Contribution of axial arm rotation to humeral head translation.
The contribution of axial arm rotation to translation of the humeral head with the arm in the hanging position was examined using nine fresh-frozen cadaveric shoulders. Three standard clinical tests were simulated: anterior and posterior translation and sulcus tests. In both the anterior translation and sulcus tests, anterior and inferior displacements were significantly restricted in internal rotation but not in neutral and external rotation. In the posterior translation test, no significant differences in displacement could be observed in internal, neutral, or external rotation. Since anterior and inferior translations of the humeral head were significantly affected by the rotation of the arm, we recommend that the anterior translation and sulcus tests be performed in various rotations.


Intravenous Magnesium: Prompt Use for Asthma in Children Treated in the Emergency Department (IMPACT-ED): Protocol for a Multicenter Pilot Randomized Controlled Trial.
Children managed for asthma in an emergency department (ED) may be less likely to be hospitalized if they receive intravenous magnesium sulfate (IVMg). Asthma guidelines recommend IVMg for severely sick children but note a lack of evidence to support this recommendation. All previous trials of IVMg in children with asthma have been too small to answer whether IVMg is effective and safe. A few major questions remain about IVMg. First, it has not been tested early in the course of ED treatment, when the impact on hospitalization would be greatest. Second, the clinical impact of hypotension, a known adverse effect of IVMg, has not been well characterized in previous research. Third, no trials have compared different IVMg doses or serial serum magnesium (total and ionized) concentrations to optimize dosing, so the most effective dose is unknown. A large, conclusive, randomized, placebo-controlled clinical trial of IVMg might be challenging due to the need to enroll and complete study procedures quickly, a lack of understanding of blood pressure changes after IVMg, and a lack of pharmacologic information to guide the optimal doses of IVMg to be tested. Therefore, a pilot study to inform the above gaps is warranted before conducting a definitive trial. The objectives of this study are to (1) demonstrate the feasibility of enrolling children with severe acute asthma in the ED in a multicenter, randomized controlled trial of a placebo, low-dose IVMg, or high-dose IVMg; (2) demonstrate the feasibility of timely delivery of study medication, assessment of blood pressure, and evaluation of adverse events in a standardized protocol; and (3) externally validate a previously constructed pharmacokinetic model and develop a combined pharmacokinetic/pharmacodynamic model for IVMg using magnesium (total and ionized) serum concentrations and their correlation with measures of efficacy and safety. This pilot trial tests procedures and gathers information to plan a definitive trial. The pilot trial will enroll as many as 90 children across 3 sites, randomize each child to 1 of 3 study arms, measure blood pressure frequently, and collect 3 blood samples from each participant with corresponding clinical asthma scores. The project was funded by the National Heart, Lung, and Blood Institute (1 R34HL152047-2) in March 2022. Enrollment began in September 2022, and 43 children have been enrolled as of April 2023. We will submit the results for publication in late 2023. The results of this study will guide the planning of a large, definitive, multicenter trial powered to evaluate if IVMg reduces hospitalization. Blood pressure measurements will inform a monitoring plan for the larger trial, and blood samples and asthma scores will be used to validate pharmacologic models to select the optimal dose of IVMg to be evaluated in the definitive trial. ClinicalTrials.gov NCT05166811; https://clinicaltrials.gov/ct2/show/NCT05166811. DERR1-10.2196/48302.


Combination therapy with lamivudine and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker for hepatitis B virus-associated glomerulonephritis with mild to moderate proteinuria: a clinical review of 38 cases.
The treatment of HBV-associated glomerulonephritis (HBV-GN) is still a challenge in clinical practice now. The objective of this study was to report the pathological characteristics of HBV-GN presenting with mild to moderate proteinuria and to evaluate the therapeutic efficacy of lamivudine (LAM) in combination with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) as compared to ACEI/ARB monotherapy. We conducted a retrospective observational study in HBV-GN patients between 2005 and 2014. The patients were classified into two groups: Group 1 included patients treated with LAM plus ACEI/ARB (n = 20), and group 2, patients treated with ACEI/ARB alone (n = 18). Their clinical and pathological characteristics were collected; we analyzed the therapeutic responses and assessed the correlation between renal and liver pathologies. Our results showed that the most common type of HBV-GN was IgA nephropathy. LAM plus ACEI/ARB therapy was better in reducing 24-h urinary protein excretion, alanine aminotransferase, and aspartate aminotransferase levels, while maintaining the level of kidney function. The proportion of patients who achieved remission (CR + PR) was higher in the LAM plus ACEI/ARB group than in the ACEI/ARB monotherapy group (χ 2 = 5.371, P = 0.035). In the HBV-GN patients with mild to moderate proteinuria, LAM plus ACEI/ARB not only improved liver function but also better reduced 24-h proteinuria.


[Imaging methods].
A number of abnormalities of the shoulder joint can cause pain or dysfunction. Imaging of this complex joint is demanding. Standard radiographs are considered to represent the basis of all imaging. For more detailed diagnoses, especially concerning soft tissue, more advanced imaging methods are required. Standard arthrography (without combination with either CT or MRI) is rarely indicated anymore. Bone scintigraphy is another imaging method with limited use in shoulder joint abnormalities (neoplasm, infection, occult fracture). Sonography is useful in abnormalities of the rotator cuff and the biceps tendon. This method is commonly employed for screening. CT is useful in the demonstration of complex fractures. CT arthrography is indicated in instability of the glenohumeral joint and is competing with MR arthrography. MRI and MR arthrography are the imaging method of choice for many indications, mainly due to their free choice of imaging planes and excellent contrast resolution. These methods provide the most detailed diagnosis mainly with regard to abnormalities of the rotator cuff (partial versus intact or full-thickness tears) and the biceps tendon and are useful in the assessment of instability.


Rate constants for the reaction of cl with a series of C4 to C6 ketones using the relative rate method.
Rate constants for the reaction of Cl with eight ketones were measured relative to the rate constant of propane in approximately 900 Torr of N2 at ambient temperature. Experiments were carried out in a Pyrex reactor with GC analysis of the consumption of the ketones and propane. Chlorine atoms were generated by irradiation of Cl2 in the initial mixture using a black-light-blue fluorescent lamp. The rate constants determined in these experiments (10-11 cm3 molecule-1 s-1) are: butanone (3.8 +/- 0.3); 2-pentanone (11.6 +/- 1.0); 3-pentanone (8.3 +/- 0.7); 2-hexanone (19.4 +/- 1.9); 3-hexanone (15.3 +/- 1.1); cyclopentanone (10.4 +/- 0.9); 3-methyl-2-butanone (6.2 +/- 0.5); and 4-methyl-2-pentanone (12.8 +/- 1.0). The results for 2-pentanone, 3-pentanone, 2-hexanone, 3-hexanone, 3-methyl-2-butanone, and 4-methyl-2-pentanone are significantly higher (by a factor of 3 for 2-hexanone) than reported in two previous absolute rate studies. The likely explanation for this discrepancy is discussed.


Two-stage management of mega occipito-encephalocele.
We report three cases of large occipito-encephaloceles that were managed in the Neurosciences Unit, Hospital Universiti Sains Malaysia over the last 5 years. All patients had pre-operative MRI (magnetic resonance imaging) evolution and mapping of the sagittal sinus tract. The cerebrospinal fluid (CSF) of all three patients were initially diverted by means of ventricular shunt two weeks prior to shunt removal. The slow drainage of CSF prevented electrolyte and volume disturbances due to sudden decompression during their definitive occipital encephalocele operations. After 3 years follow-up, all these patients are progressing well.


Assessment of malnutrition in hip fracture patients: effects on surgical delay, hospital stay and mortality.
The importance of malnutrition in elderly hip fracture patients has long been recognised. All patients operated upon for a hip fracture over a five-year period were assessed according to two nutritional markers : a) serum albumin levels and b) peripheral blood total lymphocyte count. Patients were subdivided into groups according to the four possible combinations of these results. Outcomes according to four clinical outcome parameters were validated: a) waiting time to operation b) length of hospitalisation, c) in-hospital mortality, and d) one-year postoperative mortality. Significant differences were found between malnourished patients and those with normal laboratory values with regard to surgical delay and one year postoperative mortality. Malnourished patients were also more likely to be hospitalised longer than a month and to die during their hospital stay, but the difference was not significant. The combination of serum albumin level and total lymphocyte count can be used as an independent prognostic factor in hip fracture patients.


The role of the father in child sleep disturbance: child, parent, and parent-child relationship.
The majority of studies on child sleep problems focus primarily on mothers, neglecting paternal influences. Guided by the transactional framework, we explored how child temperament, paternal and maternal stress, and the parent-child interactions differ between families having children with sleep disturbances and a selected comparison group. The role of paternal involvement in child caregiving as a moderator of these differences was assessed. The sample consisted of 51 children (1-3 years old) and their mothers and fathers. Data were collected during home visits, when mothers and fathers completed questionnaires and were interviewed. In addition, mother-child and father-child interactions were videotaped. Results indicate that compared to the comparison group, fathers rated children with sleep disturbances as fussier, both their mothers and fathers experienced higher levels of stress, and reported using more bedtime interactions that interfere with child's sleep-wake self-regulation. In addition, their fathers were less sensitive during father-child interaction and less involved in child caregiving. Finally, paternal involvement moderated the group differences seen in maternal stress, suggesting that high paternal involvement acted as a buffer to protect parents of children with sleep disturbances from experiencing parental stress. The important role of fathers in families having children with sleep disturbances is discussed.


Postoperative Opioid Consumption is Greater after Simultaneous versus Staged Bilateral Total Knee Arthroplasty.
Increased exposure to opioids around total knee arthroplasty (TKA) can lead to a risk of long-term dependence. We hypothesized that performing simultaneous bilateral total knee arthroplasty (simBTKA) over staged surgery (staged bilateral total knee arthroplasty [stgBTKA]) may decrease the total amount of opiates used. We retrospectively reviewed 29 patients who underwent simBTKAs performed between February 2015 and November 2020 and identified 23 that did not use opioids ≤90 days prior to surgery. These were frequency matched for gender and body mass index to 50 stgBTKAs completed within 6 months who also were opioid-free ≤90 days prior to their first surgery. Using our state's prescription database, we reviewed postsurgery opioid refills and morphine milligram equivalents (MMEs) for the two groups and compared their initial MME prescription at discharge and their total MME consumption 6 months postoperatively. Total MME consumption for the stgBTKA group included all prescriptions following the first and 6 months after the second surgery, whereas for the simBTKA group, total consumption included the 6 months after their two same-day surgeries. The simBTKA group had more MMEs prescribed initially (median = 375) than did the stgBTKA group after second surgery (median = 300; p < 0.007), larger postoperative-refill MMEs in the first 30 days (median = 300) than stgBTKA (median = 0; p = 0.221) and increased total MME consumption 6 months after surgery (median = 675) compared with stgBTKA after second surgery (median = 450; p = 0.077). However, both groups had similar monthly consumptions rates, with medians I MMEs/month of 112 for simBTKA versus 96 for stgBTKA (p = 0.585). Our results suggest there is no significant difference in opioid consumption between simBTKA and stgBTKA. In fact, we found that simBTKA patients received larger opioid amounts in the immediate postoperative period as well as slightly larger amounts at 30 days.


Costs and Use of Health Care in Patients With Celiac Disease: A Population-Based Longitudinal Study.
Celiac disease (CD) affects 1% of the population. Its effect on healthcare cost, however, is barely understood. We estimated healthcare use and cost in CD, including their temporal relationship to diagnosis. Through biopsy reports from Sweden's 28 pathology departments, we identified 40,951 prevalent patients with CD (villous atrophy) as of January 1, 2015, and 15,086 incident patients with CD diagnosed in 2008-2015, including 2,663 who underwent a follow-up biopsy to document mucosal healing. Each patient was compared with age- and sex-matched general population comparators (n = 187,542). Using nationwide health registers, we retrieved data on all inpatient and nonprimary outpatient care, prescribed diets, and drugs. Compared with comparators, healthcare costs in 2015 were, on average, $1,075 (95% confidence interval, $864-1,278) higher in prevalent patients with CD aged <18 years, $715 ($632-803) in ages 18-64 years, and $1,010 ($799-1,230) in ages ≥65 years. Half of all costs were attributed to 5% of the prevalent patients. Annual healthcare costs were $391 higher 5 years before diagnosis and increased until 1 year after diagnosis; costs then declined but remained 75% higher than those of comparators 5 years postdiagnosis (annual difference = $1,044). Although hospitalizations, nonprimary outpatient visits, and medication use were all more common with CD, excess costs were largely unrelated to the prescription of gluten-free staples and follow-up visits for CD. Mucosal healing in CD did not reduce the healthcare costs. The use and costs of health care are increased in CD, not only before, but for years after diagnosis. Mucosal healing does not seem to lower the healthcare costs.


[Extrapulmonary tuberculosis--important differential diagnosis].
In this paper, we present two cases of extrapulmonary tuberculosis, the first case with tuberculosis of the larynx and the second with tuberculosis lymfadenitis. In both cases malignant lesions were primarily proposed. We emphasize that definitive diagnosis requires culture and specification of Mycobacterium tuberculosis. We draw attention to the fact that extrapulmonary tuberculosis is still a differential diagnostic consideration.


Distressing emotions in female caregivers of people with AIDS, age-related dementias, and advanced-stage cancers.
To describe and compare the depressive mood, anxiety, anger, and sleep problems of informal female caregivers of people with AIDS, age-related dementias (ARD), and cancer (CA). Caregivers recruited from clinics serving people with AIDS, ARD, and CA were interviewed using structured instruments measuring depressive symptoms, anxiety, anger, and sleep problems. Data analysis compared these emotions in the caregivers and related aspects of the caregiving situation to these emotions within each group. Caregivers did not differ significantly in depressive mood, but did differ in anxiety and anger and sleep problems. Individual items on each scale were compared to provide more descriptive detail. In each group, distressing emotions were significantly related to each other and to sleep problems. Caregivers of people with AIDS, ARD, and CA experience distressing emotions that may affect their mental and physical health. A comprehensive approach to mental health nursing therapy will best meet the needs of caregivers in relieving their distress.


Knowledge and attitudes of schoolchildren about the prevention of accidents.
Accidents are frequent in childhood because of the lower risk perception and greater vulnerability to disasters. This study aimed to analyze the knowledge and attitudes of schoolchildren concerning the prevention of accidents and associated factors. This is a cross-sectional and quantitative study conducted in November and December/2017 in Simão Dias, Sergipe, Brazil. Ninety-seven schoolchildren aged between 7 and 9 years of age from a sample calculation were evaluated through interviews with representative images. The results showed that little more than half of the children consider the use of personal protective equipment as a way of preventing injuries in case of accidents (58.8%; n=57), and is infrequent among those with low education level (PR: 0.66; 95%CI: 0.16- 0.99). The knowledge or use of this equipment was 60.8% (n=59) for safety belt, 54.6% (n=53) for helmet, 47.4% (n=46) for knee pad and 40.2% (n=39) for elbow support. Regarding attitudes, 20.6% (n=20) answered that there is no problem putting their (unwashed) hand on the wound and 12.4% (n=12) crossing the street accompanied without an adult. It was concluded that the knowledge and attitudes of schoolchildren concerning the prevention of accidents are misguided.


Infectious Complications in Pediatric, Adolescent and Young Adult Patients Undergoing CD19-CAR T Cell Therapy.
CD19-specific chimeric antigen receptor (CAR) T cell therapy has changed the treatment paradigm for pediatric, adolescent and young adult (AYA) patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, data on the associated infectious disease challenges in this patient population are scarce. Knowledge of infections presenting during treatment, and associated risk factors, is critical for pediatric cellular therapy and infectious disease specialists as we seek to formulate effective anti-infective prophylaxis, infection monitoring schemas, and empiric therapy regimens. In this work we describe our institutional experience in a cohort of 38 pediatric and AYA patients with CD19-positive malignancy treated with lymphodepleting chemotherapy (fludarabine/cyclophosphamide) followed by a single infusion of CD19-CAR T cells (total infusions, n=39), including tisagenlecleucel (n=19; CD19/4-1BB) or on an institutional clinical trial (n=20; CD19/4-1BB; NCT03573700). We demonstrate that infections were common in the 90 days post CAR T cells, with 19 (50%) patients experiencing a total of 35 infections. Most of these (73.7%) occurred early post infusion (day 0 to 28; infection density of 2.36 per 100 patient days-at-risk) compared to late post infusion (day 29 to 90; infection density 0.98 per 100 patient days-at-risk), respectively. Bacterial infections were more frequent early after CAR T cell therapy, with a predominance of bacterial blood stream infections. Viral infections occurred throughout the post infusion period and included primarily systemic reactivations and gastrointestinal pathogens. Fungal infections were rare. Pre-infusion disease burden, intensity of bridging chemotherapy, lymphopenia post lymphodepleting chemotherapy/CAR T cell infusion and development of CAR-associated hemophagocytic lymphohistiocytosis (carHLH) were all significantly associated with either infection density or time to first infection post CAR T cell infusion. A subset of patients (n=6) had subsequent CAR T cell reinfusion and did not appear to have increased risk of infectious complications. Our experience highlights the risk of infections after CD19-CAR T cell therapy, and the need for continued investigation of infectious outcomes as we seek to improve surveillance, prophylaxis and treatment algorithms.


Aging and thermal stability of Mg/SiC and Mg/Y2O3 reflection multilayers in the 25-35 nm region.
Reflection measurements in the 25-35 nm region were made for Mg/SiC and Mg/Y2O3 multilayers kept in a low-humidity atmosphere for 4 or 5 years. Aged Mg/SiC multilayers keep their reflectances, and the reflectance value at 31.2 nm is 0.44 at 10 degrees of the normal angle of incidence. Aged Mg/Y2O3 multilayers change reflectance as top layer materials, and the best value at 30.1 nm is 0.40 at 10 degrees. Reflection measurements are also made for Mg-based multilayers that are annealed from room temperature to 400 degrees C at 50 degrees C intervals. Both multilayers keep their reflectance at annealing temperatures of 200 degrees C. These results suggest that both Mg-based multilayers can be applied to practical optics.


Processing and targeting of proteins derived from polyprotein with 2A and LP4/2A as peptide linkers in a maize expression system.
In the transformation of multiple genes, gene fusion is an attractive alternative to other methods, including sexual crossing, re-transformation, and co-transformation, among others. The 2A peptide from the foot-and-mouth disease virus (FMDV) causes the co-translational "cleavage" of polyprotein and operates in a wide variety of eukaryotic cells. LP4, a linker peptide that originates from a natural polyprotein occurring in the seed of Impatiens balsamina, can be split between the first and second amino acids in post-translational processing. LP4/2A is a hybrid linker peptide that contains the first nine amino acids of LP4 and 20 amino acids of 2A. The three linkers have been used as a suitable technique to link the expression of genes in some transgenic plants, but to date the cleavage efficiency of three linkers have not been comprehensively demonstrated in the same transformation system, especially in the staple crop. To verify the functions of 2A, LP4, and LP4/2A linker peptides in transgenic maize, six fusion protein vectors that each encoded a single open reading frame (ORF) incorporating two report genes, Green Fluorescent Protein (GFP) and β-glucuronidase (GUS), separated by 2A (or modified 2A), LP4 or LP4/2A were assembled to compare the cleavage efficiency of the three linkers in a maize transient expression system. The results demonstrated the more protein production and higher cleavage splicing efficiency with the polyprotein construct linked by the LP4/2A peptide than those of the polyprotein constructs linked by 2A or LP4 alone. Seven other fusion proteins that each encoded a single ORF incorporating two different genes GFP and Red Fluorecent Protein (RFP) with different signal peptides were assembled to study the subcellular localization of genes linked by LP4/2A. The subcellular localization experiments suggested that both types of signal peptide, co-translational and post-translational, could lead their proteins to the target localization in maize protoplast transformed by LP4/2A polyprotein construct and it implied the LP4/2A linker peptide could alleviate the inhibition of 2A processing by the carboxy-terminal region of upstream protein of 2A when translocated into the ER.


[Therapeutic management in severe and difficult asthma in adults].
Classification of severity of bronchial asthma is a basic point for therapeutic management in adults. In the paper definitions of severe and difficult asthma are presented. The therapeutic possibilities are pointed according to new guidelines published in the recent period and own Author's clinical experience.


Inhibitory action of relaxin on human cervical smooth muscle.
The influence of purified porcine relaxin on contractility of human cervical smooth muscle was investigated in vitro. Strips of cervical tissue were obtained by needle biopsy from pregnant and nonpregnant women and were mounted in a superfused organ chamber for isometric measurement of contractile activity. Relaxin (0.005-25 micrograms/ml) inhibited the spontaneous contractions in cervical strips from 18% of nonpregnant, 68% of early pregnant, and in 100% of term pregnant women. These results indicate that relaxin has an inhibitory action on cervical smooth muscle and that this effect is more constantly detected as pregnancy proceeds.


Significance of the age of transfused blood for prognosis after transcatheter aortic valve implantation.
INTRODUCTION Blood transfusion after transcatheter aortic valve implantation (TAVI) is frequently required owing to the high vulnerability of this patient group and procedure-related bleeding. OBJECTIVES We assessed the impact of postprocedural blood transfusion and the age of transfused red blood cell (RBC) units on prognosis after TAVI. PATIENTS AND METHODS This was a single-center, observational analysis conducted between the years 2009 and 2014. The adopted endpoints were early and long-term mortality after TAVI. The risk factors for mortality included in-hospital bleeding and vascular complications, the number of transfused RBC units, transfusion of at least 2 RBC units, the age of transfused RBCs, and standard deviation of the age of RBCs. RESULTS The study included 178 patients (mean [SD] age, 80.07 [7.47] years; range, 55-91 years). The follow-up ranged between 1 month and 5.8 years (mean [SD], 20.1 [15.2] months) after discharge; 14 early deaths (7.8%) and 27 late deaths (16.5%) were noted. In-hospital bleeding and vascular complications increased the risk of early deaths (hazard ratio [HR], 2.113; 95% CI, 1.011-4.418; P = 0.046 and HR, 2.265; 95% CI, 1.270-4.039; P = 0.005). Transfusion of younger RBCs (HR, 1.044; 95% CI, 1.004-1.085; P = 0.028) and a greater discrepancy in the age of transfused RBCs (HR, 1.153; 95% CI, 1.042-1.275; P = 0.006) were positively correlated with the risk of late deaths only in a univariate analysis. A higher number of transfused RBC units was the only independent predictor of long-term mortality (HR, 1.149; 95% CI, 1.024-1.291; P = 0.018). CONCLUSIONS The higher number of RBC units transfused early after TAVI worsens long-term prognosis. Shorter-storage RBCs and a greater discrepancy in RBC age in multitransfused elderly patients after TAVI might have a deleterious effect on life expectancy.


A factor analytic approach to distinguish pure and co-occurring dimensions of proactive and reactive aggression.
This study used a confirmatory factor model to distinguish pure and co-occurring dimensions of proactive and reactive aggression, and examined the relation between parenting variables and these dimensions of aggression in a sample of 100 children (9 to 12 years of age; 69 boys). Confirmatory factor analysis (CFA) supported 3 dimensions of proactive and reactive aggression: pure proactive, pure reactive, and their co-occurrence. Parenting variables differentially related to the pure and co-occurring dimensions of aggression. Findings indicate that CFA provides a promising approach for conceptualizing aggression on a continuum and allows researchers to distinguish pure and co-occurring dimensions of proactive and reactive aggression.


Treatment of Articular Cartilage Defects: A Descriptive Analysis of Clinical Characteristics and Global Trends Reported from 2001 to 2020.
To evaluate the clinical characteristics and global trends in the surgical treatment of articular cartilage defects. Studies in English published between January 1, 2001 and December 31, 2020 were retrieved from MEDLINE, WOS, INSPEC, SCIELO, KJD, and RSCI on the "Web of Science." Patient data were extracted, including age, sex, defect location and laterality, duration of follow-up and symptoms, and body mass index (BMI). Data were further stratified according to the surgical method, lesion location, procedural type and geographical area, and time period. A comparative analysis was performed. Overall, 443 studies involving 26,854 patients (mean age, 35.25 years; men, 60.5%) were included. The mean lesion size and patient BMI were 3.51 cm2 and 25.61 kg/m2, respectively. Cartilage defects at the knees, talus, and hips affected 20,850 (77.64%), 3,983 (14.83%), and 1,425 (5.31%) patients, respectively. The numbers of patients who underwent autologous chondrocyte implantation, arthroscopic debridement/chondroplasty, osteochondral allograft (OCA), osteochondral autologous transplantation, and microfracture were 7,114 (26.49%), 5,056 (18.83%), 3,942 (14.68%), 3,766 (14.02%), and 2,835 (10.56%), respectively. European patients were the most numerous and youngest. North American patients had the largest defects. The number of patients increased from 305 in 2001 to 3,017 in 2020. In the last 5 years, the frequency of OCAs showed a greatly increasing trend. Clinical characteristics and global trends in the surgical treatment of articular cartilage defects were revealed. The choice of operation should be based on the patient characteristics and defect location, size, and shape, as well as the patient's preference.


11q23 translocations split the "AT-hook" cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene.
Translocations involving chromosome band 11q23, found in acute lymphoid and myeloid leukemias, disrupt the MLL gene. This gene encodes a putative transcription factor with homology to the zinc fingers and other domains of the Drosophila trithorax gene product and to the "AT-hook" motif of high mobility group proteins. To map potential transcriptional activation or repression domains of the MLL protein, yeast GAL4 DNA-binding domain and MLL hybrid protein-expressing plasmids were cotransfected with chloramphenicol acetyltransferase reporter plasmids in a transient transfection system. We found that MLL contains a strong activation domain and a repression domain. The former, located telomeric (3') to the breakpoint region, activated transcription 18-fold to > 200-fold, depending on the promoter and cell line used for transfection. A repression domain that repressed transcription 4-fold was located centromeric (5') to the breakpoint region of MLL. The MLL AT-hook domain protein was expressed in bacteria and was utilized in a gel mobility shift assay to assess DNA-binding activity. The MLL AT-hook domain could bind cruciform DNA, recognizing structure rather than sequence of the target DNA. In translocations involving MLL, loss of an activation domain with retention of a repression domain and a DNA-binding domain on the der(11) chromosome could alter the expression of downstream target genes, suggesting a potential mechanism of action for MLL in leukemia.


Adenoviral-mediated, high-level, cell-specific transgene expression: a SYN1-WPRE cassette mediates increased transgene expression with no loss of neuron specificity.
Viral vectors are excellent tools for studying gene function in the brain, although a limitation has been the ability to effectively target transgene expression to specific neuronal populations. This generally cannot be overcome by the use of neuron-specific promoters, as most are too large to be used with current viral vectors and expression from these promoters is often relatively weak. We therefore developed a composite expression cassette, comprising 495 bp of the weak human SYN1 (synapsin-1) promoter and 800 bp of the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE). Studies in hippocampal cultures, organotypic cultures, and in vivo showed that the 3' addition of the WPRE to the SYN1 element greatly increased enhanced green fluorescent protein expression levels with no loss of neuronal specificity. In vivo studies also showed that transgene expression was enhanced with no loss of neuronal specificity in dentate-gyrus neurons for at least 6 weeks following transfection. Therefore, unlike most powerful promoter systems, which mediate expression in neurons and glia, this SYN1-WPRE cassette can target powerful long-term transgene expression to central nervous system neurons when delivered at relatively low titers of adenovirus. Its use should therefore facilitate both gene therapy studies and investigations of neuronal gene function.


Prevalence, characteristics and predicting risk factors of adverse drug reactions among hospitalized older adults: A systematic review and meta-analysis.
Occurrence of adverse drug reactions is a major global health problem mostly affecting older adults. Identifying the magnitude and predictors of adverse drug reactions is crucial to developing strategies to mitigate the burden of adverse drug reactions. This study's objectives were to estimate and compare the prevalences of adverse drug reactions, to characterize them and to identify the predictors among hospitalized older adults. A comprehensive systematic literature search including both prevalence and risk factors of adverse drug reactions in hospitalized older adults was conducted using PubMed, Scopus and Google Scholar, involving all articles published in English. Descriptive statistics and comparison of means was performed using SPSS version 20.0 and metaprop command was performed in STATA version 13.0. Heterogeneity was assessed using I 2 statistic. A total of 18 studies, involving 80,695 participants with a median age of 77 years, were included in this study. The pooled prevalence of adverse drug reaction was 22% (95% confidence interval: 17%, 28%; I 2 = 99.23%). Among high-income countries, the prevalence of adverse drug reactions was 29% (95% confidence interval: 16%, 42%) as compared to 19% (95% confidence interval: 14%-25%) in low and middle-income countries (p value = 0.176). Of the 620 adverse drug reactions categorized, most were type A (89%), which are generally predictable and preventable. Two-thirds (795, 67%) of the adverse drug reactions were probable and most (1194, 69%) were mild or moderate. The majority (60%) of the categorized adverse drug reactions were preventable and less than one-third (31%) were severe. The most consistently reported predictors of adverse drug reactions in hospitalized older patients were medication-related factors, including polypharmacy and potentially inappropriate medications followed by disease-related factors-renal failure, complex comorbidity, heart failure and liver failure. Almost one-quarter of all hospitalized older adults experienced at least one adverse drug reaction during their hospital stay. The majority of the adverse drug reactions were preventable. Medication-related factors were the most consistently reported predictors of adverse drug reactions followed by disease-related factors.


Water-soluble and biocompatible sono/photosensitizer nanoparticles for enhanced cancer therapy.
Most sono/photosensitizers of cancer sonodynamic/photodynamic therapy (SDT/PDT), such as hypocrellin SL052, are water-insoluble, therefore restricting their clinical applications. In this article, we present a water-soluble nanocarrier to load the SDT/PDT sensitizer SL052 with improved pharmacokinetics and therapeutic efficacy. Nanoclusters of polyvinylpyrrolidones with SL052 formed water-soluble nanoparticles (SL052-NPs) while retaining the chemical structure of SL052. The experimental results show that SL052-NPs improve the drug's physicochemical properties and significantly enhance the efficacy of SL052 in terms of pharmacokinetics and cancer killing. Water-soluble SL052-NPs can be used to deliver the drug to deep cancer tissues. A potential benefit of SL052-NPs is that polyvinylpyrrolidones can help SL052 evade the reticuloendothelial system, thereby increasing circulation half-life and improving drug biodistribution. SL052-NPs greatly improved the physicochemical properties of SL052 without modifying its chemical structure, allowing for deep-site cancer drug delivery, imaging for diagnosis, and ultrasound or photocontrolled localized cancer therapy.


Switchable DNA Catalysts for Proximity Labeling at Sites of Protein-Protein Interactions.
Proximity labeling (PL) has emerged as a powerful approach to elucidate proteomes within a defined radius around a protein of interest (POI). In PL, a catalyst is attached to the POI and tags nearby endogenous proteins, which are then isolated by affinity purification and identified by mass spectrometry. Although existing PL methods have yielded numerous biological insights, proteomes with greater spatial resolution could be obtained if PL catalysts could be activated at more specific subcellular locations, such as sites where both the POI and a chemical stimulus are present or sites of protein-protein interactions (PPIs). Here, we report DNA-based switchable PL catalysts that are attached to a POI and become activated only when a secondary molecular trigger is present. The DNA catalysts consist of a photocatalyst and a spectral quencher tethered to a DNA oligomer. They are catalytically inactive by default but undergo a conformational change in response to a specific molecular trigger, thus activating PL. We designed a system in which the DNA catalyst becomes activated on living mammalian cells specifically at sites of Her2-Her3 heterodimers and c-Met homodimers, PPIs known to increase the invasion and growth of certain cancers. While this study employs a Ru(bpy)3-type complex for tagging proteins with biotin phenol, the switchable DNA catalyst design is compatible with diverse synthetic PL photocatalysts. Furthermore, the switchable DNA PL catalysts can be constructed from conformation-switching DNA aptamers that respond to small molecules, ions, and proteins, opening future opportunities for PL in highly specific subcellular locations.


Focal adhesions as mechanosensors: the two-spring model.
Adhesion-dependent cells actively sense the mechanical properties of their environment through mechanotransductory processes at focal adhesions, which are integrin-based contacts connecting the extracellular matrix to the cytoskeleton. Here we present first steps towards a quantitative understanding of focal adhesions as mechanosensors. It has been shown experimentally that high levels of force are related to growth of and signaling at focal adhesions. In particular, activation of the small GTPase Rho through focal adhesions leads to the formation of stress fibers. Here we discuss one way in which force might regulate the internal state of focal adhesions, namely by modulating the internal rupture dynamics of focal adhesions. A simple two-spring model shows that the stiffer the environment, the more efficient cellular force is built up at focal adhesions by molecular motors interacting with the actin filaments.


HIV and the nervous system.
Neurological manifestations are common in HIV-infected individuals. Autopsy data suggest that the brain may be affected in as many as 80 per cent of cases. While opportunistic infections represent a major cause of neurological morbidity and mortality, there is growing evidence that HIV is itself neurotropic and can directly affect the nervous system.


Exchange factor EFA6R requires C-terminal targeting to the plasma membrane to promote cytoskeletal rearrangement through the activation of ADP-ribosylation factor 6 (ARF6).
ADP-ribosylation factor 6 (ARF6) small GTPase regulates membrane trafficking and cytoskeleton rearrangements at the plasma membrane (PM) by cycling between the GTP-bound active and GDP-bound inactive conformations. Guanine nucleotide exchange factors (GEFs) activate ARF6. The exchange factor for ARF6 (EFA6) R has been identified as a biomarker for ovarian cancer. EFA6R shares the catalytic Sec7, pleckstrin homology (PH), and coiled coil (CC) domains of the other EFA6 family GEFs. Here we report the functional characterization of EFA6R. Endogenous EFA6R was present in the plasma membrane fraction. The exogenously expressed FLAG- and GFP-tagged EFA6R were targeted to the PM. In vitro, GFP-EFA6R associated weakly but preferentially with phosphatidylinositol 4,5-bisphosphate (PIP2) through the PH domain. EFA6R required both its PH and CC domains localized at the C terminus to target the PM. Consistent with this, EFA6R lacking the CC domain (EFA6RΔCC) was released from the PM into the cytosol upon PIP2 depletion, whereas EFA6R release from the PM required both PIP2 depletion and actin destabilization. These results suggest that the dual targeting via the PH and CC domains is important for the PM localization of EFA6R. EFA6R specifically catalyzed the GTP loading of ARF6 in mammalian cells. Moreover, EFA6R regulated ARF6 localization and thereby actin stress fiber loss. The GEF activity of EFA6R was dependent on the presence of the Sec7 domain. The PH and CC domains were also required for the in vivo GEF activity of EFA6R but could be functionally replaced by the CAAX motif of K-Ras, suggesting a role for these domains in the membrane targeting of EFA6R.


Heat Tolerance of the Brown Recluse Spider (Araneae: Sicariidae): Potential for Pest Control.
The brown recluse spider, Loxosceles reclusa Gertsch & Mulaik, is a well-known venomous spider common in the south-central United States where infestations can reach thousands of individuals in a single structure. Bites from this spider pose a risk of dermonecrotic lesions (loxoscelism) or, rarely, more serious systemic effects. The heat tolerance of this spider is understudied but may offer an alternative pest control solution to pesticides or fumigation, both of which have their disadvantages. We subjected brown recluse spiders to increasing temperatures to establish the upper lethal temperature (LT). Using probit analysis to generate probability of mortality at increasing temperatures, we then exposed adult spiders to the observed LT50 to simulate whole-room heat treatment. Laboratory results predict exposure to 48°C for 130 min will achieve 100% mortality of adult spiders. Field tests need to be conducted to determine the efficacy of heat treatment in a variety of real-world situations.


[Perforations following endoscopic retrograde cholangiopancreatography (ERCP)].
Endoscopic retrograde cholangiopancreatography (ERCP) associated with sphincterotomy is a useful procedure that is widely used in cases of choledocholithiasis and bile duct obstruction. In spite of being a safe test, there is a risk of complications like pancreatitis, haemorrhaging or perforation. Post-ERCP duodenal perforation is a rare event but has serious consequences if it is not treated early. The lesion mechanism, the place and extension of the perforation, as well as the clinical picture and radiographic findings will guide patient management, which must be individualised and constantly reevaluated. Its mortality is closely related to diagnostic and therapeutic delay. In those cases where a conservative attitude is adopted, close vigilance will be maintained facing the possibility of a worsening of the clinical picture and a change in its management.


Transplantation potential of peripheral blood stem cells induced by granulocyte colony-stimulating factor.
The major effect of granulocyte colony-stimulating factor (G-CSF) is to induce neutrophilia in previously untreated animals or after chemotherapy or marrow transplantation in humans, primates and rodents. In addition, it has been reported that migration of committed progenitor cells to the blood occurs during G-CSF therapy. In this article, by using sex mismatched transplants and a molecular probe for Y-chromosome specific DNA sequences, we show that among the peripheral blood cells during G-CSF therapy are substantial numbers of primitive stem cells capable of (1) reconstituting the hematopoietic system in the long term, and (2) making a contribution to the lymphoid populations of the thymus, in radiation ablated recipients. These data suggest that blood from patients treated with G-CSF may provide a convenient source of the most primitive stem cells for autologous or allogeneic bone marrow transplantation.


Alteration of trace element distribution and testis ACE activity in mice with high peritoneal aluminum.
The present investigation was conducted to assess the effects of subacute aluminum (Al) exposure on testicular zinc (Zn), copper (Cu), and iron (Fe) distribution in mice. Animals were intraperitoneally exposed to 0, 13, or 35 mg Al/kg body weight/d for a period of 14 d. Al concentrations in serum and testis in Al-treated animals were significantly higher than those of controls. The serum concentrations of Fe were lower, whereas serum Zn and Cu showed a pattern comparable to that of controls. The accumulation of testicular Fe and Cu remarkably increased in Al-exposed groups, whereas the Zn concentration in testis was significantly reduced only at the highest dose of Al exposure. The values of testicular thiobarbituric acid reactive substances (TBARS) were also increased after Al administration, indicating increased lipid peroxidation and oxidative stress. In addition, when the testicular Al was increased, the testis-specific angiotensin-converting enzyme (testis ACE) was noted. The results of this study indicated that part of the effect of Al intoxication on testis might contribute to abnormal metabolism of other minerals, such as Fe, Zn, and/or Cu. It was also suggested that reduced testis ACE activity presumably plays an important role in oxidative damage of Al-induced testicular toxicity.


Long-Term Stable Lithium Metal Anode in Highly Concentrated Sulfolane-Based Electrolytes with Ultrafine Porous Polyimide Separator.
Highly concentrated solutions composed of lithium bis(fluorosulfonyl)imide (LiFSI) and sulfolane (SL) are promising liquid electrolytes for lithium metal batteries because of their high anodic stability, low flammability, and high compatibility with lithium metal anodes. However, it is still challenging to obtain the stable lithium metal anodes in the concentrated electrolytes due to their poor wettability to the conventional polyolefin separators. Here, we report that the highly concentrated 1:2.5 LiFSI/SL electrolyte coupled with a three-dimensionally ordered macroporous polyimide (3DOM PI) separator enables the stable lithium plating/stripping cycling with an average Coulombic efficiency of ca. 98% for over 400 cycles at 1.0 mA cm-2. The 3DOM PI separator shows good electrolyte wettability and large electrolyte uptake due to its high porosity and polar constituent of the imide structure, allowing superior cycling performance in the highly concentrated solution, compared with the polyolefin separators. Electrochemical and spectroscopic analyses reveal that the superior cycling stability in the concentrated electrolyte is attributed to the formation of highly stable and Li+ ion conductive solid electrolyte interphase (SEI) layer derived from FSI- anions, which reduces the side reactions of SL with lithium metal, prevents the growth of lithium dendrites, and suppresses the increase in cell impedance over long-term cycling. Our findings demonstrate that polar and porous separators could effectively improve the affinity to the concentrated electrolytes and allow the formation of the anion-derived SEI layer by increasing the salt concentration of the electrolytes, achieving the long-term stable lithium metal anode.


Overview and summary of the Food Safety and Inspection Service risk assessment for Salmonella enteritidis in shell eggs, October 2005.
In 1998, the United States Department of Agriculture's Food Safety and Inspection Service (FSIS) and the Food and Drug Administration completed a risk assessment that indicated multiple interventions along the farm-to-table chain were needed to reduce the risk of human illness from Salmonella Enteritidis in shell eggs. Based on newly available data and improved modeling techniques, FSIS completed an updated risk assessment to examine the effect of pasteurization and refrigeration on reducing human illnesses from S. Enteritidis in shell eggs. The risk assessment model was written in Visual Basic for Applications (Microsoft, Redmond, WA) and run using Monte Carlo methods. The model estimated that if all shell eggs produced in the United States were pasteurized for a 3-log10 reduction of S. Enteritidis, the annual number of illnesses from S. Enteritidis in eggs would decrease from approximately 130,000 to 40,000. Pasteurization for a 5-log10 reduction of S. Enteritidis was estimated to reduce the annual number of illnesses to 19,000. The model also estimated that if all eggs produced in the United States were stored and held at 7.2 degrees C within 12 hours of lay, the annual number of illnesses from S. Enteritidis in eggs would decrease from 130,000 to 28,000. As a result, rapid cooling and pasteurization of shell eggs were predicted to be highly effective mitigations for reducing illnesses from consumption of S. Enteritidis in shell eggs.


Homozygous deletion of the DSG3 terminal exon associated with acantholytic blistering of the oral and laryngeal mucosa.
We report a novel homozygous 49.6 kb deletion of chromosome 18q12.1 involving the last exon of DSG3 in dizygotic twins with phenotype consistent with acantholytic blistering of the oral and laryngeal mucosa (ABOLM). The twin siblings presented predominantly with friability of the laryngeal and respiratory mucosa. This is only the second report in the literature of this unusual autosomal recessive blistering disorder. The diagnosis explains the mucosal phenotype of a pemphigus-like disorder without evidence of autoimmune dysfunction. The exclusion of an autoimmune basis has management implications. The deletion also involved the DSG2 gene, which is associated with arrhythmogenic right ventricular dysplasia (ARVD). The affected siblings and heterozygous parents do not show any cardiac phenotype at this time. Functional studies would further clarify how deletions resulting in loss of function of DSG3 may cause the reported phenotypes of DSG3-related ABOLM.


Progression from low- to high-grade in a glioblastoma model reveals the pivotal role of immunoediting.
The mutual reshape of tumor and immune system cells during tumor progression is a widely accepted notion in different cancers including gliomas. The importance of this phenomenon in shaping glioma progression and the mechanisms governing it, however, are not fully elucidated. Taking advantage of a well-characterized in vivo glioma model we performed an analysis of glioma cells transcriptomes at different stages of progression and unveiled the reorganization of glioma-immune system interactions. Specifically, we show that the inability of low-grade glioma cells to orthotopically graft in syngeneic immunocompetent mice, positively correlates with the abundance of infiltrating lymphocytes in donor tumors and with a highly immunostimulatory transcriptional profile. Notably, during tumor progression glioma cells downregulate these genes and the immune infiltrate shifts towards a pro-tumorigenic phenotype. Challenging low-grade gliomas by grafting into immunodeficient hosts revealed the crucial role of the adaptive immune system in constraining glioma progression. Finally, we observed that although progression still takes place in immunodeficient mice, it is slower, likely due to a milder selection thus reinforcing the view of a pivotal role for the immune system in regulating glioma progression.


A case of unique subepidermal blistering disease with autoantibodies against a novel dermal 200-kD antigen.
Several autoimmune subepidermal blistering diseases with autoantibodies against the epidermal basement membrane zone (BMZ) have been identified. Each shows distinct immunological findings. Our patient showed clinical features which were indicative of bullous pemphigoid or linear IgA bullous dermatosis. In his serum, circulating IgG antibodies binding to the dermal side of skin split with 1 M NaCl were detected. To clarify the immunological character of the patient, we performed further studies. Western immunoblot analysis using normal human skin extracts and indirect immunofluorescence (IF) with affinity-purified IgG antibodies to the detected dermal protein were done. Western immunoblot analysis demonstrated IgG antibodies reacting with a dermal 200-kD protein. Affinity-purified IgG antibodies to the 200-kD protein reacted to the dermal side of the split by indirect IF. Therefore, this dermal 200-kD protein is believed to be the epidermal BMZ antigen. Our patient showed an immunologically unique subepidermal blistering disease.


Service delivery options for secondary students with language disorders.
Numerous adolescents are still undetected, unserved, and underserved by speech-language pathologists, resulting in astronomical financial and psychological costs to them and society. The purpose of this article is to provide an overview of past and present service delivery options for adolescents with language disorders. Before illustrating the authors' recommended model, the following background is provided: an overview of the three stages of adolescent development, characteristic expectations and problems for older students with language disorders, and a rationale for adolescent speech-language services. The comprehensive service delivery model for secondary-level speech-language students, designed and reported by the authors, consists of six components: information dissemination, identification, assessment, program planning, intervention, and follow-up. Some of the unique features of the comprehensive model are presenting services as a course for credit, providing grades, and using supportive course titles such as Individualized Communication Class.


Satisfaction with mental health services among people with schizophrenia in five European sites: results from the EPSILON Study.
Patient satisfaction with services is an important outcome variable that is increasingly used in mental health service evaluation. This study includes 404 people with schizophrenia in five European sites and addresses five questions focused on site, service, and patient characteristics as variables that might explain service satisfaction, using the Verona Service Satisfaction Scale. Patient satisfaction differed significantly across sites (highest in Copenhagen, lowest in London). In all sites, patients were least satisfied with involvement of relatives in care and information about illness. A multiple regression model showed that lower levels of total service satisfaction were associated with living in London or Santander, being retired/unemployed, having more hospital admissions, having more severe psychopathology, having more unmet needs, or having lower satisfaction with life. This model explained 31 percent of variance in service satisfaction. Our data show that service satisfaction can be seen as a result of (1) the ability of the service to provide a standard of care above a certain quality threshold, and (2) the perception of each patient that the care received has been tailored to the patient's own problems.


Investigating the Association Between Obsessive-Compulsive Disorder Symptom Subtypes and Health Anxiety as Impacted by the COVID-19 Pandemic: A Cross-Sectional Study.
Since the COVID-19 outbreak was declared a global pandemic, public health messages have emphasised the importance of frequent handwashing in limiting the transmission of the virus. Whilst crucial in controlling transmission, such messaging may have an adverse effect on individuals with OCD. A cross-sectional study was conducted, with a total of 332 participants recruited. Participants who scored above the optimal cut-off score on the Obsessive-Compulsive Inventory Revised edition (OCI-R) were included in the analysis (n = 254). Scores on the six subscales of the OCI-R were correlated with responses to a COVID-19 Impact measure. Factor analysis of the COVID-19 Impact measure revealed that items loaded on two components of the measure (handwashing and distress-avoidance). Canonical correlation analyses revealed significant associations between the OCI-R subscales and COVID-19 Impact measure, F (12, 490) = 8.14, p = 0.001, and the SHAI subscales with the COVID-19 Impact Measure, F (4, 498) = 8.18, p = 0.001). Specifically, washing and checking OCI-R subscales correlated with both components of the COVID-19 Impact measure, as did the health anxiety and beliefs SHAI subscales. Content analysis revealed disruption to treatment delivery and worsening symptom severity in participants with contamination-related OCD. Contamination and checking OCD subtypes have been associated with increased hand-washing behaviour and avoidance of distress-inducing cues. Consideration should be given to targeted support tailored to patients with these subtypes of OCD.


Advances and Prospects of Ultrasound Targeted Drug Delivery Systems Using Biomaterial-modified Micro/Nanobubbles for Tumor Therapy.
The incidence of malignant tumors is rising rapidly and tends to be in the younger, which has been one of the most important factors endangering the safety of human life. Ultrasound micro/nanobubbles, as a noninvasive and highly specific antitumor strategy, can reach and destroy tumor tissue through their effects of cavitation and acoustic perforation under the guidance of ultrasound. Meanwhile, micro/nanobubbles are now used as a novel drug carrier, releasing drugs at a target region, especially on the prospects of biomaterial-modified micro/nanobubbles as a dual modality for drug delivery and therapeutic monitoring. Successful evaluation of the sonoporation mechanism(s), ultrasound parameters, drug type, and dose will need to be addressed before translating this technology for clinical use. Therefore, this paper collects the literature on the experimental and clinical studies of ultrasound biomaterial-modified micro/nanobubbles therapy in vitro and in vivo in recent years.


Alpha-1 blockade inhibits compensatory sodium reabsorption in the proximal tubules during furosemide-induced volume contraction.
The renal effects of alpha-1 adrenoceptor blockade (i.v. infusion of doxazosin, 50 micrograms/kg prime; 30 micrograms/kg/h) on tubular sodium reabsorption during acute furosemide-induced volume contraction (i.v. infusion of furosemide, 7.5 mg/kg/h for 3 h) was investigated by clearance technique in conscious rats. By measuring inulin clearance, lithium clearance and urinary excretion rates of sodium and water, the changes in proximal and distal tubular sodium handling were dissociated. In furosemide-infused rats given doxazosin (n = 11) or volume replacement (n = 9), the fractional lithium excretion increased from 30% (control) to a steady-state value of 51% (last hour of furosemide infusion), whereas in rats infused with furosemide only (n = 9), the fractional lithium excretion increased transiently to a peak value of 52% and then declined to a steady-state value of 39%. Doxazosin attenuated the acute natriuretic response to furosemide by 54%, mainly due to increased sodium reabsorption in the distal nephron segment. This effect was associated with a significant lower mean arterial pressure compared with rats given furosemide only. The results are compatible with a contributory role of proximal tubular alpha-1 adrenoceptors in mediating compensatory Na reabsorption during furosemide-induced volume contraction.


Replacing statistical significance and non-significance with better approaches to sampling uncertainty.
A sample provides only an approximate estimate of the magnitude of an effect, owing to sampling uncertainty. The following methods address the issue of sampling uncertainty when researchers make a claim about effect magnitude: informal assessment of the range of magnitudes represented by the confidence interval; testing of hypotheses of substantial (meaningful) and non-substantial magnitudes; assessment of the probabilities of substantial and trivial (inconsequential) magnitudes with Bayesian methods based on non-informative or informative priors; and testing of the nil or zero hypothesis. Assessment of the confidence interval, testing of substantial and non-substantial hypotheses, and assessment of Bayesian probabilities with a non-informative prior are subject to differing interpretations but are all effectively equivalent and can reasonably define and provide necessary and sufficient evidence for substantial and trivial effects. Informative priors in Bayesian assessments are problematic, because they are hard to quantify and can bias the outcome. Rejection of the nil hypothesis (presented as statistical significance), and failure to reject the nil hypothesis (presented as statistical non-significance), provide neither necessary nor sufficient evidence for substantial and trivial effects. To properly account for sampling uncertainty in effect magnitudes, researchers should therefore replace rather than supplement the nil-hypothesis test with one or more of the other three equivalent methods. Surprisal values, second-generation p values, and the hypothesis comparisons of evidential statistics are three other recent approaches to sampling uncertainty that are not recommended. Important issues beyond sampling uncertainty include representativeness of sampling, accuracy of the statistical model, individual differences, individual responses, and rewards of benefit and costs of harm of clinically or practically important interventions and side effects.


An improved ultra-performance liquid chromatography-electrospray ionization/quadrupole-time-of-flight high-definition mass spectrometry method for determining ingredients of herbal Fructus corni in blood samples.
Fructus Corni (FC), a well-known traditional Chinese medicine (TCM), derived from the dry ripe sarcocarp of Cornus officinalis Sieb. et Zucc (Cornaceae), has been widely prescribed to treat disease in China for centuries. It has attracted increasingly much attention as one of the most popular and valuable herbal medicine in clinic. However, the systematic analysis of the chemical constituents of FC is difficult to determine and remain unclear. In this work, a rapid, sensitive, and reliable ultra-performance liquid chromatography-electrospray ionization/quadrupole-time-of-flight high-definition mass spectrometry (UPLC-ESI/QTOF/MS) with automated data analysis (MetaboLynx™) in negative ion mode were established to characterize the chemical constituents of FC and simultaneously identify components in blood after oral administration of FC, respectively. The analysis was performed on a Waters UPLC™ HSS T3 (2.1 × 100 mm, 1.8 μm) using gradient elution system. MS/MS fragmentation behaviors were proposed for aiding the structural identification of the components. With optimized conditions, a total of 34 peaks were obtained from FC, 23 of which were tentatively characterized by comparing the retention time and mass spectrometry data and retrieving the reference literatures. Of note, the 25 compounds were identified after oral administration of FC, which might be the potential active components in vivo. The present study demonstrates the potential of UPLC-ESI/QTOF/MS approach for the rapid and reliable characterization of the metabolites of natural products.


[Relationship of genetic polymorphism of microsomal epoxide hydrolase with susceptibility of chronic benzene poisoning].
To explore the relationship between genetic polymorphisms of microsomal epoxide hydrolase (mEH) and susceptibility of chronic benzene poisoning (BP). A case-control study was conducted. 152 BP patients and 152 workers occupationally exposed to benzene without poisoning manifestations were investigated. Polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) was applied to detect the single nucleotide polymorphisms (SNPs) on c.113 and c.139 of mEH gene. The risk of BP for individuals carrying mEHc.113 C/C genotype was 0.60 (OR = 0.60, 95% CI: 0.37 - 0.97, P = 0.04) of those carrying T/T and T/C genotypes. In non-smoking population, the risk of BP for subjects carrying mEHc.113 C/C genotype was 0.56 (OR = 0.56, 95% CI: 0.33 - 0.96, P = 0.03) of those carrying T/T and T/C genotypes, and in non-drinking population, the individuals carrying mEHc.113 C/C genotype was 0.51 (OR = 0.51, 95% CI: 0.30 - 0.86, P = 0.01) of those carrying T/T and T/C genotypes. The subjects carrying mEHc.113 C/C genotype and together with non-smoking or non-drinking habit may have lower risk of chronic benaene poisoning.


Concomitant Infections of Influenza A H1N1 and Disseminated Cryptococcosis in an HIV Seropositive Patient.
Respiratory viral infections, especially influenza have a potential to form a fatal association with cryptococcosis in the setting of compromised immunity. Considering the lethality of these two infections, we report an unusual case of dual infection of pandemic influenza A H1N1 and disseminated cryptococcosis in an HIV seropositive individual.


Transport of axonal enzymes in surviving segments of frog sciatic nerve.
Redistribution of axonal enzymes as a function of time in vitro was studied in an unbranched segment of frog sciatic nerve. Cholinesterase activity moved peripherally at a rate of 99 mm/day and centrally at 19 mm/day. One-quarter of the total nerve content of the enzyme was estimated to be in motion, one-eighth in each direction. Mitochondrial enzymes (hexokinase and glutamic dehydrogenase) moved peripherally at 20-31 mm/day, centrally at 11-20 mm/day. Only 10% of the total content of these mitochondrial enzymes was in motion. No movement of choline acetylase or 6-phosphogluconic dehydrogenase activity was seen even after 4 days in vitro. However, in a 12 day in vivo experiment choline acetylase moved toward the periphery at a rate of 0.34 mm/day. After a day or so in vitro the distal accumulations of cholinesterase and glutamic dehydrogenase decreased, with a concomitant and quantitatively equivalent increase in enzyme activities at the proximal end of the nerve. It is postulated that during incubation a mechanism for reversing the direction of flow develops in the peripheral stump of the nerve. Vinblastine inhibited central and peripheral flow of both cholinesterase and glutamic dehydrogenase. Movement of cholinesterase was not affected by ouabain, thalidomide, or phenobarbital, nor by K(+) excess (110 mM) or absence.


Defining instances and limbs during performance of the standing turn.
Conventions have been reported to describe walking and turning gait. No such descriptions appear for the 180° standing turn and as such there are inconsistencies in the literature reporting on this movement. The complexity of explaining the standing turning motion, variation in number of steps when turning, and differing strategies used means conventions will make research reporting easier to comprehend and less likely for errors in interpretation. We propose definitions of the 180° standing turning motion and steps used to complete a turn for able-bodied and pathological populations to encourage consistency in reporting. It is recommended that the definitions be applied in future research on standing turns.


Magnetic resonance imaging of pressure sores in spinal cord injured patients: accuracy in predicting osteomyelitis.
Identify key magnetic resonance imaging (MRI) features that have a significant correlation with osteomyelitis of pressure ulcers in spinal injury patients. Retrospective review study. Adult patients admitted to the National Spinal Injuries Centre with spinal cord injury (SCI) and signs of pressure ulceration investigated with MRI. Analysis of MRI examinations and clinical records collected over a 4-year period. Images were independently assessed by 2 experienced radiologists for osteomyelitis based on assigned predictive indicators including cortical bone erosion, soft tissue edema, deep collections, heterotopic new bone, hip effusion, and abnormal signal change of the marrow. Thirty-seven patients underwent 41 MRI scans. The prevalence of osteomyelitis was highly correlated with cortical bone erosion (r = 0.84) and abnormal bone marrow changes on T1-weighted images (r = 0.82).


Ameliorative Effects and Mechanism of Buyang Huanwu Decoction on Pulmonary Vascular Remodeling: Network and Experimental Analyses.
Pulmonary hypertension (PH) is a severe and progressive cardiovascular disease. Its pathological mechanism is complex, and the common pathological feature is pulmonary vascular remodeling. The efficacy of existing therapeutic agents is limited. Traditional Chinese medicine (TCM) has its unique advantages in the prevention and treatment of complex diseases. In this study, the approaches of network pharmacology combined with biological verification are employed to explore the role of Buyang huanwu decoction (BYHWD) in the treatment of PH. The active ingredients in BYHWD were first screened based on the ADME properties of the compounds. In turn, the mean of data mining was utilized to analyze the potential targets of BYHWD for the treatment of PH. On this basis, a series of interaction networks were constructed for searching the core targets. The genes including AKT1, MMP9, NOS3/eNOS, and EGFR were found to be possible key targets in BYHWD. The results of enrichment analysis showed that the targets of BYHWD focused on smooth muscle cell proliferation, migration, and apoptosis, which are classic biological processes involved in pulmonary vascular remodeling and are closely related to the PI3K-Akt-eNOS pathway. The methods of biological experiments were adopted to verify the above results. The present study elucidated the mechanism of BYHWD in the treatment of PH and provided new ideas for the clinical use of TCM in the treatment of PH.


Are measures employed in the assessment of balance useful for detecting differences among groups that vary by age and disease state?
This study explored the usefulness of measures commonly employed in the examination of persons with balance impairment to discriminate between performances of young and older adults and older adults with and without neurological disease. Eighteen young adults, 22 healthy older adults, 12 individuals with Parkinson disease, and 20 older adults with peripheral neuropathy were recruited from the community.Performances on the following measures were compared: Mini Mental State Exam, grip strength, timed chair rise, semitandem and tandem stance, Timed Up and Go (TUG), and Berg Balance Scale (BBS). Survival analysis was used to analyze semitandem and tandem stance. Grip strength and other tests were analyzed using analysis of variance. Tukey multiple comparison procedure was employed to assess differences in performance among groups. Significant differences in performance were found for all measures. Grip and timed chair rise discriminated young and older adult groups. Timed chair rise, tandem stance, TUG, and BBS detected differences between healthy individuals and those with disease. Semitandem stance and BBS discriminated between individuals with disease conditions. When examining individuals with balance difficulty, combinations of measures are needed to discriminate between clinically distinct groups.


[Considerations of psychopathology in mental retardation].
There is a high incidence of psychiatric disorders in mentally retarded subjects: one third to two thirds of mentally retarded subjects exhibit psychiatric disorders, a proportion which is much higher than that found in subjects with normal intelligence. The issue is to clarify the nature of the relationship between cognitive and psychiatric disorders (generally analyzed in a dichotomous approach). A way to analyze the phenomenon is to consider a psychopathological approach, which can define the underlying mechanisms responsible for this incidence. The aim of this paper is to analyze the explicatory value of deficient cognitive development, as the main factor determining a specific personality organization. Direct and indirect effects of cognitive impairment on the development of personality disorders are described: the first, in terms of how cognitive deficit (i.e. severity, homogeneity in several cognitive domains, pattern of development) disorganizes personality; the second, in terms of impact that cognitive deficit could have on the child's relationship with the external world, especially with the mother. In order to illustrate these viewpoint, the paper discusses the role of cognitive functions in the development of personality. Specifically, the way the normal child processes his perceptual and motor experiences is analyzed, that is pursuit of new causal links in his knowledge seeking activity of mastering the world. The child's primitive relationship with the world is then aimed at learning, exploring and searching for new causal links. In the light of these considerations, what the child with Mental Retardation experiences is discussed. A series of psychopathological mechanisms in Mental Retardation are postulated. The organization of the Mentally Retarded child's internal world is described, as reflected in Rorschach protocols, which outline a chaotic and primitive internal world, but with a specificity of its own. Finally, the paper discusses the hampering effect that cognitive impairment has on the quality of the relationship with the caregiver. This effect can be seen in terms of the child's interactive capacity and, at the same time, in terms of the emotional impact on the caregiver that derives from interacting with a mentally retarded child. From the above considerations a global approach to the psychopathology of cognitive and affective aspects of Mental Retardation seems warranted. Both aspects acquire a specific significance when seen in light of a specific personality organization. Defining the characteristic of this specific organization seems to be the key to a more comprehensive approach to psychiatric disorders of Mental Retardation.


Nelfinavir, an HIV-1 protease inhibitor, induces oxidative stress-mediated, caspase-independent apoptosis in Leishmania amastigotes.
Visceral leishmaniasis has now emerged as an important opportunistic disease in patients coinfected with human immunodeficiency virus type-1 (HIV-1). Although the effectiveness of HIV-1 protease inhibitors, such as nelfinavir, in antiretroviral therapies is well documented, little is known of the impact of these drugs on Leishmania in coinfected individuals. Here, we show that nelfinavir generates oxidative stress in the parasite, leading to altered physiological parameters such as an increase in the sub-G1 DNA content, nuclear DNA fragmentation and loss of mitochondrial potential, which are all characteristics of apoptosis. Pretreatment of axenic amastigotes with the caspase inhibitor z-VAD-fmk did not inhibit the increase in sub-G1 DNA content in nelfinavir-treated parasites, suggesting therefore that this antiviral agent does not kill Leishmania amastigotes in a caspase-dependent manner. Furthermore, we observed that the mitochondrial resident protein endonuclease G is involved. We also demonstrate that parasites overexpressing GSH1 (the rate limiting enzyme of glutathione biosynthesis) were more resistant to nelfinavir when compared to untransfected controls. These data suggest that nelfinavir induces oxidative stress in Leishmania amastigotes, culminating in caspase-independent apoptosis, in which DNA is degraded by endonuclease G. This study provides a rationale for future, long-term design of new therapeutic strategies to test nelfinavir as a potential antileishmanial agent as well as for possible future use in Leishmania/HIV-1 coinfections.


Fusiform superior cerebellar artery aneurysm presenting with contralateral abducens nerve paresis--case report.
A 25-year-old female suddenly developed headache and diplopia. On admission, neurological examination revealed neck stiffness and left abducens nerve paresis. A computed tomographic scan suggested subarachnoid hemorrhage. Left vertebral angiogram showed an aneurysm on the anterior pontine segment of the right superior cerebellar artery (SCA) and marked flexion and meandering of the basilar artery to the left. At surgery, an atherosclerotic, fusiform aneurysm was found through the right subtemporal transtentorial approach, and the right SCA was clipped just proximal to the aneurysm. Thirteen cases of SCA aneurysm have been described in the literature, but none was a fusiform aneurysm.


Molecular basis of D variants between Uigur and Han blood donors in Xinjiang.
The D antigen is the most antigenic in the Rh blood group system. Variation in the D antigen may have the potential to cause alloimmunization. D variant may have different molecular backgrounds in people of different ethnic groups. The aim of this study was to investigate serological and molecular differences related to the D antigen among Chinese ethnic groups. Blood samples of six different races in Xinjiang were screened for D variants using serological test. The suspected D variants were further analyzed by using polymerase chain reaction and sequencing to determine the RHD genotype. Fourteen D elute phenotypes (DELs), included 11 Han, 2 Uigur and 1 Hui, were detected together with two weak Ds, one in the Han and one in the Uigur. The 14 DELs possessed the RHD (K409K) allele. The weak D found in the Han was of type 15, but the Uigur phenotype was of weak D type 5. Our results suggest that the Uigur population has both Han and Caucasian characteristics in the Rh blood group system, but the RHD genotypes of other minorities settled in China need to be further studied. A different strategy for Rh typing based on ethnic specificity should be used to detect D variants.


Metal-Organic Framework Materials in Perovskite Solar Cells: Recent Advancements and Perspectives.
Organic-inorganic hybrid perovskite solar cells (PSCs) are among the most promising candidates for the next generation of photovoltaic devices because of the significant increase in their power conversion efficiency (PCE) from less than 10% to 25.7% in past decade. The metal-organic framework (MOF) materials owing to their unique properties, such as large specific surface area, abundant binding sites, adjustable nanostructures, and synergistic effects, are used as additives or functional layers to enhance the device performance and long-term stability of PSCs. This review focuses on the recent advancements in the applications of MOFs as/in different functional layers of PSCs. The photovoltaic performance, impact, and advantages of MOF materials integrated into the perovskite absorber, electron transport layer, hole transport layer, and interfacial layer are reviewed. In addition, the applicability of MOFs to mitigate leakage of Pb2+ from halide perovskites and corresponding devices is discussed. This review concludes with the perspectives on further research directions for employing MOFs in PSCs.


Use of alcohol biomarkers to identify alcohol misuse in organ donors.
Phosphatidylethanol is a direct alcohol biomarker for identifying alcohol misuse. It carries several advantages over other alcohol biomarkers, including a detection half-life of several weeks and little confounding by patient characteristics or organ dysfunction. The aim of this study is to derive an optimal phosphatidylethanol cut point to identify organ donors with alcohol misuse, and to assess the impact of alcohol misuse on organ allocation. Discrimination of phosphatidylethanol was evaluated using the area under the ROC curve from a mixed effects logistic regression model. Phosphatidylethanol had an area under the ROC curve of 0.89 (95% CI 0.80-0.98). A phosphatidylethanol cut point of ≥84 ng/mL provided optimal discrimination for the identification of alcohol misuse with a sensitivity of 75% (95% CI 52.9%-89.4%) and a specificity of 97% (95% CI 91%-99%), a positive predictive value of 82% (95% CI 59%-94%), and a negative predictive value of 95% (95% CI 89%-98%). In deceased organ donors who had been critically ill, phosphatidylethanol had good test characteristics to discriminate alcohol misuse. Other alcohol biomarkers performed poorly in deceased organ donors. Liver allocation was decreased in donors with alcohol misuse by proxy history, but not in those with phosphatidylethanol >84 ng/mL, revealing possible information bias in liver allocation.


Antibacterial activities of Ramalin, usnic acid and its three derivatives isolated from the Antarctic lichen Ramalina terebrata.
The development of new antibacterial compounds is an urgent issue to meet the evolution of resistivity of pathogenic bacteria against the available drugs. The objective of this study was to investigate the antibacterial compounds from the Antarctic lichen species Ramalina terebrata. A total of five compounds, usnic acid, usimine A, usimine B, usimine C, and ramalin, were isolated by bioactivity guided-fractionation of the methanol extract of R. terebrata after several chromatographic procedures. The qualitative antibacterial activities of the crude extract and isolated compounds were determined by the disk diffusion method while the minimum inhibitory concentration (MIC) determination assay gave the quantitative strength of the test samples. All the test samples showed antibacterial activity against Bacillus subtilis. The crude extract and usnic acid showed antibacterial activity against Staphylococcus aureus. The MIC values of the isolated compounds against B. subtilis were in the range of 1 to 26 microg/mL. These observed experimental data showed the strong antibacterial potential of these compounds against B. subtilis.


Hematopoietic stem cell autografts in support of myeloablative therapy for multiple myeloma.
This paper reports the experience of a single investigator team on the use of autografting in support of myeloablative therapy for multiple myeloma. This demonstrates continued progress toward decreased morbidity, and virtual elimination of mortality, as a result of rapid hematopoietic recovery, due to the use of peripheral blood stem cell grafts in newly diagnosed patients receiving several non-cross-resistant induction regimens followed by two autologous transplants, complete remission rates in excess of 50% can be achieved. Prognostic factors have also been identified for event-free and overall survival.


Chromium(VI) biosorption by dried Rhizopus arrhizus: effect of salt (NaCl) concentration on equilibrium and kinetic parameters.
Some industrial wastewaters contain high quantities of salts besides heavy metal ions. The presence of salt ions leads to high ionic strength, which may significantly affect the performance of the biosorption process so the effect of salts on the biosorption of heavy metal ions should be investigated. In this study the biosorption of chromium(VI) from saline solutions on dried Rhizopus arrhizus was studied as a function of pH, initial chromium(VI) and salt (NaCl) concentrations in a batch system. The biosorption capacity of R. arrhizus strongly depended on solution pH and maximum chromium(VI) sorption capacity of sorbent was obtained at pH 2.0 both in the absence and in the presence of increasing concentrations of salt. Chromium(VI)-salt biosorption studies were performed at this pH value. Equilibrium uptakes of chromium(VI) increased with increasing chromium(VI) concentration up to 250mgl(-1) and decreased considerably by the presence of increasing concentrations of salt. At 100mgl(-1), initial chromium(VI) concentration, dried R. arrhizus biosorbed 78.0mgg(-1) of chromium(VI) in 72h without salt medium. When salt concentration was raised to 50gl(-1), this value dropped to 64.0mgg(-1) of chromium(VI) at the same conditions resulting in 17.9% decrease of biosorption capacity. The equilibrium sorption data were analysed by using Freundlich, Langmuir, Redlich-Peterson and Langmuir-Freundlich (Sips), the two and three parameters adsorption models, using non-linear regression technique and isotherm constants were evaluated depending on salt concentration. The Langmuir-Freundlich (Sips) was the best suitable adsorption model for describing the biosorption of chromium(VI) individually and in salt-containing medium. Pseudo-first-order, pseudo-second-order and saturation type kinetic models described the biosorption kinetics accurately at all chromium(VI) concentrations in the absence and in the presence of changing concentrations of salt. Isotherm and saturation type kinetic constants varied due to the level of salt were expressed as a function of initial salt concentration.


Use of computational modeling combined with advanced visualization to develop strategies for the design of crop ideotypes to address food security.
Sustainable crop production is a contributing factor to current and future food security. Innovative technologies are needed to design strategies that will achieve higher crop yields on less land and with fewer resources. Computational modeling coupled with advanced scientific visualization enables researchers to explore and interact with complex agriculture, nutrition, and climate data to predict how crops will respond to untested environments. These virtual observations and predictions can direct the development of crop ideotypes designed to meet future yield and nutritional demands. This review surveys modeling strategies for the development of crop ideotypes and scientific visualization technologies that have led to discoveries in "big data" analysis. Combined modeling and visualization approaches have been used to realistically simulate crops and to guide selection that immediately enhances crop quantity and quality under challenging environmental conditions. This survey of current and developing technologies indicates that integrative modeling and advanced scientific visualization may help overcome challenges in agriculture and nutrition data as large-scale and multidimensional data become available in these fields.


Cardiorespiratory responses to glutamatergic antagonists in the caudal ventrolateral medulla of rats.
The role of caudal ventrolateral medullary (CVLM) depressor neurons in influencing arterial pressure and ventilation as well as the baroreflex control of arterial pressure was investigated, and the part played by excitatory N-methyl-D-aspartate (NMDA) and non-NMDA receptors in mediating the responses was determined. In urethane-anesthetized, spontaneously breathing rats unilateral microinjections into the caudal depressor area of the broad-band glutamatergic antagonist kynurenic acid (KYN, 5 nmol or 1.58 nmol), or NMDA antagonist 2-amino-5-phosphonovaleric acid (2-APV, 2.7 nmol), or the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 0.257 nmol) caused a respiratory arrest within 4 min and the animals had to be artificially ventilated. Respiratory frequency increased on injecting KYN and CNQX while it did not change significantly with 2-APV. Apnea resulted from progressive decrease in tidal volume. During the apnea ventilation with 5% CO2 did not revive breathing. Mean arterial pressure (MAP) increased significantly with KYN and 2-APV injections but not with CNQX. The baroreflex decrease of MAP, elicited by left or right aortic depressor nerve stimulation, was significantly reduced or abolished after bilateral microinjections of all 3 antagonists. Ventilation as well as the baroreflex usually recovered after 1-1.5 h. Microinjections of the same doses of antagonists into the facial nucleus, as well as application of KYN (25 nmol) to the ventral medullary surface above the hypoglossal rootlets, had no significant effect. The results support previous findings that the CVLM neurons of the rat inhibit sympathetic neurons providing the vasomotor tone, and that an intact CVLM is obligatory for mediating the baroreflex decrease of arterial pressure. The results also indicate that: (1) the CVLM is essential for sustaining ventilation in the rat; (2) only NMDA receptors are involved in maintaining baseline blood pressure while both NMDA and non-NMDA receptors mediate the baroreceptor depressor reflex; and (3) both NMDA and non-NMDA receptor activation is necessary to sustain ventilation.


[Russell's syndrome: a case of long-term survival and review of the literature].
We report the case of a two years old, normally eating child, affected by organic macies and severe dystrophy. After the negative response of blood and laboratory examinations let us exclude a malabsorption syndrome, only the performance of neuro-radiologic exams showed evidence of a subthalamic tumor as the cause of a "Diencephalic syndrome". Diencephalic syndrome or Russell's syndrome is a diencephalic tumor induced disease, which sets in the first time of life. The disease clinical markers are a severe emaciation with appetite preservation and absence or very scarce evidence of any telltale neurological sign. The tumoral histo-pathology most frequently shows a low grade of malignancy astrocytoma, whose eradication is very often difficult because of particular anatomic site. Treatment of choice includes an excisional biopsy with chemotherapy and radiotherapy. We report a clinical case of long-term survival and review of the literature.


[Carcinoembryonic antigen as a marker of proliferative diseases of the lymphatic system in patients with chronic renal failure--case report].
In patients with CKD, anaemia mainly develops due to a decreased renal synthesis of erythropoietin. The anaemia, both normochromic and normocytic, becomes more severe as the glomerular filtration rate progressively decreases. Tumor markers are used to detect or monitor proliferative diseases. Carcinoembryonic antigen (CEA) is usually produced in the gastrointestinal tract, but its production is terminated before birth. The main application of this indicator is to monitor the treatment and the presence of metastases of colorectal cancer. We present a case of 86-year-old woman who was diagnosed with renal anaemia in stage 4 of chronic kidney disease (CKD), treated by periodic blood transfusions. This paper presents the difficulties in diagnosis and treatment of anemia with complex and different than renal origin anemia in patients with CKD. Patients require the detailed haematological diagnosis. Pointed out the usefulness of CEA in the diagnosis of lymphoma with co-existing renal failure. The use of erythropoietin in doses of nephrology allowed to avoid further blood transfusion.


Angiographic deterioration of target coronary artery narrowing as a result of percutaneous balloon angioplasty.
We evaluated the long-term angiographic outcome of balloon angioplasty by comparing original and follow-up target coronary narrowing. Rather than using restenosis to determine outcome, as in most angioplasty studies, we took an unusual approach and analyzed outcome in terms that are commonly used in progression and regression studies after medical interventions. Quantitative angiographic measurements were undertaken in 315 narrowings with an initial diameter stenosis <90% before and after angioplasty and at follow-up. Angiographic deterioration (>10% increase in follow-up diameter stenosis) was identified in 44 (14%) narrowings. Angiographic deterioration was not influenced by age, sex, risk factors, lipid profile, or the indication for angioplasty. Deterioration was also not predicted by the severity, length, or the location of the narrowing. The deteriorating narrowings had a higher recoil after dilatation compared with narrowings with angiographic improvement (21% +/- 31% vs 12% +/- 17%, p = 0.006); the residual stenosis after angioplasty was therefore higher. The late loss was also significantly increased compared with narrowings with angiographic improvement (65% +/- 26% vs 8% +/- 24%, p < 0.001). We conclude that the incidence of angiographic deterioration of coronary disease as a result of restenosis is uncommon but not negligible. Interventional cardiologists should resist the temptation to dilate mild, silent coronary narrowings because the procedure might have an unfavorable angiographic (and probably clinical) effect.


High-performance hybrid complementary logic inverter through monolithic integration of a MEMS switch and an oxide TFT.
A hybrid complementary logic inverter consisting of a microelectromechanical system switch as a promising alternative for the p-type oxide thin film transistor (TFT) and an n-type oxide TFT is presented for ultralow power integrated circuits. These heterogeneous microdevices are monolithically integrated. The resulting logic device shows a distinctive voltage transfer characteristic curve, very low static leakage, zero-short circuit current, and exceedingly high voltage gain.


Search for the Decomposition Process of 2,4,6-Trinitrotoluene by an Evolutionary Algorithm.
In this paper, we explored stable states in the system of 2,4,6-trinitrotoluene (TNT) crystal with a few additional hydrogen radicals (Hadd's) using a structure-search scheme based on first-principles calculations and an evolutionary algorithm (EA) to get insights into the decomposition process of TNT. We introduced three evolutionary operators acting on Hadd's and transforming only local structures of TNT molecules: "displacement", "permutation", and "mating". We searched for stable structures by increasing the number of Hadd's (n) from 1 to 2, 3, 4, 6, and 8 and constructed a convex-hull diagram for the formation energy from solid TNT and solid hydrogen. We showed that the system of n = 6 had the largest energy reduction, in which five of the eight TNT molecules in the calculation cell were transformed into NO, H2O, C2H3N, C2NO3H3, C8N2O4H7, C9N2O8H5, and C14N7O12H11. Analysis of the structural transformations observed during the EA search indicates that (1) the Hadd's approaching the TNT molecules react with C, forming a six-membered ring, and with N and O in nitro groups, leaving the TNT molecules as NO, H2O, C2H3N, and C2NO3H3, and (2) the partially decomposed TNT molecules are bonded to one another via C, N, and O.


Fate of heavy metals during municipal solid waste incineration.
A thermodynamic analysis was performed to determine whether it is suitable to predict the heavy metal (HM) speciation during the Municipal Solid Waste Incineration process. The fate of several selected metals (Cd, Pb, Zn, Cr, Hg, As, Cu, Co, Ni) during incineration was theoretically investigated. The equilibrium analysis predicted the metal partitioning during incineration and determined the impact of operating conditions (temperature and gas composition) on their speciation. The study of the gas composition influence was based on the effects of the contents of oxygen (reducing or oxidising conditions) and chlorine on the HM partitioning. The theoretical HM speciation which was calculated in a complex system representing a burning sample of Municipal Solid Waste can explain the real partitioning (obtained from literature results) of all metals among the various ashes except for Pb. Then, the results of the thermodynamic study were compared with those of characterisation of real incinerator residues, using complementary techniques (chemical extraction series and X-ray micro-analyses). These analysis were performed to determine experimentally the speciation of the three representative metals Cr, Pb, and Zn. The agreement is good for Cr and Zn but not for Pb again, which mainly shows unleachable chemical speciations in the residues. Pb tends to remain in the bottom ash whereas thermodynamics often predicts its complete volatilisation under chlorides, and thus its presence exclusively in fly ash.


Patterns of opioid prescribing in emergency departments during the early phase of the COVID-19 pandemic.
The COVID-19 pandemic was superimposed upon an ongoing epidemic of opioid use disorder and overdose deaths. Although the trend of opioid prescription patterns (OPP) had decreased in response to public health efforts before the pandemic, little is known about the OPP from emergency department (ED) clinicians during the COVID-19 pandemic. We conducted a pre-post study of adult patients who were discharged from 13 EDs and one urgent care within our academic medical system between 01/01/2019 and 09/30/2020 using an interrupted time series (ITS) approach. Patient characteristics and prescription data were extracted from the single unified electronic medical record across all study sites. Prescriptions of opioids were converted into morphine equivalent dose (MED). We compared the "Covid-19 Pandemic" period (C19, 03/29/2020-9/30/2020) and the "Pre-Pandemic" period (PP, 1/19/2020-03/28/2020). We used a multivariate logistic regression to assess clinical factors associated with opioid prescriptions. We analyzed 361,794 ED visits by adult patients, including 259,242 (72%) PP and 102,552 (28%) C19 visits. Demographic information and percentages of patients receiving opioid prescriptions were similar in both groups. The median [IQR] MED per prescription was higher for C19 patients (70 [56-90]) than for PP patients (60 [60-90], P < 0.001). ITS demonstrated a significant trend toward higher MED prescription per ED visit during the pandemic (coefficient 0.11, 95% CI 0.05-0.16, P = 0.002). A few factors, that were associated with lower likelihood of opioid prescriptions before the pandemic, became non-significant during the pandemic. Our study demonstrated that emergency clinicians increased the prescribed amount of opioids per prescription during the COVID-19 pandemic compared to the pre-pandemic period. Etiologies for this finding could include lack of access to primary care and other specialties during the pandemic, or lower volumes allowing for emergency clinicians to identify who is safe to be prescribed opioids.