Double burden of malnutrition and its associated factors among women in low and middle income countries: findings from 52 nationally representative data.
Double burden of malnutrition (DBM) is an emerging global public health problem. The United Nations member states adopted eradicating all forms of malnutrition as an integral component of the global agenda. However, there is evidence of a high burden of undernutrition among women and rising rates of overweight and obesity, especially in low and middle income countries (LMICs). Therefore, this study aimed to investigate the prevalence and associated factors of underweight, overweight, and obesity among women of reproductive age in LMICs. Data for the study were drawn from a recent 52 Demographic and Health Surveys (DHS) conducted in LMICS. We included a sample of 1,099,187 women of reproductive age. A multilevel multinomial logistic regression model was used to identify factors associated with DBM. Adjusted relative risk ratio (RRR) with a 95% Confidence Interval (CI) was reported to show an association. The prevalence of underweight, overweight, and obesity in LMICs among women of reproductive age was 15.2% (95% CI: 15.1-15.3), 19.0% (95% CI: 18.9- 19.1), and 9.1% (95% CI: 9.0-9.2), respectively. This study found that women aged 24-34 years, aged ≥ 35 years, with primary, secondary, and above educational level, from wealthy households, using modern contraceptives, exposed to media (radio and television), and with high parity (more than one birth) were more likely to have overweight and obesity and less likely to have underweight. Moreover, the risk of having obesity (RRR = 0.59; 95% CI = 0.58-0.60 and overweight (RRR = 0.78; 95% CI = 0.77-0.79) were lower among rural women, while the risk of being underweight was (RRR = 1.13; 95% CI = 1.11-1.15) higher among rural women compared to urban women. The prevalence of underweight, overweight, and obesity was high among women of reproductive age in LMICs. Underweight, overweight, and obesity are influenced by sociodemographic, socioeconomic, and behavioral-related factors. This study shows that, in order to achieve Sustainable Development Goal 2, a multifaceted intervention approach should be considered to prevent both forms of malnutrition in women of reproductive age. This can be achieved by raising awareness and promoting healthy behaviors such as healthy eating and physical activity, especially among educated women, women from wealthy households, and women exposed to the media.


The effects of expansions, questions and cloze procedures on children's conversational skills.
The effectiveness of expansion as a technique for facilitating children's language and conversational skills is well known (Scherer and Olswang, 1984). Expansion, however, can appear alone or in combination with other techniques. Using a repeated measures design, this study aimed to compare the effects of expansion alone (EA); expansion combined with wh-questions (EQ); and expansion followed by a cloze procedure (EC) on the conversational skills of eight preschool children with conversational difficulties. Results showed that while there were no significant differences in child verbal topic maintaining responses across all techniques, EA elicited a significantly higher number of topic extensions, more non-verbal topic maintaining responses and fewer 'non-relevant responses' from the children, than either EQ or EC. The positive effects of each technique on the pragmatic appropriateness in conversations suggest that they could be used strategically in language intervention to ensure greater therapeutic effect.


A comparison between ultrasound therapy and laser therapy for symptomatic cervical ectopy.
The purpose of this study was to compare the clinical efficacy of ultrasound (US) therapy and laser therapy in patients with symptomatic benign ectopy of the uterine cervix. Patients with symptomatic benign ectopy of the cervix (n = 200) were enrolled in this study. Abundant leukorrhea, contact bleeding, recurrent cervicitis and pelvic pain were also evaluated. Patients were allocated alternately to the US and laser groups. In the laser group, Nd: YAG laser was used for tissue vaporization destruction. In the US group, the therapeutic US device Seapostar (Chongqing Haifu [HIFU] Technology, Co. Ltd., Chongqing, China) was applied. Neither anesthesia nor analgesia was used. Results showed that patients in both groups tolerated the procedure well and had excellent treatment outcomes. A symptomatic cure rate of 97.33% was obtained in the US group, and 98.81% was obtained in the laser group (p > 0.05). Ectopy areas were managed with a success rate of 95.95% in the US group, and 96.43% in the laser group (p > 0.05). The rate of side effects (including vaginal reactive discharge and colporrhagia) was found to be lower in the US group than that in the laser group. Mild-to-moderate bleeding occurred in US group (8.42%) and laser group (45.56%). The bleeding rate in the US group is significantly lower than that in the laser group (p < 0.01). We conclude that focused US can treat symptomatic ectopy of the cervix successfully, with excellent clinical results and minimal risk. Focused US therapy appears to be a promising new treatment method for symptomatic ectopy of the uterine cervix.


Sigh rate during emotional transitions: More evidence for a sigh of relief.
Evidence suggests that sighs regulate stress and emotions, e.g. by facilitating relief. This study aimed to investigate sigh rates during relief. In addition, links between sighs, anxiety sensitivity and HPA-axis activity were explored. Healthy volunteers (N=29) were presented cues predicting the valence of subsequent stimuli. By sequencing cues that predicted pleasant or unpleasant stimuli with or without certainty, transitions to certain pleasantness (relief) or to certain unpleasantness (control) were created and compared to no transitions. Salivary cortisol, anxiety sensitivity and respiration were measured. Sigh frequency was significantly higher during relief than during control transitions and no transition states, and higher during control transitions than during no transition states. Sigh frequency increased with steeper cortisol declines for high anxiety sensitive persons. Results confirm a relationship between sighs and relief. In addition, results suggest that sigh frequency is importantly related to HPA-axis activity, particularly in high anxiety sensitive persons.


Development of a pre- and postoperative physical activity promotion program integrated in the electronic health system of patients with bladder cancer (The POPEYE study): An intervention mapping approach.
Uptake of sufficient physical activity before and after radical cystectomy is important to improve physical and psychosocial outcomes in bladder cancer (BC) patients. In this paper, we describe the development of an evidence-based and theory-informed intervention, guided by the steps of the Intervention Mapping approach, to promote physical activity before and after radical cystectomy in patients with BC. The intervention is a home-based physical activity program. The preoperative timeframe of the intervention is 4 or 12 weeks, depending on administration of neoadjuvant chemotherapy. Postoperatively, the intervention will last for 12 weeks. The intervention consists of a digital oncological platform (DOP), several consultations with healthcare professionals, personal booklet and follow-up phone calls. DOP includes information, diaries, visual representation of progress, mailbox, videos of peers and treating physician explaining the benefits of physical activity, photo material of exercises and a walking program with an activity tracker. Individual goals will be set and will be self-monitored by the patient through DOP. Patients will receive alerts and regular feedback. Intervention Mapping ensures transparency of all intervention components and offers a useful approach for the development of behaviour change interventions for cancer patients and for translation of theories into practice.


Correction: A Versatile Bioreactor for Dynamic Suspension Cell Culture. Application to the Culture of Cancer Cell Spheroids.
[This corrects the article DOI: 10.1371/journal.pone.0154610.].


Building Polyvalent DNA-Functionalized Anisotropic AuNPs using Poly-Guanine-Mediated In-Situ Synthesis for LSPR-Based Assays: Case Study on OncomiR-155.
DNA-functionalized gold nanoparticles (DNA-AuNPs) hold great promise for numerous biomedical applications, especially the building of well-defined nanosystems. Previously reported methods for the preparation of DNA-AuNPs all rely on the use of DNA-bearing free thiol or disulfide groups at their 3'/5' ends. But here we report a novel polyvalent DNA-AuNPs conjugation approach by in-situ fast synthesis of AuNPs at the polyguanine (G12 ) strands. As confirmed by both TEM images and gel electrophoresis analysis, many poly G strand can form an individual anisotropic AuNP and so each AuNP functionalized with a dense layer of DNA, resulting in the formation of polyvalent (p)DNA-AuNPs. The general applicability of this novel approach was further verified in hybridization test and UV-Vis spectroscopy results show that pDNA-AuNPs conjugation is more attractive in biomedical diagnosis and specific sequence detection like microRNA-155 by using an extra-strand poly G with "sticky end" that are complementary to the target sequence.


Psychiatric aspects of learning difficulties.
This article describes the process of clinical assessment that may lead to differential treatment of psychiatric-related learning difficulties. The authors review differences in information processing among individuals with attention, affective, and primary thought disorders.


Detection of protein in polyacrylamide gels using an improved silver stain.
A much improved silver staining procedure for the detection of protein in polyacrylamide gels of 0.8-3.0 mm thickness is described. It achieves very high sensitivity (detecting less than 0.01 ng bovine serum albumin/mm2) by overstaining and subsequently removing nonspecific background stain using a modified, reliable destaining procedure. Maximum sensitivity follows prediamine equilibration in 0.1% (w/v) formaldehyde solution. With two-dimensional electrophoresis the improved staining procedure reveals greater than 200 polypeptides in unconcentrated human urine and greater than 150 polypeptides in a single human fingerprint.


Zero-shot transfer learned generic AI models for prediction of optimally ripe climacteric fruits.
Ideally, ripe fruits offer appropriate nutritional content and best quality in terms of taste and flavour. Prediction of ripe climacteric fruits acts as the main marketing indicator for quality from the consumer perspective and thus renders it a genuine industrial concern for all the stakeholders of the fruit supply chain. However, the building of fruit-specific individual model for the prediction of ripeness level remains an existing challenge due to the scarcity of sufficient labeled experimental data for each fruit. This paper describes the development of generic AI models based on the similarity in physico-chemical degradation phenomena of climacteric fruits for prediction of 'unripe' and 'ripe' levels using 'zero-shot' transfer learning techniques. Experiments were performed on a variety of climacteric and non-climacteric fruits, and it was observed that transfer learning works better for fruits within a cluster (climacteric fruits) as compared to across clusters (climacteric to non-climacteric fruits). The main contributions of this work are two-fold (i) Using domain knowledge of food chemistry to label the data in terms of age of the fruit, (ii) We hypothesize and prove that the zero-shot transfer learning works better within a set of fruits, sharing similar degradation chemistry depicted by their visual properties like black spot formations, wrinkles, discoloration, etc. The best models trained on banana, papaya and mango dataset resulted in s zero-shot transfer learned accuracies in the range of 70 to 82 for unknown climacteric fruits. To the best of our knowledge, this is the first study to demonstrate the same.


Acute angulation of the aortic arch predisposes a patient to ascending aortic dilatation and aortic regurgitation late after the arterial switch operation for transposition of the great arteries.
We assessed the contribution of acute aortic arch angulation and enhanced systolic pulse wave reflection to dilatation of the ascending aorta and aortic regurgitation late after the arterial switch operation for transposition of the great arteries. We performed aortography, radial artery applanation tonometry, and transthoracic echocardiography in 47 children (aged 5-6 years) who underwent the arterial switch operation and in 20 matched healthy controls. The aortic arch angle, ratio of ascending/descending aortic diameter, degree of aortic regurgitation, central pulse pressure, aortic augmentation pressure, and augmentation index were measured. The aortic arch angle was more acute (55 +/- 6.5 degrees vs 68 +/- 5 degrees, respectively, P < .001) and the ratio of the ascending/descending aorta diameter was significantly greater (1.98 +/- 0.4 vs 1.55 +/- 0.06, respectively, P < .001) in the patients who underwent the arterial switch operation compared with controls. Augmentation pressure and augmentation index were higher in the patients who underwent the arterial switch operation than in controls (7.5 +/- 4.6 vs 3.4 +/- 5.8, respectively P = .04; 21 +/- 10 vs 8 +/- 13, respectively, P = .005). A more acute aortic angle was associated with a higher aortic augmentation index (r = 0.41, P < .01), a greater ratio of the ascending to descending aorta (r = -0.6, P < .001), and the degree of aortic regurgitation (r = 0.39, P < .01). Sharper angulation of the aortic arch is associated with early pulse wave reflection, dilatation of the ascending aorta, and aortic regurgitation late after the arterial switch operation for transposition of the great arteries.


Tumefactive Demyelination: A Common Radiological Masquerader of Malignancy and the Expeditious Diagnostic Applicability of Crush Smear Cytology.
Tumefactive demyelinations (TDs) are demyelinating central nervous system lesions that masquerade as neoplastic lesions on radiological images. Brain biopsy is often required for confirmatory diagnosis. Since crush cytology has become a routine practice, a thorough knowledge of the cytomorphologic features of TD is required to prevent misdiagnosis. In this report, we describe the cytomorphological and histomorphological features of a case of TD.


Neural Networks for Cause of Hospitalization and Final Cause of Death Extraction from Discharge Summaries.
Determining the cause of death of hospitalized patients with cardiovascular disease is of the utmost importance. This is usually recorded in free text form. In this study we aimed to develop a series of supervised natural language processing algorithms to extract cardiovascular causes of hospitalization and final causes of death.


When snowball sampling leads to an avalanche of fraudulent participants in qualitative research.
Fraudulent research participants create negative consequences for the rigour and soundness of research. A case study is presented from a qualitative study where the research team believed several fraudulent participants fabricated information during an interview about being a caregiver for a person living with dementia and chronic wounds. Participants were recruited through a free online research registry. Individual semi-structured interviews were held virtually. The study was paused after the nurse scientist with qualitative methodology experience identified that participants were giving illogical and repetitive responses across interviews. The team developed a revised screening tool to help reduce fraudulent participants from enrolling in the study. None of the data collected were used for analysis. Information is provided on how the team dealt with the situation, lessons learned for future studies, and recommendations for gerontological nurse researchers. Researchers should be aware that some participants are misrepresenting themselves for financial incentives and this can compromise the soundness of findings. Thorough screening tools are one way to identify and prevent fraud.


Antiemetic efficacy of prophylactic ondansetron in laparoscopic surgery: randomized, double-blind comparison with metoclopramide.
In a randomized, double-blind study, we have compared the prophylactic antiemetic efficacy of ondansetron with that of metoclopramide in 123 patients undergoing general anaesthesia for day-case gynaecological laparoscopic surgery. The patients received either i.v. ondansetron 4 mg or metoclopramide 10 mg immediately before a standard anaesthetic. The number of patients with no nausea or vomiting in the ondansteron group was 50 (82%) compared with 29 (47%) in the metoclopramide group (P < 0.001). In those patients with a previous history of postoperative nausea and vomiting, nausea was less severe in those receiving ondansetron compared with those receiving metoclopramide (P < 0.05). We conclude that preoperative prophylactic administration of i.v. ondansetron was superior to metoclopramide in preventing nausea and vomiting after general anaesthesia for day-case gynaecological laparoscopic surgery.


Resistance to targeted therapies in acute myeloid leukemia.
The introduction of new targeted therapies to the treatment algorithm of acute myeloid leukemia (AML) offers new opportunities, but also presents new challenges. Patients diagnosed with AML receiving targeted therapies as part of lower intensity regimens will relapse inevitably due to primary or secondary resistance mechanisms. In this review, we summarize the current knowledge on the main mechanisms of resistance to targeted therapies in AML. Resistance to FLT3 inhibitors is mainly mediated by on target mutations and dysregulation of downstream pathways. Switching the FLT3 inhibitor has a potential therapeutic benefit. During treatment with IDH inhibitors resistance can develop due to aberrant cell metabolism or secondary site IDH mutations. As a unique resistance mechanism the mutated IDH isotype may switch from IDH1 to IDH2 or vice versa. Resistance to gemtuzumab-ozogamicin is determined by the CD33 isotype and the degradation of the cytotoxin. The main mechanisms of resistance to venetoclax are the dysregulation of alternative pathways especially the upregulation of the BCL-2-analogues MCL-1 and BCL-XL or the induction of an aberrant cell metabolism. The introduction of therapies targeting immune processes will lead to new forms of therapy resistance. Knowing those mechanisms will help to develop strategies that can overcome resistance to treatment.


Gymnemasylvestre derived compounds inhibit GSH depletion and increase cGMP and nitric oxide to attenuate advanced glycation end products induced hypertrophic growth in renal tubular epithelial cells.
The accumulation of advanced glycation end products (AGE) plays significant role in developing tubular hypertrophy during diabetic nephropathy (DN). Reactive oxygen species and nitric oxide (NO) are directly involved in the progression of DN. We have studied the effect of standardized Gymnemasylvestre organic extract (GE) on AGE induced cellular hypertrophy using rat renal tubular epithelial cells (NRK 52E). AGE (400 μg/ml) induced cytotoxicity to NRK 52E cells as determined by MTT assay at 0-72 h. We report cellular hypertrophy mediated cytotoxicity by AGE which was the result of significant reduction in the cellular nitric oxide and cGMP levels associated with increased lipid peroxidation and antioxidant depletion (P < 0.05). Upon treatment with GE the cell viability was increased with reduced cellular hypertrophy by 1.7 folds when compared to AGE treated group. GE could significantly increase NO by 1.9 folds and cGMP by 2.8 folds and inhibited GSH depletion by 50% during AGE induced toxicity. The antioxidant enzyme activity of catalase was increased by 50% while, glutathione peroxidase and superoxide dismutase enzyme activities were significantly increased by 42% and 67% with decreased lipid peroxidation (49%) upon GE treatment. Thus, GE attenuates AGE induced hypertrophic growth by inhibiting GSH depletion and partly through increased NO/cGMP signaling.


Vascular pathology and pathogenesis of cognitive impairment and dementia in older adults.
It is well recognized that brains of older people often harbor cerebrovascular disease pathology including vessel disease and vascular-related tissue injuries and that this is associated with vascular cognitive impairment and contributes to dementia. Here we review vascular pathologies, cognitive impairment, and dementia. We highlight the importance of mixed co-morbid AD/non-AD neurodegenerative and vascular pathology that has been collected in multiple clinical pathologic studies, especially in community-based studies. We also provide an update of vascular pathologies from the Rush Memory and Aging Project and Religious Orders Study cohorts with special emphasis on the differences across age in persons with and without dementia. Finally, we discuss neuropathological perspectives on the interpretation of clinical-pathological studies and emerging data in community-based studies.


Breast-Cancer Biomarker (C-erbB-2) Detection in Saliva/Serum Based on In1-xGaxAs/Si Hetero Junction Dopingless TFET Biosensor.
This research article reports the electrical detection of breast-cancer biomarker (C-erbB-2) in saliva/serum based on In1-xGaxAs/Si heterojunction dopingless tunnel FET (HJ-DL-TFET) biosensor for highly sensitive and real-time detection. The work takes into account the interface charge modulation effect in dopingless extended gate heterostructure TFET with embedded nanocavity biosensors for the precise, reliable, and fast detection of antigens present in the body fluids such as saliva in place of blood serum. The reported biosensor is numerically simulated in 2D using the SILVACO ATLAS exhaustive calibrated simulation framework. For the biomolecule immobilization, the proposed biosensor has a dual cavity engraved beneath the dual gate structure. This improves the control of biomolecules over the source-to-channel tunneling rate, as well as the control over the electrical performance parameters of the proposed biosensor. Here, a numerical model for the C-erbB-2 interface charge equivalent is also developed. The analysis of device sensitivity in both saliva and serum environments for various C-erbB-2 concentrations has been carried out. Our study reveals that III-V In1-xGaxAs/Si heterojunction with x composition of 0.2 and extended gate geometry provides an increased tunneling probability, improves the gate control to get a higher ION/IOFF ratio and higher sensitivity. In addition to this, the impact of interface charges corresponding to the different amounts of C-erbB-2 biomarkers on the biosensor sensitivity (in terms of ION/IOFF ratio) yields higher sensitivity of the order of 106.


RNA structural elements determine frequency and sites of nonhomologous recombination in an animal plus-strand RNA virus.
For highly variable RNA viruses, RNA recombination significantly contributes to genetic variations which may lead to changes of virulence, adaptation to new hosts, escape from the host immune response, and emergence of new infectious agents. Using a system based on transfection of cells with synthetic nonreplicable subgenomic transcripts derived from bovine viral diarrhea virus (family Flaviviridae), the existence of a replication-independent mechanism of RNA recombination, in addition to the commonly accepted replicative copy-choice recombination, has been previously proven (A. Gallei et al., J. Virol. 78:6271-6281, 2004). To identify RNA signals involved in efficient joining of RNA molecules, RNA recombination in living cells was targeted to the 3' nontranslated region. Molecular characterization of 40 independently emerged recombinant viruses revealed that the majority of recombination sites are located in single-stranded regions of the RNA molecules. Furthermore, the results of this study showed that the frequency of RNA recombination directly correlated with the RNA amounts of both recombination partners. The frequency can be strongly increased by modification of the 5' triphosphates and 3' hydroxyls of the recombining RNA molecules to 5' hydroxyl and 3' monophosphoryl ends, respectively. Analysis of recombinants that emerged after transfection with such modified RNA molecules revealed a complete integration and efficient end-to-end joining of the recombination partner(s) in at least 80% of recombinants, while unmodified RNA molecules recombined exclusively at internal positions. These results are in line with the hypothesis that endoribonucleolytic cleavage and a subsequent ligation reaction can cause RNA recombination.


Adenosine A2A receptor gene polymorphisms (ADORA2A) are associated with maximal concentric contraction pain.
To test associations of adenosine A2A receptor gene (ADORA2A) polymorphisms with maximal concentric contraction pain, caffeine-induced perceptual changes, and responses to mild eccentric injury. Targeted candidate gene association study. ADORA2A (rs5751876) was genotyped in 26 adults. Pain of a maximal elbow flexor contraction was assessed. Participants performed 18 eccentric actions of the elbow flexors. Arm volume was measured before and 24- and 48-h post-injury. At 24- and 48-h post-injury, caffeine or placebo capsules were given using a randomized cross-over design and effort and pain were assessed. Maximal concentric contraction pain was higher for the CC compared to the CT/TT group (effect size d = 0.89) and lower for the TT compared to the CT/CC group (d = 0.62). There were moderate sized differences between CC and TT/CT groups for post-injury exertion and arm volume 24-h post injury. ADORA2A polymorphisms are moderately associated with muscle pain during maximal contractions in uninjured muscle.


Ultrastructure and histochemistry of rat myocardial capillary endothelial cells in response to diabetes and hypertension.
Insufficient growth and rarefaction of capillaries, followed by endothelial dysfunction may represent one of the most critical mechanisms involved in heart damage. In this study we examined histochemical and ultrastructural changes in myocardial capillary endothelium in two models of heart failure streptozotocin-induced diabetes mellitus (STZ) and NO-deficient hypertension in male Wistar rats. Diabetes was induced by a single i.v. dose of STZ (45 mg/kg) and chronic 9-week stage was analysed. To induce NO-deficient hypertension, animals were treated with inhibitor of NO synthase L-nitroarginine methylester (L-NAME) (40 mg/kg) for 4 weeks. Left ventricular tissue was processed for enzyme catalytic histochemistry of capillary alkaline phosphatase (AlPh), dipeptidyl peptidase IV (DPP IV), and endothelial NO synthase/NADPH-diaphorase (NOS) and for ultrastructural analysis. In diabetic and hypertensive rats, lower/absent AlPh and DPP IV activities were found in focal micro-areas. NOS activity was significantly reduced and persisted only locally. Quantitative evaluation demonstrated reduction of reaction product intensity of AlPh, DPP and NOS by 49.50%, 74.36%, 20.05% in diabetic and 62.93%, 82.71%, 37.65% in hypertensive rats. Subcellular alterations of endothelial cells were found in heart of both groups suggesting injury of capillary function as well as compensatory processes. Endothelial injury was more significant in diabetic animals, in contrast the adaptation was more evident in hypertensive ones. CONCLUDING: both STZ-induced diabetes- and NO-deficient hypertension-related cardiomyopathy were accompanied by similar features of structural remodelling of cardiac capillary network manifested as angiogenesis and angiopathy. The latter was however, predominant and may accelerate disappearance of capillary endothelium contributing to myocardial dysfunction.


Measuring molecular frequencies in the 1-10 μm range at 11-digits accuracy.
High-resolution spectroscopy in the 1-10 μm region has never been fully tackled for the lack of widely-tunable and practical light sources. Indeed, all solutions proposed thus far suffer from at least one of three issues: they are feasible only in a narrow spectral range; the power available for spectroscopy is limited; the frequency accuracy is poor. Here, we present a setup for high-resolution spectroscopy, whose approach can be applied in the whole 1-10 μm range. It combines the power of quantum cascade lasers (QCLs) and the accuracy achievable by difference frequency generation using an orientation patterned GaP crystal. The frequency is measured against a primary frequency standard using the Italian metrological fibre link network. We demonstrate the performance of the setup by measuring a vibrational transition in a highly-excited metastable state of CO around 6 μm with 11 digits of precision.


Diethyl 3,3'-[(3-fluoro-phen-yl)methyl-ene]bis-(1H-indole-2-carboxyl-ate).
In the title compound, C29H25FN2O4, the mean planes of the indole ring systems are approximately perpendicular to one another [dihedral angle = 88.3 (4)°]. The benzene ring is twisted with respect to the indole ring systems by 49.8 (5) and 77.6 (3)°. In the crystal, pairs of N-H⋯O hydrogen bonds link the mol-ecules into the inversion dimers which are further linked into supra-molecular chains propagating along the [110] direction.


Primary sclerosing cholangitis: clinical and immunopathological review of 21 cases.
Twenty-one patients with primary sclerosing cholangitis were seen during 1979-87. The mean age at onset of disease was 51.7 years (range: 13-78 years) with a male: female ratio of 2.5:1. Six (29%) were asymptomatic at the time of diagnosis. Eleven patients (52%) had ulcerative colitis. Cholangiography demonstrated abnormalities limited to the intrahepatic ducts in 10 cases, with both intrahepatic and extrahepatic involvement in 11. Histological features on liver biopsy included: portal tract inflammation and cholestasis in all; paucity of bile ducts in 56%; piecemeal necrosis in 19% and cirrhosis in 6%. Circulating autoantibodies and elevated serum immunoglobulins were found in half of the patients and HLA-B8 was detected in 53%. A deficiency of circulating CD3 and CD8 cells was not found in the 12 patients tested. The mean follow-up was 51 months (range: 3-180 months). Three patients died from non-hepatic causes and another has received liver transplantation. A Kaplan-Meier curve predicted 70% survival at 72 months.


Interactions of the cytoplasmic domains of human and simian retroviral transmembrane proteins with components of the clathrin adaptor complexes modulate intracellular and cell surface expression of envelope glycoproteins.
The cytoplasmic domains of the transmembrane (TM) envelope proteins (TM-CDs) of most retroviruses have a Tyr-based motif, YXXO, in their membrane-proximal regions. This signal is involved in the trafficking and endocytosis of membrane receptors via clathrin-associated AP-1 and AP-2 adaptor complexes. We have used CD8-TM-CD chimeras to investigate the role of the Tyr-based motif of human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and human T-leukemia virus type 1 (HTLV-1) TM-CDs in the cell surface expression of the envelope glycoprotein. Flow cytometry and confocal microscopy studies showed that this motif is a major determinant of the cell surface expression of the CD8-HTLV chimera. The YXXO motif also plays a key role in subcellular distribution of the envelope of lentiviruses HIV-1 and SIV. However, these viruses, which encode TM proteins with a long cytoplasmic domain, have additional determinants distal to the YXXO motif that participate in regulating cell surface expression. We have also used the yeast two-hybrid system and in vitro binding assays to demonstrate that all three retroviral YXXO motifs interact with the micro1 and micro2 subunits of AP complexes and that the C-terminal regions of HIV-1 and SIV TM proteins interact with the beta2 adaptin subunit. The TM-CDs of HTLV-1, HIV-1, and SIV also interact with the whole AP complexes. These results clearly demonstrate that the cell surface expression of retroviral envelope glycoproteins is governed by interactions with adaptor complexes. The YXXO-based signal is the major determinant of this interaction for the HTLV-1 TM, which contains a short cytoplasmic domain, whereas the lentiviruses HIV-1 and SIV have additional determinants distal to this signal that are also involved.


Antifungal activity of liquiritin in Phytophthora capsici comprises not only membrane-damage-mediated autophagy, apoptosis, and Ca2+ reduction but also an induced defense responses in pepper.
Phytophthora capsici causes a severe soil-borne disease in a wide variety of vegetables; to date, no effective strategies to control P. capsici have been developed. Liquiritin (LQ) is a natural flavonoid found in licorice (Glycyrrhiza spp.) root, and it is used in pharmaceuticals. However, the antifungal activity of LQ against P. capsici remains unknown. In the present study, we demonstrated that LQ inhibits P. capsici mycelial growth and sporangial development. In addition, the EC50 of LQ was 658.4 mg/L and LQ caused P. capsici sporangia to shrink and collapse. Next, LQ severely damaged the cell membrane integrity, leading to a 2.0-2.5-fold increase in relative electrical conductivity and malondialdehyde concentration, and a 65-70% decrease in sugar content. Additionally, the H2O2 content was increased about 2.0-2.5 fold, but the total antioxidant activity, catalase activity and laccase activity were attenuated by 40-45%, 30-35% and 70-75%. LQ also induced autophagy, apoptosis, and reduction of intracellular Ca2+ content. Furthermore, LQ inhibited P. capsici pathogenicity by reducing the expression of virulence genes PcCRN4 and Pc76RTF, and stimulating the plant defense (including the activated transcriptional expression of defense-related genes CaPR1, CaDEF1, and CaSAR82, and the increased antioxidant enzyme activity). Our results not only elucidate the antifungal mechanism of LQ but also suggest a promising alternative to commercial fungicides or a key compound in the development of new fungicides for the control of the Phytophthora disease.


Ciliary tissue transplantation in the rabbit.
Irreversible damage of the ciliary body can be responsible for prolonged ocular hypotony and phthisis bulbi, which, currently, cannot be treated. The aim of this study was to achieve survival of morphologically normal ciliary tissue (CT) transplants in the anterior chamber of a rabbit's eye. Outbred female New Zealand albino rabbits received CT allografts, which were placed on to the surface of the host iris. We evaluated the influence of ciclosporin (CsA), VEGF and donor perfusion on graft survival. Operated eyes were assessed clinically and histologically, and revascularization of the grafts was determined by fluorescein angiography. All grafts became dark and ischemic during the first five to seven days after transplantation. Reperfusion of the grafted tissue was complete at approximately ten days after transplantation. In untreated animals, transplants became infiltrated by inflammatory cells, which led to destruction of the tissue. This was prevented by systemic use of CsA. Transplants treated with VEGF prior to transplantation had fewer ischemic areas but epithelial cell survival was not improved. Whole body donor perfusion prior to preparation of the grafts resulted in less inflammation and, histologically, in a better quantity and quality of the epithelial cells in the CT transplants. Ciliary tissue can be successfully transplanted but the ciliary epithelium suffers from ischemia and in untreated animals the whole transplant is rejected in the classical fashion. If the donor is perfused and the host immunosuppressed, histologically normal ciliary epithelium can be preserved together with rapid revascularization, minimal inflammation and good survival of the transplant, although fibrosis continued to occur during the two months after transplantation.


Physiological adaptation and plasticity to water stress of coastal and desert populations of Heliotropium curassavicum L.
In spite of the ten times higher evaporative demand in a desert versus a coastal habitat, plants of populations of Heliotropium curassavicum from both show similar stomatal conductances in the field as well as under controlled conditions. The desert plants however have a plastic stomatal response to dry air growing conditions which results in a greater photosynthetic performance at negative water potentials. The root and stem resistance to water flow is lower in the desert plants resulting in the maintenance of a high transpiration rate without a large reduction in water potential.


Anti-Helicobacter pylori compounds from the ethanol extracts of Geranium wilfordii.
ETHNOPHARMOCOLOGICAL RELEVANCE: Geranium wilfordii Maxim has been extensively used in Chinese Herbal Medicine for treating gastrointestinal disorders, diarrhea and dysentery. In the current study we aimed to investigate the anti-Helicobacter pylori activity of ethanol extracts of Geranium wilfordii Maxim and its main active compounds, corilagin and 1,2,3,6-tetra-O-galloyl-β-D-glucose. The plant materials were extracted three times with ethanol and the concentrated filtrate was successively fractioned into chloroform, ethyl acetate, and n-BuOH-soluble portions which were examined in vitro for the anti-Helicobacter. pylori activity. Employing a standard strain and five clinical isolates of Helicobacter pylori, the extract, fractions and compounds of Geranium wilfordii Maxim were assessed in vitro. The ethanol fraction, ethyl acetate fraction, corilagin, and 1,2,3,6-tetra-O-galloyl-β-D-glucose were found to be strongly inhibitory to Helicobacter. pylori (MICs: 40, 30, 4, and 8μg/ml respectively). The results of the present study showed that the ethanol and the ethyl acetate extracts from Geranium wilfordii Maxim displayed as well the most significant inhibition to the growth of Helicobacter. pylori, of which corilagin and 1,2,3,6-tetra-O-galloyl-β-D-glucose have been identified main anti-Helicobacter pylori active constituents.


Deep inspiration breath hold in the prone position retracts the heart from the breast and internal mammary lymph node region.
Deep inspiration breath hold in the prone position causes a caudal shift of the heart away from the nearly unmodified breast and internal mammary lymph node region, suggesting better heart protection for left-sided whole breast irradiation with or without regional nodal radiotherapy.


DNA adducts from acetaldehyde: implications for alcohol-related carcinogenesis.
Alcoholic beverage consumption is classified as a known human carcinogen, causally related to an increased risk of cancer of the upper gastrointestinal tract. The formation of acetaldehyde from ethanol metabolism seems to be the major mechanism underlying this effect. Acetaldehyde is carcinogenic in rodents and causes sister chromatid exchanges and chromosomal aberrations in human cells. The best-studied DNA adduct from acetaldehyde is N(2)-ethyl-2'-deoxyguanosine, which is increased in liver DNA obtained from ethanol-treated rodents and in white blood cells obtained from human alcohol abusers. However, the carcinogenic relevance of this adduct is unclear in view of the lack of evidence that it is mutagenic in mammalian cells. A different DNA adduct, 1,N(2)-propano-2'-deoxyguanosine (PdG), can also be formed from acetaldehyde in the presence of histones and other basic molecules. PdG has been shown to be responsible for the genotoxic and mutagenic effects of crotonaldehyde. The PdG adduct can exist in either of two forms: a ring-closed form or a ring-opened aldehyde form. Whereas the ring-closed form is mutagenic, the aldehyde form can participate in the formation of secondary lesions, including DNA-protein cross-links and DNA interstrand cross-links. The formation of these types of complex secondary DNA lesions resulting from PdG may explain many of the observed genotoxic effects of acetaldehyde described above. Repair of PdG and its associated adducts is complex, involving multiple pathways. Inherited variation in the genes encoding the proteins involved in the repair of PdG and its secondary adducts may contribute to susceptibility to alcoholic beverage-related carcinogenesis.


Morphine dependence changes the role of droperidol on pain-related electric activities in caudate nucleus.
Droperidol causes the blockage of the dopamine receptors in the central nervous system that are involved in pain transmission. However, the mechanism of action of droperidol in pain-related neurons is not clear, and it is still unknown whether opioids are involved in the modulation of this processing. The present study examines the effect of droperidol on the pain-evoked response of pain-excitation neurons (PENs) and pain-inhibition neurons (PINs) in the caudate nucleus (Cd) of rats. The trains of electric impulses applied to the sciatic nerve were used as noxious stimulation. Our results revealed that droperidol decreased the frequency of PEN discharge, and increased the frequency PIN discharge evoked by the noxious stimulation in the Cd of normal rats, while administration of droperidol to morphine-dependent rats produced the opposite response. Those demonstrated that droperidol is involved in the modulation of nociceptive information transmission in Cd, and there were completely opposite responses to painful stimulation between normal and morphine-dependent rats after administration of droperidol.


On the role of C1-inhibitor as inhibitor of tissue-type plasminogen activator in human plasma.
An enzyme immuno assay was developed to measure complexes of tissue-type plasminogen activator (t-PA) with C1-inhibitor in order to study the role of C1-inhibitor as an inhibitor of t-PA in plasma. In vitro experiments with melanoma and recombinant t-PA learned that purified C1-inhibitor reacts with both single chain t-PA and two chain t-PA. The rate constants ranged from 3.0 to 5.2 M-1s-1. In plasma, melanoma and recombinant two chain t-PA were hardly inhibited by C1-inhibitor, in contrast to melanoma and recombinant single chain t-PA which were inhibited to the same extent by endogenous C1-inhibitor as they were by purified C1-inhibitor. In vivo, t-PA/C1-inhibitor complex could be measured in plasma in a few cases in healthy volunteers (0.62 +/- 0.43 ng/ml t-PA equivalents), after exercise (0.84 +/- 0.25 ng/ml t-PA equivalents) and after a desmopression infusion (0.26 +/- 0.04 ng/ml t-PA equivalents). However, t-PA/C1-inhibitor complex was found in plasma in all cases after venous occlusion (1.7 +/- 0.5 ng/ml t-PA equivalents), in peritoneal fluid from patients suffering from peritoneal inflammatory disease (2.2 +/- 1.3 ng/ml t-PA equivalents) and in plasma from healthy volunteers during a t-PA infusion (27.7 +/- 18.5 ng/ml t-PA equivalents at peak level). In the last case, about 8% of the infused dose of recombinant t-PA (alteplase) was inhibited by C1-inhibitor at peak level.(ABSTRACT TRUNCATED AT 250 WORDS)


Anxiety sensitivity taxon and trauma: discriminant associations for posttraumatic stress and panic symptomatology among young adults.
The present investigation examined whether the anxiety sensitivity (AS) taxon interacts with theoretically relevant traumatic types of aversive life events to show discriminant (concurrent) associations with posttraumatic stress symptoms, but not panic attacks or bodily vigilance among young adults. The interaction between the AS Taxon Scale and trauma exposure accounted for significant variance above and beyond negative affectivity and each of the main effects in terms of a posttraumatic stress disorder (PTSD) symptom-severity criterion variable, but not for posttraumatic-related thoughts and beliefs or either panic-relevant criterion variable. Thus, results suggest that although the AS taxon may function as a common cognitive diathesis for PTSD and panic outcomes, the AS taxon coupled with traumatic life events may confer emotional vulnerability that is specific to PTSD symptoms. These findings are discussed in terms of theoretical and clinical implications for PTSD and panic vulnerability.


Analysis of antibiotic surgical prophylaxis in hospitalized children suffering upper and lower extremity injuries.
Surgical prophylaxis may account for one-third of all antibiotic use in paediatric hospitals. To evaluate the appropriateness of surgical prophylaxis and to analyse adherence of surgeons to surgical prophylaxis guidelines. Retrospective study at a university paediatric hospital. Patients younger than 18 years with injuries of lower and upper extremities were included. The study period was from January 1st 2011-December 31st 2013 and January 1st 2001-December 31st 2003. The appropriateness of the antibiotic use was analysed in accordance with international and local guidelines. Antibiotic prophylaxis was needed by 1125 (55.0 %) patients in 2011-2013 and by 816 (44.4 %) patients in 2001-2003. However, it was administered to only 66.0 % of those in need of prophylaxis in 2011-2013 and to 70.8 % of those in 2001-2003. A single antibiotic dose was administered to 73.8 % of those who received antibiotics in 2011-2013 and to 34.1 % of those in 2001-2003. The timing of the first dose was correct in 370 (52.9 %) prescriptions in 2011-2013 and in 10 (20.4 %) prescriptions in 2001-2003. The most often used antibiotics for prophylaxis were cefazolin in 2011-2013 and cefuroxime in 2001-2003. Overall adherence rate to the international and hospital guidelines was low, indicating that in order to improve this situation, there is a need for multiple interventions.


The effect of prostacyclin on angiotensin II-induced placental vasoconstriction.
Significant alterations in vascular responsiveness to angiotensin II have been documented during pregnancy. We have observed that prostacyclin, a potent vasodilating prostaglandin, does not dilate the ovine placental vasculature. However, we thought it might modulate the placental vasoconstriction produced by angiotensin II. Regional blood flows and resistances were measured by the radioactive microsphere technique in six near-term sheep. Blood flows were measured in the control condition and 15 minutes after beginning an infusion of angiotensin II at 5 micrograms/min (T1). Additional measurements were made 15 minutes after the addition of 50 micrograms/min of prostacyclin to the angiotensin II infusate (T2) and 15 minutes after withdrawing prostacyclin from the angiotensin II infusion (T3). Mean arterial pressure rose in response to angiotensin II and decreased significantly with prostacyclin administration. The renal and uterine nonplacental vascular beds showed the expected vasoconstriction in response to angiotensin II, which was then reversed to control levels by prostacyclin infusion. Unexpectedly, prostacyclin did not reverse the angiotensin II vasoconstriction in the placenta but further increased resistance (p less than 0.03). Placental resistance changed from 0.33 +/- 0.04 peripheral resistance units in the control condition to 0.42 +/- 0.06 peripheral resistance units for T1 (p less than 0.03), and prostacyclin infusion further increased placental resistance to 0.63 +/- 0.10 peripheral resistance units for T2 (p less than 0.03). We conclude that the placental vascular response to prostacyclin is different from that of other organs and that prostacyclin does not dilate, but further constricts the placenta in the near-term sheep with angiotensin II-induced systemic vasoconstriction.


Microbiological analysis of sepsis complicating non-surgical biliary drainage in malignant obstruction.
Cholangitis with sepsis is a common complication of non-surgical biliary drainage and represents a difficult management problem. Microbiological data for 18 septic episodes in 15 patients following endoscopic biliary drainage (EBD) and 14 septic episodes in 14 patients following percutaneous transhepatic drainage (PTD) were reviewed. In the EBD group, all 18 patient episodes of sepsis had blood cultures and 10 had bile cultures obtained. In total, 17 gram-negative isolates and 5 gram-positive isolates were grown in the EBD sepsis group. All of the 14 PTD patients had bile cultures and 13 had blood cultures. In total, 23 gram-negative isolates and 26 gram-positive isolates were grown in the PTD sepsis group. When PTD cultures were compared with EBD cultures, there were significantly more gram-positive cultures (26 vs. 5) associated with PTD sepsis than EBD sepsis (p less than 0.0005). Analysis of the antibiotic sensitivities revealed that a combination of ticarcillin clavulanate with gentamicin covered 20 of the 22 (91%) EBD organisms and 38 of the 49 (78%) PTD organisms. Based on this data, ticarcillin clavulanate with gentamicin is the therapy of choice for EBD and PTD sepsis at our institution.


Effect of heparin on coronary arterial patency after thrombolysis with tissue plasminogen activator in acute myocardial infarction.
Infarct artery patency rates at 90 minutes after coronary thrombolysis using recombinant tissue-type plasminogen activator (rt-PA) with and without concurrent heparin anticoagulation have been shown to be comparable. The contribution of heparin to efficacy and safety after thrombolysis with rt-PA is unknown. In this pilot study, 84 patients were treated within 6 hours of onset of acute myocardial infarction (mean of 2.7 hours) with the standard dose of 100 mg of rt-PA over 3 hours. Forty-two patients were randomized to receive additionally immediate intravenous heparin anticoagulation (5,000 U of intravenous bolus followed by 1,000 U/hour titrated to a partial thromboplastin time of 1.5 to 2.0 times control) while 42 patients received rt-PA alone. Coronary angiography performed on day 3 (48 to 72 hours, mean 57) after rt-PA therapy revealed infarct artery patency rates of 71 and 43% in anticoagulated and control patients, respectively (p = 0.015). Recurrent ischemia or infarction, or both, occurred in 3 (7.1%) anticoagulated patients and 5 (11.9%) control patients (difference not significant). Mild, moderate and severe bleeding occurred in 52, 10 and 2% of the group receiving anticoagulation, respectively, and 34, 2 and 0% of patients in the control group, respectively (p = 0.006). These data indicate that after rt-PA therapy of acute myocardial infarction, heparin therapy is associated with substantially higher coronary patency rates 3 days after thrombolysis but is accompanied by an increased incidence of minor bleeding complications.


Early and Severe Symptomatic Cerebral Vasospasm After Mild Traumatic Brain Injury.
Symptomatic cerebral vasospasm has been reported in a low percentage of patients with moderate or severe traumatic brain injury (TBI) as defined by Glasgow Coma Scale (GCS) score. We present a case of mild TBI (GCS score 14) complicated by early and severe symptomatic cerebral vasospasm. A 63-year-old woman was admitted following mild TBI with a GCS score of 14. Concurrent with the onset of sonographic vasospasm, the patient developed severe neurologic symptoms consistent with ischemia of the left middle cerebral artery territory. Confounding causes of these symptoms were excluded. Each occurrence of these symptoms resolved with intra-arterial calcium channel blocker therapy. Early and severe symptomatic vasospasm may occur as a complication of mild TBI. GCS score alone may be an inadequate risk predictor of symptomatic cerebral vasospasm. Aggressive interventional management may be justified, such as with intra-arterial calcium channel blockers, to optimize the likelihood of a favorable outcome.


Suppression of serum luteinizing hormone in postmenopausal women by an orally administered nonpeptide antagonist of the gonadotropin-releasing hormone receptor (NBI-42902).
Parenteral administration of peptide GnRH analogs is widely used in clinical practice for the suppression of pituitary gonadotropins. NBI-42902 is an orally available, high-affinity nonpeptide antagonist of the human GnRH receptor. The objective was to evaluate the safety, pharmacokinetics, and inhibitory effects on gonadotropin secretion of NBI-42902 in postmenopausal women. This was a phase I, double-blind, placebo-controlled, single-dose study with sequential dose escalation. Fifty-six healthy, postmenopausal women were included. FSH levels were greater than 40 IU/liter, and body mass index was within 20% of ideal values for all subjects. Subjects were administered 5, 10, 25, 50, 75, 100, 150, or 200 mg NBI-42902 as an oral solution. Safety, tolerability, and serum LH and FSH concentrations were evaluated. NBI-42902 was well tolerated. Serum LH concentrations rapidly declined, and dose-dependent suppression was observed. Maximal change from baseline LH concentrations ranged from -19 +/- 5% in the 5-mg group to -55 +/- 2% in the 150-mg group. Suppression of FSH was less pronounced (-15 to -22% of baseline). NBI-42902 was rapidly absorbed after oral administration with a terminal elimination half-life ranging from 2.7 +/- 0.3 to 4.8 +/- 0.8 h. A clear relationship between plasma NBI-42902 concentrations and LH suppression was evident. Dose-dependent LH suppression was achieved by oral administration of a nonpeptide GnRH antagonist suggesting that compounds such as NBI-42902 may enable adjustable gonadotropin suppression as part of novel treatment strategies for benign gynecological conditions.


[CFTR F508DEL mutation and 5T allele in patients with chronic pancreatitis and pancreatic adenocarcinoma].
Mutations in the CFTR gene may be associated with various types of pancreatic pathology and result in higher risk of pancreatic disorders. While delta F508 is the most common mutation in cystic fibrosis patients, the allel 5T is associated with atypical forms of cystic fibrosis. The aim of this study was to establish the frequencies of F508del mutation and 5T allele in the CFTR gene in patients with chronic pancreatitis and pancreatic cancer, as well as to investigate whether these genetic variants represent risk factors for pancreatic diseases. The study has encompassed 50 patients with chronic pancreatitis and 50 patients with pancreatic adenocarcinoma, as well as 124 healthy individuals. The analysis of F508del mutation and alleles 5T, 7T and 9T of the polythymidine tract was performed on DNA extracted from periferal blood by PCR-mediated site-direted mutagenesis (PSM) method. The frequency of F508del mutation in the group of patients with chronic pancreatitis (3.0%) was significantly increased (p = 0.032) in comparison to the group of healthy individuals (0.4%), while other analyzed differences were not statistically significant. The results of this study indicate that F508del mutation in the CFTR gene respresents a risk factor for the development of chronic pancreatitis.


Effect of congestive heart failure on safety and efficacy of left atrial appendage closure in patients with non-valvular atrial fibrillation.
To evaluate the influence of congestive heart failure (CHF) on safety and efficacy of left atrial appendage closure (LAAC) in non-valvular atrial fibrillation (NVAF) patients. A total of 401 patients who consecutively underwent LAAC with Watchman and LAmbre devices were divided into CHF (85 cases) and non-CHF (316 cases) groups. Comparisons between groups were performed against data. No significant differences were found in implantation success and periprocedural complication rates between the two groups. During a mean 2.2 years of follow-up, the incidence rate of thromboembolism, major bleeding, device-related thrombus, and non-cardiovascular death was comparable. However, patients with CHF had significantly increased risk of all-cause death (P = 0.015), cardiovascular death (P = 0.014), and combined efficacy endpoints (P = 0.02). After performing propensity score matching, the risk of all-cause death (P = 0.01), cardiovascular death (P = 0.01), and combined efficacy endpoints (P = 0.006) was still higher. The logistic regression analyses identified CHF (OR: 3.642, 95% CI: 1.296-10.232, P = 0.014) as an independent predictor of cardiovascular death. Implantation of atrial appendage occluder is effective and safe in NVAF patients with CHF. The increased risk of mortality and combined efficacy endpoints in patients with CHF versus non-CHF after LAAC may be associated with the high risk of CHF itself.


Prevalence of vancomycin-resistant enterococci in hospitalized patients and those living in the community in the Czech Republic.
Between July 1, 2002 and December 31, 2003, rectal swabs from both hospitalized patients and community subjects in the Czech Republic were taken to ascertain the prevalence of vancomycin-resistant enterococci (VRE). The swabs were used for isolating and identifying enterococci and their susceptibility to antibiotics. Vancomycin resistance phenotypes were verified by PCR detection of vanA, vanB, vanC1 and vanC2 genes. A molecular biology analysis was performed in Enterococcus faecium VanA strains. During the observed period, 2691 rectal swabs from the hospitalized patients and 6529 rectal swabs from the subjects in community setting were examined. In total, 31 VRE of hospital origin and 13 community-population strains were isolated. The prevalence of VRE in the gastrointestinal tract was 1.9% in the hospitalized patients and 0.4% in the community subjects. The prevailing strains were Enterococcus faecium VanA (61.3%) in the VRE of hospital origin and Enterococcus gallinarum VanC (46.2%) in the community VRE. Mutual comparison between the hospital and community Enterococcus faecium VanA strains showed no similarity.


Salvage/adjuvant brachytherapy after ophthalmic artery chemosurgery for intraocular retinoblastoma.
To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemosurgery (OAC) for retinoblastoma. This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG). Brachytherapy was used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which 12 had localized vitreous seeding. No patients developed metastasis or died of retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95% confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an additional 6 eyes developed out-of-target volume recurrences, which were controlled with additional treatments. Patients with an ocular complication had a mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which was statistically less (P=.045) than patients without ocular complication who had a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG responses from pre- versus postplaque were unchanged or improved in more than half the eyes. Brachytherapy following OAC is effective, even in the presence of vitreous seeding; the majority of eyes maintained stable or improved retinal function following treatment, as assessed by ERG.


Knowledge of cervix cancer, human papilloma virus (HPV) and HPV vaccination at the moment of introduction of the vaccine in women in Belgium.
To test the knowledge of women, attending a gynecology clinic, on HPV, cervix cancer awareness and the knowledge and willingness to use HPV vaccine for themselves or their children. Routine gynecological and obstetrical care with ambulatory service in a medium-sized general hospital in a small town in Belgium (Heilig Hart Hospital, Tienen). Questionnaire to be filled out by 381 consecutive women while in the attendance room for consultation with one of the four gynecologists. Fisher T or Chi(2) were used as statistical methods. Knowledge about HPV as a cause of cervix cancer and the existence of a vaccine was roughly 50%. Women with lower education were more likely to know nothing about the cause of cervix cancer than women with higher education (54 versus 39%, P = 0.016). Half of the women were willing to accept the vaccine, whatever the cost price, and 40% required more information or refunding. Compared to women above 40, young age (25 years or less) was a risk factor for poor knowledge of HPV (P = 0.007), cervix cancer (P = 0.016) and the HPV vaccine (P = 0.07), regardless of a higher degree of education (79% postgraduate degree versus 43.4% in the 40+-year-old women, P = 0.006). Women with a daughter (64.7%) or a son (69.2%) were more inclined to vaccinate their daughter than women without children (46.3%, P < 0.0001). None of the women declined the vaccination because it was meant to protect against a sexually transmitted disease (STD). Upon introduction and marketing of the first HPV vaccine, only 50% of women attending a routine gynecology clinic were aware of the role of HPV in cervix cancer and the possibility of getting a vaccination against it. Unexpectedly, despite a high degree of education, young women seem to have a low awareness of cervix cancer, its cause and the preventive measures. Contrary to some women in the USA, Western European women are less likely to decline the HPV vaccine because it will protect them against STD. In Belgium, women who are childless or poorly educated and especially young women should be the targets of campaigns that motivate them to prevent HPV-induced cervix cancer.


Insomnia, fatigue and psychosocial well-being during COVID-19 pandemic: A cross-sectional survey of hospital nursing staff in the United States.
To describe the levels of insomnia, fatigue and intershift recovery, and psychological well-being (burnout, post-traumatic stress and psychological distress), and to examine differences in these measures based on work-related characteristics among nursing staff during COVID-19 pandemic in the United States. The COVID-19 pandemic has created a major physical and psychological burden on nursing staff in the United States and worldwide. A better understanding of these conditions will lead to tailored support and resources for nursing staff during and after the pandemic. Cross-sectional study. Hospital nurses and nursing assistants (N = 587) were recruited online between May-June 2020. The survey included measures on insomnia (Insomnia Severity Index) fatigue and intershift recovery (Occupational Fatigue and Exhaustion Recovery-15), burnout (Maslach Burnout Inventory-Human Services Survey), post-traumatic stress (Short Post-Traumatic Stress Disorder Rating Interview) and psychological distress (Patient Health Questionnaire-4), and questions on work and demographics. The STROBE checklist was followed for reporting. The sample had subthreshold insomnia, moderate-to-high chronic fatigue, high acute fatigue and low-to-moderate intershift recovery. The sample experienced increased emotional exhaustion and depersonalisation, increased personal accomplishment, moderate psychological distress and high post-traumatic stress. Nurses who cared for COVID-19 patients had significantly scored worse on almost all measures than their co-workers. Certain factors such as working hours per week and the frequency of 30-min breaks were significant. Nursing staff experienced poor sleep, fatigue and multiple psychological problems during the COVID-19 pandemic. Moreover, staff who were involved in the care of COVID-19 patients, worked more than 40 h per week and skipped 30-min breaks showed generally worse self-reported outcomes. Nursing administration is recommended to monitor for fatigue and distress on nursing units, re-visit current scheduling practices, reinforce rest breaks and provide access to mental health and sleep wellness resources with additional support for their front-line nursing groups.


Inhibition of pyruvate transport by fatty acids in isolated cells from rat small intestine.
1. A technique is described for the rapid separation of intestinal epithelial cells from the incubation medium by passage through a silicon-oil layer and collection in acid, in which their soluble constituents are released. 2. The inhibition by fatty acids of pyruvate oxidation is further studied. Measurement of pyruvate transport in epithelial cells at 0 degree C showed that short- and medium-chain fatty acids as well as ricinoleate inhibit this transport. Propionate inhibits pyruvate transport by another mechanism than octanoate. 3. Differences between pyruvate propionate and octanoate transport across the epithelial cell membrane were obtained in efflux studies. These studies revealed that acetate, propionate, butyrate and high concentrations of bicarbonate readily stimulate the efflux of pyruvate, probably by anionic counter-transport. No effects were seen with octanoate and hexanoate. The data obtained in these efflux studies suggest that lipophilicity and the pKa values of the monocarboxylic acids determine the contribution of non-ionic diffusion to overall transport. 4. Saturation kinetics, competitive inhibition by short-chain fatty acids and counter-transport suggest a carrier-mediated transport of pyruvate.


Tat-CCT2 Protects the Neurons from Ischemic Damage by Reducing Oxidative Stress and Activating Autophagic Removal of Damaged Protein in the Gerbil Hippocampus.
CCT2 is a eukaryotic chaperonin TCP-1 ring complex subunit that mediates protein folding, autophagosome incorporation, and protein aggregation. In this study, we investigated the effects of CCT on oxidative and ischemic damage using in vitro and in vivo experimental models. The Tat-CCT2 fusion protein was efficiently delivered into HT22 cells in a concentration- and time-dependent manner, and the delivered protein was gradually degraded in HT22 cells. Incubation with Tat-CCT2 significantly ameliorated the 200 µM hydrogen peroxide (H2O2)-induced reduction in cell viability in a concentration-dependent manner, and 8 µM Tat-CCT2 treatment significantly alleviated H2O2-induced DNA fragmentation and reactive oxygen species formation in HT22 cells. In gerbils, CCT2 protein was efficiently delivered into pyramidal cells in CA1 region by intraperitoneally injecting 0.5 mg/kg Tat-CCT2, as opposed to control CCT2. In addition, treatment with 0.2 or 0.5 mg/kg Tat-CCT2 mitigated ischemia-induced hyperlocomotive activity 1 d after ischemia and confirmed the neuroprotective effects by NeuN immunohistochemistry in the hippocampal CA1 region 4 d after ischemia. Tat-CCT2 treatment significantly reduced the ischemia-induced activation of astrocytes and microglia in the hippocampal CA1 region 4 d after ischemia. Furthermore, treatment with 0.2 or 0.5 mg/kg Tat-CCT2 facilitated ischemia-induced autophagic activity and ameliorated ischemia-induced autophagic initiation in the hippocampus 1 d after ischemia based on western blotting for LC3B and Beclin-1, respectively. Levels of p62, an autophagic substrate, significantly increased in the hippocampus following treatment with Tat-CCT2. These results suggested that Tat-CCT2 exerts neuroprotective effects against oxidative stress and ischemic damage by promoting the autophagic removal of damaged proteins or organelles.


A cross-sectional study on food patterns and adiposity among individuals with abnormal glucose homeostasis.
Dietary habits play an important role in the prevention of chronic disease; however, few studies have assessed the major dietary patterns in Middle Eastern countries. This study identifies major dietary patterns among Iranian people with abnormal glucose homeostasis. This cross-sectional study was conducted at the Diabetes Research Center, Isfahan, Iran among 425 subjects with abnormal glucose homeostasis. Patients were of ages 35 - 55 years and had family histories of diabetes. We assessed dietary intake by the use of a food frequency questionnaire (FFQ) that contained 39 food items. General obesity was defined as a BMI ≥ 30 kg/m2 and central obesity was defined as waist circumference (WC) ≥ 88 in women and WC ≥ 102 in men. Five major dietary patterns were revealed by factor analysis: 'western', 'healthy', 'vegetarian', 'high-fat dairy', and 'chicken and plants'. Those in the top tertile of the 'western pattern' had greater odds for general (OR = 1.73; 95% CI = 1.07 - 2.78) and central obesity (OR = 2, 95% CI = 1.24 - 3.22), however these associations were not significant after adjustment for confounding variables. The 'high-fat dairy pattern' was associated with greater odds of general obesity only after adjusting for confounding variables (OR = 1.73; 95%CI = 1.01 - 2.96). The dietary pattern characterized by high intake of hydrogenated fat and sugar was shown to be positively associated with a risk of general and central obesity, however further prospective studies are required to confirm our findings.


Fluorescence of NBD-labelled troponin-I as a probe for the kinetics of thin filament activation in skeletal muscle fibers.
Using fluorescence of NBD-labelled troponin I incorporated into skinned fibers of the rabbit psoas muscle by chasing native troponin by troponin with the NBD-labelled TnI subunit we attempted to study kinetics of thin filament activation at different Ca(++)-concentrations. Since fluorescence of NBD-labelled TnI is sensitive to both, changes in Ca++, and strong cross-bridge attachment, we were able to induce changes thin filament activation by rapidly dropping the fraction of strongly attached cross-bridges to very low levels, e.g. by switching from isometric to isotonic contraction conditions. At any [Ca++], the time course of the resulting changes in fluorescence of NBD-labelled TnI was found at least an order of magnitude faster than the time course of force redevelopment subsequent to the period of isotonic contraction. Modelling shows that with the kinetics of thin filament activation derived from these studies, common kinetic schemes of the actomyosin ATPase predict regulation to act via changes in cross-bridge cycling kinetics, as we had previously proposed.


Multicenter reperfusion trial of intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in acute myocardial infarction: controlled comparison with intracoronary streptokinase.
The recent establishment of a firm therapeutic role for reperfusion in acute myocardial infarction has stimulated interest in the development of more ideal thrombolytic agents. Anisoylated plasminogen streptokinase activator complex (APSAC) is a new plasminogen activator possessing properties that are promising for intravenous thrombolytic application in acute myocardial infarction. To assess the reperfusion potential of intravenous APSAC, a multi-center, angiographically controlled reperfusion trial was performed. An approved thrombolytic regimen of intracoronary streptokinase served as a control. Consenting patients with clinical and electrocardiographic signs of acute myocardial infarction were studied angiographically and 240 qualifying patients with documented coronary occlusion (flow grade 0 or 1) were randomized to treatment in less than 6 h of symptom onset (mean 3.4 h, range 0.4 to 6.0) with either intravenous APSAC (30 U in 2 to 4 min) or intracoronary streptokinase (160,000 U over 60 min). Both groups also received heparin for greater than or equal to 24 h. Reperfusion was evaluated angiographically over 90 min and success was defined as advancement of grade 0 or 1 to grade 2 or 3 flow. Rates of reperfusion for the two treatment regimens were 51% (59 of 115) at 90 min after intravenous APSAC and 60% (67 of 111) after 60 min of intracoronary streptokinase (p less than or equal to 0.18). Reperfusion at any time within the 90 min was observed in 55 and 64%, respectively (p less than or equal to 0.16). Time to reperfusion occurred at 43 +/- 23 min after intravenous and 31 +/- 17 min after intracoronary therapy. The success of intravenous therapy was dependent on the time to treatment: 60% of APSAC patients treated within 4 h exhibited reperfusion compared with 33% of those treated after 4 h (p less than or equal to 0.01). Reperfusion rates were also dependent on initial flow grade (p less than or equal to 0.0001): 48% (81 of 168) for grade 0 (APSAC = 43%, streptokinase = 54%), but 78% for grade 1 (APSAC = 78%, streptokinase = 77%). APSAC given as a rapid injection was generally well tolerated, although the median change in blood pressure at 2 to 4 min was greater after APSAC than after streptokinase (-10 versus -5 mm Hg). Mean plasma fibrogen levels fell more at 90 min after the sixfold higher dose of APSAC than after streptokinase (to 32 versus 64% of control). Reported bleeding events were more frequent after APSAC but occurred primarily at the site of catheter insertion and no event was intracranial.(ABSTRACT TRUNCATED AT 400 WORDS)


Preeclampsia is not associated with elevated muscle sympathetic reactivity.
To determine whether increased chemoreflex tonic activity is associated with augmented muscle sympathetic nervous system activity (MSNA) in women diagnosed with preeclampsia. Women with preeclampsia (n = 19; 32 ± 5 yr old, 31 ± 3 wk of gestation) were matched by age and gestational age with pregnant women (controls, n = 38, 32 ± 4 yr old, 31 ± 4 wk gestation; 2:1 ratio). MSNA (n = 9 preeclampsia) was assessed during baseline, peripheral chemoreflex deactivation (hyperoxia), and a cold pressor test (CPT). Baroreflex gain and diastolic blood pressure at which there is a 50% likelihood of MSNA occurring (T50) and plasma noradrenaline concentrations were measured. Baseline mean arterial pressure (MAP: 106 ± 11 vs. 87 ± 10 mmHg, P < 0.0001), noradrenaline concentrations (498 ± 152 pg/mL vs. 326 ± 147, P = 0.001), and T50 (79 ± 7 vs. 71 ± 9 mmHg, P = 0.02) were greater in women with preeclampsia than in controls. However, baseline MSNA (burst incidence [BI]: 41 ± 16 vs. 45 ± 13 bursts/100 hb, P = 0.4) was not different between groups. Responses to hyperoxia (ΔBI -5 ± 7 vs. -1 ± 8 bursts/100 hb, P = 0.1; ΔMAP -1 ± 3 vs. -2 ± 3 mmHg, P = 0.7) and CPT (ΔBI 15 ± 7 vs. 12 ± 11 bursts/100 hb, P = 0.6; ΔMAP 10 ± 4 vs. 12 ± 11 mmHg, P = 0.6) were not different between groups. Our findings question the assumption that increased MSNA contributes to hypertension in women with preeclampsia. The chemoreflex does not appear to contribute to an increase in MSNA in women with preeclampsia.NEW & NOTEWORTHY We wanted to determine whether increased chemoreflex tonic activity is associated with augmented muscle sympathetic nervous system activity (MSNA) in women diagnosed with preeclampsia. The chemoreflex does not contribute to increased MSNA in women with preeclampsia. Our data also challenge the belief that preeclampsia is associated with sympathetic neural hyperactivity. Thus, targeting sympathetic neural hyperactivity as therapeutic strategy is unlikely to be the most efficacious approach to treatment and management.


Preexposure during or following adolescence differently affects nicotine-rewarding properties in adult rats.
Many people come in contact with psychoactive drugs, yet not all of them become addicts. Epidemiology shows that a late approach with cigarette smoking is associated with a lower probability to develop nicotine dependence. Exposure to nicotine during periadolescence, but not similar exposure in the postadolescent period, increases nicotine self-administration in rats, but underlying mechanisms remain poorly understood. We investigated whether exposure to nicotine during or after adolescence would alter rewarding properties of the same drug at adulthood, as assessed by place conditioning. Periadolescent (PND 34-43) or postadolescent (PND 60-69) rats were injected with saline or nicotine (0.4 mg kg(-1)) for 10 days. The rats received three pairings with saline and three pairings with nicotine (0, 0.3, or 0.6 mg kg(-1)) 5 weeks after pretreatment. The rats were then tested for place conditioning in a drug-free state. Upon first exposure to the apparatus, animals pretreated with nicotine during adolescence showed elevated novelty-induced activation. The 0.3 (but not the 0.6) mg kg(-1) dose failed to produce both ongoing locomotor sensitization and place conditioning in animals pretreated with nicotine following adolescence. This suggests a rightward shift in the dose-response curve, namely, a reduced efficacy of nicotine. Conversely, the same dose was effective in saline-pretreated controls and noteworthy in rats pretreated during adolescence. Exposure following the adolescent period might diminish the risk to develop nicotine dependence. As for human implications, findings are consistent with a reduced vulnerability to nicotine addiction in people who start smoking late in their life.


Molecular determinants of protein evolvability.
The plethora of biological functions that sustain life is rooted in the remarkable evolvability of proteins. An emerging view highlights the importance of a protein's initial state in dictating evolutionary success. A deeper comprehension of the mechanisms that govern the evolvability of these initial states can provide invaluable insights into protein evolution. In this review, we describe several molecular determinants of protein evolvability, unveiled by experimental evolution and ancestral sequence reconstruction studies. We further discuss how genetic variation and epistasis can promote or constrain functional innovation and suggest putative underlying mechanisms. By establishing a clear framework for these determinants, we provide potential indicators enabling the forecast of suitable evolutionary starting points and delineate molecular mechanisms in need of deeper exploration.


Monoamines in the parabrachial nucleus of the cardiomyopathic hamster.
The development of dystrophic cardiac muscle is related to increases in sympathetic nervous system activity but little is known regarding possible central neural mechanisms that may be involved in cardiomyopathy. The inbred cardiomyopathic hamster is an animal model for studying the development and mechanisms of necrosis in cardiac muscle which resemble non-vascular myocardial diseases of man. Because monoamines are known to play a major role in central regulation of the cardiovascular system, we compared the distribution and density of tyrosine hydroxylase (TH) and 5-hydroxytryptamine (5-HT) immunostaining in the brains of cardiomyopathic hamsters (strain CHF-146), a related strain (CHF-148) of non-cardiomyopathic albino hamsters, and golden Syrian hamsters for possible differences in neurochemical organization. At the time of sacrifice, the cardiomyopathic hamsters exhibit small, calcified lesions on the surface of the ventricular cardiac muscle (early necrotic phase). Brain sections from each group were processed identically and simultaneously. The results show that there were significant differences among strains in the parabrachial nucleus with respect to the two neurochemicals examined. In golden Syrian and albino hamsters, TH and 5-HT immunoreactive axons were lightly-to-moderately stained in the lateral parabrachial nucleus. In the cardiomyopathic hamster, there were significantly more densely stained TH and 5-HT immunoreactive axons in the lateral parabrachial nucleus, in particular the inner part of the external lateral subnucleus. Because the lateral parabrachial nucleus, including the external lateral subnucleus, is known to be involved in regulation of the cardiovascular system, the differential distribution of TH and 5-HT in the parabrachial nucleus of cardiomyopathic hamsters in comparison to normal hamsters suggests that the parabrachial nucleus could be involved in sympathetic mechanisms related to the development of necrosis in cardiac muscle of the cardiomyopathic hamster.


Yeast as Models of Mitotic Fidelity.
Chromosome missegregation leads to aneuploidy which is defined as the cellular state of having a chromosome count that is not an exact multiple of the haploid number. Aneuploidy is associated with human diseases including mental retardation, neurodegenerative diseases and cancer. In addition, aneuploidy is the major cause of spontaneous abortions and its occurrence increases with aging. Therefore, it is important to understand the molecular mechanisms by which cells respond and adapt to aneuploidy. Saccharomyces cerevisiae has proven to be a good model to study the effects aneuploidy elicits on cellular homeostasis and physiology. This chapter focuses on the current understanding of how the yeast S. cerevisiae responds to the acquisition of extra chromosomes and highlights how studies in aneuploid yeasts provide insights onto the effects of aneuploidy in human cells.


The challenges to ophthalmologic follow-up care in at-risk pediatric populations.
To identify barriers to ophthalmological follow-up in high-risk children who are identified by vision screening and eye examination. The records of patients identified as needing follow-up through two free eye care programs (organized optometric and ophthalmologic screening sessions aimed at identifying and treating ocular pathology) targeted toward inner-city youths of low socioeconomic status were reviewed. Parents were contacted by phone, and a questionnaire on barriers to follow-up was administered. Callers attempted to schedule appointments at that time. Data were assessed by means of descriptive analysis. Of 93 patients, 54 (58%), were successfully contacted. Of these, 23 (25%) were eventually scheduled. Five (5%) patients elected follow-up elsewhere. Twenty (22%) with working phones were still unable to be scheduled. Additional obstacles included families' lack of awareness of the need for follow-up (13%), assumption by families that they would be contacted (5%), scheduling conflicts (4%), concerns about insurance, and difficulty finalizing referrals (2%). A total of 39 patients (42%) were not successfully contacted because of inoperable phone services, and none of the families responded to the mailed questionnaire. Inability to contact families was the greatest barrier to follow-up. Our findings suggest that immediate arrangement of follow-up care, on-site visual assessment, and a program director may be useful in increasing follow-up for high-risk children.


Can the response to a platinum-based therapy be predicted by the DNA repair status in non-small cell lung cancer?
Preclinical evidence has been accumulating on the impact of the DNA repair status on the sensitivity/resistance to anticancer agents in different tumor types, including lung cancer. The possibility to predict the response to therapy, and specifically to platinum agents, based on tumor specific DNA repair functionality would enable to tailor its use only in those patients with maximum chances to respond, avoiding the burden of toxicity in those ones with lesser chances. We here reviewed the clinical evidence on the prognostic role of DNA repair markers and/or functional assays in predicting the response to a platinum-based chemotherapy in lung cancer patients. Consequently, we focused on those proteins involved in pathways repairing platinum induced DNA inter-strand and intra-strand crosslinks. Most promising clinical trials targeting the nucleotide repair protein ERCC1 in non-small cell lung cancer later on suffered from serious drawbacks. Nevertheless, these results spurred a variety of preclinical studies on a multitude of alternative DNA repair markers. However so far, no one of the analyzed DNA repair markers can be considered a reliable and mature biomarker for selecting patients. We discuss the reasons for such failure which discloses novel strategies for the future.


Growth factors in the eye.
In this review we report the distribution and functional significance of growth factors in the eye. Representatives of the major growth factor families are found in the eye: fibroblast growth factor, insulin and insulin-like growth factor, transforming growth factor-beta, platelet-derived growth factor, nerve growth factor, epidermal growth factor and colony-stimulating factor. There are numerous examples of their actions on ocular tissues in vitro and in some cases in vivo. The findings presented clearly illustrate that a growth factor can elicit different responses depending on the context of its action; the cell type involved, the concentration of the growth factor and the presence or absence of other growth factors can all influence the cellular response both quantitatively and qualitatively. The results of these studies in the eye are of general significance to our understanding of the role of growth factors in biological processes.


Myelitis with flaccid paralysis due to Japanese encephalitis: case report and review of the literature.
Japanese encephalitis is an arthropod-borne zoonotic flavivirus infection endemic to tropical and subtropical Asia. A minority of infections leads to a symptomatic course, but affected patients often develop life-threatening encephalitis with severe sequelae. Myelitis with flaccid paralysis is a rare complication of Japanese Encephalitis, which-according to our literature search-was reported in 27 cases, some of which were published as case reports and others as case series. Overall, there is a broad clinical spectrum with typically asymmetric manifestation and partly severe motor sequelae and partly mild courses. Lower limb paralysis appears to be more frequent than upper limb paralysis. An encephalitic component is not apparent in all cases CASE PRESENTATION: We herein add the case of a 29 year-old female who developed encephalitis and myelitis with flaccid paralysis during a long-time stay in Indonesia. Diagnostic workup in Indonesia did not clearly reveal an underlying cause. Upon clinical stabilization, the patient was evacuated to her home country Germany, where further diagnostics confirmed Japanese encephalitis virus as the causative agent. The patient has partly recovered, but still suffers from residual paralysis of the upper limb. Flaccid paralysis is a rare, and likely underdiagnosed complication of Japanese encephalitis, which, to the best of our knowledge, has never been diagnosed outside endemic areas before.


Significant Morbidity and Mortality Among Hospitalized End-Stage Liver Disease Patients in Medicare.
For end-stage liver disease (ESLD) patients, care focuses on managing the life-threatening complications of portal hypertension, causing high resource utilization. To describe the end-of-life trajectory of hospitalized ESLD patients in Medicare. Using a 5% random sample of Medicare fee-for-service beneficiaries, we performed a retrospective cohort study, identifying hospitalized ESLD and heart failure (HF) patients (2007-2011). Index hospitalization end points included mortality, discharge to hospice, and length of stay. Postdischarge end points included all-cause mortality, rehospitalization, hospice enrollment, and days alive and out of hospital (DAOH). Follow-up was at one and three years after index hospitalization discharge. A reference cohort of decompensated HF patients was used for baseline comparison. At one year, the ESLD cohort (n = 22,311) had 209 DAOH; decompensated HF (n = 85,397) had 252 DAOH. Among ESLD patients, inpatient mortality was 13.5%; all-cause mortality was 64.9%. For these outcomes, rates were higher in those with ESLD than HF. In the ESLD group, rehospitalization rate was 59.1% (slightly lower than the HF group), hospice enrollment rate was 36.1%, and there were higher than expected cancer rates. For hospice-enrolled patients, the median length of time spent in hospice was nine days. The HF cohort had lower hospice enrollment, but more days enrolled. The results of this study show that morbidity and mortality rates associated with end of life in ESLD are substantial. There is an acute need for alternative approaches to manage the care of ESLD patients.


Impact of a comprehensive cardiac rehabilitation programme versus coronary revascularisation in patients with stable angina pectoris: study protocol for the PRO-FIT randomised controlled trial.
Currently, in the majority of patients with stable angina pectoris (SAP) treatment consists of optimal medical treatment, potentially followed by coronary angiography and subsequent coronary revascularisation if necessary". Recent work questioned the effectiveness of these invasive procedures in reducing re-events and improving prognosis. The potential of exercise-based cardiac rehabilitation on clinical outcomes in patients with coronary artery disease is well-known. However, in the modern era, no studies compared the effects of cardiac rehabilitation versus coronary revascularisation in patients with SAP. In this multicentre randomised controlled trial, 216 patients with stable angina pectoris and residual anginal complaints under optimal medical treatment will be randomised to: 1) usual care (i.e., coronary revascularisation), or 2) a 12-month cardiac rehabilitation (CR) programme. CR consists of a multidisciplinary intervention, including education, exercise training, lifestyle coaching and a dietary intervention with a stepped decline in supervision. The primary outcome will be anginal complaints (Seattle Angina Questionnaire-7) following the 12-month intervention. Secondary outcomes include cost-effectiveness, ischemic threshold during exercise, cardiovascular events, exercise capacity, quality of life and psychosocial wellbeing. In this study, we will examine the hypothesis that multidisciplinary CR is at least equally effective in reducing anginal complaints as the contemporary invasive approach at 12-months follow-up for patients with SAP. If proven successful, this study will have significant impact on the treatment of patients with SAP as multidisciplinary CR is a less invasive and potentially less costly and better sustainable treatment than coronary revascularisations. Netherlands Trial Register, NL9537. Registered 14 June 2021.


Assessment of Neurology Residency Program Websites across North America during COVID-19.
With virtual interviews for residency applications, residency program websites have become increasingly important resources for applicants. We evaluated the comprehensiveness of US and Canadian neurology residency program website, comparing this to published rankings of the best neurology and neurosurgery hospitals (for US programs) and number of residency positions (for US and Canadian programs). US program websites were found to be largely more comprehensive than Canadian websites, more extensive websites were associated with better program rankings and fewer residency seats in the US, and US regional differences in comprehensiveness were present. We recommend standardized guidelines to increase website comprehensiveness across programs.


Evaluation of patients presenting with febrile seizures in an Iranian referral hospital: emphasis on the frequency of meningitis and co-infections.
Febrile seizures are one of the most common diseases that physicians encounter in pediatric emergency departments. Two important aspects of managing patients presenting with a febrile seizure are meningitis exclusion and co-infection investigation. This study was designed to determine any infection that occurs concomitantly with a febrile seizure episode and also to assess the frequency of meningitis among children presenting with febrile seizures. This retrospective cross-sectional study was conducted at the Children's Medical Center, an Iranian pediatric referral hospital. All patients aged 6 months to 5 years presenting with febrile seizures from 2020 to 2021 were included. Patients' data were collected from the medical report files. The presence of respiratory, gastrointestinal, and urinary infections was evaluated. Moreover, the detection of SARS-CoV-2 using reverse transcription polymerase chain reaction (RT-PCR) was performed for suspicious cases. The results of urine and stool analysis, as well as blood, urine, and stool cultures were checked. The frequency of lumbar puncture (LP) performance and its results were studied. The relationship between white blood cells (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein in meningitis was evaluated. A total of 290 patients were referred to the Children's Medical Center, Tehran, Iran, due to fever and seizures. The mean age of the patients was 21.5 ± 13.0 months, and 134 (46.2%) were female. Out of 290 patients, 17% presented with respiratory infections. Nasopharyngeal SARS-CoV-2 RT-PCR was requested for 50 patients (17%), of which nine (3%) were reported positive and two patients had multi-inflammatory syndrome in children (MIS-C). Fever without local signs, gastroenteritis, and urinary tract infections were found in 40%, 19%, and 14% of the patients, respectively. LP was requested for 97 participants (33.4%) to evaluate central nervous system infection, of which 22 cases were suggestive of aseptic meningitis. Among laboratory tests, leukocytosis was significantly related to aseptic meningitis (odds ratio = 11.1, 95% CI = 3.0- 41.5). The blood culture testing result was positive in seven patients; all of them were due to skin contamination. Evaluation of patients for possible meningitis is necessary for febrile seizure management. Although the prevalence of bacterial meningitis in these patients is not high, according to this study and other studies conducted in Iran, aseptic meningitis, especially after Measles, Mumps, and Rubella (MMR) vaccination should be considered. Leukocytosis and increased CRP can predict the occurrence of aseptic meningitis in these patients. However, further studies with a larger sample size are highly recommended. Moreover, during the COVID-19 pandemic, it is recommended to pay attention to an acute COVID-19 infection or evidence of MIS-C in children with fever and seizure.


Preparation and evaluation of solid-phase microextraction fibers based on monolithic molecularly imprinted polymers for selective extraction of diacetylmorphine and analogous compounds.
All of the studies on solid-phase microextraction based on molecularly imprinted polymers up to now have been carried out on the synthesis of the polymer on the surface of the fiber which is brittle and the polymer coating strips during handling. The objective of this study was to develop a method for fabrication of a monolithic and robust solid-phase microextraction fiber on the basis of molecularly imprinted polymer for selective extraction of diacetylmorphine and its structural analogues followed by their GC or GC/MS analysis. A fiber was produced by copolymerization of methacrylic acid-ethylene glycol dimethacrylate imprinted with diacetylmorphine. The effective factors influencing the polymerization have been investigated and are detailed here. Also, the influences of pH, extraction time and temperature on the extraction efficiency of analytes were investigated. The prepared fiber was thermally stable up to 300 degrees C which has vital importance in SPME coupled with GC or GC/MS. The adsorption isotherm modeling was performed by fitting the data of studied compounds to bi-Langmuir isotherm model. The evaluated equilibrium constants for diacetylmorphine were 0.011 and 1824.72 microM(-1), and the number of binding sites was 170.37 and 4.64 nmolg(-1), respectively. This fiber was successfully used for extraction of template molecule from aqueous solution and further analysis with GC or GC/MS. The high extraction efficiency was obtained for diacetylmorphine, 6-monoacetylcodeine, and 6-monoacetylmorphine, yielding the detection limits of 300, 47, and 1 ngmL(-1), respectively.


Perfusing and ventilating the patient's lungs during bypass ameliorates the increase in extravascular thermal volume after coronary bypass grafting.
To test the hypothesis that bilateral extracorporeal circulation (ECC) (Drew technique) ameliorates the increase in extravascular thermal volume (ETV) observed after conventional cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting. Thirty-four consecutive patients underwent either bilateral ECC (n = 24, additional cannulation of pulmonary artery and left atrium and lungs perfused and ventilated during bypass) or conventional CPB (n = 10, right atrial and aortic cannulation, lungs statically inflated to 4 mbar (0.41 cm H(2)O) with oxygen, 500 mL/min). Determinations of ETV (thermodye dilution technique) and intraoperative fluid balance were made before surgery, at the end of surgery, and 4 hours thereafter. In addition, interleukin (IL)-8, thromboxane B2 (TxB(2)), and endothelin (ET)-1 concentrations were measured in the right atrium and pulmonary vein at specified time points. Comparisons of ETV made at the start of surgery, after aortic declamping, and after termination of ECC, respectively, revealed an increase from 4.8 +/- 0.2 mL/kg (mean +/- SEM) to 6.7 +/- 0.4 mL/kg, and 6.3 +/- 0.3 mL/kg with conventional CPB but ETV remained unchanged at 5.2 +/- 0.3 mL/kg, 5.1 +/- 0.2 mL/kg, and 4.9 +/- 0.3 mL/kg with bilateral ECC. Priming volume (1,580 +/- 10 mL versus 2,213 +/- 77 mL, p < 0.001) and intraoperative fluid balance (+1,955 +/- 233 mL versus +2,654 +/- 210 mL, p < 0.05) were less with conventional CPB. Concentrations of IL-8, TxB(2), and ET-1 were not different between groups. Despite a significantly greater prime volume and a more positive intraoperative fluid balance, ETV did not change with bilateral ECC but increased with conventional CPB. Thus, using the patient's lungs as an oxygenator during bypass mitigates the increase in extravascular pulmonary fluid.