOP1 in Arabidopsis accelerated root growth and AtMATE and AtALMT1 expression under Al stress conditions. These analyses indicate that GhSTOP1 is essential for the expression of several genes which are necessary for acid soil tolerance mechanisms and lateral root initiation.


[Pseudomonas aeruginosa colonisation in bronchiectatic patients and clinical reflections].
Bronchiectasis is characterized with irreversible dilatation according to destruction of epithelium, elastic and muscular layer. Most important cause of bronchiectasis is chronic bacterial infections. Pseudomonas aeruginosa colonisation is frequently seen in bronchiectatic patients. We aimed to find out P. aeruginosa colonisation frequency and clinical, radiological and spirometric reflections due to colonisation. We analysed 83 cases retrospectively. Mean age was 58.2 and 54.2% of them were female. Bronchiectasis were localised 19.3% in left lung, 19.3% right and 61.4% bilaterally. 29 (35.8%) normal, 28 (34.6%) obstructive, 7 (8.6%) restrictive, 17 (21%) mixed type disorders are detected in spirometric measures. Sputum culture performed in 50 cases. No microorganism colonisation determined in 30 (60%) cases, P. aeruginosa colonisation 16 (32%), Haemophilus influenzae 2 (4%), 1 (2%) Streptococcus pneumoniae and Proteus mirabilis 1 (2%) cases. P. aeruginosa colonisation determined more frequent in males (p<0.05). No significant correlation detected between colonisation and age or smoking habits (p>0.05). In cases with colonisation; clubbing and hemoptysis were significantly frequent (p<0.05). Only peribronchial thickening was significantly correlated with colonisation in radiological findings (p<0.05). In blood gase analysis PaO2, oxygen saturation were lower and PaCO2 higher in cases colonised with P. aeruginosa but it was not statisticaly significant (p>0.05). Hospitalization rate was higher in P. aeruginosa colonised cases (p>0.05). It is an important problem about mortality because of higher hemoptysis and hospitalisation requirement rate in P. aeruginosa colonised cases.


Electrocardiographic evidence of reperfusion occurring before hospital admission. A Grampian Region Early Anistreplase Trial (GREAT) sub-study.
The benefits of thrombolysis are believed to be related to the speed of reperfusion of the infarct-related artery. In this sub-study, evidence for the occurrence of reperfusion before admission to hospital has been sought. In a randomized double-blind controlled trial, 311 patients with suspected acute myocardial infarction were given anistreplase 30 units i.v., either at home at a median 101 min (early group, n = 163), or in hospital at a median 240 min after symptom onset (large group, n = 148). Paired electrocardiograms recorded at home and on admission to hospital were available for study in 143 and 137 patients in early and late groups. Reduction in ST elevation between home and hospital electrocardiograms of > 25% in a single lead was taken as evidence of reperfusion. Patients with significant ST elevation in either electrocardiogram comprised the sub-study groups, and numbered 63/143 (44%) and 68/137 (50%) in early and late groups respectively. A reduction of > 25% in the single lead demonstrating greatest ST elevation on the presenting electrocardiogram was observed in 37/63 (59%) and 23/68 (34%) patients in the early and late sub-study groups (difference 25%, 95% confidence interval 8% to 42%, P = 0.003). It was found that domiciliary thrombolysis was associated with electrocardiographic evidence of an increased rate of reperfusion occurring before admission to hospital. Evidence of reperfusion occurring pre-hospital, whether spontaneous or following thrombolytic therapy, was associated with a better outcome.


Optimization of transfection of human endothelial cells.
Recently developed transfection methods for mammalian cells provide a powerful means for the study of gene function. Unfortunately, human endothelial cells were relative refractory to the classic transfection techniques. In this study we compared the usability of calcium phosphate, DEAE-dextran transfection, transferrinfection, lipofection, and electroporation for the transfection of early passage HUVECs and for the human endothelial cell lines ECV 304 and EA.hy 926. The classic transfection methods resulted in no or only marginal expression of the reporter gene E. coli beta-galactosidase. For lipofection experiments we compared the commercially available liposome formulations DOTAP and Transfectam with liposomes prepared of dimethyldioctadecylammoniumbromide (DDAB) or 1,2-dimyristyloxypropyl-3-dimethylhydroxyethyl ammonium bromide (DMRIE) as the cationic lipid compound and dioleylphosphatidylethanolamine (DOPE) or Azolectin (a crude fraction of soybean lipids, commercially available as phosphatidylcholine II) as neutral co-lipid. Because the protocol for the chemical synthesis of DMRIE has not been published yet, we developed a protocol for the chemical synthesis of this cationic lipid. With transfection protocols optimized for each cell line, we could achieve transfection efficiencies up to 2%. Compared to the other methods used, the lipofection proved to be a reliable technique for the efficient transfection of the human endothelial cell lines ECV 304 and EA.hy 926. Although we achieved a maximum transfection efficiency of 0.45% for the lipofection of HUVEC, the electroporation seemed to be the better choice for these cells.


Squamous cell carcinoma of the lower eyelid penetrating into the orbit - case report.
The aim of our study is to report a case of pigmented squamous cell carcinoma of the palpebral conjunctiva referred to our clinic because of eye pain. A 86 year old patient suffering from eye pain due to a lower right eyelid tumour was admitted to our department. The basic ophthalmic examination and CT scans of orbits were performed. A lesion was surgically removed and histologically examined. The best corrected visual acuity in the left eye was 0.1 and there was light perception in the right eye. Ocular examination of the right eye revealed hard, pigmentendand vascularized mass in the lower palpebral conjunctiva penetrating into the lid margin and the orbit, epiphora, bacterial conjunctivitis and vascularized corneal scar with adherent leucoma. Histopathologic examination revealed a squamous cell carcinoma. The accurate diagnosis and correct management of the malignant eyelid tumours always requires histological examination. Surgical removal and additional radiotherapy in the case of extensive SCC conjuctival lesions is necessary. .


Peer Review Practices for Evaluating Biomedical Research Grants: A Scientific Statement From the American Heart Association.
The biomedical research enterprise depends on the fair and objective peer review of research grants, leading to the distribution of resources through efficient and robust competitive methods. In the United States, federal funding agencies and foundations collectively distribute billions of dollars annually to support biomedical research. For the American Heart Association, a Peer Review Subcommittee is charged with establishing the highest standards for peer review. This scientific statement reviews the current literature on peer review practices, describes the current American Heart Association peer review process and those of other agencies, analyzes the strengths and weaknesses of American Heart Association peer review practices, and recommends best practices for the future.


Water and temperature relations of growth and ochratoxin A production by Aspergillus carbonarius strains from grapes in Europe and Israel.
This study investigated the in vitro effects of water activity (a(w); 0.85-0.987) and temperature (10-40 degrees C) on growth and ochratoxin A (OTA) production by two strains of Aspergillus carbonarius isolated from wine grapes from three different European countries and Israel on a synthetic grape juice medium representative of mid-veraison (total of eight strains). The synthetic grape juice medium was modified with glycerol or glucose and experiments carried out for up to 56 days for growth and 25 days for OTA production. The lag phase prior to growth, growth rates and ochratoxin production were quantified. Statistical comparisons were made of all factors and multiple regression analysis used to obtain surface response curves of a(w) x temperature for the eight strains and optimum growth and OTA production by A. carbonarius. The lag phase increased from <1 day at 25-35 degrees C and 0.98 a(w) to >20 days at marginal temperatures and water availabilities. Generally, most A. carbonarius strains grew optimally at 30-35 degrees C, regardless of solute used to modify a(w), with no growth at <15 degrees C. The optimum a(w) for growth varied from 0.93 to 0.987 depending on the strain, with the widest a(w) tolerance at 25-30 degrees C. There was no direct relationship among growth, environmental factors and country of origin of individual strains. Optimum conditions for OTA production varied with strain. Some strains produced optimal OTA at 15-20 degrees C and 0.95-98 a(w). The maximum OTA produced after 10 days was about 0.6-0.7 microg g(-1), with a mean production over all eight strains of 0.2 microg g(-1) at optimum environmental conditions. This work demonstrates that optimum conditions for OTA production are very different from those for growth. While growth rates differed significantly between strains, integration of the OTA production data suggests possible benefits for use of the information on a regional basis. Very little detailed information has previously been available on the ecology of A. carbonarius. This knowledge is critical in the development and prediction of the risk models of contamination of grapes and grape products by this species under fluctuating and interacting environmental parameters.


Ecological fitting is the forerunner to diversification in a plant virus with broad host range.
The evolution and diversification of ssRNA plant viruses are often examined under reductionist conditions that ignore potentially much wider biotic interactions. The host range of a plant virus is central to interactions at higher levels that are organized by both fitness and ecological criteria. Here we employ a strategy to minimize sampling biases across distinct plant communities and combine it with a high-throughput sequencing approach to examine the influence of four habitats on the evolution of Watermelon mosaic virus (WMV). Local, regional and global levels of genetic diversity that correspond to spatial and temporal extents are used to infer haplotype relationships using network and phylogenetic approaches. We find that the incidence and genetic diversity of WMV were structured significantly by host species and habitat type. A single haplotype that infected 11 host species of a total of 24 showed that few constraints on host species use exist in the crop communities. When the evolution of WMV was examined at broader levels of organization, we found variation in genetic diversity and contrasting host use footprints that broadly corresponded to habitat effects. The findings demonstrated that nondeterministic ecological factors structured the genetic diversity of WMV. Habitat-driven constraints underlie host use preferences.


Quinapril treatment curtails decline of global longitudinal strain and mechanical function in hypertensive rats.
Left ventricular (LV) global longitudinal strain (GLS) has been proposed as an early imaging biomarker of cardiac mechanical dysfunction. To assess the impact of angiotensin-converting enzyme (ACE) inhibitor treatment of hypertensive heart disease on LV GLS and mechanical function. The spontaneously hypertensive rat (SHR) model of hypertensive heart disease ( n = 38) was studied. A subset of SHRs received quinapril (TSHR, n = 16) from 3 months (mo). Wistar Kyoto rats (WKY, n = 13) were used as controls. Tagged cardiac MRI was performed using a 4.7 T Varian preclinical scanner. The SHRs had significantly lower LV ejection fraction (EF) than the WKYs at 3 mo (53.0 ± 1.7% vs. 69.6 ± 2.1%, P < 0.05), 14 mo (57.0 ± 2.5% vs. 74.4 ± 2.9%, P < 0.05) and 24 mo (50.1 ± 2.4% vs. 67.0 ± 2.0%, P < 0.01). At 24 mo, ACE inhibitor treatment was associated with significantly greater LV EF in TSHRs compared to untreated SHRs (64.2 ± 3.4% vs. 50.1 ± 2.4%, P < 0.01). Peak GLS magnitude was significantly lower in SHRs compared with WKYs at 14 months (7.5% ± 0.4% vs. 9.9 ± 0.8%, P < 0.05). At 24 months, Peak GLS magnitude was significantly lower in SHRs compared with both WKYs (6.5 ± 0.4% vs. 9.7 ± 1.0%, P < 0.01) and TSHRs (6.5 ± 0.4% vs. 9.6 ± 0.6%, P < 0.05). ACE inhibitor treatment curtails the decline in global longitudinal strain in hypertensive rats, with the treatment group exhibiting significantly greater LV EF and GLS magnitude at 24 mo compared with untreated SHRs.


Mitigating photorefractive effect in thin-film lithium niobate microring resonators.
Thin-film lithium niobate is an attractive integrated photonics platform due to its low optical loss and favorable optical nonlinear and electro-optic properties. However, in applications such as second harmonic generation, frequency comb generation, and microwave-to-optics conversion, the device performance is strongly impeded by the photorefractive effect inherent in thin-film lithium niobate. In this paper, we show that the dielectric cladding on a lithium niobate microring resonator has a significant influence on the photorefractive effect. By removing the dielectric cladding layer, the photorefractive effect in lithium niobate ring resonators can be effectively mitigated. Our work presents a reliable approach to control the photorefractive effect on thin-film lithium niobate and will further advance the performance of integrated classical and quantum photonic devices based on thin-film lithium niobate.


Surgical Treatment of Primary Hyperparathyroidism: Which Therapy to Whom?
Primary hyperparathyroidism (pHPT) is characterized by an increase in the levels of PTH and Ca, or one of these (Ca, PTH) as a result of a dysregulation of calcium (Ca) metabolism due to inappropriate excess parathyroid hormone (PTH) autonomously produced from one or more than one parathyroid glands. Ninety to 95% of pHPT is a sporadic type, which is not associated with the familial history and other endocrine organ tumors, and 5-10% of it is hereditary. While 80-85% of pHPT arises from a single parathyroid adenoma, 4-5% is caused by a double adenoma, 10-15% by multigland hyperplasia and less than 1% by parathyroid cancer. The diagnosis of pHPT is reached biochemically. The only curative treatment of pHPT is surgery. The choice of surgery in pHPT may vary depending on whether the patient has hereditary HPT or thyroid disease requiring surgical treatment, preoperative localization studies and the findings in these studies, the possibilities of using intraoperative PTH and the preference of the surgeon. The preoperatively determined surgical strategy can be revised according to intraoperative findings in case of need to achieve excellent results. The two main approaches in the surgical treatment of pHPT are BNE (bilateral neck exploration) and MIP (minimal invasive parathyroidectomy). Although BNE is a consistently valid option that has excellent results in the surgical treatment of pHPT and is considered the gold standard, MIP is the ideal approach in selected patients with clinically and radiologically considered a single-gland disease. Negative imaging is not a contraindication for parathyroid surgery and is not a criterion for the presence or absence of surgical indication. Although both methods are safe and effective in the surgical treatment of sporadic pHPT, there is still controversy regarding the effectiveness of both methods. Surgical intervention should establish the risk-benefit balance well, minimize the risk of persistent and recurrent disease and provide the highest cure rate without increasing the risk of complications. Complication rates are higher in the secondary surgery, thus in secondary procedures, selective surgery should be performed under guidance of an imaging modality. The surgical strategy should be determined to achieve maximum cure with minimum dissection and minimal morbidity. In this study, we aimed to determine the type of surgical treatment and pHPT patients suitable for the surgical treatment.


Transient selection during vaccinia virus recombination with insertion vectors without selectable markers.
Isolation of recombinant viruses after DNA transfection remains the most time-consuming and labor-intensive feature in the production of vaccinia virus (VV) recombinants. This procedure has been aided by the design and incorporation of both positive and negative selectable markers into the insertion vectors. Use of these selectable markers is not always feasible or desirable. In the absence of selectable markers, individual plaque characterization is required. A method of transient selection during transfection and recombination is described that does not require that any selectable marker be present in the insertion vector sequence. This method relies on the co-transfection of a guanine phosphoribosyl transferase (gpt) selectable marker on an unlinked plasmid into VV-infected cells pretreated for gpt selection. Following recombination, the output virus can be plated on cells without any further selection and screened for recombinant virus. While the total recombinant virus population is slightly reduced, the total progeny virus is reduced even further, resulting in more than sevenfold enhancement in the frequency of recombinant virus, which allows for more efficient identification.


Increasing obesity and comorbidity in patients undergoing primary total hip arthroplasty in the U.S.: a 13-year study of time trends.
Few, if any data are available are available regarding the time-trends in characteristics of patients who have undergone primary THA. Our objective was to examine the time-trends in key demographic and clinical characteristics of patients undergoing primary total hip arthroplasty (THA). We used the data from the Mayo Clinic Total Joint Registry from 1993-2005 to examine the time-trends in demographics (age, body mass index (BMI)), medical (Deyo-Charlson index) and psychological comorbidity (anxiety, depression) and underlying diagnosis of patients undergoing primary THA. Chi-square test and analysis for variance were used. Multivariable-adjusted logistic regression (age, sex, comorbidity-adjusted) compared 1993-95 to other study periods. Odds ratio (OR) and 95% confidence interval (CI) are presented. The primary THA cohort consisted of 6,168 patients with 52% women. In unadjusted analyses, compared to 1993-95, significantly more patients (by >2-times for most) in 2002-05 had: BMI ≥ 40, 2.3% vs. 6.3%; depression, 4.1% vs. 9.8%; and anxiety, 3.4% vs. 5.7%; and significantly fewer had an underlying diagnosis of rheumatoid/inflammatory arthritis, 3.7% vs. 1.5% (p ≤ 0.01 for all). In multivariable-adjusted models, compared to 1993-95, significantly more patients in 2003-05 had (all p-values ≤ 0.01): BMI ≥ 40, OR, 2.79 (95% CI: 1.85, 4.22); Deyo-Charlson Index ≥ 3, 1.32 (1.07, 1.63); depression, 2.25 (1.66, 3.05); and anxiety, 1.71 (1.19, 2.15). Respectively, fewer patients had a diagnosis of RA/inflammatory arthritis: 0.28 (0.17, 0.46; p < 0.01). Over the 13-year study period, Deyo-Charlson index increased by 22% (0.9 to 1.1) and the mean age decreased by 0.7 years (65.0 to 64.3) (p < 0.01 for both). Obesity, medical and psychological comorbidity increased and the underlying diagnosis of RA/inflammatory arthritis decreased rapidly in primary THA patients over 13-years. Our cohort characteristics are similar to previously described characteristics of national U.S. cohort, suggesting that these trends may be national rather than local trends. This is important information for policy makers to take into account for resource allocation. Studies of THA outcomes and utilization should take these rapidly changing patient characteristics into account.


Biochemical characterization of protein composition and protein phosphorylation patterns in stacked and unstacked thylakoid membranes of the prochlorophyte Prochlorothrix hollandica.
We describe a procedure to separate stacked and unstacked membranes from the prochlorophyte Prochlorothrix hollandica that is based on methods used for the separation of grana and stroma thylakoids from chloroplasts. Stacked membranes were isolated from Triton X-100-treated whole thylakoid preparations, unstacked membranes from French press disrupted cells. Membrane fractions were isolated by differential centrifugation. The stacked membranes were enriched in photosystem (PS) II and a chlorophyll a/b-binding antenna complex, whereas the unstacked membranes contained PS I and the ATP synthase. No evidence for a PS I-associated chlorophyll a/b antenna system was obtained. The PS II-associated chlorophyll a/b antenna complex is composed of several apoproteins in the molecular mass range from 32 to 38 kDa. The 38-kDa protein of this complex becomes phosphorylated on its stromal surface by a light-activated kinase, but, unlike the light-harvesting II complex of chloroplasts, it does not migrate from grana to stroma membrane regions. Overall, the thylakoid membranes of Prochlorothrix exhibit a remarkably similar organization to those of chloroplasts, especially in terms of the non-random distribution of protein complexes between grana and stroma thylakoid membranes. However, in contrast to the rapidly reversible phosphorylation-dependent state 1-state 2 response of light-harvesting complex associated with PS II in chloroplasts, the slowly reversible phosphorylation in Prochlorothrix leads only to a functional uncoupling from PS II but not to its redistribution between stacked and unstacked membrane regions.


The Adh-related gene of Drosophila melanogaster is expressed as a functional dicistronic messenger RNA: multigenic transcription in higher organisms.
Essentially all eukaryotic cellular mRNAs are monocistronic, and are usually transcribed individually. Two tandemly arranged Drosophila genes, alcohol dehydrogenase (Adh) and Adh-related (Adhr), are transcribed as a dicistronic transcript. From transcripts initiated from the Adh promoter, two classes of mRNA are accumulated, one is monocistronic and encodes Adh alone, the other is dicistronic and includes the open reading frames of both Adh and Adhr. The dicistronic transcript is found in polysomes and the Adhr protein product is detected by antibody staining. We present evidence that the accumulation of the dicistronic mRNA is controlled at the level of the 3' end processing.


Dealing with the exponential wall in electronic structure calculations.
An alternative to the density functional theory is the use of wavefunction based electronic structure calculations for solids. In order to perform them, the Exponential Wall (EW) problem has to be resolved. It is caused by an exponential increase of the number of configurations with increasing electron number N. There are different routes one may follow. One is to characterize a many-electron wavefunction by a vector in Liouville space with a cumulant metric rather than in Hilbert space. This removes the EW problem. Another is to model the solid by an impurity or fragment embedded in a bath which is treated at a much lower level than the former. This is the case in the Density Matrix Embedding Theory (DMET) or the Density Embedding Theory (DET). The latter two are closely related to a Schmidt decomposition of a system and to the determination of the associated entanglement. We show here the connection between the two approaches. It turns out that the DMET (or DET) has an identical active space as a previously used Local Ansatz, based on a projection and partitioning approach. Yet, the EW problem is resolved differently in the two cases. By studying a H10 ring, these differences are analyzed with the help of the method of increments.


[Structure, occurrence and functional significance of nonlinear phenomena in sounds of terrestrial mammals].
Subharmonics, deterministic chaos, biphonations, sidebands and frequency jumps, known under joining name nonlinear phenomena, represent acoustical appearances that occur in calls of various mammals, from insectivorous to humans. Although the physical basis for appearances of the nonlinear phenomen is known in principle, such aspects as occurrence and functional significance of nonlinear phenomena, are poorly understood. We described here the structural peculiarities of these appearances based on domestic dogs' whines demonstrating all kinds of the nonlinear phenomena. The nonlinear phenomena result directly from the work of mammalian vocal apparatus--lunges, vocal folds, and vocal tract, which are responsible for its inherent functional characteristics. The mammalian vocal folds represent a system of two coupled oscillators functioning in different vibratory regimes depending on degree of synchronization in their vibrations and occurrence of coupling between the vocal folds. This functioning does not need in direct neural control for turning on the complex regimes of vocal folds' vibration and switching from one regime to another. Besides, many mammals possess anatomical structures, such as vocal membranes, pads on vocal folds, or laryngeal air sacs, that are to participate in sound production as additional oscillators extend the range of possibilities for arising of nonlinear phenomena in vocalization. On the basis of published and own data, we provide and overview of the occurrence of nonlinear phenomena in sounds of humans, nonhuman primates, canids, and rodents, and discuss the supposed functional significance of these acoustical appearances in mammalian vocal communication systems. From one side, nonlinear phenomena may be related to various physiological disorders in humans and animals. In such cases, their appearance in calls may be nonadaptive, because they permit conspecifics' to avoid owners of such "ill" voices, and points easy prey to predators. From another side, in some cases the nonlinear phenomena may arise especially for performing of some signal functions in species communication system: to enhance reliability of individual recognition, to transmit information about size of a caller over the large distance, to permit individuals of not great size mimicry acoustically under more larger animal, to introduce variety into monotonous vocal sequences in order to force other group members to pay attention to a caller, and to facilitate distance estimation to a caller and direction of its movement.


Recent immunomodulatory strategies in transplantation.
Despite preservation methods, surgical procedures, current immunosuppressive therapy regimens advances, organ transplantation is accompanied with a poor long-term survival and significant mortality. This has led to an increased interest to optimize outcomes while minimizing associated toxicity by using alternative methods for maintenance immunosuppression, organ rejection treatment, and monitoring of immunosuppression. Advance in long-standing allograft outcomes may depend on new drugs with novel mechanisms of action with minimal toxicity. Newer treatment techniques have been developed, including using novel stem cell-based therapies such as mesenchymal stem cells, phagosomes and exosomes. Immunoisolation techniques and salvage therapies, including photopheresis and total lymphoid irradiation have emerged as alternate therapeutic choices. The present review evaluates the recent clinical advances in immunosuppressive therapies for organ transplantation.


Procedural Factors That Affect Psychophysical Measures of Spatial Selectivity in Cochlear Implant Users.
Behavioral measures of spatial selectivity in cochlear implants are important both for guiding the programing of individual users' implants and for the evaluation of different stimulation methods. However, the methods used are subject to a number of confounding factors that can contaminate estimates of spatial selectivity. These factors include off-site listening, charge interactions between masker and probe pulses in interleaved masking paradigms, and confusion effects in forward masking. We review the effects of these confounds and discuss methods for minimizing them. We describe one such method in which the level of a 125-pps masker is adjusted so as to mask a 125-pps probe, and where the masker and probe pulses are temporally interleaved. Five experiments describe the method and evaluate the potential roles of the different potential confounding factors. No evidence was obtained for off-site listening of the type observed in acoustic hearing. The choice of the masking paradigm was shown to alter the measured spatial selectivity. For short gaps between masker and probe pulses, both facilitation and refractory mechanisms had an effect on masking; this finding should inform the choice of stimulation rate in interleaved masking experiments. No evidence for confusion effects in forward masking was revealed. It is concluded that the proposed method avoids many potential confounds but that the choice of method should depend on the research question under investigation.


Periocular cutaneous melanoma arising in a radiotherapy field.
A 78-year-old woman had a periocular cutaneous melanoma in the radiation field of a meningioma. A medial canthal melanoma arose 32 years after primary radiation for a sphenoid wing meningioma and 22 years after supplemental radiation for meningioma recurrence. Histologic sections taken from skin surrounding the melanoma showed widespread melanocytic atypia and 2 separate foci of melanoma in situ. Cutaneous melanoma can arise in a radiation field after a long latency period and should be considered an uncommon form of secondary malignancy.


Photon-based High-dose Single-fraction Radiosurgery, an Effective Treatment Modality for Large and Posterior Uveal Melanoma.
Uveal melanoma (UM) is the most common primary intraocular malignant tumor. This malignancy is frequently treated using brachytherapy, stereotactic radiotherapy, or proton therapy. The objective of this study was to assess the role of stereotactic radiosurgery in the treatment of large and posterior UM. From January 2014 to July 2021, we treated 65 patients (median age=71 years; range=31-89 years) affected by UM. Inclusion criteria were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2, life expectancy >6 months, tumor thickness >10 mm, diameter >16 mm or posterior UM. The treatment was delivered with a True Beam™ LINAC with arc modulation technique. All patients received 27 Gy in one fraction (biological effective dose ≈100 Gy, assuming an α/β of 10). The median follow-up was 36 (range=3-90) months. Acute toxicities were reported in 14 patients, whereas late toxicity occurred in 45 (69.2%). Fifteen patients (23.0%) underwent enucleation: eight (12.3%) for failure of local control and seven (10.7%) for late treatment co-morbidities. The 5-year local control, and progression-free, metastasis-free, enucleation-free, and overall survival rates were 80%, 43%, 62%, 65% and 56%, respectively. In multivariate analysis, tumor dimensions significantly influenced survival [larger basal diameter: progression-free [hazard ratio (HR)=2.42] and overall (HR=2.61) survival; greater thickness: overall survival (HR=2.36)]. In multivariate analysis, patients without local control had a higher risk of distant metastasis (HR=3.25). Stereotactic radiosurgery offers an effective and safe approach for selected cases of UM due to the satisfactory results in terms of local control, eye conservation and survival.


The rise and fall of deception in social psychology and personality research, 1921 to 1994.
The frequency of the use of deception in American psychological research was studied by reviewing articles from journals in personality and social psychology from 1921 to 1994. Deception was used rarely during the developmental years of social psychology into the 1930s, then grew gradually and irregularly until the 1950s. Between the 1950s and 1970s the use of deception increased significantly. This increase is attributed to changes in experimental methods, the popularity of realistic impact experiments, and the influence of cognitive dissonance theory. Since 1980 there appears to have been a decrease in the use of deception as compared to previous decades which is related to changes in theory, methods, ethical standards, and federal regulation of research.


Subcutaneous interleukin-2 in combination with vinblastine for metastatic renal cancer: cytolytic activity of peripheral blood lymphocytes.
Eight patients with progressive metastatic renal cell carcinoma were selected for one course of subcutaneous recombinant interleukin-2 (IL-2) plus vinblastine (VBL) treatment lasting for seven weeks. Seven of the eight patients were evaluable for response, eight for toxicity. Peripheral blood lymphocytes (PBL) from the evaluable patients were isolated and frozen prior to, during, and after the treatment courses; kinetics of their cytolytic activity was assessed and compared under standard conditions in 51Cr microcytotoxicity assay with natural killer (NK)-sensitive and NK-resistant human tumor targets. Among the evaluable patients treated, there was 1 partial responder (10+ months, regressions occurred in lung, retroperitoneal lymph nodes and adrenal metastases) and 3 patients achieved a stable disease (10+, 10+, 5+ months). Systemic toxicity was mild to moderate with treatment-limiting adverse effects in one patient (severe thrombocytopenia, grade IV). In the IL-2-treated patients, the cytolytic activity of PBL directed against NK-sensitive targets rapidly decreased during the first week of IL-2 treatment, approaching the negative values on day 10. Then the cytolytic activity was slowly increasing and reached its maximum within another two weeks. Afterwards, the cytolytic activity of PBL was again decreasing and the approximate values of the initial cytolysis were reached after 6-8 weeks. In contrast, with NK-resistant targets such characteristic kinetics of PBL cytolytic activity was not observed. The kinetics of PBL-mediated cytolysis was similar in IL-2-responders and non-responders, so that no correlation of in vivo and in vitro effects of subcutaneous IL-2 and VBL treatment could be established.


Relation Between Tissue Iron Content and Polarization of Macrophages in Diabetic Ulcer and the Transitional Zone of Diabetic Ulcers with Major Amputation.
Most diabetic lower-limb amputations probably result from combinations of contributing causes rather than from unitary causes. Iron-induced damage might modulate the development of chronic diabetes complications. In this study, the relationship between tissue iron levels and polarization of macrophages in induction of angiogenesis was investigated in diabetic ulcer samples and the transitional zone of diabetic ulcers. Patients with diabetic ulcers who underwent amputation were included. The transitional zone of diabetic ulcers, from the same diabetic patients, was used as a control group. After tissue preparation, Perls Prussian blue staining and immunohistochemistry for CD11c, CD163, and CD68 markers were done. Vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF), Tie2, and protein kinase B (also known as AKT) transcription of genes were measured by real-time polymerase chain reaction. For statistical analysis, we used independent samples t-test or its nonparametric equivalents, Mann-Whitney U test was used for quantitative variables, and chi-square (or Fisher's exact test) for qualitative variables. According to the results, the ratio of M2 to M1 macrophages was decreased in ulcers tissue compared to the transitional zone of diabetic ulcers. The expression of angiogenesis-related genes was increased due to hypoxia induction such as HIF and VEGF in ulcer tissue (P < .0001), but the expression of vascular stability-related genes such as Tie2 was decreased (P < .0001).In amputated diabetic ulcers, the polarization of macrophages is toward the classic type, but no connection was found in terms of tissue iron and help in the polarization of macrophages.


G. Buchanan on inguinal hernia treatment: a review 111-years after.
The Scottish surgeon G. Buchanan (1827-1905) has contributed to the development of pediatric inguinal herniorrhaphy in line with Listerian principles, and is the author of the first separate publication on the subject to appear as early as 1879. His largely forgotten work is being reassessed.


Unlocking the potential of microbiome editing: A review of conjugation-based delivery.
In recent decades, there has been a rapid increase in the prevalence of multidrug-resistant pathogens, posing a challenge to modern antibiotic-based medicine. This has highlighted the need for novel treatments that can specifically affect the target microorganism without disturbing other co-inhabiting species, thus preventing the development of dysbiosis in treated patients. Moreover, there is a pressing demand for tools to effectively manipulate complex microbial populations. One of the approaches suggested to address both issues was to use conjugation as a tool to modify the microbiome by either editing the genome of specific bacterial species and/or the removal of certain taxonomic groups. Conjugation involves the transfer of DNA from one bacterium to another, which opens up the possibility of introducing, modifying or deleting specific genes in the recipient. In response to this proposal, there has been a significant increase in the number of studies using this method for gene delivery in bacterial populations. This MicroReview aims to provide a detailed overview on the use of conjugation for microbiome engineering, and at the same time, to initiate a discussion on the potential, limitations and possible future directions of this approach.


A fatal case of West Nile virus infection in a bone marrow transplant recipient.
West Nile virus (WNV) can cause severe, potentially fatal neurological illnesses, which include encephalitis, meningitis, Guillain-Barré syndrome, and anterior myelitis. Because of the short viremic phase, WNV infection is most commonly diagnosed by detection of immunoglobulin M antibody to WNV in serum or cerebrospinal fluid (CSF). We describe a patient with T cell lymphoma who had undergone a T cell-depleted bone marrow transplantation and developed fatal WNV infection. The results of serological tests of blood samples and of CSF tests were negative. Diagnosis was made postmortem by a positive result of reverse-transcriptase polymerase chain reaction (ABI 7700; TaqMan) for WNV in stored CSF and serum samples.


Malignant phyllodes tumour with intraductal and invasive carcinoma and lymph node metastasis.
Phyllodes tumours constitute 2-3 percent of fibroepithelial breast tumours, with a 1-2 percent rate of malignancy. Metastasis is usually haematogeneous, and axillary lymph node dissection is not routinely performed. Carcinoma in a phyllodes tumour is distinctly uncommon, but has been known to occur in benign phyllodes tumours. We describe a 51-year-old woman with a malignant phyllodes tumour with foci of intraductal carcinoma within the tumour and adjacent breast tissue. Though the carcinoma was found to be invasive based on the presence of carcinomatous lymph node metastasis, extensive sampling did not yield an invasive component within the breast, probably because of the marked stromal overgrowth of the phyllodes. A malignant phyllodes tumour with foci of intraductal carcinoma and axillary lymph node metastases was diagnosed rather than carcinosarcoma. Chemotherapy and irradiation were included in the postoperative management. Coexistence of phyllodes tumour and carcinoma is rare, and extensive sampling may be necessary to find the foci of carcinoma within an extensive and obviously malignant stromal overgrowth. There is little consensus on the treatment and prognosis in these cases, and it is recommended that treatment be tailored to individual patients, based on the presence of invasion, lymph node metastasis and/or distant metastasis.


Rhodium(iii)-catalyzed diamidation of olefins via amidorhodation and further amidation.
Rh(iii)-catalyzed synthesis of vicinal diamides has been realized via elaboration of an authenticated Rh-C(sp3) species generated via initial intramolecular amidorhodation of olefins. The second amidation was achieved using both electrophilic and nucleophilic amidating reagents. The reactions proceeded under mild conditions with good yield, broad substrate scope, and excellent functional-group tolerance.


Primary malignant lymphoma of the uterus.
The clinical and pathological findings in a 59-year-old woman with a primary malignant lymphoma of the corpus uteri are described. There was a period of eight months between detection of the uterine lesion and evidence of disease elsewhere in the body. The patient died of disseminated lymphoma, and the distribution of secondary deposits were suggestive of spread via the right ovarian-uterine venous system.The criteria for acceptance of a diagnosis of primary uterine lymphoma are discussed and the previous literature is reviewed. There have been nine acceptable cases of primary uterine lymphoma recorded: four in the corpus uteri and five in the cervix. The differential diagnosis from stromal sarcoma, anaplastic endometrial adenocarcinoma, leiomyosarcoma, and benign lymphoid hyperplasia is discussed.


A Knockin Reporter Allows Purification and Characterization of mDA Neurons from Heterogeneous Populations.
Generation of midbrain dopaminergic (mDA) neurons from human pluripotent stem cells provides a platform for inquiry into basic and translational studies of Parkinson's disease (PD). However, heterogeneity in differentiation in vitro makes it difficult to identify mDA neurons in culture or in vivo following transplantation. Here, we report the generation of a human embryonic stem cell (hESC) line with a tyrosine hydroxylase (TH)-RFP (red fluorescent protein) reporter. We validated that RFP faithfully mimicked TH expression during differentiation. Use of this TH-RFP reporter cell line enabled purification of mDA-like neurons from heterogeneous cultures with subsequent characterization of neuron transcriptional and epigenetic programs (global binding profiles of H3K27ac, H3K4me1, and 5-hydroxymethylcytosine [5hmC]) at four different stages of development. We anticipate that the tools and data described here will contribute to the development of mDA neurons for applications in disease modeling and/or drug screening and cell replacement therapies for PD.


[Bronchospasm during anesthesia in a patient with Pena-Shokeir syndrome].
A 3-month-old boy with Pena-Shokeir syndrome underwent tracheotomy under general anesthesia. Patients with this syndrome may present anesthetic problems involving difficulties in tracheal intubation, possibilities of malignant hyperthermia, as well as perioperative respiratory complications related to hypoplasia of the lung. General anesthesia was induced and maintained with sevoflurane (2-3%) and nitrous oxide (0-50%) in oxygen (50-100%). The patient developed bronchospasm during tracheotomy. Atropine and epinephrine were administered intravenously and 5% sevoflurane was inhaled. The bronchospasm was improved gradually and surgery was successfully finished. Pena-Shokeir syndrome is an uncommon disease first reported by Pena & Shokeir in 1974 and characterized by congenital multiple arthrogryposis, characteristic facies, camptodactyly and pulmonary hypoplasia. In the perioperative management for a patient with Pena-Shokeir syndrome, special attention should be paid to abnormalities in the upper and lower respiratory systems, especially bronchospasm.


Determinants of tuberculosis treatment outcome under directly observed treatment short courses in Adama City, Ethiopia.
Tuberculosis (TB) is a leading cause of death among infectious agents, ranking above HIV/AIDS. Though much effort has been done, Ethiopia remained one of those countries which share the greatest burden of TB. Evaluating the TB treatment outcome is one method of TB control measures. Therefore, the aim of the current study was to assess TB treatment outcome and its determinants under directly observed treatment short courses in Adama City, Central Ethiopia. An institutional based cross sectional study was conducted in all public and private health facilities of Adama city from March 1st 2016 to December 31st, 2016. The data were entered and analyzed by using SPSS version 21.0 statistical software. The results were presented using descriptive statistics. Univariate and multivariate logistic regression model was used to evaluate the potential determinants of unsuccessful treatment outcome. Among 281 patients evaluated, 90(32%) were cured, 137(48.8%) have completed the treatment, 4(1.4%) were treatment failure, 36(12.8%) were lost to follow up, and 14 (5%) died. The overall treatment success rate was 80.8%. Age 15-24 (Adjusted odds ratio (AOR): 4.97; 95% Confidence interval (CI): 1.13-21.90), distance less than 5 kilometers from treatment center (AOR: 3.1; 95% CI: 1.42-6.77), being seronegative for human immunodeficiency virus (HIV) (AOR: 20.38; 95% CI: 7.80-53.24) were associated with successful TB treatment outcome. The treatment outcome of all forms tuberculosis patients in Adama city was unsatisfactory when referred with the national pooled estimate of 86% and WHO 2030 international target of ≥90%. Thus, enhancing client supervision, treatment monitoring; and working on provision TB treatment services at nearby health facilities should be a priority concern to improve the success rate of treatment outcome. Further studies are also recommended to explore important factors which were not examined by current study.


Enhanced Triplet Sensitizing Ability of an Iridium Complex by Intramolecular Energy-Transfer Mechanism.
The photodynamic properties involving both intra- and intermolecular triplet energy transfers (ET) of a bichromophoric photosensitizer having a tris-cyclometalated Ir(III) tethered with a pyrene derivative are studied. Due to the triplet energy gap of the two chromophores, a reversible intramolecular triplet ET equilibrium is quickly established upon photoexcitation, with the triplet exciton mainly residing on the acceptor side in the photostationary state. By virtue of the very small decay rate of triplet pyrene, a considerably extended triplet lifetime (2 ms) is observed. Next, the intermolecular triplet-triplet ET properties are investigated. Using steady-state and time-resolved spectroscopy, the ET rate constants from the Ir complex and pyrene unit in the sensitizer to an external triplet acceptor (unattached, free pyrene derivative) in solution are found to be around 109 s-1 and 108 M -1 s-1, respectively. In spite of a lower ET rate constant, the tethered pyrene serves as the main intermolecular ET channel because of the large, favorable intramolecular ET equilibrium ( K ∼ 103). Importantly, this cascade ET process, from Ir complex to linked pyrene, and then to free pyrene, offers an overall improved ET efficiency than a direct ET from Ir complex to free pyrene, by virtue of the much smaller spontaneous decay rate compared to that of the metal complex. Finally, the more efficient ET ability is demonstrated experimentally by applying the molecule as sensitizer in a triplet-triplet annihilation upconversion. The bichromophoric sensitizer achieved upconverted emission intensity 5 times higher than a monochromophoric Ir-complex analogue.