Role of constraint in catalysis and high-affinity binding by proteins.
Using a model for catalysis of a dynamic equilibrium, the role of constraint in catalysis is quantified. The intrinsic rigidity of proteins is shown to be insufficient to constrain the activated complexes of enzymes, irrespective of the mechanism. However, when minimization of the surface excess free energy of water surrounding a protein is considered, model proteins can be designed with regions of sufficient rigidity. Structures can be designed to focus surface tension or hydrophobic attraction as compressive stress. A monomeric structure has a limited ability to concentrate compressive stress and constrain activated complexes. Oligomeric or multidomain proteins, with domains surrounding a rigid core, have unlimited ability to concentrate stress, provided there are at least four domains. Under some circumstances, four is the optimum number, which could explain the frequency of tetrameric enzymes in nature. The minimum compressive stress in oligomers increases with the square of the radius. For tetramers of similar size to natural enzymes, this stress agrees reasonably well with that needed to constrain the activated complex. A similar principle applies to high affinity binding proteins. The models explain the trigonal pyramidal shape of fibroblast growth factor and provide a basis for interpretation of protein crystal structures.


Analysis of pyridine dinucleotides in cultured rat hepatocytes by high-performance liquid chromatography.
An isocratic reverse-phase high-performance liquid chromatography method for the separation and quantitation of total pyridine dinucleotides in hepatocyte cultures is described. Cells are extracted with cold 3 M perchloric acid or 0.5 N sodium hydroxide containing 50% (v/v) ethanol and 35% cesium chloride for the determination of the oxidized or reduced pyridine dinucleotides, respectively. Pyridine dinucleotides in the neutralized extracts were separated on an Excellopak ODS C18 (4.6 X 150 mm) column with 0.1 M potassium phosphate, pH 6.0, containing 3.75% methanol as the mobile phase. NAD+ and NADP+ were detected spectrophotometrically at 254 nm. The response was linear from 5 to 4000 pmol with recoveries of NAD+ and NADP+ of 98 and 101.1%, respectively. NADH and NADPH were monitored fluorometrically by activation at 370 nm and emission in the 400-700 nm range. The reduced pyridine dinucleotides had a linear response from 7.5 to 60 pmol with recoveries of NADH and NADPH of 99.4 and 101.3%, respectively. The coefficients of variation for all of the pyridine dinucleotide standards were less than 3.5%.


Mouthguard use and attitudes regarding dental trauma among elite cross-country mountain biking and field hockey athletes.
Cross-country mountain biking and field hockey are two Olympic sports that pose a potential risk for dentofacial trauma. However, mouthguard use is not mandatory in either of these sports and knowledge about tooth rescue among athletes is often neglected. The aim of this cross-sectional epidemiological survey was to evaluate the prevalence of sports-related dentofacial injuries, mouthguard use, and attitudes regarding tooth rescue among cross-country mountain biking and field hockey athletes participating at pre-Olympic competitions held in Rio de Janeiro, Brazil. A convenience sample of 217 athletes from 33 countries participating in cross-country mountain biking (n = 82; mean age = 30.96 ± 8.52 years) and field hockey (n = 135; mean age = 19.72 ± 2.46 years) pre-Olympic competitions were examined clinically, and they answered a questionnaire regarding previous history of sports-related dentofacial injuries, attitudes toward mouthguard use, and tooth rescue. There were 120 (55.30%) males and 97 (44.70%) females who participated in the study. The prevalence of facial trauma was higher in mountain biking (54.88%) than in field hockey (26.66%, P < .001). Fracture was the most prevalent facial injury in mountain biking (80%), while laceration was the most prevalent in field hockey (30.55%). Extensive dental injuries occurred more often in mountain biking (47.37%) than in hockey (12.50%). The teeth most often affected were the maxillary central incisors in both mountain biking (57.89%) and field hockey (93.75%). Mouthguard use was more frequent among field hockey athletes (41.48%) than in mountain biking (1.22%, P < .001). The overall knowledge about tooth rescue was low, and most of the athletes in both sports did not know what to do in case of an avulsed tooth. Prevalence of dentofacial injuries among XCO-MTB and field hockey athletes participating at this pre-Olympic event was high. The majority of the athletes in this study did not use mouthguards and were unaware of recommendations in the case of an avulsed tooth.


Genetic epidemiology of hemoglobinopathies among Iraqi Kurds.
Hemoglobinopathies are major health problems among Iraqi Kurds, who are a distinct ethnic group inhabiting North and Northeastern Iraq. We reviewed published literature on these disorders in this part of the world, and it was revealed that the most prevalent is β-thalassemia with carrier rates of 3.7-6.9%. Alpha thalassemia is less prevalent with carrier rates of 0.03-1.22%, while the sickle cell gene is variably distributed with carrier rates of 0.06-1.2%. Other structural hemoglobinopathies and δβ-thalassemia are sporadic. Twenty-seven different β-thalassemia mutations were identified, with seven constituting 82% of 1039 chromosomes characterized, namely: IVS-II-1 (G>A), IVS-I-6 (T>C), IVS-I-I (G>A), codon 8 (-AA), codon 8/9 (+G), IVS-I-110 (G>A), and codon 5 (-CT). There were notable regional variations in the distribution of β-thalassemia mutations, with Cd44 being mainly prevalent in the North, while IVS-I-110 is mainly prevalent in the East. In relevance to α-thalassemia, ten different mutations were detected, with the four most frequent constituting 92.4% of 262 alleles characterized being: -α3.7, --MED, α-5ntα, and αPolyA1α. In relevance to sickle cell gene, it is seen in the northern part of the region bordering Turkey, with comparable prevalence rates, and is associated, similar to Turkey, mainly with the Benin haplotype, unlike that in Southern Iraq where it is associated with the Arab-Indian haplotype, similar to Eastern Arabian Peninsula. Given the high prevalence of hemoglobinopathies in the region, and the high rates of consanguineous marriages, a preventive program was initiated in 2008, and results of its first 5 years were promising, though there are still many outstanding challenges that require addressing.


Oral contraceptive induced paraballism.
We report a case of paraballism in a young female, which became apparent 4 months after initiating oral contraception. When the oral contraceptive was discontinued, the paraballism decreased and was replaced by choreic movements for a period of approximately 2 weeks. The abnormal movements disappeared gradually. Only 13 cases of paraballism have been reported in medical literature, and none has been attributed to the use of oral contraceptives.


Comparison of chromium and cobalt serum levels between a modular neck stem and its monoblock counterpart in primary total hip arthroplasty.
The addition of junctions in modular stems implies a greater susceptibility to corrosion. The aim of this study is to compare serum chromium and cobalt levels after using a bimodular stem and its monoblock counterpart in primary total hip arthroplasty. Postoperative clinical scores were also compared. A prospective cohort study between 2012 and 2015 was designed. One arm of the cohort included patients with the cementless modular neck stem H-Max M® and the other with the cementless monoblock stem counterpart H-Max S®. No statistically significant difference was found in chromium value between groups (p = 0.621) at two years postoperative. Cobalt value was higher in the modular group (p = < 0.001). No statistically significant difference was found in clinical postoperative scores except for the Harris Hip Score, with better results at six months in modular group (p = 0.007). Higher serum cobalt level in the modular group has limited the use of modular stems in our daily practice. Advantages of modular stem were not found. II.


Fear, isolation and the importance of support: A qualitative study of parents' experiences of feeding a child born with esophageal atresia.
Feeding and swallowing difficulties in children are increasing due to improved survival rates of children with complex medical conditions. Despite being common complications of esophageal atresia (EA), EA related feeding difficulties have received little attention in research. Establishing positive feeding interactions and practices are important for child health and development, and for parental and child mental health. The current study aimed to investigate the parental experiences of feeding a child born with EA. An international online survey was developed and disseminated to parents of children born with EA, aged 0-12 years, in collaboration with a patient charity for EA. Reflexive Thematic Analysis was used to analyze the qualitative survey responses. 176 participants were included in the qualitative sample from a larger international online survey study, chosen by a process of selective coding. Three themes were constructed during the analysis: 1) Anxiety, trauma and loss; 2) Isolated and unsupported; and 3) Supported. The results indicated that parents of children born with EA experienced significant anxiety related to their child's swallowing and feeding difficulties and traumatic experiences during feeding, and that these led to parents feeling a sense of loss and sadness. It was also found that support, or a lack of support, within parents' social environment might mediate parental experiences of child's feeding difficulties. This study highlighted the importance of support for parents of children born with EA, and suggested a need for improved guidance for feeding and swallowing difficulties.


TRIM9 is specifically expressed in the embryonic and adult nervous system.
The TRIM family members are defined by the presence of the tripartite motif (RING, B-box and coiled-coil domains or RBCC). They have been implicated in a variety of processes, such as regulation of development and oncogenesis. We report the expression analysis of a member of this family, TRIM9. Its expression is mainly confined to the central nervous system. The developing neocortex, the dorsal thalamus, the midbrain, the basal area of the hindbrain and spinal cord show high level of expression during embryogenesis. In adult brain, TRIM9 is detected in the Purkinje cells of the cerebellum, in the hippocampus, and in the cortex.


Zn isotope fractionation in a pristine larch forest on permafrost-dominated soils in Central Siberia.
Stable Zn isotopes fractionation was studied in main biogeochemical compartments of a pristine larch forest of Central Siberia developed over continuous permafrost basalt rocks. Two north- and south-oriented watershed slopes having distinctly different vegetation biomass and active layer depth were used as natural proxy for predicting possible future climate changes occurring in this region. In addition, peat bog zone exhibiting totally different vegetation, hydrology and soil temperature regime has been studied. The isotopic composition of soil profile from Central Siberia is rather constant with a δ(66)Zn value around 0.2‰ close to the value of various basalts. Zn isotopic composition in mosses (Sphagnum fuscum and Pleurozium schreberi) exhibits differences between surface layers presenting values from 0.14 to 0.2‰ and bottom layers presenting significantly higher values (0.5 - 0.7‰) than the underlain mineral surface. The humification of both dead moss and larch needles leads to retain the fraction where Zn bound most strongly thus releasing the lighter isotopes in solution and preserving the heavy isotopes in the humification products, in general accord with previous experimental and modeling works [GCA 75:7632-7643, 2011]. The larch (Larix gmelinii) from North and South-facing slopes is enriched in heavy isotopes compared to soil reservoir while larch from Sphagnum peatbog is enriched in light isotopes. This difference may result from stronger complexation of Zn by organic ligands and humification products in the peat bog compared to mineral surfaces in North- and South-facing slope. During the course of the growing period, Zn followed the behavior of macronutrients with a decrease of concentration from June to September. During this period, an enrichment of larch needles by heavier Zn isotopes is observed in the various habitats. We suggest that the increase of the depth of rooting zone, and the decrease of DOC and Zn concentration in soil solution from the root uptake zone with progressively thawing soil could provoke heavy isotopes to become more available for the larch roots at the end of the vegetative season compared to the beginning of the season, because the decrease of DOC will facilitate the uptake of heavy isotope as it will be less retained in strong organic complexes.


Evidence of different complementation groups amongst human genetic disorders characterized by radiosensitivity.
The genetic diversity of a clinically heterogeneous group of ionizing radiation-sensitive human mutants has been examined. In this group, the relationship between ataxia telangiectasia (A-T), Alzheimer's disease (AD) and Down's syndrome (DS) was studied, on the basis of their cellular radiosensitivity. Cell-fusion analysis was used to determine the presence of different complementation groups. In a series of 4A-T, 5AD and 4DS cell lines, 8 complementation groups were documented. These findings suggest that this group of primary neuronal degenerative disorders might have some overlap in their genetic defects.


Myopia associated with optic nerve gliomas in neurofibromatosis type 1.
Optic nerve gliomas occur with increased frequency in neurofibromatosis type 1 (NF1) and constitute NF1's most frequent cause of visual loss. Axial elongation of the globe may occur in NF1 as a consequence of glaucoma, but in the absence of glaucoma that occurrence has received limited attention. We present 4 patients with NF1 who were found to have myopia and anisometropia in association with unilateral or asymmetric optic nerve gliomas. In one patient, progressive enlargement of the optic nerve glioma corresponded with further increases in myopia. To our knowledge, the association of myopia ipsilateral to the presence or growth of optic nerve gliomas has not been reported.


Effects of an interpersonal-psychotherapy-oriented childbirth education programme for Chinese first-time childbearing women at 3-month follow up: randomised controlled trial.
Developing a sense of well-being and achieving maternal role competence are considered critical components of maternal adaptation. Given the growing evidence of postpartum depression and its devastating effects, effective childbirth psychoeducation programme to promote maternal role competence, psychological well-being and prevent postpartum depression is essential and of an urgent priority. To examine the effects of an interpersonal psychotherapy oriented childbirth education programme on social support, maternal role competence, postpartum depression and psychological well-being in Chinese first-time childbearing women at three-month postpartum. Randomised controlled trial in a regional teaching hospital, Guangzhou, China with 194 first-time pregnant women, of whom 96 received interpersonal-psychotherapy-oriented childbirth education programme and 98 standard care. The intervention was developed from principles of interpersonal psychotherapy which consisted of two 90-min antenatal classes and a telephone follow-up within two weeks after delivery. Outcomes measurements included Perceived Social Support Scale, Parenting Sense of Competence Scale-Efficacy subscale, Edinburgh Postnatal Depression Scale and General Health Questionnaire, were compared over three-month follow up. The study group had significantly better improvement on perceived social support (p<0.01), maternal role competence (p<0.01), postpartum depressive symptoms (p<0.01) and psychological well-being (p<0.01) when compared with the control group. The study group also had significantly higher level of social support (t=2.33, p=0.021), maternal role competence (t=2.43, p=0.016) and less depressive symptoms (t=-2.39, p=0.018) at three-month postpartum when compared with the control group. The childbirth psychoeducation programme can substantially benefit first time Chinese mothers. It could be implemented as a routine care with ongoing evaluation. Future studies could focus on women in lower social classes, with multiple pregnancy and complicated pregnancy.


[What do we know about atypical fractures in patients on biphosphonates treatment? A literature review using a case series].
Retrospective review of long term biphosphonates treated patients who sustained a subtrochanteric or diaphyseal femoral fracture with an atypical pattern. A literature review is presented as an update of the topic. A retrospective study was conducted on 13 subtrochanteric or diaphyseal fractures in female patients treated with biphosphonates at our institution from September 2007 to March 2011. Four cases of subtrochanteric fractures and 13 diaphyseal fractures were detected. Four patients had bilateral fractures. All cases but one (that affected only the lateral cortex) were complete fractures. Surgically, these kinds of fractures are demanding due to the hardness of the bones. It is difficult to know if there is any relationship between bisphosphonates treatment and atypical femoral fractures. Nevertheless, current literature supports a greater benefit of their use in preventing vertebral and non-vertebral fractures. For this reason, biphosphonates continue being considered as a first choice in the prevention of osteoporotic fractures. Patients on long-term treatment with bisphosphonates may present atypical femoral fractures as a complication. It is considered that the maximum period for biphosphonates treatment should not exceed 5 years.


Restriction of human papillomavirus DNA testing in primary cervical screening to women above age 30: systematic review.
Cervical screening with human papillomavirus (HPV) testing is less specific for high-grade cervical intraepithelial neoplasia (≥CIN3) than cytology. The aim of this systematic review was to determine whether a restriction of HPV testing to women aged at least 30 years would eliminate the problem. On the basis of the data from randomized controlled trials, we calculated the relative detection of CIN1 and CIN2, and the relative risks of false-positive tests (positive tests without subsequent ≥CIN3) per age group and trial for HPV testing versus cytology. For women aged at least 30 years in trials with a low cytology abnormality rate, detection of CIN1 increased significantly by 50-90% in the two trials with reported data; detection of CIN2 was doubled in three trials; the risks of false-positive HPV tests were also doubled. In trials with a high cytology abnormality rate, these risks were similar for HPV testing and cytology. Adverse effects of HPV testing were for both types of cytology settings, generally higher for women below than above the age of 30. Adverse effects were less common among women aged at least 30 years than among younger women. However, in older women HPV testing still led to more CIN1/CIN2 diagnoses and false-positive tests than cytology.


Increased patient satisfaction by integration of palliative care into geriatrics-A prospective cohort study.
Integration of oncology and palliative care has been shown to increase quality of life in advanced disease. To meet the needs of the growing older population, integration of palliative care and geriatrics has been proposed but scarcely described. The aim of this study was to integrate palliative care into geriatrics by a structured care guide, the Swedish Palliative Care Guide, and to evaluate its effect on patient satisfaction, health-related quality of life and symptom burden, compared to a control group. Geriatric in-patients over 65 years of age were included in the study, those with cognitive impairment were excluded. Data was collected before (baseline) and after the implementation (intervention) of the Swedish Palliative Care Guide. Patient satisfaction was evaluated two weeks after discharge with questions from a national patient survey. Health-related quality of life was measured with EQ-5D-3L and symptom burden with Edmonton Symptom Assessment Scale. In total, 400 patients were included, 200 in the baseline- and intervention group, respectively. Mean age was 83 years in both groups. Patient satisfaction was significantly higher in nine out of ten questions (p = 0.02-<0.001) in the intervention group compared to baseline. No differences between the groups were seen in health-related quality of life or symptom burden. A significant effect on patient satisfaction was seen after implementation of the Swedish Palliative Care Guide in geriatric care. Thus, integration of palliative care and geriatrics could be of substantial benefit in the growing population of older adults with multimorbidity and frailty.


The prognostic value of N-terminal proB-type natriuretic peptide in patients with acute respiratory distress syndrome.
We investigated whether N-terminal proB-type natriuretic peptide (NT-proBNP) predicts the prognosis of patients with acute respiratory distress syndrome (ARDS). Between December 1, 2012, and May 31, 2015, this observational study recruited patients admitted to our tertiary medical center who met the Berlin criteria for ARDS and who had their NT-proBNP measured. The main outcome was 28-day mortality. We enrolled 61 patients who met the Berlin criteria for ARDS: 7 were classified as mild, 29 as moderate, and 25 as severe. The median APACHE II scores were 23 (interquartile range [IQR], 18-28), and SOFA scores were 11 (IQR, 8-13). The median lung injury score was 3.0 (IQR, 2.50-3.25), and the median level of NT-proBNP was 2011 pg/ml (IQR, 579-7216). Thirty-four patients died during this study, and the 28-day mortality rate was 55.7%. Patients who die were older and had significantly (all p < 0.05) higher APACHE II scores and NT-proBNP levels than did patients who survived. Multivariate analysis identified age (HR: 1.546, 95% CI: 1.174-2.035, p = 0.0019) and NT-proBNP (HR: 1.009, 95% CI: 1.004-1.013, p = 0.0001) as significant risk factors of death. NT-proBNP was associated with poor outcomes for patients with ARDS, and its level predicted mortality.


The impact of dietary and tooth-brushing habits to dental caries of special school children with disability.
The daily oral activities may severely influence oral health of children with disabilities. In this survey, we analyzed the impact of dietary and tooth-brushing habits to dental caries in special school children with disabilities. This cross-sectional survey investigated 535 special school children with disabilities aged 6-12 years, 60.93% males, 39.07% females from 10 special schools in Taiwan. Oral examinations were carried out by dentists with a Kappa score of their inter-examiner agreement exceeding 0.8. Data on demographics, diet, and tooth-brushing habits of children with disabilities were collected using a standardized questionnaire completed by parents/caregivers. More than three quarters of the participants were combined with severe or profound disability. Children with profound severity in disability had a higher percentage (67.37%) in teeth-brushing by parents/caregivers compared to those children with mild/moderate severity in disability which had a higher percentage (81.60%) in teeth-brushing by themselves. Children whose teeth were brushed by parents/caregivers had a better dental health, and lower caries prevalence. The main risk factors related to decayed teeth of children with disabilities are frequency of sweets intake, ability to brush teeth and with plaque or not. The dental health education, prevention program and periodical oral check-up to children with disabilities and their parents/caregivers should be reinforced. Brushing skill should be taught to children according to their type, severity and individual characteristics of disability.


Chemistry of zinc(II) fluorophore sensors.
The biological role of the zinc(II) ion has been recognized in DNA and RNA synthesis, apoptosis, gene expression, or protein structure and function. Therefore, development of useful zinc(II) sensors has recently been attracting much interest. Chemistry for selective and efficient detection of trace Zn2+ is a central issue. Recently, various types of zinc-fluorophores are emerging, comprising bio-inspired aromatic sulfonamide derivatives, zinc-finger peptides attached to fluorescent dyes, or fluorophore-pendant macrocyclic polyamines. The chemical principles, properties and limitations of these Zn2+-fluorophores are discussed.


Governing with competency. Assessing trustees' strengths and opportunities for improvement helps boards prepare for the future.
Boards have several options for applying competencies to governance.


Effect to gastric alkalinization on lower esophageal sphincter pressure and serum gastrin.
The purpose of this study was to measure the effect of alkaline intragastric pH on lower esophageal sphincter pressure (LESP) and on serum gastrin concentration in man. One hundred ten milliliters each of 0.1 N NaHCO3 and control solution were instilled into the stomach for 30 min in random order. Neither LESP nor serum gastrin were higher during the alkali instillation than during the control instillation. Individual subject's peak gastrin and peak LESP during the alkali period were not significantly higher than the corresponding basal values. We conclude that intragastric alkalinization did not increase total radioimmunoassayable serum gastrin concentration or LESP.


MicroRNA expression profile in murine central nervous system development.
MicroRNAs (miRNAs) regulate gene expression in a post-transcriptional sequence-specific manner. In order to better understand the possible roles of miRNAs in central nervous system (CNS) development, we examined the expression profile of 104 miRNAs during murine brain development. We obtained brain samples from animals at embryonic days (E) E15, E17, and postnatal days (P) P1 and P7. Total RNA was isolated from tissue and used to obtain mature miRNAs by reverse transcription. Our results indicate that there is a group of 12 miRNAs that show a distinct expression profile, with the highest expression during embryonic stages and decreasing significantly during development. This profile suggests key roles in processes occurring during early CNS development.


Eleven-marker 10-color flow cytometric assessment of measurable residual disease for T-cell acute lymphoblastic leukemia using an approach of exclusion.
Measurable/minimal residual disease (MRD) status has been suggested as a powerful indicator of clinical-outcome in T-cell lymphoblastic leukemia/lymphoma (T-ALL). Multicolor flow cytometric (MFC)-based T-ALL MRD reports are limited and traditionally based on the utilization of markers-of-immaturity like TdT and CD99. Moreover, studies demonstrating the multicolor flow cytometric (MFC) approach for the assessment of T-ALL MRD are sparse. Herein, we describe an 11-marker, 10-color MFC-based T-ALL MRD method using an "approach of exclusion." The study included 269 childhood T-ALL patients treated with a modified-MCP841 protocol. An 11-marker, 10-color MFC-based MRD was performed in bone marrow (BM) samples at the end-of-induction (EOI) and end-of-consolidation (EOC) time-points using Kaluza-version-1.3 software. We studied EOI-MRD in 269 and EOC-MRD in 105 childhood T-ALL patients. EOI-MRD was detectable in 125 (46.5%) samples (median, 0.3%; range, 0.0007-66.3%), and EOC-MRD was detectable in 34/105 (32.4%) samples (median, 0.055%; range, 0.0008-27.6%). Leukemia-associated immunophenotypes (LAIPs) found useful for MRD assessment were dual-negative CD4/CD8 (40.9%), dual-positive CD4/CD8 (23.3%) and only CD4 or CD8 expression (35.8%); dim/subset/dim-negative surface-CD3 (39%), dim/subset/dim-negative/negative CD5 (28.3%), dim/dim-negative/negative/heterogeneous CD45 (44.7%) and co-expression of CD5/CD56 (7.5%). EOI-MRD-positive status was found to be the most-relevant independent factor in the prediction of inferior relapse-free and overall survival. We described an 11-marker 10-color MFC-based highly sensitive MRD assay in T-ALL using an approach of exclusion. The addition of CD4 and CD8 to the pan-T-cell markers in a 10-color assay is highly useful in T-ALL MRD assessment and extends its applicability to almost all T-ALL patients.


Neuropsychological consequences of sleep disturbance in children with epilepsy.
A growing body of research reveals strong relationships between sleep disturbance, sleep architecture, and neuropsychological functioning in children. Children with epilepsy experience numerous neuropsychological comorbidities, including cognitive deficiencies and emotional/behavioral difficulties; thus, it is reasonable to consider the moderating role of sleep in this population. This review summarizes findings involving the prevalence and characteristics of sleep problems often experienced by children with epilepsy. The complex and bidirectional relationship between sleep and seizure frequency is discussed. Research pertaining to the relationship between sleep disturbance and daytime cognition as well as behavior reveals a substantial association between these variables. Clinically relevant practices related to the assessment and treatment of sleep-related complications are reviewed, and directions for further research involving intervention and assessment are also reviewed.


Modulation of apoptosis in human lymphocytes by adenosine analogues.
We previously described that 2-chloroadenosine (2CA) and 2-chloro-2'-deoxyadenosine (2CdA) induced apoptosis in human peripheral blood mononuclear cells (PBMC). In this study we tested different adenosine analogues on PBMC and we found that the modifications introduced in the 2CA structure prevented the molecule from exerting its apoptotic effect. On the other hand, substitutions on 2CdA are tolerated, although with a significant decrease in activity.


Comparison of the variable loop regions of myosin heavy chain genes from Antarctic and temperate isopods.
The evolutionary adaptations of functional genes to life at low temperatures are not well characterised in marine and fresh water invertebrates. Temperature has been shown to affect the functional characteristics of fish muscles, with changes in the velocity of shortening and ATPase activity being associated with myosin heavy chain (MyHC) isoform composition and the structure of the surface loop regions. Two PCR products spanning loops 1 and 2 of a MyHC gene from an Antarctic isopod (Glyptonotus antarcticus) were sequenced and compared with those of a temperate isopod (Idotea resecata), slow and fast fibres from lobster (Homarus gammarus) and a cold water amphipod (Eulimnogammarus verrucosus), revealing specific differences between the species, possibly related to fibre type and habitat temperature. The loop 2 region from G. antarcticus myosin was cloned and used for Northern analysis of total RNA from the other species. The cloned myosin cDNA hybridised specifically to a 6.6-kb transcript, in G. antarcticus muscle. In contrast, cDNA probes for lobster slow myosin and actin hybridised to muscle RNA from all species, demonstrating that a distinct MyHC isoform is expressed in the Antarctic isopod, as opposed to the temperate species. The inter- and intra-specific sequence differences in loop 2 region suggest that this may be a site for muscle adaptation to enable function at the low temperatures found in the Southern Ocean.


Efficient initiation of S-phase in yeast requires Cdc40p, a protein involved in pre-mRNA splicing.
The S. cerevisiae CDC40 gene was originally identified as a cell-division-specific gene that is essential only at elevated temperatures. Cells carrying mutations in this gene arrest with a large bud and a single nucleus with duplicated DNA content. Cdc40p is also required for spindle establishment or maintenance. Sequence analysis reveals that CDC40 is identical to PRP17, a gene involved in pre-mRNA splicing. In this paper, we show that Cdc40p is required at all temperatures for efficient entry into S-phase and that cell cycle arrest associated with cdc40 mutations is independent of all the known checkpoint mechanisms. Using immunofluorescence, we show that Cdc40p is localized to the nuclear membrane, weakly associated with the nuclear pore. Our results point to a link between cell cycle progression, pre-mRNA splicing, and mRNA export.


Collection and preservation of human placental blood.
High-risk premature infants require red cell transfusions for anemia. Placental blood for autologous transfusions can be collected sterilely into citrate-phosphate-dextrose and stored at 4 degrees C. During storage for 8 days, the placental red cell content of adenosine triphosphate remained normal. The 2,3,-diphosphoglycerate concentration of cells stored 8 days declined sharply; however, the P50 value of the oxyhemoglobin dissociation curve declined to 24.4 +/- 2.40 torr. During storage, placental blood underwent an exchange of extracellular Na+ and K+, but no change in glutathione content. Hemolysis was less than 1 percent. Bacteriologic and fungal cultures remained sterile. These in vitro studies suggest that human placental blood can be collected safely and preserved effectively for autologous red cell transfusion therapy.


Tempol ameliorates cardiac fibrosis in streptozotocin-induced diabetic rats: role of oxidative stress in diabetic cardiomyopathy.
Long-standing diabetes is associated with increased oxidative stress and cardiac fibrosis. This, in turn, contributes to the progression of cardiomyopathy. The present study was sought to investigate whether the free radical scavenger, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol) can protect against diabetic cardiomyopathy and to explore the specific underlying mechanism(s) in this setting. Diabetes was induced in rats by a single intraperitoneal injection dose of streptozotocin (50 mg/kg). These animals were treated with tempol (18 mg kg(-1) day(-1), orally) for 8 weeks. Our results showed significant increases in collagen IV and fibronectin protein levels and a marked decrease in matrix metalloproteinase-2 (MMP-2) activity measured by gelatin-gel zymography alongside elevated cardiac transforming growth factor (TGF)-β level determined using ELISA or immunohistochemistry in cardiac tissues of diabetic rats compared with control. This was accompanied by an increased in the oxidative stress as evidenced by increased reactive oxygen species (ROS) production and decreased antioxidant enzyme capacity along with elevated lactate dehydrogenase (LDH) and creatine kinase (CK-MB) serum levels as compared with the control. Tempol treatment significantly corrected the changes in the cardiac extracellular matrix, TGF-β, ROS or serum LDH, CK-MB levels, and normalized MMP-2 activity along with preservation of cardiac tissues integrity of diabetic rats against damaging responses. Moreover, tempol normalized the elevated systolic blood pressure and improved some cardiac functions in diabetic rats. Collectively, our data suggest a potential protective role of tempol against diabetes-associated cardiac fibrosis in rats via reducing oxidative stress and extracellular matrix remodeling.


Relating between the voice and voice-hearer: Validation of a revised version of the Voice And You.
Advancements in CBT for distressing voices have led to the development of understandings and the treatment of voice hearing within relational frameworks. In this study, we aim to validate and revise the Voice And You (VAY), one of the first measures that was developed to assess distressing relationships with voices. Data was pooled from 5 sources (n = 192) including the VAY and an interview-based assessment of voice-hearing. The VAY was subjected to confirmatory factor analysis and revised based on item loadings. Criterion validity was assessed by correlating the VAY with measures of voice-related distress and other voice characteristics from the Psychotic Symptom Rating Scales (PSYRATS) interview. For the original VAY, we found sufficient model fit for the voice-to-hearer relating factors (voice dominance and intrusiveness), but not for the hearer-to-voice relating factors (hearer dependence and distance). A revised version showed sufficient overall model-fit while retaining the level of criterion validity of the original scale. Thus, we derived a revised, valid, and parsimonious 14 item VAY (VAY-R) that provides a feasible tool to assess the interrelating between hearer and voice. Nevertheless, hearer-to-voice relating needs a more differentiated assessment of hearer relating styles that includes the possibility of actively engaging with the voice.


Safety of baricitinib in East Asian patients with moderate-to-severe active rheumatoid arthritis: An integrated analysis from clinical trials.
We evaluated the safety of baricitinib in an East Asian (EA) patient population with moderate-to-severely active rheumatoid arthritis (RA), through an integrated sub-analysis of data from the overall baricitinib RA clinical program. Data from EA patients who received any dose of baricitinib from five completed studies (1 Phase 2, 4 Phase 3) and an ongoing long-term extension study were pooled up to 1 September, 2016. Exposure-adjusted incidence rates (EAIR) and incidence rates (IRs), both per 100 patient-years (PY), were calculated. This analysis included 740 EA patients with 1294 PY of total baricitinib exposure (maximum 3.5 years). Overall, 109 patients discontinued baricitinib due to adverse events (AEs); EAIR: 8.4. No deaths were reported in this cohort. Serious AEs were reported by 125 patients (EAIR: 9.7). Serious infections were the most common serious AEs (n = 53, IR: 4.15). IR of herpes zoster infection was 6.2; the majority of events were of mild-to-moderate severity. Three cases (IR: 0.23) of tuberculosis were reported. The IRs of malignancy (excluding non-melanoma skin cancer) was 0.99 and EAIR specifically of lymphoma was 0.1. The IR of major adverse cardiovascular events was 0.26, and deep vein thrombosis was reported in four patients (EAIR: 0.3). Two cases of gastrointestinal perforations (EAIR: 0.2) were reported. Integrated data show that baricitinib is well-tolerated in EA patients with moderate-to-severely active RA in the context of demonstrated efficacy, which is generally consistent with safety results of the overall study population.


Neoadjuvant chemotherapy for atypical teratoid rhabdoid tumors (AT/RTs).
Atypical teratoid rhabdoid tumor (AT/RT) is a rare, clinically highly malignant tumor. The extent of the surgical resection may affect survival. However, it is often difficult to perform gross total resection (GTR) at an initial surgery because of the large tumor size and high vascularity. Neoadjuvant chemotherapy may reduce not only the size but also the vascularity. We report our experience, review the literature, and analyze its effectiveness. A retrospective chart review of patients who underwent neoadjuvant chemotherapy and second-look surgery was performed. Demographic data, treatment courses, changes in tumor after the chemotherapy, extent of resection and estimated blood loss (EBL) during the second-look surgery, and outcome of each children were evaluated. There are 4 cases. The average age at diagnosis was 13.3 months (2-30 months). Two to 4 courses of neoadjuvant chemotherapy were performed. MRI after the chemotherapy showed reduction of tumor volume, and tumor vascularity at the second-look surgery decreased in all cases. GTR was achieved in 3 cases, and NTR in 1 case. The mean EBL/estimated blood volume (EBL/EBV) was 21.3% (1.5-39%). The mean follow-up period was 23 months (2-48 months). At the last follow-up, 2 patients were alive without recurrence of the tumor (the follow-up periods were 48 and 16 months). Neoadjuvant chemotherapy for AT/RTs might reduce both tumor size and vascularity, which enabled the maximal tumor resection. It may contribute to improve the prognosis of AT/RT through facilitating the tumor resection.


[Postpartum urinary and fecal incontinence in gemelar pregnancy according to route and mode of delivery].
The incidence of multiple pregnancies increased in the last two decades. Several studies seeking the incidence of pelvic floor pathology, particularly urinary incontinence and its risk factors, conclude that a previous cesarean and vaginal delivery even more, carry an increased risk for developing urinary and fecal incontinence, compared with patients nulligravida. To determine the different risk factors for urinary incontinence after a twin pregnancy. 331 women from 20 to 50 years of age without symptoms prior to pregnancy were interviewed, attending antenatal care of twin pregnancy in the Hospital La Paz, Madrid. The interview included the ICIQ-SF (International Consultation on Incontinence Questionnaire-Short Form). We recorded maternal age, gestational age, parity, episiotomy, weights of both newborns, the need for urinary protectors and fecal or gas incontinence. The prevalence of urinary incontinence postpartum according ICIQ-SF >0 was 23%; 20.4% in the caesarean group, 25.3% in the eutocic delivery group and 35.5% in the instrumental delivery group (p = 0.033). The prevalence of moderate to severe incontinence (ICIQ-SF >6) was 14.8%; 12.3% in caesarean group, 14.5% in the eutocic delivery group and 32.3% in the instrumental delivery group (p = 0.005). The prevalence of fecal incontinence was 3.4%; 4.8% in eutocic delivery group, 1.9% in the caesarean group and 9.7% in the instrumental delivery group (p = 0.058). The risk of urinary incontinence after a twin pregnancy was higher among patients who had an instrumental delivery when compared with patients with eutocic delivery or cesarean section. The total fetal weight and maternal age did not appear as risk factors in our study. Any woman who had an instrumental delivery for twins should be followed up by a pelvic floor specialist.


Exogenous ATP causes the contraction of intact fibroblasts in vitro.
The contraction of intact fibroblasts was investigated in vitro. The addition of ATP to the cells lead to a rapid, reversible reduction of cell area, which appeared to be a contraction. The change of cell area was measured using image analysis. ATP (15 mM) elicited the maximal contraction, with a 50% reduction in area achieved within 90 s. Adenosine was a partial agonist for the contraction. The contraction was dependent on control of the environmental calcium; cells in a calcium- and magnesium-free environment underwent spontaneous contraction. Replenishing the calcium and magnesium lead to stability of the cells. Since fibroblast contraction is involved in wound healing at many sites in the body, this system provides a physiological model for the direct investigation of fibroblasts with intact cell membranes, and allows for the testing of drugs which may influence wound healing in vivo.


Cribriform-morular variant of papillary thyroid carcinoma: characteristic histologic feature of adenomatous polyposis. A case report.
We report the case of a 24-year-old woman with familial adenomatous polyposis and diagnosed with cribriform-morular variant of papillary thyroid carcinoma. Neck ultrasound and computed tomography identified multiple nodules in the thyroid gland and neck lymph nodes. The cytological analysis was compatible with the diagnosis of papillary cancer of the thyroid. Total thyroidectomy with lymph node dissection was performed. The histological analysis established the diagnosis of cribriform-morular variant of papillary thyroid carcinoma. Despite preoperative findings suggesting an aggressive form of thyroid cancer with lymph node involvement, the final diagnosis was a variant of papillary thyroid carcinoma often associated with familial adenomatous polyposis and known to have a good prognosis.


Assessment of curing behavior of light-activated dental composites using intensity correlation based multiple reference optical coherence tomography.
Monitoring the curing kinetics of light-activated resin is a key area of research. These resins are used in restorative applications and particularly in dental applications. They can undergo volumetric shrinkage due to poor control of the depth dependent curing process, modulated by the intensity and duration of the curing light source. This often results in the formation of marginal gaps, causing pain and damage to the restoration site. In this study, we demonstrate the capabilities of a correlation method applied using a multiple references optical coherence tomography (MR-OCT) architecture to monitor the curing of the resin. A MR-OCT system is used in this study to monitor the curing of the resin. The system operates at the center wavelength of 1310 nm with an A-scan rate of 1200 A-scans per second. The axial and lateral resolution of the system is ∼13 μm and ∼27 μm. The method to determine the intensity correlation between adjacent B-frames is based on the Pearson correlation coefficient for a region of interest. Calculating the correlation coefficient for multiple B-frames related to the first B-frame at regular spaced time points, shows for a noncured resin a reduction of the correlation coefficient over time due to Brownian motion. The time constant of the reduction of the correlation value is a measure for the progress of the polymerization during LED light irradiation of the resin. The proposed approach is potentially a low-cost, powerful and unique optical imaging modality for measuring the curing behavior of dental resin and other resins, coatings, and adhesives in medical and industrial applications. To demonstrate the proposed method to monitor the curing process, a light-activated resin composite from GRADIA DIRECT ANTERIOR (GC Corporation, Japan) is studied. The curing time of resin was measured and monitored as a function of depth. The correlation coefficient method is highly sensitive to Brownian motion. The process of curing results in a change in intensity as measured by the MR-OCT signal and hence can be monitored using this method. These results show that MR-OCT has the potential to measure the curing time and monitor the curing process as a function of depth. Moreover, MR-OCT as a product has potential to be compact, low-cost and to fit into a smartphone. Using such a device for monitoring the curing of the resin will be suitable for dentists in stationary and mobile clinical settings.


Meta-genome analysis of a newly enriched azo dyes detoxification halo-thermophilic bacterial consortium.
Treating textile wastewaters were always inhibited by its higher salt concentration and temperature. In this study, a halo-thermophilic bacterial consortium YM was enriched with ability to decolorize acid brilliant scarlet GR (ABS) at 55 °C and 10% salinity. Under optimum conditions of pH (8), temperature (55 °C), and salinity (10%), YM decolorized 97% of ABS under anaerobic conditions. Alteribacillus was identified to be the dominant genus in consortium YM. Consortium YM showed significant decolorization ability under a wide range of salinity (1%-10%), pH (7-9) and temperature (45 °C-60 °C). The degradation pathway of ABS was proposed by the combination of UV-vis spectral analysis, Fourier transform infrared (FTIR), gas chromatography mass spectrometric (GC-MS), and metagenomic analysis. Azoreductase, which was an important enzyme in decolorization process, was identified with great variation in the genome of consortium YM. Meanwhile, the metabolic intermediates after decolorization was identified with low biotoxicity by phytotoxicity tests. This study first identified that Alterbacillus play an important role in azo dye decolorization and degradation process under halo-thermophlic conditions and provided significant knowledge for azo dye decolorization and degradation process.


Continuous usage intention of mobile health services: model construction and validation.
Mobile health (mHealth) services can not give full play to their value if only it is used in the short term, and their continuous usage can achieve better effects in health management. This study aims to explore the factors that affect continuous usage intentions of mHealth services and their mechanism of action. First, considering the uniqueness of health services and social environmental factors, this study constructed an extended Expectation Confirmation Model of Information System Continuance (ECM-ISC) to investigate factors that may influence the intention of continuous usage of mHealth services based on three dimensions, namely individual characteristics, technology and environment. Second, the survey method was used to validate the research model. The questionnaire items were derived from validated instruments and discussed by experts and data were collected both online and offline. The structural equation model was used for data analysis. There were 334 avidity questionnaires through cross-sectional data and these participants had used mHealth services ever. The reliability and validity of the test model were good, in which Cronbach's Alpha values of 9 variables exceeded 0.9, composite reliability 0.8, the average variance extracted value 0.5, and the factor loading 0.8. The modified model had a good fitting effect and strong explanatory power. It accounted for 89% of the variance in expectation confirmation, 74% of the variance in perceived usefulness, 92% of the variance in customer satisfaction, and 84% of the variance in continuous usage intention. Compared with the initial model hypotheses, perceived system quality was deleted according to the heterotrait-monotrait ratio, so paths related to it were deleted; perceived usefulness wasn't positively associated with customer satisfaction, and its path was also deleted. Other paths were consistent with the initial hypothesis. The two new added paths were that subjective norm was positively associated with perceived service quality (β = 0.704, P < 0.001), and perceived information quality (β = 0.606, P < 0.001). Electronic health literacy (E-health literacy) was positively associated with perceived usefulness (β = 0.379, P < 0.001), perceived service quality (β = 0.200, P < 0.001), and perceived information quality (β = 0.320, P < 0.001). Continuous usage intention was influenced by perceived usefulness (β = 0.191, P < 0.001), customer satisfaction (β = 0.453, P < 0.001), and subjective norm (β = 0.372, P < 0.001). The study constructed a new theoretical model including E-health literacy, subjective norm and technology qualities to clarify continuous usage intention of mHealth services, and empirically validated the model. Attention should be paid to E-health literacy, subjective norm, perceived information quality, and perceived service quality to improve continuous usage intention of users and self-management by mHealth Apps managers and governments. This research provides solid evidence for the validity of the expanded model of ECM-ISC in the mHealth field, which can be a theoretical and practical basis for mHealth operators' product research and development.


Liothyronine use in a 17 year observational population-based study - the tears study.
To look at adverse outcomes for patients on liothyronine compared to l-thyroxine. Some trials have examined the relative merits of liothyronine but none have looked at adverse outcomes in large numbers. An observational study of all patients prescribed thyroid hormone replacement in Tayside Scotland (population 400 000) from 1997 to 2014. A study group of patients having ever used liothyronine (n = 400) was compared to those who had only used l-thyroxine (n = 33 955). All patients were followed up until end-point, death or leaving Tayside. Mortality rates and admissions with cardiovascular disease, atrial fibrillation, fractures, breast cancer and mental diseases were compared. Incident use of bisphosphonates, statins, antidepressants and antipsychotics was compared. Compared to patients only taking l-thyroxine, those using liothyronine had no increased risk of cardiovascular disease [hazard ratio (HR) 1·04; 95% CI 0·70-1·54], atrial fibrillation (HR 0·91: 0·47-1·75), or fractures (HR 0·79: 0·49-1·27) after adjusting for age. There was no difference in the number of prescriptions for bisphosphonates or statins. There was an increased risk of new prescriptions for antipsychotic medication (HR 2·26: 1·64-3·11 P < 0·0001) which was proportional to the number of liothyronine prescriptions. There was a non-significant trend towards an increase in breast cancer and new use of antidepressant medications. During follow-up, median TSH was higher for patients on l-thyroxine alone (2·08 vs 1·07 mU/L; P < 0·001). For patients taking long-term liothyronine we did not identify any additional risk of atrial fibrillation, cardiovascular disease or fractures. There was an increased incident use of antipsychotic medication during follow-up.


Nutrition, synchronization, and management of beef embryo transfer recipients.
A commercially viable cattle embryo transfer industry was established during the early 1970s. Initially, techniques for transferring cattle embryos were exclusively surgical. However, by the early 1980s, most embryos were transferred nonsurgically. For an embryo transfer program to be effective, numerous factors need to be in place to ensure success. Nutrition, estrous cycle control, and recipient management are all responsible for the success or failure in fertility for a given herd. Utilization of body condition scores is a practical method to determine nutritional status of the recipient herd. Prepartum nutrition is critical to ensure that cows calve in adequate body condition to reinitiate postpartum estrous cycles early enough to respond to synchronization protocols. Estrus synchronization for embryo transfer after detected estrus or for fixed-time embryo transfer without estrus detection are effective methods to increase the number of calves produced by embryo transfer. In addition, resynchronization of nonpregnant recipients effectively ensures that a high percentage of recipients will return to estrus during a 72 h interval and are eligible for subsequent embryo transfers. Numerous additional factors need to be assessed to ensure that the recipient herd achieves its reproductive potential. These factors include assessing the merits of nulliparous, primiparous, or multiparous cows, ensuring that facilities allow for minimal stress, and that the herd health program is well-defined and followed. Numerous short- and long-term factors contribute to recipients conceiving to a transferred embryo, maintaining the embryo/fetus to term, delivering the calf without assistance and raising and weaning a healthy calf.


Behavioral Analytics for Myopic Agents.
Many multi-agent systems have a single coordinator providing incentives to a large number of agents. Two challenges faced by the coordinator are a finite budget from which to allocate incentives, and an initial lack of knowledge about the utility function of the agents. Here, we present a behavioral analytics approach for solving the coordinator's problem when the agents make decisions by maximizing utility functions that depend on prior system states, inputs, and other parameters that are initially unknown. Our behavioral analytics framework involves three steps: first, we develop a model that describes the decision-making process of an agent; second, we use data to estimate the model parameters for each agent and predict their future decisions; and third, we use these predictions to optimize a set of incentives that will be provided to each agent. The framework and approaches we propose in this paper can then adapt incentives as new information is collected. Furthermore, we prove that the incentives computed by this approach are asymptotically optimal with respect to a loss function that describes the coordinator's objective. We optimize incentives with a decomposition scheme, where each sub-problem solves the coordinator's problem for a single agent, and the master problem is a pure integer program. We conclude with a simulation study to evaluate the effectiveness of our approach for designing a personalized weight loss program. The results show that our approach maintains efficacy of the program while reducing its costs by up to 60%, while adaptive heuristics provide substantially less savings.


Virtual screening indicates potential inhibitors of the P2X7 receptor.
Anti-inflammatory agents can be synthetic or natural compounds and are often used to attenuate different levels of inflammation. Inflammatory diseases, due to the involvement of multiple systems, are becoming difficult to treat, involve long durations of therapy where applicable, have a high cost of management and have a deleterious impact on public health. The search for natural and synthetic compounds with anti-inflammatory activity is an important strategy in drug design. Bioactive synthetic drugs may be repurposed for other pharmacological applications, and natural product chemical structures offer unlimited opportunities for new drug discoveries due to the unparalleled availability of chemical diversity. Virtual screening of 2774 molecules on the mouse P2X7 protein showed that potential ligands are composed of five flavonoids (narirutin, diosmin, complanatuside, hesperidin, and oroxin B) and other drugs such as velpatasvir, itacitinib and lifitegrast. In vitro studies in mouse cells confirmed the inhibitory activity of the indicated ligands on the P2X7 receptor by applying virtual screening. The behavior of protein bonded to the ligands was verified by analysis of the molecular dynamic simulation trajectories for four of the most potent inhibitor compounds, indicating that the ligands velpatasvir, itacitinib, lithospermic acid and narirutin remained in the binding site indicated by molecular docking.


Rapid pacing for the off-pump insertion of the Jarvik left ventricular assist device.
We present our technique for the implantation of the Jarvik 2000 left ventricular assist device (Jarvik Heart, Inc, New York, NY) without cardiopulmonary bypass by the induction of rapid pacing that allows the insertion of the apical device into the left ventricle, minimizing blood loss and surgical complications. Although the off-pump implantation of left ventricular assist devices is not new, our experience of rapid pacing has not been previously reported to our knowledge.


Perinatal mental health and women's lived experience of the COVID-19 pandemic: A scoping review of the qualitative literature 2020-2021.
The COVID-19 pandemic resulted in global physical distancing restrictions and lockdown orders. Despite the clear documentation of increased mental distress amongst adult populations during the pandemic, there is limited evidence about the mental health challenges of people in the perinatal period (pregnancy, birth and postpartum). The aim of this review is to summarise the qualitative research about women's lived experience and emotional wellbeing during the COVID-19 pandemic. A comprehensive search strategy was developed. Twenty peer-reviewed qualitative research articles published in English from January 1, 2020, to December 15, 2021, were included. Data synthesis outlined the evidence from common themes in a narrative format. Themes during pregnancy included: (1) information seeking: anxiety and fear; (2) experiencing isolation and disruptions to my social support; (3) 'Going it alone' in pregnancy care; (4) anticipatory grieving and despair; (5) finding 'silver linings' in social restrictions. One key theme during birth was "birthing in a crisis". Themes during postpartum included: (1) isolating 'Early motherhood is much like lockdown'; (2) breastfeeding: triumphs and tribulations; (3) facing disruptions during postpartum care; (4) 'Affecting us for years to come' - COVID-19 was not the only trauma; (5) 'silver linings' during postpartum care. This review provides important insights into how experiences of isolation, decreased social support and adaptions to maternity services affect women's mental health. Maternity services should consider how perinatal mental health support may be integrated into the care of women who may still be required to isolate or have reduced visitors during their perinatal care. The restrictions and disruptions to maternity care due to the COVID-19 pandemic were likely to impact the mental health of women in the perinatal period (pregnancy, birth and postpartum). What is already known is that public health measures due to COVID-19 increased the prevalence of common perinatal mental disorders (CPMDs) and exacerbated common risk factors for CPMDs (i.e., poor social support). The qualitative research with women in the perinatal period during the pandemic provides unique insights into how these events impacted perinatal mental and emotional health. In particular, the ways that global physical distancing measures and maternity care adaptations contributed to women's feelings of distress, isolation, and depression/despair. Silver linings such as more uninterrupted time with immediate family were also identified.


Sexually Explicit Online Media, Body Satisfaction, and Partner Expectations Among Men who have Sex with Men: a Qualitative Study.
Limited research has investigated the perceived influence of sexually explicit online media (SEOM) on body satisfaction and partner expectations of men who have sex with men (MSM). Semi-structured qualitative interviews were conducted with 16 MSM, covering the perceived influence of MSM-specific SEOM. All nine men who broached the topics of body satisfaction and partner expectations reported that MSM-specific SEOM set unreasonably high physical appearance expectations for themselves and/or their potential partners. Although MSM-specific SEOM might be negatively affecting body satisfaction and partner expectations among MSM, its ubiquity may make it a useful tool to support body positivity.


An integrative analytical framework to identify healthy, impactful, and equitable foods: a case study on 100% orange juice.
To identify healthy, impactful, and equitable foods, we combined health scores from six diverse nutrient profiling systems (NPS) into a meta-framework (meta-NPS) and paired this with dietary guideline adherence assessment via multilevel regression and poststratification. In a case-study format, a commonly debated beverage formulation - 100% orange juice (OJ) - was chosen to showcase the utility and depth of our framework, systematically scoring high across multiple food systems (i.e. a Meta-Score percentile = 93rd and Stability percentile = 75th) and leading to an expected increase of US dietary fruit guideline adherence by ∼10%. Moreover, the increased adherence varies across the 300 sociodemographic strata, with the benefit patterns being sensitive to absolute or relative quantification of the difference of adherence affected by OJ. In sum, the adaptable, integrative framework we established deepens the science of nutrient profiling and dietary guideline adherence assessment while shedding light on the nuances of defining equitable health effects.


Uncommon disease with unusual presentation: A case report of acute necrotizing otitis media.
Acute necrotizing otitis media (ANOM) is defined as a severe middle ear infection that results in tympanic membrane necrosis. Commonly caused by bacteria infection. It is a rare entity of otitis media, with unknown prevalence. Usually seen in immunocompromised patients. We present a case report of a 79-year-old diabetic male, who presented to the otolaryngology clinic with history of intermittent worsening nocturnal left ear pain. The clinical presentation was suggesting necrotizing otitis externa despite lacking the classical picture of external ear canal edema and granulation, in the presence of a dull bulging tympanic membrane. Then the patient developed hearing loss, along with ear discharge, high inflammatory markers, and significant imaging findings. This case represents an unusual presentation of ANOM. The patient responded well to aggressive medical treatment, along with grommet insertion. Despite the development of antibiotics, ANOM is still possible, especially in high-risk patient. A high index of suspicion, along with detailed history, physical examination, and supportive imaging are needed, to diagnose ANOM. Aggressive treatment with antibiotics should be started immediately, guided by the culture results, to improve the prognosis and prevent further complications.


Reduced levels of actin gamma 1 predict poor prognosis in ovarian cancer patients.
To investigate the expression and function of actin gamma 1 (ACTG1) in ovarian cancer. We performed immunohistochemical staining of 176 ovarian cancer tissue samples in a human tissue microarray to detect expression of ACTG1. Staining intensity was examined in relation to clinicopathological parameters. To investigate the prognostic value of ACTG1, ACTG1 mRNA data from 300 ovarian cancer patients in The Cancer Genome Atlas database were examined. The immunohistochemical results demonstrated that levels of ACTG1 were reduced in the samples of human ovarian cancer tissue that were examined, and the levels negatively correlated with various clinicopathological parameters. Levels of ACTG1 mRNA also negatively correlated with clinical stage. In Kaplan-Meier survival analysis, higher levels of ACTG1 mRNA were associated with improved overall survival. In multivariate analysis by Cox regression, ACTG1 expression was identified as an independent prognostic marker of favorable overall survival. ACTG1 may represent a valuable marker for the prognosis of ovarian cancer, and further studies of ACTG1 are warranted.


Ultrastructure of epiretinal membrane causing retinal starfold.
A prominent posterior retinal "starfold" was seen in an eye with an extensive rhegmatogenous retinal detachment. The retina was reattached with a scleral buckling operation. The epiretinal membrane causing the starfold was later removed by vitreous surgery and was studied by electron microscopy, permitting the first such clinicopathologic correlation in a human eye. The membrane was composed of vitreous collagen, newly formed collagen, and cells. The cell types included retinal pigment epithelial (RPE) cells, fibrous astrocytes, and macrophages. The fibrous astrocytes and some of the RPE cells contained intracytoplasmic microfilaments of the type thought to be myofibrils. These may account for contraction of the membrane, causing the starfold configuration of the underlying and adjacent retina.


Hydrocarbons and other risks in a beekeeping area of México: the precautionary principle for prevention and biotechnology for remediation.
The Yucatan Peninsula is the most important beekeeping region. However, the presence of hydrocarbons and pesticides violates the human right to a healthy environment twice over; it can affect human beings directly due to its toxicological characteristics, but it also constitutes a risk, not very well dimensioned, regarding the loss of biodiversity of the ecosystem via the impact on pollination. On the other hand, the precautionary principle obliges the authorities to prevent damage to the ecosystem that may be caused by the productive activity of individuals. Although there are studies that separately warn about the decrease of bees in the Yucatan due to industrial activity, this work has the novelty of presenting an intersectoral analysis of the risk that includes the soy industry, the swine industry and the tourist industry. The latter incorporates a new risk not considered until now, which is the presence of hydrocarbons in the ecosystem. Additionally, we can demonstrate that hydrocarbons, such as diesel and gasoline, should be avoided when using no genetically modified organisms (GMOs) in bioreactors. The objective of this work was to propose the precautionary principle around the risks in a beekeeping area and to propose biotechnology without using GMOs.


Platelet transfusion is associated with 90-day and 1-year mortality for adult patients requiring veno-arterial extracorporeal membrane oxygenation.
Studies examining one-year mortality respecting component blood transfusion are sparse. We hypothesize that component blood product transfusions are negatively associated with 90-day and 1-year survival for all patients requiring veno-arterial (VA) or veno-venous (VV) ECMO. This was an IRB-approved retrospective cohort analysis of 676 consecutive patients requiring ECMO at the University of Pittsburgh between 2005 and 2016. Patients were analysed both as an entire cohort and as two subsets with respect to ECMO modality (VA vs. VV). Additional data collected and analysed included patient characteristics, laboratory values and blood product transfusion. Multivariable analysis revealed that platelet transfusion was associated with 90-day mortality (OR: 1·05, P = 0·037) and one-year mortality for the entire cohort (OR = 1·05, P = 0·046,). Platelet transfusion volume was also associated with mortality in the VA-ECMO subset of patients at both 90 days (OR = 1·08, P = 0·03) and one year (OR: 1·11, P = 0·014). Age, peak International Normalized Raton ECMO, nadir haemoglobin (on ECMO) and final haemoglobin (after ECMO) were significantly associated with mortality for patients requiring VA-ECMO. For VV-ECMO patients, age, INR and peak creatinine on ECMO were associated with mortality. No individual component blood product was associated with one-year mortality for patients requiring VV-ECMO. Platelet transfusion was associated with increased 90-day and 1-year mortality for patients requiring VA-ECMO.


Comparative Proteome of Acetobacter pasteurianus Ab3 During the High Acidity Rice Vinegar Fermentation.
As a traditional Asian food for several centuries, vinegar is known to be produced by acetic acid bacteria. The Acetobacter species is the primary starter for vinegar fermentation and has evolutionarily acquired acetic acid resistance, in which Acetobacter pasteurianus Ab3 is routinely used for industrial production of rice vinegar with a high acidity (9 %, w/v). In contrast to the documented short-term and low acetic acid effects on A. pasteurianus, here we investigated the molecular and cellular signatures of long-term and high acetic acid responses by proteomic profiling with bidimensional gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF/MS) analyses. Protein spots of interest were selected based on the threshold ANOVA p value of 0.05 and minimal twofold of differential expression, leading to the identification of 26 proteins that are functionally enriched in oxidoreductase activity, cell membrane, and metabolism. The alterations in protein functioning in respiratory chain and protein denaturation may underlay cellular modifications at the outer membrane. Significantly, we found that at higher acidity fermentation phase, the A. pasteurianus Ab3 cells would adapt to distinct physiological processes from that of an ordinary vinegar fermentation with intermediate acidity, indicating increasing energy requirement and dependency of membrane integrity during the transition of acetic acid production. Together, our study provided new insights into the adaptation mechanisms in A. pasteurianus to high acetic acid environments and yield novel regulators and key pathways during the development of acetic acid resistance.


[The changes of IGF-I in testis and epididymis on a rat model with oligozoospermia/azoospermia induced by cyclophosphamide].
To evaluate the effect of the levels of IGF-I in the epididymis and the expression of IGF-I in the testis of adult male rat after the administration of cyclophosphamide. Ninety-six male adult rats (8 weeks age) were divided into 6 groups. The doses given to the rats of the groups 1 to 5 were 10, 20, 40, 80 and 100 mg/(kg x d), respectively. The remaining group was served as control. All those rats were sacrificed and IGF-I were quantitatively determined by ELISA techniques 2 and 4 weeks after the administration of the drug (by gastric fudge). Immunohistochemical SP technique was used to examine expression of IGF-I in rat testis. The levels of cell factors (IGF-I) in the epididymis of the rats were gradually reduced with the increasing time and dose after administration of the drug. In the mean time the expression of IGF-I in the tissues of the testis of those rats were also gradually reduced. In the time of oligozoospermia/azoospermia induced by the administration of cyclophosphamide, the expression levels of IGF-I in the genetic system were significantly reduced. The possible mechanism of these changes could be attributed to the lower spermatogenesis function of the testis caused by the administration of cyclophosphamide.


Percutaneous stenting of anastomotic stenoses in tubular interposition grafts used to repair aortic coarctation in adults.
Stenting is the usual treatment for recoarctation following resection with direct end-to-end anastomosis. We describe for the first time stenting to relieve anastomotic stenoses in tubular interposition grafts, which are used to repair approximately 10% of coarctations. Success in these two adults expands further the spectrum of large conduits that may be relieved of stenosis by stenting.


Considerations About Antimicrobial Stewardship in Settings with Epidemic Extended-Spectrum β-Lactamase-Producing or Carbapenem-Resistant Enterobacteriaceae.
Infections caused by gram-negative bacteria (GNB) resistant to multiple classes of antibiotics are increasing in many hospitals. Extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant Enterobacteriaceae in particular are now endemic in many parts of the world and represent a serious public health threat. In this era, antimicrobial stewardship programs are essential as targeted and responsible use of antibiotics improves patient outcomes and hopefully limits the selective pressure that drives the further emergence of resistance. However, some stewardship strategies aimed at promoting carbapenem-sparing regimens remain controversial and are difficult to implement when resistance rates to non-carbapenem antibiotics are increasing. Coordinated efforts between stewardship programs and infection control are essential for reversing conditions that favor the emergence and dissemination of multidrug-resistant GNB within the hospital and identifying extra-institutional "feeder reservoirs" of resistant strains such as long-term care facilities, where colonization is common despite limited numbers of serious infections. In settings where ESBL resistance is endemic, the cost-effectiveness of expanded infection control efforts and antimicrobial stewardship is still unknown. Once a patient has been colonized, selective oral or digestive decontamination may be considered, but evidence supporting its effectiveness is limited in patients who are already colonized or in centers with high rates of resistance. Moreover, temporary success at decolonization may be associated with a higher risk of relapse with strains that are resistant to the decolonizing antibiotics.


The role of lysosomes and microtubules in cardiac protein degradation.
The mechanisms and regulatory factors involved in cardiac proteolysis are incompletely understood. Agents that interfere with lysosomal function (e.g., chloroquine, leupeptin, methyladenine) cause a 25-30% reduction in the overall rate of protein degradation. In the same hearts, however, the rate of myosin breakdown remains unchanged. Disaggregation of micro-tubules with colchicine is accompanied by a 15% reduction in the rate of degradation of total protein and of myosin. In the same hearts, the degradation of "organellar" protein, including mitochondrial cytochromes, is reduced by over 30%. Thus, it appears that the degradation of different classes of cardiac proteins may be accomplished and regulated by different processes. Lysosomes are important in overall proteolysis, but appear not to be involved in the regulation of myosin breakdown. Microtubules are also involved in the proteolytic process, and appear to be especially important for the breakdown of proteins from mitochondria and perhaps other organelles.


Isonicotinamide enhances Sir2 protein-mediated silencing and longevity in yeast by raising intracellular NAD+ concentration.
Sirtuins are an evolutionarily conserved family of NAD(+)-dependent protein deacetylases that function in the regulation of gene transcription, cellular metabolism, and aging. Their activity requires the maintenance of an adequate intracellular NAD(+) concentration through the combined action of NAD(+) biosynthesis and salvage pathways. Nicotinamide (NAM) is a key NAD(+) precursor that is also a byproduct and feedback inhibitor of the deacetylation reaction. In Saccharomyces cerevisiae, the nicotinamidase Pnc1 converts NAM to nicotinic acid (NA), which is then used as a substrate by the NAD(+) salvage pathway enzyme NA phosphoribosyltransferase (Npt1). Isonicotinamide (INAM) is an isostere of NAM that stimulates yeast Sir2 deacetylase activity in vitro by alleviating the NAM inhibition. In this study, we determined that INAM stimulates Sir2 through an additional mechanism in vivo, which involves elevation of the intracellular NAD(+) concentration. INAM enhanced normal silencing at the rDNA locus but only partially suppressed the silencing defects of an npt1Δ mutant. Yeast cells grown in media lacking NA had a short replicative life span, which was extended by INAM in a SIR2-dependent manner and correlated with increased NAD(+). The INAM-induced increase in NAD(+) was strongly dependent on Pnc1 and Npt1, suggesting that INAM increases flux through the NAD(+) salvage pathway. Part of this effect was mediated by the NR salvage pathways, which generate NAM as a product and require Pnc1 to produce NAD(+). We also provide evidence suggesting that INAM influences the expression of multiple NAD(+) biosynthesis and salvage pathways to promote homeostasis during stationary phase.


The oscillatory effects of rhythmic median nerve stimulation.
Entrainment of brain oscillations can be achieved using rhythmic non-invasive brain stimulation, and stimulation of the motor cortex at a frequency associated with sensorimotor inhibition can impair motor responses. Despite the potential for therapeutic application, these techniques do not lend themselves to use outside of a clinical setting. Here, the aim was to investigate whether rhythmic median nerve stimulation (MNS) could be used to entrain oscillations related to sensorimotor inhibition. MEG data were recorded from 20 participants during 400 trials, where for each trial 10 pulses of MNS were delivered either rhythmically or arrhythmically at 12 or 20 Hz. Our results demonstrate a frequency specific increase in relative amplitude in the contralateral somatosensory cortex during rhythmic but not arrhythmic stimulation. This was coupled with an increase in inter-trial phase coherence at the same frequency, suggesting that the oscillations synchronised with the pulses of MNS. The results show that 12 and 20 Hz rhythmic peripheral nerve stimulation can produce entrainment. Rhythmic MNS resulted in synchronous firing of neuronal populations within the contralateral somatosensory cortex meaning these neurons were engaged in processing of the afferent input. Therefore, MNS could prove therapeutically useful in disorders associated with hyperexcitability within the sensorimotor cortices.


Combination bronchodilators: antagonism of airway smooth muscle contractions in vitro.
The component drugs of fixed-dose combination bronchodilators may interact in a synergistic manner to antagonize airway contractions. To examine this hypothesis, combinations of ephedrine (E) and theophylline (Th) or salbutamol (S) and theophylline were tested for their ability to relax contracted guinea-pig airway smooth muscle in vitro. The combination bronchodilator effect was compared to the summed effects of the component drugs given individually (i.e. a theoretical additive response, Ta). Relaxation responses to combination bronchodilators were considered less-than-additive if significantly less than Ta, additive if non-significant and greater-than-additive or synergistic if the values were significantly greater than Ta. It was found that the E-Th combinations interacted primarily in an additive fashion to relax contractions induced by histamine, acetylcholine and 5-hydroxytryptamine at concentrations that produced one-half maximal contractile response (ED50). Similarly S-Th combinations interacted in an additive manner to reverse histamine and acetylcholine contractions. In the case of both E-Th and S-Th combinations, the drugs were more effective in reducing the smooth muscle contractions when given during rather than prior to the response. It may be concluded that beta-sympathomimetics and methylxanthines when combined do not interact in a synergistic fashion to produce relaxation of contracted airway smooth muscle.


The Crisis in Children's Mental Health: What About the Babies?
The American Academy of Child and Adolescent Psychiatry (AACAP), the American Academy of Pediatrics (AAP), and the Children's Hospital Association (CHA) declared a national emergency in children's mental health.1 Much of the reporting has focused on children and teens, particularly with regard to increased emergency department visits and suicide attempts. Very little has been publicized about children between birth and 5 years of age, who may be among the most vulnerable to the psychosocial impacts of COVID-19. This commentary will outline some of the impacts of COVID-19 on very young children and their families and highlight activities of members of the Infant and Preschool Committee to address these impacts.


Safe medication practice: attitudes of medical students about to begin their intern year.
Interns are expected to prescribe effectively and safely. This study aimed to assess medical students' perceptions of their readiness to prescribe, associated risks and outcome if involved in an error, as well as their perceptions of available support. We carried out a survey of 101 students prior to their intern year using a structured questionnaire. An indication of agreement with 21 closed statements was sought. Thematic clusters were identified by factor analysis. Most students (84) felt they would be able to prescribe for most simple complaints and complete discharge prescriptions (81). In high-risk situations, fewer students felt comfortable with prescribing: only 54 felt sufficiently confident to prescribe warfarin and 66 felt confident enough to order i.v. fluids. Many felt support such as guidelines was available (87) and that, if in doubt, they could clarify instructions and seek advice. Students were aware of errors occurring within the medication system; however, most (99) believed that the medicines they prescribed would be safely administered. There was a mixed perception of medication errors: 40 felt that their prescribing errors would not be dealt with constructively and 79 indicated that a culture existed at their hospitals where clinicians would be blamed if they made a prescribing error. At the end of medical school education and prior to assuming responsibility for prescribing, students felt unprepared and perceived that negative outcomes would result if they were involved in errors. These findings indicate that much more work is needed to prepare doctors to prescribe safely, improve the safety of prescribing systems and address the issue of blame.


Ultrastructural and immunocytochemical characterization of cultured cells from rat molar stellate reticulum.
By scanning electron microscopy, the cultured cells were stellate and had numerous filipodia--characteristics of stellate reticulum cells in vivo. By transmission electron microscopy, they contained bundles of intermediate filaments, numerous mitochondria, large electron-dense granules and desmosomes--all features of the stellate reticulum in vivo. Moreover, the stellate reticulum was the only region of the enamel organ in vivo that contained large, electron-dense granules. By immunocytochemistry, the cultured cells contained cytokeratins, confirming their epithelial nature, and stellate reticulum cells in vivo and in vitro did not have an EGF receptor. Thus, these combined ultrastructural and immunocytochemical findings suggest that the cell culture was of stellate reticulum.


Baby brain: training executive control in infancy.
A recent study shows that a relatively short period of cognitive training can improve infants' ability to sustain and flexibly deploy attention. Thus, it appears important aspects of cognition can be modified using 'brain-training' techniques at an early age.


Violations of Weber's law tell us more about methodological challenges in sensorimotor research than about the neural correlates of visual behaviour.
The violation of Weber's law in grasping has been presented as evidence for the claim that grasping is guided by visual information which is distinct from the information used in perceptual tasks. Previously, we contested this claim and argued that biomechanical constraints of the hand might explain why Weber's law cannot be reliably uncovered in grasping movements. In a recent article Manzone and colleagues (2017) show that pantomime grasping follows Weber's law even with objects whose width is close to the hand's biomechanical limit. In this commentary we explain why the biomechanical account does not necessarily predict the violation of Weber's law in a pantomime grasping task and why it seems problematic to use adherence or violation of Weber's law as a criterion to assign tasks to different anatomical pathways.


Regulation of extrarenal vitamin D metabolism as a tool for colon and prostate cancer prevention.
Though 1,25-dihydroxyvitamin D3 (1,25-D3) as well as some vitamin D analogs have an antimitotic as well as a differentiating action, therapeutic application in tumor patients is still precluded due to their hypercalcemic action at the necessary concentration. Our observation that early during progression, colon tumor cells express CYP27B1, the enzyme essential for 1,25-D3 synthesis, as well as the vitamin D receptor (VDR) at a higher level than normal colon cells led to the speculation that, by induction of this expression, a physiological defense against tumor progression could be activated and enhanced. In some Asian countries where soy products are a main staple, prostate and breast tumor incidence is extremely low. We speculated that this could be due to regulation of CYP enzymes by phytoestrogens present in soy such as genistein. In prostate tumor cells, the 1,25-dihydroxyvitamin D3 catabolizing enzyme CYP24 is frequently highly expressed. We were able to demonstrate that genistein down-regulates expression of CYP24 to almost nil, which would result in enhancement of local 1,25-D3 levels and improved mitotic control of tumor cells.


Polymerization of coniferyl alcohol by Mn3+ -mediated (enzymatic) oxidation: Effects of H2 O2 concentration, aqueous organic solvents, and pH.
The objective of this study was to evaluate the ability of one versatile peroxidase and the biocatalytically generated complex Mn(III)-malonate to polymerize coniferyl alcohol (CA) to obtain dehydrogenation polymers (DHPs) and to characterize how closely the structures of the formed DHPs resemble native lignin. Hydrogen peroxide was used as oxidant and Mn2+ as mediator. Based on the yields of the polymerized product, it was concluded that the enzymatic reaction should be performed in aqueous solution without organic solvents at 4.5 ≤ pH ≤ 6.0 and with 0.75 ≤ H2 O2 :CA ratio ≤ 1. The results obtained from the Mn3+ -malonate-mediated polymerization showed that the yield was almost 100%. Reaction conditions had, however, effect on the structures of the formed DHPs, as detected by size exclusion chromatography and pyrolysis-GC/MS. It can be concluded that from the structural point of view, the optimal pH for DHP formation using the presently studied system was 3 or 4.5. Low H2 O2 /CA ratio was beneficial to avoid oxidative side reactions. However, the high frequency of β-β linkages in all cases points to dimer formation between monomeric CA rather than endwise polymerization. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 34:81-90, 2018.


[Effects of hemofiltration on lipid peroxidation and lipidograms in multiple organ failure syndrome in patients with peritonitis].
Hemofiltration was used in multiple-modality treatment of 45 patients with peritonitis who developed polyorgan failure. Lipid peroxidation parameters and lipidograms were under study. Lipid peroxidation was activated and supply with alpha-tocopherol drastically decreased. Hemofiltration helped improve the antioxidant defense.


Associations between academic burnout, resilience and life satisfaction among medical students: a three-wave longitudinal study.
Research shows that there are connections among academic burnout, resilience, and life satisfaction in medical students. However, no study has yet examined the temporal relationships between academic burnout, resilience, and life satisfaction among medical students. This longitudinal study aimed to examine the temporal associations between academic burnout, resilience, and life satisfaction and to explore the possible mediating role of resilience in the relationship between academic burnout and life satisfaction among medical students. This is a three-wave longitudinal study covering the preclinical education period of 20 months. From October 2018 to June 2020, a total of 190 students majoring in clinical medicine filled out the Chinese College Student Academic Burnout Inventory (CCSABI), the Connor-Davidson Resilience Scale (CD-RISC) and the Satisfaction With Life Scale (SWLS) three times. Cross-lagged models were constructed to examine the temporal relationships between academic burnout, resilience, and life satisfaction and longitudinal mediation models were constructed to explore the possible mediating role of resilience in the association of academic burnout with life satisfaction. Among medical students, resilience uni-directionally and positively predicted life satisfaction, while academic burnout uni-directionally and negatively predicted life satisfaction. However, the temporal association between resilience and academic burnout was negative and somewhat bidirectional. Resilience had a significant mediating effect on the relationship between academic burnout and life satisfaction in medical students. Medical educators need to identify and take effective measures to combat academic burnout problems which can lead to reduced life satisfaction among medical students. Resilience-based interventions may be promising in buffering the negative impacts of academic burnout and improving life satisfaction. It is recommended that effective resilience-promotion interventions be developed and implemented in medical education to help enhance medical students' psychological well-being.


The effect of selected prosodic errors on the intelligibility of deaf speech.
A trained speech pathologist listened to recordings of 40 deaf children, each reading 15 sentences and recorded instances of four types of prosodic errors: adventitious sounds, excessive phoneme duration, pitch breaks, and pauses. The scores were correlated with previously obtained intelligibility scores. It was found that adventitious sounds, except those obviously operating as transitional sounds to ease the movement from one place of articulation to another, had the greatest negative effect on intelligibility, followed by very long duration and pitch breaks. Medium and long pauses, long duration, prologned closure (i.e., long duration plosives), and adventitious transitional sounds had a lesser negative effect. Short pauses had a small positive effect on intelligibility. The method used to identify the errors was one that can hopefully be evolved into an evaluative instrument for practical use in schools for the deaf.


Complex roles of tissue inhibitors of metalloproteinases in cancer.
Matrix metalloproteinases (MMPs) is tightly associated with extracellular matrix (ECM) turnover, which plays a very active role in tumor invasion and metastasis. Tissue inhibitors of metalloproteinases (TIMPs) plays a critical role in the homeostasis of ECM by regulating the activity of MMPs. TIMPs are well-known for their ability to inhibit MMP activity thereby inhibiting tumor growth and metastasis. However, many evidences suggest that TIMPs are multifunctional proteins, which regulate cell proliferation, apoptosis, proMMP-2 activation, and angiogenesis. These effects may be through MMP-dependent or MMP-independent pathways. Recent data indicate that TIMPs have many paradoxical roles in tumorigenesis. In particular, both inhibitory effect and stimulatory effect on tumorigenesis have been demonstrated in many animal models in which TIMPs were overexpressed in cancer cells or in mice. Elevated TIMP levels are reported in association with cancer progression and identified as poor prognostic indicators in several human tumor types. Herein, we review the complex roles of TIMPs in cancer growth and metastasis.


A new characteristic karyotypic anomaly in lymphoproliferative disorders.
A new characteristic chromosome anomaly t(11;14)(q14;q32?) in lymphoproliferative disorders (LPD) is described in 4 cases. The extra material was found on a "14 chromosome (14q+) and belonged to the long arm of one "11 chromosome in 3 cases and to the long arm of a "14 in the other case. These cases confirm that the distal end of chromosome 14q may function as a "receptor site," according to the hypothesis of Kaiser-McCaw et al. and also tend to indicate that chromosome "14 may not be unique in showing so-called "donor" and "receptor sites," and that other chromosomes, in casu chromosome "11, may behave similarly.


Effects of retinoids on phorbol ester-stimulated epidermal DNA synthesis and hyperplasia in hairless mice.
We investigated the effects of the retinoids, all-trans retinoic acid (t-RA), 13-cis retinoic acid, etretinate, and arotinoid ethyl ester, on 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced DNA synthesis, and epidermal hyperplasia in hairless mouse skin. Topical application of these retinoids produced dose-dependent inhibition of the TPA-induced epidermal DNA synthesis as measured by [3H]thymidine incorporation at 15 h after TPA application. However, this inhibition was only transient and did not affect the corresponding increase in epidermal cell layers measured at 40 or 70 h after TPA application. Fluocinonide also inhibited the epidermal DNA synthesis and failed to block TPA-induced epidermal hyperplasia. However, fluocinonide did effectively suppress the inflammation caused by TPA. In this paper we have shown that the suppression of TPA-stimulated DNA synthesis is a general property of topically applied retinoids. The biologic significance of a temporary suppression of TPA-stimulated epidermal DNA synthesis by the retinoids and fluocinonide is not understood at this time.


Is e-mail communication effective in changing ordering patterns in the emergency department? A case study of computed tomography for pulmonary embolus.
We sought to evaluate the effectiveness of e-mail communication to reduce the utilization of computed tomography for pulmonary thromboembolism (PE) in young patients (aged 40 and under) in our institution. An e-mail was sent to all of our institution's emergency department (ED) physicians in response to a series of negative PE studies in young females. The periods 90 days before and 90 days after were evaluated to assess the total number of PE studies performed in patients aged 40 and younger, the rate of positivity, and the utilization of D-dimer and ventilation/perfusion scans during each period. Over the 180-day period, a total of 65 PE studies were ordered in patients aged 40 and younger in the ED. Studies were positive for PE in 1 of 33 (3%) before the e-mail and 4 of 32 (12.5%) after (P = .343). There was no difference in the number of D-dimer studies ordered during each period for patients studied with computed tomography. Ventilation/perfusion scanning was not performed on any ED patients younger than 40 during the 180-day period. One-time e-mail communication was not effective in changing ED ordering habits of PE studies. Scant information exists in regard to effective clinician-to-clinician communication. Further evaluation for successful mechanisms to promote health practice reform and quality improvement is necessary.


Appropriateness of anemia management in hemodialysis patients.
The anemia of end stage renal disease (ESRD) is common and often severe complication that can be managed successfully by erythropoiesis-stimulating agents (ESA) administration. To investigate current practice of anemia management in hemodialysis patients and to assess the appropriateness of anemia management by comparing observed practice to the Kidney Disease Outcomes Quality Initiative (KDOQI) guideline recommendations. The study was conducted at two hemodialysis centers in Riyadh, Saudi Arabia. Data on anemia parameters, comorbidities, ESA dosing and iron supplementation were collected. The data were collected for 7 months retrospectively from April to the end of May 2008 and prospectively from June to October 2008. Patients who were over 18 years of age with ESRD undergoing hemodialysis were included. Patients were excluded if they have cancer or receiving chemotherapy or radiotherapy. Data were collected from 87 patients. Mean Hgb value for those patients was 11.16 ± 0.97 g/dL. Thirty-nine patients (45%) had mean Hgb values between 11.0 and 12.0 g/dL the target range recommended by KDOQI guideline. The mean weekly prescribed dose of erythropoietin was 8099 ± 5946 IU/Week (135 ± 99 IU/kg/Week). Information on ferritin concentrations was available for 48 (55%) patients. The mean serum ferritin concentration for those patients was 693 ± 420.5 ng/mL. Fifty-two patients had transferrin saturation (TSAT) values recorded. The mean TSAT value was 38.5 ± 19.7%. There is an opportunity to improve anemia management in hemodialysis patients particularly thorough evaluation of causes of inadequate response rate and better monitoring and management of iron status.