Kinetics of gastro-intestinal transit and carotenoid absorption and disposal in ileostomy volunteers fed spinach meals.
Reports of low carotenoid absorption from food sources has undermined their postulated 'protective' role as one of the active agents in diets rich in vegetable matter. This study quantified beta-carotene and lutein absorption from a representative green vegetable with different degrees of processing, using both mass balance and metabolic modelling of triglyceride-rich lipoprotein plasma fraction (TRL) response. Whole or chopped-leaf cooked spinach was fed to volunteers (n = 7, paired) with vegetable oil (40 g) in yoghurt. Blood and ileal effluent samples were collected for up to 24 h. Effluent and TRL samples were analysed for lutein and beta-carotene by HPLC. A digesta transit model was used to describe meal transit and a single compartment model used to predict percentage absorption from the plasma TRL response. Mass balance showed 25% of lutein and beta-carotene were absorbed from chopped spinach, compared with 25% beta-carotene and 40 % lutein from whole-leaf spinach. Increased lutein absorption correlated to slower gastrointestinal (GI) transit for the whole-leaf meal. An area under the curve (AUC) response for the TRL fraction, found in 50% of cases, was not confined to those with the greatest percentage absorption. Absorption by mass balance and TRL AUC indicate a half-life of newly absorbed carotenoid around 11 min GI residence time appears to have an effect on the absorption of lutein but not beta-carotene. Rapid clearance is probably the main reason for absence of measurable plasma concentration excursions. Lack of plasma response cannot be interpreted as lack of carotenoid absorption without knowledge of the absorption and disposal kinetics.


Associations between PTSD symptoms and suicide risk: A comparison of 4-factor and 7-factor models.
While posttraumatic stress disorder (PTSD) symptoms in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are categorized into four clusters, emerging studies suggest the disorder is best characterized by seven symptom clusters: re-experiencing, avoidance, negative affect, anhedonia, externalizing behaviors, and anxious and dysphoric arousal symptoms. However, data are sparse regarding the relation between this novel model of DSM-5 PTSD symptoms and suicide risk. Using data from the National Survey for Stress and Health, a sample of 6180 Japanese individuals, we evaluated the relationship between suicide ideation and PTSD symptoms using 4- and 7-factor models. Different association patterns were observed between each model and suicidal ideation. In the 4-factor model, we found re-experiencing feelings (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.01-1.06, p = 0.002), negative alterations in cognition and mood symptoms (OR = 1.08, 95%CI = 1.06-1.09, p < 0.001), and hyperarousal (OR = 1.03, 95% CI = 1.01-1.05, p = 0.014) were associated with increased suicide ideation. In the 7-factor model, we found re-experiencing feelings (OR = 1.04, 95%CI = 1.02-1.06, p = 0.001), negative affect (OR = 1.04, 95%CI = 1.01-1.07, p = 0.012), anhedonia (OR = 1.08-1.16, 95%CI, p < 0.001), and externalizing behavior (OR = 1.12, 95%CI = 1.07-1.17, p < 0.001) were associated with increased suicide risk. A more refined 7-factor model of DSM-5 PTSD symptoms may help us understand their associations with comorbid psychopathology and suicide. Prevention and treatment efforts that target distinct aspects of the PTSD phenotype may be more effective in mitigating key clinical and functional outcomes in this population.


Parental reflective functioning and coping among parents of toddlers with severe developmental disabilities: An early integrative bio-psycho-social rehabilitative intervention in daycare facilities.
Parental reflective functioning has a positive effect on parents' wellbeing. It is associated with positive outcomes for their children. However, there is little research on it among parents of toddlers with severe developmental disabilities. We examined an early bio-psycho-social rehabilitative intervention with parents of toddlers with severe developmental disabilities in daycare programs and its contribution to their parental reflective functioning and coping. Seventy parents of children (ages 3 months to two and half years) responded to measures before and after the intervention in their children's daycare programs. Structural equation modeling of the mediation model revealed that the therapeutic inputs were associated with more adaptive coping strategies by increasing parental reflective functioning. Parents who participated in an intervention of 13 sessions or more significantly increased their reflective functioning. The path analysis showed that parental reflective functioning after the intervention mediated the association between its prior level and the therapeutic inputs, and the parents' proactivity and search for support. Parental reflective functioning positively affects parents' adaptive coping styles. A bio-psycho-social intervention targeting parental reflective functioning benefits parents of toddlers with severe developmental disabilities.


[Characteristics of the morphofunctional changes in the liver of C3HA mice due to immunization with a homogenate of normal syngeneic liver].
Immunization of C3HA mice with homogenate of normal syngeneic liver at a dosage causing elevation of antitumor resistance damages the liver of recipients. The damage involves the formation of foci of necrosis and the alteration in activities of some tissue specific and embryonal enzymes. The damage is reversible; its degree and the rate of reverse depends on a dosage of homogenate injected.


Knockout of the Placenta Specific 8 Gene Affects the Proliferation and Migration of Human Embryonic Kidney 293T Cell.
Candidate oncogene placenta specific 8 (PLAC8) has been identified to participate in different cellular process and human diseases. However, the effects of PLAC8 on cell proliferation and migration in human kidney cancer (KC) remained unclear. In current study, physiological effects of PLAC8 in immortalized human embryonic kidney cell line (HEK293T) were investigated in vitro. Two PLAC8 knockout (KO) cell lines were established via CRISPR/Cas9-mediated methods combined with fluorescence activated single cell sorting. To classify the characteristic of PLAC8 during cell proliferation and migration in HEK293T, cellular proliferative activity was analyzed by cell counting and colony formation assay. Cell cycle distribution was analyzed by flow cytometry. Cellular motile activity was analyzed by wound-healing and migration assay. Further underlying molecular mechanism was explored via western blot. With the KO cell lines, it was found that PLAC8 KO could decrease cell proliferation. Moreover, the inhibitory effects of PLAC8 KO on cell proliferation were associated with a G2/M arrest in cell cycle progression concomitant with a remarkable inhibition of Cyclin B1 and elevation of Cyclin A. The alteration of cell cycle proteins and E-cadherin might further associate with the enhancement of cell motility. Our study revealed a novel role for PLAC8 in cell proliferation and migration of HEK293T cells, which might shed light on further study of PLAC8 on human KC.


One hundred doctors at The Retreat. A contribution to the subject of mental disorder in the medical profession.
A study of the cases of 100 doctors admitted to The Retreat, York, confirmed the findings of a'Brook et al (1967) in all important respects, addiction being the outstanding feature of the series.


Rat brain hexokinase: location of the substrate hexose binding site in a structural domain at the C-terminus of the enzyme.
A glucose analog, N-(bromoacetyl)-D-glucosamine (GlcNBrAc), previously used to label the glucose binding sites of rat muscle Type II and bovine brain Type I hexokinases, also inactivates rat brain hexokinase (ATP:D-hexose 6-phosphotransferase, EC 18.104.22.168) with pseudo-first-order kinetics. Inactivation occurs predominantly via a "specific" pathway involving formation of a complex between hexokinase and GlcNBrAc, but significant nonspecific (i.e., without prior complex formation) inactivation also occurs, and equations to describe this behavior are derived. Inactivation is dependent on deprotonation of a residue with an alkaline pKa, consistent with the modified residue being a sulfhydryl group as reported to be the case with the hexokinase of bovine brain. The affinity label modifies three residues (per molecule of enzyme) at indistinguishable rates, but only one of these residues appears to be critical for activity. Amino acid analysis of the modified enzyme indicates derivatization of three cysteine residues; there was no indication of modification of other residues potentially reactive with haloacetyl derivatives. Kinetic analysis and effects of protective ligands were consistent with location of the critical sulfhydryl at the glucose binding site. Peptide mapping techniques permitted localization of the critical residue, and thus the glucose binding site, in a 40-kDa domain at the C-terminus of the enzyme. This is the same domain recently shown to include the ATP binding site. Thus, catalytic function is assigned to the C-terminal domain of rat brain hexokinase.


Patterns of pathologic response in the cornea.
The cornea, like most tissues, manifests only a limited number of responses to the wide variety of diseases and insults that assault it. To facilitate a systematic understanding of these responses, we have divided the cornea into four zones: the epithelium; the epithelial basement membrane, Bowman's layer and anterior stroma; the stroma; and the endothelium and Descemet's membrane. We describe six pathologic processes or responses in each zone: defects; fibrosis and vascularization; edema and cysts; inflammation and immune response; deposits; and proliferation. We illustrate this paradigm with a chart that contains examples of each pathologic process in each zone.


Cytogenetic abnormalities in non-small cell lung carcinoma: similarity of findings in conventional and feeder cell layer cultures.
Primary tumors from 39 patients with non-small cell lung carcinoma (NSCLC) were examined for cytogenetic abnormalities by conventional short-term harvest (1-39 days) of primary cultures of minced solid-tumor tissues and by harvest of monolayer cultures of tumor tissue (6 days to 5 months) on murine fibroblast feeder layers. A successful karyotype was obtained with both methods in nine of 39 cases. Among the remaining 30 cases, a successful karyotype was obtained in eight cases by the conventional method only and in three cases by the feeder cell method only. The success rates were 44% for the conventional method, and 31% for the feeder cell method, and the combined success rate was 51% for one or the other method. The feeder culture method, in which harvests were usually performed at later times than with the conventional method, generally produced metaphases with superior banding, which allowed clearer definition of cytogenetic abnormalities. In addition, cell lines were established in eight of these cases by the feeder cell method. Karyotypes from the longer-term harvests typically were very similar to those from short-term conventional cultures. Minor numerical differences and/or a few additional structural abnormalities were noted in seven of the nine cases analyzed by both methods. Overall, however, even in karyotypes from 5-month cultures, the prominent recurrent changes and modal chromosome numbers observed in short-term cultures were still present. The results indicate that long-term culture with fibroblast feeder cells is a valid means of obtaining cells from solid lung tumors for cytogenetic and molecular analysis.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of a concept to classify anamnesis-related risk of complications and oral diseases in patients attending the clinical course in dental education.
Aim of the current study was the assessment of risk classes according to a previously established system to classify the anamnesis-related risk of complications and of oral diseases in a cohort of patients attending the dental student course for dental preventive measures. Patients attending the student course between April 2020 and December 2021 were included. To assess the medical history, a specific anamnesis tool was used, which included the classification of different potential anamneis-related risks originating from general diseases, medications or lifestyle factors into a low, moderate or high risk of complications and/or risk of oral diseases. Thereby, the risk of complications was defined as the increaeed probability of harm during dental measures (professional tooth cleaning, invasive dental treatment or any kind of manipulation, which may cause a bacteremia), e.g. infectious endocarditis. On the other hand, the risk of oral diseases was an increaeed probability of development and/or progression of oral diseases like caries, periodontitis or mucosal diseases. Those risk classes were subsequently analyzed under consideration of age and gender. 858 patients, with a mean age of 50.48 ± 20.72 [median: 52.0] years, and a nearly balanced gender distribution (50.8% female and 49.2% male) were included. In the overall cohort, the risk of complications related with dental measures was low in 38.3%, moderate in 42.4% and high in 19.3% of participants. The risk of oral diseases was low in 33.1%, moderate in 37.2% and high in 29.7% of participants. Both, the risk of complications and the risk of oral diseases increased with patients' age (p < 0.01). Thereby, the risk of complications as well as the risk of oral diseases related to general diseases and medication significantly increased with age (p < 0.01). Nearly one fifth of patients in dental student couse show a high risk of complications related with dental measures. Morever, nearly one third of those individuals have a high anamnesis-related risk of oral diseases. With increasing age, the amount of patients in high risk classes becomes higher. Future dental education and research should address the high relevance of anamnesis-related risk factors.


Ziprasidone 40 and 120 mg/day in the acute exacerbation of schizophrenia and schizoaffective disorder: a 4-week placebo-controlled trial.
A double-blind, placebo-controlled, multicenter study, was performed to evaluate the efficacy and safety of ziprasidone in 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder. Patients were randomized to receive ziprasidone 40 mg/day, 120 mg/day or placebo for 28 days. Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total, CGI-S. BPRS depression cluster and BPRS anergia cluster scores (all P < 0.05). Similarly, the percentages of patients classified as responders on the BPRS (> or = 30% reduction) and the CGI improvement (score < or = 2) were significantly greater with ziprasidone 120 mg/day compared with placebo (P < 0.05). The number of patients who experienced an adverse event was similar in all three treatment groups, and discontinuation due to adverse events was rare (five of 91 ziprasidone-treated patients). The most frequently reported adverse events, that were more common in either ziprasidone group than in the placebo group, were dyspepsia, constipation, nausea and abdominal pain. There was a notably low incidence extrapyramidal side-effects (including akathisia) and postural hypotension and no pattern of laboratory abnormalities or apparent weight gain. Ziprasidone-treated patients were not clinically different from placebo-treated patients on the Simpson-Angus Rating scale, Barnes Akathisia scale and AIMS assessments. These results indicate that ziprasidone 120 mg/day is effective in the treatment of the positive, negative and affective symptoms of schizophrenia and schizoaffective disorder with a very low side-effect burden.


Pure pyrolytic carbon: preparation and properties of a new material, On-X carbon for mechanical heart valve prostheses.
Historically, the pyrolytic carbon used in mechanical prosthetic heart valves contained small amounts of silicon, this being a necessary additive to achieve consistently the hardness required for wear resistance. New processing technology has allowed the deposition of pyrolytic carbon without silicon, while maintaining adequate hardness to ensure wear resistance. A parametric study of coating parameters identified the conditions necessary to produce the optimal pure carbon material. In comparison with silicon-alloyed carbon, the pure carbon was found to be about 20% stronger, have a strain-to-failure about 25% higher and have a greater toughness. The enhanced strength, deformability and toughness of the new carbon permits designers to utilize component shapes and dimensions that could not be manufactured using the silicon-alloyed carbons. Such design features have hemodynamic benefits resulting in valve performance improvements.


Adiposity and serum parameters in hamsters fed energy restricted diets supplemented or not with trans-10,cis-12 conjugated linoleic acid.
Numerous studies have demonstrated that conjugated linoleic acid (CLA) modulates body composition, reducing body fat accumulation in various mammalian species. However, very few studies have been carried out to assess the effect of CLA on previously stored body fat. The aim of the present work was to analyse the effectiveness of trans-10,cis-12 CLA in improving alterations produced by high-fat feeding in body fat and serum parameters when it was included in an energy-restricted diet. For this purpose male Syrian Golden hamsters were fed on high-fat diet for 7 weeks in order to increase their body fat content, and a further 25% energy-restricted diet supplemented or not with 0.5% trans-10,cis-12 CLA for 3 weeks. Adipose tissues, liver and gastrocnemious muscles were dissected and weighed. Adipocyte diameter and number were assessed in epididymal adipose tissue. Total cholesterol, triacylglycerols, non-esterified fatty acids and glucose were measured in serum. Three weeks of energy restriction resulted in a reduction in body weight and white adipose tissue size in all anatomical locations, without changes in liver and gastrocnemious muscle weights. Epididymal adipocyte size was reduced, but total adipocyte number remained unchanged. Serum cholesterol, triacylglycerols and glucose were significantly reduced. No differences were observed between the restricted groups (control and CLA supplemented). In conclusion, under our experimental conditions, the addition of trans-10,cis-12 CLA to the diet does not increase the benefits produced by energy restriction.


Use of post-discharge opioid consumption patterns as a tool for evaluating opioid prescribing guidelines.
Leftover pills from postoperative opioid prescriptions place patients and members of their communities at risk for opioid misuse. We aimed to better understand patients' post-discharge opioid consumption patterns to inform new methods of postoperative opioid prescribing. We assessed post-discharge opioid consumption of general surgery patients and assessed the adequacy of discharge opioid prescriptions. We then compared patient opioid consumption to a number of theoretical discharge prescriptions based on different opioid prescribing guidelines and a proposed discharge prescription based on the metric 24-h pre-discharge opioid consumption (PDOC). 62/99 patients (62.6%) returned an opioid log book. Median 24-h PDOC was 22.5 MME (IQR 5.0-45.0) and median discharge prescription size was 15 pills (IQR:10-20). Prescriptions were adequate for 83.7% of patients. The median number of pills used was 3 (IQR:0-11) and median time to opioid cessation was 3 days (IQR:0-5). Actual prescriptions were consistent with national opioid prescribing guidelines. Prescriptions based on the formula 2 × 24-h PDOC would have decreased the number of leftover pills by 7.5 per patient. Despite prescribing opioids consistent with national opioid prescribing guidelines, patients still receive too many pills. Improved opioid prescribing could be accomplished by use of the formula 2 × 24-h PDOC.


Pulmonary pseudofibrosis and pseudomass lesions.
Abnormal size and/or number of the pulmonary and bronchial vessels and lymphatics may mimic pulmonary parenchymal lesions (pseudofibrosis). Abnormalities of the central pulmonary artery, pulmonary vein, thoracic aorta, and brachiocephalic branches may mimic intrathoracic mass lesions (pseudomass lesions). Radiologists should interpret these radiographic findings in the light of other accompanying radiographic findings and the clinical presentation.


Exploring personality features in patients with affective disorders and history of suicide attempts: a comparative study with their parents and control subjects.
Personality traits are important candidate predictors of suicidal behavior. Several studies have reported an association between personality/temperament traits and suicidal behavior, suggesting personality traits as intermediary phenotypes related to suicidal behavior. Thus, it is possible that suicide attempts can be accounted for by increased familial rates of risk personality traits. The aim of this work was to evaluate personality traits in affective disorder patients with attempted suicide and to compare them with the personality trait scores of their parents. In addition, ITC scores in the two groups were compared with a healthy control sample. The patients evaluated met the DSM-IV criteria for major depression disorder or dysthymia and had a documented history of suicide attempts. Psychiatric diagnoses of patients and parents were done according to the SCID-I and the personality was assessed using the Temperament and Character Inventory. We analyzed 49 suicide attempt subjects and their parents (n = 95) and 89 control subjects. We observed that temperament and character dimensions were similar between patients and their parents (P > 0.05). In particular, we observed that high HA and low P, SD, and CO were shared among families. Our study is the first to report that the personality traits of affective disorder patients with a history of attempted suicide are shared between patients and their parents.


Determination of perfluorinated carboxylic acids in biological samples by high-performance liquid chromatography.
This paper describes a method for the quantitative determination of perfluorinated carboxylic acids (PFCAs), perfluorohexanoic acid (C6-PFCA), perfluoroheptanoic acid (C7-PFCA), perfluorooctanoic acid (C8-PFCA), perfluorononanoic acid (C9-PFCA) and perfluorodecanoic acid (C10-PFCA), in biological samples. PFCA in liver homogenates was extracted as an ion pair with tetrabutylammonium (TBA) ion into organic solvent, then the PFCA was derivatized with 3-bromoacetyl-7-methoxycoumarin (BrAMC) and quantified by HPLC with fluorescence detection. This method is applicable for the studies on tissue accumulation and elimination of PFCAs in animals after the administration.


Gender-based violence against women with visual and physical disabilities.
Studies conducted in several countries have documented that women with disabilities are more vulnerable to experience gender-based violence than women without disabilities. A total of 96 women, 45 with visual disabilities and 51 with physical disabilities, were interviewed to determine the prevalence of violence and its possible relations with socio-economic, socio-demographic and disability-related factors. Possible consequences of violence in health and psychological well-being were also analyzed. Results showed a higher prevalence of abuse in this group of women than the estimated prevalence in the general female population in Spain. Abused women were found to have lower income and higher levels of physical dependence and family responsibilities than non-victims. In addition, violence was associated with lower levels of emotional well-being, psychological health, self-esteem and perceived social support beyond those attributable to the disability. These results are discussed in light of some theoretical models that establish some links between disability and gender-based violence.


Distribution and aspects of population dynamics of the zebra mussel, Dreissena polymorpha (Pallas, 1771), in the lake IJsselmeer area (The Netherlands).
The distribution, settling and growth of the zebra mussel, Dreissena polymorpha Pallas, in Lake IJsselmeer and Lake Markermeer in The Netherlands were studied from 1980 to 1985. In these lakes D. polymorpha is the most important food source for wintering diving ducks. The study was part of an investigation into the carrying capacity of the lakes for these birds.


Nontechnical Skill Assessment of the Collective Surgical Team Using the Non-Technical Skills for Surgeons (NOTSS) System.
To validate the Non-Technical Skills for Surgeons (NOTSS) system for assessment of the collective surgical teams' nontechnical skills after observing recordings of actual OR environment. The NOTSS system is a widely accepted tool to measure nontechnical skills of individual surgeons, and has mostly been used in the simulated setting. Surgical procedures are rarely performed by a single surgeon, but by a surgical team of attending surgeons, surgical assistants, and surgical trainees. Therefore, assessment of nontechnical skills may benefit from holistic assessment of the collective surgical teams. Five trained participants assessed surgical team and attending surgeon using the NOTSS system after watching ten 20-minute long videos obtained from live OR. A set of reference ratings was provided by a multidisciplinary expert committee. We performed analyses to assess system sensitivity; examine inter-rater reliability of ratings; investigate concurrent construct validity; and assess feasibility and acceptability of using the NOTSS system to measure surgical team performance. There was adequate system sensitivity when comparing participants' and reference ratings. Inter-rater reliability among the participants' ratings was good except for decision-making category. The level of inter-rater reliability was similar when rating teams and attending surgeons. There was strong positive correlation between teams' and attending surgeons' NOTSS ratings at category [Pearson coefficient 0.86, 95% confidence interval (CI) 0.82-0.89] and element levels (0.83, 95% CI 0.80-0.85), demonstrating evidence of concurrent construct validity. The participants felt that the use of NOTSS system to measure teams' nontechnical skills was acceptable and feasible to a fair extent. The NOTSS system, although developed for assessment of individual surgeons, is a useful tool for observing and rating surgical teams.


Multifocal muscle candidiasis of the legs in a patient with acute myeloid leukemia: A case report.
Opportunistic infections frequently develop in immunocompromised patients, such as those with hematological malignancies, causing significant mortality. Early diagnosis of invasive fungal infections is often important and difficult due to the difficult nature of confirming infection using cytologic and histologic findings. However, we report the first case of candidal infection leading to muscle abscesses in the legs of a patient with leukemia. A 60-year-old man with acute myeloid leukemia (AML) presented with multifocal muscle abscesses of the legs. Multifocal muscle candidiasis of the legs was confirmed by fine-needle aspiration biopsy of 2 of the calf lesions. After treatment with amphotericin B and flucytosine for 1 month, the patient was administered intravenous caspofungin for 3 months. A CT scan of the abdomen and an MRI of the lower calves showed significant improvement. This case highlights that fungal infection should be considered when patients present with multiple abscesses, emphasizing the value of early biopsy to confirm diagnosis and facilitate precision treatment.


Understanding rich oxygen vacant hollow CeO2@MoSe2 heterojunction for accelerating photocatalytic CO2 reduction.
Solar-driven CO2 reduction into gas fuels is desirable for a sustainable carbon cycle. To improve the photocatalytic activity of CO2RR, the unique rich oxygen (Vo) vacant hollow CeO2@MoSe2 is designed. The introduction of Vo is conducive to the capture of electrons by CO2 and promotes the process of photocatalytic CO2RR. The heterojunction formed by introducing the narrow band gap semiconductor MoSe2 increases the absorption range of visible light and improves the separation efficiency of photogenerated carriers. The hollow structure improves the CO2 adsorption capacity and improves the use of light effect. Therefore, the prepared firstname.lastname@example.com wt% MoSe2 exhibits enhanced photocatalytic activity for CO2RR. The yield of CH4 and CO is 10.2 µmol and 33.2 µmol in 4 h. Moreover, the photocatalytic mechanism is discussed through DFT and in-situ DRIFTS. This work provides new insights to the role of Vo in active CO2 photoconversion and exploits an important application of CO2 reduction.


Protein-water interactions.
By recognizing the forces that drive water transport across cell membranes or across tissues, we can see how water is driven to and from proteins. We learn from examples. When a dissolved protein (bovine serum albumin) accumulates water relative to small solutes, it effectively withdraws a number of water molecules from the bath; the number of water molecules changes with the identity but not with the concentration of small solutes. When a large ionic channel (VDAC or alamethicin) opens, it withdraws water from its bathing solution; excluded solute stabilizes the closed state in proportion to activity of water, the osmotic stress created by the solute, rather than in proportion to the activity of the solute itself. Hemoglobin too acts like an osmometer whose loading of oxygen shifts with the chemical potential of water. Assemblies of many macromolecules (proteins, nucleic acids, polysaccharides, lipids), subjected to the osmotic stress of completely excluded solutes, fight dehydration with powerful, exponentially varying intermolecular forces. Should we speak of these sensitivities and responses as solute effects or water effects? Intuitive but rigorous thermodynamics, developed in a set of appendixes, provides a surprisingly practical guide to alternatives in language.


DNA methylation in peripheral blood measured by LUMA is associated with breast cancer in a population-based study.
Our purpose was to identify epigenetic markers of breast cancer risk, which can be reliably measured in peripheral blood and are amenable for large population screening. We used 2 independent assays, luminometric methylation assay (LUMA) and long interspersed elements-1 (LINE-1) to measure "global methylation content" in peripheral blood DNA from a well-characterized population-based case-control study. We examined associations between methylation levels and breast cancer risk among 1055 cases and 1101 controls and potential influences of 1-carbon metabolism on global methylation. Compared with women in the lowest quintile of LUMA methylation, those in the highest quintile had a 2.41-fold increased risk of breast cancer (95% confidence interval: 1.83-3.16; P, trend<0.0001). The association did not vary by other key tumor characteristics and lifestyle risk factors. Consistent with LUMA findings, genome-wide methylation profiling of a subset of samples revealed greater promoter hypermethylation in breast cancer case participants (P=0.04); higher LUMA was associated with higher promoter methylation in the controls (P=0.05). LUMA levels were also associated with functional sodium nitroprusside in key 1-carbon metabolizing genes, MTHFR C677T (P=0.001) and MTRR A66G (P=0.018). LINE-1 methylation was associated with neither breast cancer risk nor 1-carbon metabolism. Our results show that global promoter hypermethylation measured in peripheral blood was associated with breast cancer risk.


Effects of short-term severe and long-term mild STZ-induced diabetes in urethral tissue of female rats.
To estimate and compare the alterations in the urethral tissues of female rats with two diabetes models: short-term severe and long-term mild diabetes. To induce mild diabetes (blood glucose levels between 120 and 300 mg/dl), female newborns received streptozotocin (100 mg/kg body weight, sc route), and to induce short-term severe diabetes (blood glucose levels > 300 mg/d), adult animals received streptozotocin (40 mg/kg, iv route). The rats were killed on day 133 of the experimental via an i.p. Thiopentax® injection of 80 mg/kg, and the urethrovaginal tissues were harvested. Morphometric, pathological, immunohistochemical, and ultrastructural analyses were conducted. In the long-term mild diabetes group, collagen deposition, severe fibrosis, lipid droplets and numerous subsarcolemmal, and intermyofibrillar mitochondria were observed. In the short-term severe diabetes group, centrally located myonuclei and a significantly reduced striated muscle area were noted. Both diabetic models exhibited similar immunohistochemistry patterns, with changes from fast to slow fibers and a decrease in the numbers of fast fibers. Either long-term mild hyperglycemia or short-term severe hyperglycemia have detrimental impacts on muscle health. They are both involved in the failure to maintain healthy skeletal muscle that may contribute to the development of pelvic floor dysfunctions via different pathways. These results have important implications for monitoring and prevention strategies for improving the quality of life of women with diabetes mellitus and pelvic floor muscle dysfunction. Neurourol. Urodynam. 36:574-579, 2017. © 2016 Wiley Periodicals, Inc.


Urinary incontinence in elderly women: clinical findings.
Two-hundred women self-described as having urinary incontinence, aged 55 to 90 years and living in the community completed a comprehensive history and physical examination. Initial presentation of urine loss was most commonly stress incontinence symptoms (35%). Scoring of peak response to volume lost and frequency revealed urine loss necessitating a clothing change for 78% and daily loss experienced by 73%. Over half had experienced a urine loss problem for more than five years. Most (65%) had sought treatment, but a minority reported current (11%) or previous (36%) treatment. Thirty-six percent were found to have severe atrophic vaginitis with severe urethocele (10%), cystocele (13%), rectocele (12%) less common. Pelvic floor strength by clinical scoring was weak (mean, 1.05 on a 5-point scale). The vaginal electromyograph first contraction peak mean was 5.94 microvolts sustained at 50% or better for 3.92 seconds. Clinical criteria established that 66% had stress, 27% a mixture of stress and urge, only 4% pure urge incontinence, and 4% other.


India ink staining of proteins on nitrocellulose paper.
India ink staining of proteins that have been electrotransfer blotted onto nitrocellulose paper is described. This stain proved to be a useful adjunct to the enzyme-linked immunoelectrotransfer blot technique. It is more sensitive than Coomassie blue, amido black, and fast green stains and is simple to use.


In Vitro Cytokine Production by Dengue-Infected Human Monocyte-Derived Dendritic Cells.
Despite many advances on the understanding of dengue pathogenesis in the last decades, some questions remained to be clarified. The virulence of the pathogen and the host immune response are the main factors involved in pathogenesis of dengue infection. In addition, skin dendritic cells (DCs) are one of the primary targets for dengue virus infection. After infection, DCs process and present antigens to T cells and also secrete cytokines that shape the immune response. Although relevant for the development of antiviral immune response, an imbalance in the cytokine production by immune cells could lead to cytokine storm observed in severe dengue fever cases. Therefore, this chapter will describe the protocols for the in vitro differentiation of human monocytes into human monocyte-derived dendritic cells (mdDCs), followed by dengue virus infection, as well as the cytokine quantification produced by mdDCs using a cytometric bead array method.


Fit and fatigue behavior of CAD-CAM lithium disilicate crowns.
New computer-aided design and computer-aided manufacturing (CAD-CAM) lithium disilicate glass-ceramics have been marketed. However, information concerning their biomechanical behavior is lacking. The purpose of this in vitro study was to compare the fit and fatigue behavior of two recently introduced CAD-CAM lithium disilicate materials with the standard IPS e.max CAD ceramic and to investigate the effect of the thermal treatment for crystallization on crown fit. Monolithic crowns (n=15) were milled from 3 CAD-CAM lithium disilicates: IPS e.max CAD (Ivoclar AG), Rosetta SM (Hass), and T-lithium (Shenzhen Upcera Dental Technology). Marginal and internal fit were evaluated using the replica technique before and after crystallization, and the fatigue behavior of the luted crowns was evaluated by the step-stress method. One-way ANOVA and the Tukey test were used to compare fit among the materials. Fatigue failure load was evaluated by the Kaplan-Meier and Mantel-Cox tests. The effect of crystallization on fit was evaluated with the paired t test (α=.05). Marginal fit was different between IPS e.max CAD (74 μm) and Rosetta SM (63 μm) (P=.02). T-lithium was similar to the other ceramics (68 μm) (P>.05). Occlusal internal space was similar among all materials (P=.69). Fatigue failure loads of Rosetta SM (1160 N) and T-lithium (1063 N) were similar to IPS e.max CAD (1082 N) (P>.05). The fatigue failure load of Rosetta SM was higher than that of T-lithium (P=.04). Crystallization reduced the axial internal space of all materials (P<.05) without significantly affecting marginal fit (P>.05). The fit and fatigue behavior of Rosetta SM and T-lithium were similar to that of IPS e.max CAD. Crystallization reduced the internal space of the crowns.


Characterization of coral associated ciliates and their interactions with disease lesion progression of Indian Scleractinian corals.
Ciliates associated with advanced diseased lesions of Acropora sp. and Porites sp. in the field were isolated and characterised using microscopic and molecular analysis. The identified dominant coral-associated ciliates as Holosticha sp. and Cohnilembusverminus was propagated in vitro and taken for further study. Ciliates high cell numbers with substrate containing bacteria-free mucus confirms the feeding preference for nutrients in mucus instead of bacteria. Therefore, fatty acid composition of the coral mucus was analysed and noted for the different composition levels of SAFA, MUFA and PUFA in both the genera. This suggests the possible feed specific interactions of ciliates with coral mucus and tissues. Conversely, Holosticha sp. was observed for invading the host cells for its voracious ingestion of Symbiodiniaceae cells and tissues. Moreover, the aquarium based investigation revealed that the ciliates migrate to the injured and early disease signs of corals enhancing the tissue loss and disease lesion progression. Thus, our results indicate that the ciliates interact with the immunocompromised disease corals and play a major role in progression of disease lesions leading to rapid coral mortality.


Omega-3 polyunsaturated fatty acid impairment of early host resistance against Listeria monocytogenes infection is independent of neutrophil infiltration and function.
The primary objective of this study was to determine whether the n-3 PUFA-mediated changes in host response to a Listeria monocytogenes infection (e.g., cytokine production and bacterial clearance) were dependent upon neutrophils. Balb/c mice were fed one of two semi-purified diets that contained either 0 or 41 g of n-3 PUFA/kg. After 4 week, mice were injected with a neutrophil-depleting (RB6-8C5) or isotype-control antibody 24 h prior to infection. Bacterial clearance from the liver and spleen at 3 days post-challenge was measured and the concentration of five pro-inflammatory cytokines in sera 24 h post-infection were determined using a novel protein multiplexing kit. We found that neutrophil depletion impaired bacterial clearance independent of the effect of n-3 PUFA. Interestingly, we observed a rather complex interaction between neutrophil-depletion and n-3 PUFA intake on in vivo pro-inflammatory cytokine production. For example, neutrophil depletion elevated circulating IL-6 and MCP-1 (2- to 5-fold; p<0.05) in n-3 PUFA-fed mice, but less so or not at all in mice fed the control diet. In summary, our data suggest that n-3 PUFA-mediated reduction of host resistance to L. monocytogenes is independent of neutrophil activity.


Proton MR spectroscopic studies of chronic alcohol exposure on the rat brain.
To better understand the long-term pathophysiologic mechanisms of alcoholism-related organic brain damage by serially assessing brain metabolites in chronically exposed rats using both in vivo magnetic resonance spectroscopy (MRS) and high-resolution nuclear magnetic resonance (NMR) from brain extracts. The alcoholic regimen was continued up to 60 weeks. In vivo proton MRS studies were performed at 200 MHz using a small animal imaging/spectrometer. In vitro rat brain extracts were also examined using a 500 MHz vertical bore magnet. Comparison measurements were also obtained in an age-matched control group. In vivo results showed that there is a significant increase in the Cho/NAA ratio in the chronic alcohol-exposed group that reached a maximum around 16 weeks. After 44 weeks of alcohol exposure, Cho/NAA in the alcohol group decreased significantly from its maximum value to a value that was significantly lower than those from the control groups. Brain extract studies demonstrated that PC and GPC were the main components responsible for the observed in vivo spectral changes after 16 and 60 weeks of alcohol consumption, respectively. The fluctuation of choline-containing metabolites during alcohol intoxication could explain sometimes seemingly conflicting and confusing results from MRS studies in human and animal studies in which the duration of alcohol consumption and amount are varied widely.


Application of a Mixed Methods Approach to Identify Community-Level Solutions to Decrease Racial Disparities in Infant Mortality.
This study aimed to identify community-level actions to decrease racial disparities in infant mortality (IM). Six urban multidisciplinary teams generated ideas for decreasing racial disparities in IM using a mixed methods concept mapping approach. Participants rated each idea as to its necessity and action potential and grouped ideas by theme. A cluster analysis produced a series of visual representations, showing relationships between the identified actions and the clustering of actions into themes. Multidimensional scaling techniques were used to produce analyses describing the necessity of and action potential for implementing the proposed ideas. Participants identified actions communities could take to decrease racial disparities in IM and suggested applications of the knowledge gained from the mapping process. Participants produced a total of 128 actions, within 11 thematic clusters, for decreasing racial disparities in IM. The thematic clusters contained a range of elements designed to promote knowledge and understanding of the relationship between health and racism; improve educational systems and community opportunities; facilitate community-driven health promotion, marketing, and research; improve health services for women; address physical and social environments that impact community health; prioritize resource allocation of community-based services; institutionalize strategies that promote equity across all systems; and create and support legislation and policies that address social determinants of health. Correlation coefficients of the clusters ranged from 0.17 to 0.90. Average necessity ratings ranged from 2.17 to 3.73; average action potential ratings ranged from 1.64 to 3.61. Findings suggest that thematic clusters with high action potential usually represented ongoing community activities or actions communities could easily initiate. Community size, existing programs, partnerships, policies, and influential advocates were among the factors cited affecting feasibility of implementation. Clusters with lower action potential require broader, longer term, policy, institutional or system-wide changes, and significant resources. High necessity clusters often contained actions perceived as essential for change, but sometimes outside of a community's control. Participants identified a number of practical actions that were considered to hold potential for individual, community, and institutional changes which could result in decreasing racial disparities in IM.


The role of protein corona on nanodrugs for organ-targeting and its prospects of application.
Nowadays, nanodrugs become a hotspot in the high-end medical field. They have the ability to deliver drugs to reach their destination more effectively due to their unique properties and flexible functionalization. However, the fate of nanodrugs in vivo is not the same as those presented in vitro, which indeed influenced their therapeutic efficacy in vivo. When entering the biological organism, nanodrugs will first come into contact with biological fluids and then be covered by some biomacromolecules, especially proteins. The proteins adsorbed on the surface of nanodrugs are known as protein corona (PC), which causes the loss of prospective organ-targeting abilities. Fortunately, the reasonable utilization of PC may determine the organ-targeting efficiency of systemically administered nanodrugs based on the diverse expression of receptors on cells in different organs. In addition, the nanodrugs for local administration targeting diverse lesion sites will also form unique PC, which plays an important role in the therapeutic effect of nanodrugs. This article introduced the formation of PC on the surface of nanodrugs and summarized the recent studies about the roles of diversified proteins adsorbed on nanodrugs and relevant protein for organ-targeting receptor through different administration pathways, which may deepen our understanding of the role that PC played on organ-targeting and improve the therapeutic efficacy of nanodrugs to promote their clinical translation.


The role of apoptosis in aging and age-related disease: update.
Programmed death of cells by apoptosis is regarded as a protective mechanism of the organism against an accumulation and spread of defective cells. The rate of apoptosis is elevated in most types of aging cell populations. However, there are also findings about a decreased susceptibility of senescent cells in vivo and in vitro, particularly to apoptosis induced by oxidative and energetic stress. Mitochondria appear to have a key function in apoptosis regulation. Thus, apoptosis can be induced by defective mitochondrial oxidative phosphorylation. The role of apoptosis in aging and age-related disease was outlined for different organs (brain, cardio-vascular system, immune system, intestine, macula of the eye, Langerhans islets, prostate gland, oocytes of ovaries). The age-related intensification of this dismantling system of cells seems to highlight the deterioration of tissue and organ structure and function in aging.


Time-course of venous wall biomechanical adaptation in pressure and flow-overload: assessment by a microstructure-based material model.
Arteriovenous fistulae have been previously created by our group, through implantation of e-PTFE grafts between the carotid artery and jugular vein in healthy pigs, to gather comprehensive data on the time-course of the adapted geometry, composition, and biomechanical properties of the venous wall exposed to chronic increases in pressure and flow. The aim of this study was to mathematically assess the biomechanical adaptation of venous wall, by characterizing our previous in vitro inflation/extension testing data obtained 2, 4, and 12 weeks post-fistula, using a microstructure-based material model. Our choice for such a model considered a quadratic function for elastin with a four-fiber family term for collagen, and permitted realistic data characterization for both overloaded and control veins. As structural validation to the hemodynamically-driven differences in the material response, computerized histology was employed to quantitate the composition and orientation of collagen and elastin-fiber networks. The parameter values optimized showed marked differences among the overloaded and control veins, namely decrease in the quadratic function parameters and increase in the four-fiber family parameters. Differences among the two vein types were highlighted with respect to the underlying microstructure, namely the reduced elastin and increased collagen contents induced by pressure and flow-overload. Explicit correlations were found of the material parameters with the two basic scleroprotein contents, substantiating the material model used and the characterization findings presented. Our results are expected to improve the current understanding of the dynamics of venous adaptation under sustained pressure- and flow-overload conditions, for which data are largely unavailable and contradictory.


Students take protest to politicians.
Opponents of plans to replace the bursary with a loan marched in solidarity with the students who will be worst affected by the change.


Estrogen signaling deregulation related with local immune response modulation in irritable bowel syndrome.
The etiology and pathogenesis underlying irritable bowel syndrome (IBS), a common gastrointestinal disorder are still unclear. Cumulating data suggest dysregulation of inflammatory and immune response pathways and changes of epithelial barrier function. The role of estrogens albeit varied, in responses of immune system is well documented. The aim of this study was to investigate estrogen receptors engagment in IBS subtypes, i.e. constipation predominant (IBS-C) and diarrhea predominant (IBS-D). Furthermore, we analyzed whether estrogen signaling is accompanied by alteration in expression of pro- and anti-inflammatory cytokines and microRNAs that can regulate among others genes involved in immune responses. It was found that estrogen receptor α (ERα) and G protein-coupled estrogen receptor (GPER) expression is up-regulated in IBS while estrogen receptor β (ERβ) appears to be down-regulated at mRNA but up-regulated at the protein level. When gender and female age were included statistically significant overexpression of ERα in IBS-D women under the age of 50, while of GPER in IBS-D men was stated. In all studied IBS samples disturbances in expression of cytokines IL-6, IL-10 and TNF-α as well as miR-145, miR-148-5p and miR-592 were observed. This research reveals the association of estrogen receptors with IBS. Simultaneous alterations of studied immunomodulatory cytokines and microRNAs suggest that in IBS dysregulation of local immune response may involve estrogen-dependent way.


Duplicated cytoglobin genes in teleost fishes.
Cytoglobin is a recently discovered myoglobin-related O2-binding protein of vertebrates with uncertain function. It occurs as single-copy gene in mammals. Here, we demonstrate the presence of two paralogous cytoglobin genes (Cygb-1 and Cygb-2) in the teleost fishes Danio rerio, Oryzias latipes, Tetraodon nigroviridis, and Takifugu rubripes. The globin-typical introns at positions B12.2 and G7.0 are conserved in both genes, whereas the C-terminal exon found in mammalian cytoglobin is absent in the fish genes. Phylogenetic analyses show that the two cytoglobin genes diverged early in teleost evolution. This is confirmed by gene synteny analyses, which suggest a large-scale duplication event. Although both cytoglobin genes are highly conserved and have evolved under purifying selection, substitution rates are significantly higher in Cygb-1 than in Cygb-2. Similar to their mammalian ortholog, both fish cytoglobins are expressed in a broad range of tissues. However, Cygb-2 is more than 250-fold stronger expressed in neuronal tissues, suggesting a subfunctionalization of the two cytoglobin paralogs after gene duplication.


Cross-Host Protection of Marine Bacteria Against Macroalgal Disease.
Despite an increasing awareness of disease impacts on both cultivated and native seaweed populations, the development of marine probiotics has been limited and predominately focused on farmed animals. Bleaching (loss of thallus pigmentation) is one of the most prevalent diseases observed in marine macroalgae. Endemic probiotic bacteria have been characterized to prevent bleaching disease in red macroalgae Agarophyton vermiculophyllum and Delisea pulchra; however, the extent to which probiotic strains provide cross-protection to non-endemic hosts and the influence of native microbiota remain unknown. Using A. vermiculophyllum as a model, we demonstrate that co-inoculation with the pathogen Pseudoalteromonas arctica G-MAN6 and D. pulchra probiotic strain Phaeobacter sp. BS52 or Pseudoalteromonas sp. PB2-1 reduced the disease risks compared to the pathogen only treatment. Moreover, non-endemic probiotics outperformed the endemic probiotic strain Ralstonia sp. G-NY6 in the presence of the host natural microbiota. This study highlights how the native microbiota can impact the effectiveness of marine probiotics and illustrates the potential of harnessing probiotics that can function across different hosts to mitigate the impact of emerging marine diseases.


LIF-dependent primitive neural stem cells derived from mouse ES cells represent a reversible stage of neural commitment.
Primitive neural stem cells (NSCs) define an early stage of neural induction, thus provide a model to understand the mechanism that controls initial neural commitment. In this study, we investigated primitive NSCs derived from mouse embryonic stem cells (ESCs). By genome-wide transcriptional profiling, we revealed their unique signature and depicted the molecular changes underlying critical cell fate transitions during early neural induction at a global level. Together with qRT-PCR analysis, our data illustrated that primitive NSCs retained expression of key pluripotency genes Oct4 and Nanog, while exhibiting repression of other pluripotency-related genes Zscan4, Foxp1 and Dusp9 and up-regulation of neural markers Sox1 and Hes1. The early differentiation feature in primitive NSCs was also supported by their intermediate characters on cell cycle profiles. Moreover, re-plating primitive NSCs back to ESC culture condition could reverse them back to ESC stage, as shown by reversible regulation of marker genes, cell cycle profile changes and enhanced embryoid body formation. In addition, our microarray analysis also identified genes differentially expressed in primitive NSCs, and loss-of-function analysis demonstrated that Hes1 and Ccdc141 play important function at this stage, opening up an opportunity to further understand the regulation of early neural commitment.


[A modified hydroxamic acid method for the estimation of the activity of lipase (E.C. 3. 1. 1. 3)].
Optimal conditions for a modified hydroxymic acid method have been worked out with respect to the stability of the substrate emulsion; by systematically varying the ratios of the components of the solutions it was possible to develop a homogeneous reaction system which could be directly measured by spectrophotometry.


FT-GAT: Graph neural network for predicting spontaneous breathing trial success in patients with mechanical ventilation.
Intensive care unit (ICU) physicians perform weaning procedures considering complex clinical situations and weaning protocols; however, liberating critical patients from mechanical ventilation (MV) remains challenging. Therefore, this study aims to aid physicians in deciding the early liberation of patients from MV by developing an artificial intelligence model that predicts the success of spontaneous breathing trials (SBT). We retrospectively collected data of 652 critical patients (SBT success: 641, SBT failure: 400) who received MV at the Chungbuk National University Hospital (CBNUH) ICU from July 2020 to July 2022, including mixed and trauma ICUs. Patients underwent SBTs according to the CBNUH weaning protocol or physician's decision, and SBT success was defined as extubation performed by the physician on the SBT day. Additionally, our dataset comprised 11 numerical and 2 categorical features that can be obtained for any ICU patient, such as vital signs and MV setting values. To predict SBT success, we analyzed tabular data using a graph neural network-based approach. Specifically, the graph structure was designed considering feature correlation, and a novel deep learning model, called feature tokenizer graph attention network (FT-GAT), was developed for graph analysis. FT-GAT transforms the input features into high-dimensional embeddings and analyzes the graph via the attention mechanism. The quantitative evaluation results indicated that FT-GAT outperformed conventional models and clinical indicators by achieving the following model performance (AUROC): FT-GAT (0.80), conventional models (0.69-0.79), and clinical indicators (0.65-0.66) CONCLUSIONS: Through timely detection critical patients who can succeed in SBTs, FT-GAT can help prevent long-term use of MV and potentially lead to improvement in patient outcomes.


Giant extra gastrointestinal stromal tumor of lesser omentum obscuring the diagnosis of a choloperitoneum.
Herein we present an extremely rare case of a giant extra gastrointestinal stromal tumor (EGIST) of the lesser omentum obscuring the diagnosis of a choloperitoneum. A 79 years old female was admitted to our hospital with symptoms of vomiting and epigastric pain. Abdominal computer tomography revealed a sizable formation that was diagnosed as a tumor of the pancreas. In laparotomy, a choloperitoneum was diagnosed as the cause of patient's symptoms. A tumor adherent firmly to the lesser curvature of stomach was also discovered. Cholecystectomy and subtotal gastrectomy were performed. Histologically, the tumor was diagnosed as a EGIST of the lesser omentum. The patient did not receive any adjuvant therapy and after two years of follow up she is without any recurrence. Omental EGISTs may remain clinically silent despite the large tumor's size. It is difficult to differentiate a EGIST in the lesser omentum from a GIST of the lesser curvature of the stomach, despite the use of advanced radiological imaging techniques. Our case of a giant EGIST of lesser omentum obscuring the diagnosis of acute choloperitoneum is the only one reported in literature. EGISTs that arise from the omentum are very rare and complete surgical resection is the only effective treatment approach. Adjuvant therapy following resection of localized disease has become standard of care in high risk cases.


Guidelines for potential multiple organ donors (adult): part II. Mechanical ventilation, endocrine metabolic management, hematological and infectious aspects.
The role of intensive care specialists in the maintenance of deceased potential donors is not restricted to hemodynamics. Appropriate endocrine-metabolic management is fundamental to maintaining energy support and hydroelectrolytic control, which cooperate for hemodynamic stability. Hematological changes are also important, especially considering the issues caused by inappropriate transfusions. In addition, this article discusses the role of appropriate protective ventilation to prevent inflammatory responses and to provide more transplantable lungs. Finally, judicious assessment of infections and antibiotic therapy is discussed.


Genes encoding the 7S RNA and tRNA(Ser) are linked to one of the two rRNA operons in the genome of the extremely thermophilic archaebacterium Methanothermus fervidus.
Analysis of gene structure in the extremely thermophilic archaebacterium, Methanothermus fervidus, has revealed the presence of a cluster of stable RNA-encoding genes arranged 5'-7S RNA-tRNA(Ser)-16S rRNA-tRNA(Ala)-23S rRNA-5S rRNA. The genome of M. fervidus contains two rRNA operons but only one operon has the closely linked 7S RNA-encoding gene. The sequences upstream from the two rRNA operons are identical for 206 bp but diverge at the 3' base of the tRNA(Ser) gene. The secondary structures predicted for the M. fervidus 7S, 16S rRNA, tRNA(Ala) and tRNA(Ser) have been compared with those of functionally homologous molecules from moderately thermophilic and mesophilic archaebacteria. A consensus secondary structure for archaebacterial 7S RNAs has been developed which incorporates bases and structural features also conserved in eukaryotic signal-recognition-particle RNAs and eubacterial 4.5S RNAs.


N6-methyladenosine(m6A) demethylase FTO regulates cellular apoptosis following cobalt-induced oxidative stress.
Cobalt is an environmental toxicant that is known to damage human health. However, the molecular mechanisms underlying cobalt-induced neurotoxicity have not been elucidated in detail. In the present research, we used human neuroglioma H4 cells as an in vitro model. Cells were exposed to CoCl2 (0, 100, 200, 400 μM) for 24 h. We performed m6A sequencing techniques and constructed FTO-knockdown/FTO-overexpressing cells to investigate the role of FTO-mediated m6A modification in regulating apoptosis following CoCl2 induced oxidative stress. Our study has shown CoCl2 exposure led to the decrease of demethylase FTO as well as elevated oxidative stress. However, NAC treatment could partly reverse the reduction of FTO expression as well as the degree of ROS via eliminating oxidative stress. Meanwhile, MeRIP-seq and RNA-seq further revealed the potential function m6A modification in regulating apoptosis. More importantly, KEGG pathway and Gene ontology (GO) analyses further elucidated that the differentially m6A-modified genes were aggregated in apoptosis-related pathways. Mechanistic analysis indicated that knockdown of FTO facilitated CoCl2-induced apoptosis via caspase activation and G1/S cell cycle arrest. Nevertheless, overexpression of FTO partly attenuated the increased apoptosis following CoCl2 exposure. More notably, we observed that FTO regulated apoptosis in an m6A-dependent manner. Therefore, our findings reveal that CoCl2 induced ROS affected the m6A modification of apoptosis-related genes by decreasing the expression of FTO, thereby resulting in the activation of apoptosis. These findings provide important insights into CoCl2-induced apoptosis and m6A modification and propose a novel strategy for studying environmental toxicant-related neurodegeneration.


Changes in Brain Swelling and Infarction Volume over Four Days After Hypoxia Ischemia in Neonatal Rats.
The leading cause of morbidity and mortality in infants is hypoxia-ischemia (HI). The current therapies for HI have limited success, in part due to a lack of understanding of HI pathophysiology and underlying mechanisms. Herein, a neonatal rat model of HI was used to examine the changes in brain swelling and infarct volume over 4 days after HI. Forty-four P10 rat pups were sacrificed at 2, 3, or 4 days post-HI. After sacrifice, the brains were removed, sliced, and stained with TTC (2,3,5-triphenyl-2H-tetrazolium chloride). Images of TTC-stained brains were used for measurement of the ipsilateral hemisphere brain volumes and infarct volumes, calculated using standard equations. The hemispheric brain volumes of HI animals in all groups was lower than that of sham animals and decreased as the post-HI sacrifice time increased. The infarct volume of HI animals was larger than that of sham animals. Infarct volumes tended to decrease over the days post-HI. The change in infarct volume is likely the result of a combination of brain growth and repair mechanisms. However, changes in the hemispheric brain volume may include tissue growth and repair mechanism, so also may be a limitation of the current algorithm used for calculating ipsilateral hemisphere brain volume.


Anisotropic mechanosensitive pathways in the diaphragm and their implications in muscular dystrophies.
The diaphragm is the "respiratory pump;" the muscle that generates pressure to allow ventilation. Diaphragm muscles play a vital function and thus are subjected to continuous mechanical loading. One of its peculiarities is the ability to generate distinct mechanical and biochemical responses depending on the direction through which the mechanical forces applied to it. Contractile forces originated from its contractile components are transmitted to other structural components of its muscle fibers and the surrounding connective tissue. The anisotropic mechanical properties of the diaphragm are translated into biochemical signals that are directionally mechanosensitive by mechanisms that appear to be unique to this muscle. Here, we reviewed the current state of knowledge on the biochemical pathways regulated by mechanical signals emphasizing their anisotropic behavior in the normal diaphragm and analyzed how they are affected in muscular dystrophies.


Influence of dicarboxylic phosphatidylcholines on the stability and phase transition of phosphatidylcholine liposomes.
The effect of dicarboxylic phosphatidylcholines (glutaryl phosphatidylcholine) on the stability and phase transition of phosphatidylcholine liposomes is examined by using liposomes prepared with egg phosphatidylcholine or dipalmitoyl phosphatidylcholine and by varying the surface charge by addition of dicetyl phosphate. Light-scattering and osmotic behaviour studies showed that the stability of liposomes containing dicarboxylic phosphatidylcholine is influenced by the charge and the fatty acid saturation of the liposomes. Increasing the glutaryl phosphatidylcholine-to-phosphatidylcholine molar ratio in liposomes caused the formation of mixed glutaryl phosphatidylcholine/phosphatidylcholine micelles. The sensitivity of the lipid bilayers towards glutaryl phosphatidylcholine action increases with the fatty acid saturation of liposomes. Dipalmitoyl phosphatidylcholine liposomes are most sensitive to the dicarboxylic phosphatidylcholine effect. Dicetyl phosphate addition enhances the solubilization of liposomes prepared from saturated phospholipids. The effect of increasing concentrations of glutaryl phosphatidylcholine on the gel-to-liquid crystal thermal transition of dipalmitoyl phosphatidylcholine was observed. Glutaryl phosphatidylcholine modifies the thermal phase transition of the constituents of the liposome. The presence of dicetyl phosphate in liposomes affects the phase transition temperature of these liposomes. It is suggested that the formation of the mixed micelles is responsible for the phase transition modifications. These data show that the solubilization of liposomes by dicarboxylic phosphatidylcholines depends on the fatty acid composition of phosphatidylcholine and on the presence of dicetyl phosphate.


Germ cell transplantation and testis tissue xenografting in domestic animals.
Transplantation of germ cells from fertile donor mice to the testes of infertile recipient mice results in donor-derived spermatogenesis and transmission of the donor's genetic material to the offspring of recipient animals. Germ cell transplantation provides a bioassay to study the biology of male germ line stem cells, develop systems to isolate and culture spermatogonial stem cells, examine defects in spermatogenesis and treat male infertility. Although most widely studied in rodents, germ cell transplantation has been applied to larger mammals. In domestic animals including pigs, goats and cattle, as well as in primates, germ cells can be transplanted to a recipient testis by ultrasonographic-guided cannulation of the rete testis. Germ cell transplantation was successful between unrelated, immuno-competent pigs and goats, whereas transplantation in rodents requires syngeneic or immuno-compromised recipients. Genetic manipulation of isolated germ line stem cells and subsequent transplantation will result in the production of transgenic sperm. Transgenesis through the male germ line has tremendous potential in domestic animal species where embryonic stem cell technology is not available and current options to generate transgenic animals are inefficient. As an alternative to transplantation of isolated germ cells to a recipient testis, ectopic grafting of testis tissue from diverse mammalian donor species, including horses and primates, into a mouse host represents a novel possibility to study spermatogenesis, to investigate the effects of drugs with the potential to enhance or suppress male fertility, and to produce fertile sperm from immature donors. Therefore, transplantation of germ cells or xenografting of testis tissue are uniquely valuable approaches for the study, preservation and manipulation of male fertility in domestic animals.


Deficiency of SREBP1c modulates autophagy mediated lipid droplet catabolism during oleic acid induced steatosis.
Increased fatty acid and triglyceride synthesis in liver, majorly modulated by Sterol Regulator Elementing Binding Protein 1c (SREBP1c), is one of the main features of non-alcoholic fatty liver disease (NAFLD). In the present study, we aimed to identify the relation between SREBP1c and autophagy mediated lipid droplet (LD) catabolism in oleic acid (OA) induced lipid accumulation. Increased LD formation and SREBP1c induction were identified in hepatocytes (AML12 cells) following the OA administration. SREBP1c level was reduced through siRNA against SREBP1c. The amount and the size of LDs were determined by BODIPY, while protein and mRNA expressions were identified by immunoblotting and qRT-PCR, respectively. LD-lysosome colocalization was determined with immunofluorescence. Increased LD formation and SREBP1c levels were determined at 0.06 mM OA concentration. SREBP1c silencing reduced the number of LDs, while increasing mRNA levels of PPARα. On the other hand, SREBP1c silencing in non-OA and OA treated cells enhanced autophagy mediated LD catabolism. Our results implicate the effect of SREBP1c deficiency in modulating PPARα signaling and autophagy mediated LD catabolism against OA induced lipid accumulation.


Bedbugs: Helping your patient through an infestation.
Bedbugs--hematophagous parasitic arthropods of the genus Cimex--have been unwelcome bedfellows for humans for thousands of years. With increases in population density, ease of travel, and insecticide resistance, bedbugs have reemerged. As a result, physicians are often at the forefront in the diagnosis and treatment of bedbug infestation. This review summarizes the biology and epidemiology of bedbugs and provides details on the diagnosis and treatment of bedbug infestation.


[Effect of low doses of ionizing radiation on the kinetics of growth of a population of HeLa tumor cells].
While studying the effect of 0.1 Gy radiation on the growth of HeLa cells the authors have revealed an increase in the share of cells with the increased proliferative activity that cannot transfer to the resting state.


Incidence of Placement and Removal or Revision of Transvaginal Mesh for Pelvic Organ Prolapse and Stress Urinary Incontinence in the Ambulatory Setting before and after the 2011 Food and Drug Administration Notification.
In July 2011 the FDA issued a notification stating that serious complications associated with surgical mesh for transvaginal repair of pelvic organ prolapse are not rare. This statement did not include any conclusions on mesh for stress urinary incontinence. The notification was reported widely in the popular media and public opinion appeared to turn against transvaginal mesh of all types not specific to pelvic organ prolapse. We evaluated changes in practice that occurred after the notification. We used the California, South Carolina, Illinois and Maryland SASD to determine the incidence of transvaginal mesh implantation procedures for pelvic organ prolapse and stress urinary incontinence as well as the incidence of mesh revision or removal procedures for these indications. A total of 20,323 mesh related procedures were performed for pelvic organ prolapse and stress urinary incontinence in 2011. The total number of transvaginal mesh implantations for prolapse decreased from early to late 2011. The total number of revision or removal procedures increased by 49.1% and 15% for prolapse mesh and slings, respectively. There was an increase in revision or removal procedures for slings as well as for all mesh (each p <0.001). The FDA notification was associated with increased revision or removal procedures for mesh placed for stress urinary incontinence despite the notification warning only against mesh for pelvic organ prolapse. Patients may rely on popular media for medical knowledge. Better patient education may help patients make choices regarding surgery in accordance with the FDA notification.


Spatial considerations during cryopreservation of a large volume sample.
There have been relatively few studies on the implications of the physical conditions experienced by cells during large volume (litres) cryopreservation - most studies have focused on the problem of cryopreservation of smaller volumes, typically up to 2 ml. This study explores the effects of ice growth by progressive solidification, generally seen during larger scale cryopreservation, on encapsulated liver hepatocyte spheroids, and it develops a method to reliably sample different regions across the frozen cores of samples experiencing progressive solidification. These issues are examined in the context of a Bioartificial Liver Device which requires cryopreservation of a 2 L volume in a strict cylindrical geometry for optimal clinical delivery. Progressive solidification cannot be avoided in this arrangement. In such a system optimal cryoprotectant concentrations and cooling rates are known. However, applying these parameters to a large volume is challenging due to the thermal mass and subsequent thermal lag. The specific impact of this to the cryopreservation outcome is required. Under conditions of progressive solidification, the spatial location of Encapsulated Liver Spheroids had a strong impact on post-thaw recovery. Cells in areas first and last to solidify demonstrated significantly impaired post-thaw function, whereas areas solidifying through the majority of the process exhibited higher post-thaw outcome. It was also found that samples where the ice thawed more rapidly had greater post-thaw viability 24 h post-thaw (75.7 ± 3.9% and 62.0 ± 7.2% respectively). These findings have implications for the cryopreservation of large volumes with a rigid shape and for the cryopreservation of a Bioartificial Liver Device.


Temporal trend in venous thromboembolism hospitalization rates in Brazilian older adults, 2010-2020.
Aging is one of the main risk factors for venous thromboembolism (VTE). Changes in prevention, diagnosis, and treatment strategies for this condition in recent years require an analysis of its rates in health services. The objective of this study was to analyze a temporal trend of hospitalizations for VTE in Brazilian older adults. This ecological time series study used data from the Hospital Information System (HIS) on VTE hospitalizations from 2010 to 2020, selecting admissions with the main diagnosis of pulmonary thromboembolism (PTE) (I.26.0, I.26.9) and deep vein thrombosis (DVT) (I.80.0, I80.1, I80.2, I80.3, I80.8, I80.9). Hospitalization rates were calculated for each year and the Prais-Winsten. In Brazil, the trend of hospitalizations for VTE decreased, with an annual percentage change of - 40.71 (confidence interval [CI] - 50.46; - 29.04). DVT decreased, with an annual percentage change of - 43.14 (95% confidence interval [CI] - 51.36; - 33.54). All Brazilian regions showed a downward trend in hospitalizations for VTE and DVT, except for the Northeast region, which remained stable. Conversely, the trend of hospitalizations for PTE showed an upward in Brazil, with an annual percentage change of 4.33 (95% CI 1.26; 7.48). An upward trend was observed in hospitalizations for PTE in the Northeast region, and a stationary trend was observed in the other regions. The results showed a downward trend in hospitalization rates for DVT and an upward trend for PTE. The study indicates regional differences in rates and trends.


Secondary hyperparathyroidism and mortality in hip fracture patients compared to a control group from general practice.
Previously, little attention has been paid as to how disturbances in the parathyroid hormone (PTH)-calcium-vitamin D-axis, such as secondary hyperparathyroidism (SHPT), relate to mortality amongst hip fracture patients. This study aimed to (1) determine if SHPT is associated with mortality in this group of patients, (2) investigate the association between serum (s-) PTH, s-total calcium, s-25-hydroxyvitamin D (s-25(OH)D) and mortality and (3) determine the prevalence of SHPT amongst hip fracture patients and a control group. The study included 562 hip fracture patients (HF) (age ≥ 70 years) admitted to a Danish university hospital. The hip fracture patients were prospectively enrolled in a dedicated hip fracture database. Each hip fracture patient was exactly matched according to age and sex with two controls randomly chosen from a control population of 21,778 subjects who had s-PTH, s-total calcium and s-25(OH)D measured at the Copenhagen General Practitioners Laboratory after referral from their general practitioner. The control group (Con) thus consisted of 1124 subjects. General 1-year mortality: Con-female 8.4%, Con-male 15.3%, HF-female 24.6%, HF-male 33.3%, p<0.0001 (log rank). SHPT AND RELATED 1-YEAR MORTALITY: Con-no SHPT 8.9%, Con-SHPT 16.8%, HF-no SHPT 22.7%, HF-SHPT 34.9%, p<0.0001 (log rank). The mortality rates were higher for controls with SHPT (OR 2.06, 95% CI: 1.32-3.23), hip fracture patients without SHPT (OR 3.00, 95% CI: 2.14-4.20) and hip fracture patients with SHPT (OR 5.46, 95% CI: 3.32-8.97) compared to the controls without SHPT. PREVALENCE OF SHPT: Con 16%, HF 20%, p=0.09 (Chi-square). Our study clearly shows that SHPT is significantly associated with mortality in both hip fracture patients and the control group. In the multivariate Cox regression analysis, s-PTH and s-total calcium were both significantly associated with mortality, whereas s-25(OH)D was not associated with mortality in this analysis. Our study furthermore indicates that SHPT is almost equally prevalent amongst the hip fracture patients and the control group.


The ratio of the atrial areas reflects the clinical status of patients with pulmonary arterial hypertension.
Echocardiography is useful not only for detecting pulmonary hypertension (PH) but also for estimating the severity of PH by evaluating various morphological changes of the heart caused by pressure and volume overload and by ventricular interaction. We investigated whether a novel echocardiographic index, i.e., the ratio of the atrial areas (RA/LA), would be useful for evaluating the clinical status of patients with pulmonary arterial hypertension (PAH) treated with intravenous epoprostenol. We introduced epoprostenol therapy for seven PAH patients without severe tricuspid regurgitation. We evaluated clinical criteria indicative of prognosis, for example World Health Organization functional class (WHO-FC), brain natriuretic peptide (BNP) level, echocardiographic indices such as indexed RA area and RA/LA, and hemodynamics before and one year after intravenous epoprostenol therapy. There were significant improvements in both RA/LA (2.5 ± 1.0, 1.3 ± 0.4, P < 0.001) and indexed RA area (22.5 ± 8.9, 14.5 ± 5.8, P < 0.001). The improvement in RA/LA was more sensitive than that in indexed RA area (P < 0.01). Moreover, RA/LA was significantly correlated with WHO-FC (r = 0.50, P < 0.01) and BNP level (r = 0.82, P < 0.01). RA/LA is useful for evaluating the clinical status of patients with PAH treated with intravenous epoprostenol.


Ileal endometriosis (a case report).
A case of endometriosis involving small bowel is reported here. It is the first case reported at our institution in the last 10 years period.


Sublexical frequency measures for orthographic and phonological units in German.
Many recent studies have demonstrated the influence of sublexical frequency measures on language processing, or called for controlling sublexical measures when selecting stimulus material for psycholinguistic studies (Aichert & Ziegler, 2005). The present study discusses which measures should be controlled for in what kind of study, and presents orthographic and phonological syllable, dual unit (bigram and biphoneme) and single unit (letter and phoneme) type and token frequency measures derived from the lemma and word form corpora of the CELEX lexical database (Baayen, Piepenbrock, & Gulikers, 1995). Additionally, we present the SUBLEX software as an adaptive tool for calculating sublexical frequency measures and discuss possible future applications. The measures and the software can be downloaded at www.psychonomic.org.


No evidence for functional inactivation of wild-type p53 protein by MDM2 overexpression in gastric carcinogenesis.
Inactivation of wild-type p53 during gastric carcinogenesis is usually caused by mutations within exons 5-8 of the p53 gene leading to mutated, usually immunohistochemically detectable p53 proteins. However, functional inactivation of wild-type p53, mimicking mutational inactivation, may also result from binding to overexpressed MDM2 protein. While these two mechanisms of p53 inactivation are considered to be mutually exclusive, no data exist as to whether MDM2 overexpression occurs during gastric carcinogenesis. MDM2 protein overexpression was therefore studied in relation to p53 protein accumulation in gastric carcinogenesis. Forty-five paraffin-embedded gastrectomy specimens from early gastric carcinomas were examined for the presence of chronic active gastritis, chronic atrophic gastritis, subtypes of intestinal metaplasia, and dysplasia. The Lauren type was reassessed for all early carcinomas. p53 protein accumulation was examined using the monoclonal antibody DO-7. MDM2 protein overexpression was assessed with the monoclonal antibody SMP-14. Complete absence of nuclear p53 protein accumulation was observed in chronic active gastritis, chronic atrophic gastritis, and intestinal metaplasia, irrespective of the subtype. In gastric dysplasia (one mild, two moderate, one severe), only severe dysplasia was p53-positive. Intestinal-type (n = 20) and diffuse-type early gastric carcinoma (n = 25) were p53-positive in 70 and 52 per cent of the cases, respectively. MDM2 protein overexpression was not observed during gastric carcinogenesis, either in the p53-positive or in the p53-negative cases. In conclusion, it appears that functional inactivation of wild-type p53 by MDM2 protein overexpression plays no role in (early) gastric carcinogenesis.


Mathematical simulation of membrane processes and metabolic fluxes of the pancreatic beta-cell.
A new type of equation to describe enzyme-catalyzed reactions was developed, which allows the description of processes both at or near equilibrium and far from equilibrium, as they are both known to occur in the living cell. These equations combine kinetic as well as energetic characteristics within one single equation, and they describe the steady state as well as oscillations, as is shown for the glucose metabolism of the pancreatic beta-cell. A simulation of oxidative glucose metabolism could be elaborated, which allows to analyse in detail, how membrane and metabolic oscillations of the pancreatic beta-cell are generated, and how they are kinetically coupled. Glucose metabolism shows steady-state behaviour at a resting glucose concentration ([Glu]) of 4 mM. The steady state is switched to the oscillatory state by a first increase of the conductance of the glucokinase-catalyzed reaction at an elevated [Glu] of 10 mM. This is in fact sufficient to decrease the cytosolic adenosine diphosphate concentration ([ADP](c)) at constant intracellular [Ca(2+)]. The associated changes of the ATP and ADP species can reduce the conductance of ATP-sensitive K(+) channels (K(ATP)), thereby initiating bursts of the cell membrane potential (Delta(c)phi) with a concomitant influx of Ca(2+) ions from the extracellular space into the cell. The production of oscillations of [ADP](c), [Ca(2+)](c), and all other variables, including those of mitochondria, are brought about on the one hand by a [Ca(2+)](m) dependent activation of mitochondrial ATP production, on the other hand by a [Ca(2+)](c)-dependent activation of ATP utilisation in the cytosol. Both processes must be coordinated in such a way that ATP production slightly precedes its utilisation. Oscillatory frequencies (fast/slow) are determined by the conductance (high/low, respectively) of flux through pyruvate dehydrogenase and/or citric acid cycle. The simulation shows that the so-called pyruvate paradox possibly results from a relatively low membrane conductance of beta-cells for pyruvate.


Selective attachment of prokaryotes and emergence of potentially pathogenic prokaryotes on four plastic surfaces: Adhesion study in a natural marine environment.
This study employed 16S rRNA metabarcoding to establish the diversity of prokaryotic communities and specific characteristics of potentially pathogenic prokaryotic primary colonizers of four plastic materials (EPS, expanded polystyrene; PE, polyethylene; PP, polypropylene; and PET, polyethylene terephthalate). Bacteria inhabiting plastic and seawater differ; thus, distinct changes in the attached prokaryotic community were observed over an exposure time of 21 days, specifically on Days 3, 6, 9, and 12-21. Frist colonizers were Gammaproteobacteria and Alphaproteobacteria; Bacilli and Clostridia represented secondary colonizers. On Day 3, Pseudoalteromonas had a relative abundance >80 %; whereas, the prevalence of Vibrio spp. (potentially pathogenic prokaryotes) increased rapidly on Days 6 and 9. However, after Day 12, the prevalence of other potential pathogens, namely, Clostridium spp., steadily increased. Despite the diversity of the plastic surfaces, attached prokaryotes changed over time instead of showing similar adherent diversity in all plastic materials.


A few good peptides: MHC class I-based cancer immunosurveillance and immunoevasion.
The remarkable success of immune checkpoint inhibitors demonstrates the potential of tumour-specific CD8+ T cells to prevent and treat cancer. Although the number of lives saved by immunotherapy mounts, only a relatively small fraction of patients are cured. Here, we review two of the factors that limit the application of CD8+ T cell immunotherapies: difficulties in identifying tumour-specific peptides presented by MHC class I molecules and the ability of tumour cells to impair antigen presentation as they evolve under T cell selection. We describe recent advances in understanding how peptides are generated from non-canonical translation of defective ribosomal products, relate this to the dysregulated translation that is a feature of carcinogenesis and propose dysregulated translation as an important new source of tumour-specific peptides. We discuss how the synthesis and function of components of the antigen-processing and presentation pathway, including the recently described immunoribosome, are manipulated by tumours for immunoevasion and point to common druggable targets that may enhance immunotherapy.


Establishment of reference CD4+ T cell values for adult Indian population.
CD4+ T lymphocyte counts are the most important indicator of disease progression and success of antiretroviral treatment in HIV infection in resource limited settings. The nationwide reference range of CD4+ T lymphocytes was not available in India. This study was conducted to determine reference values of absolute CD4+ T cell counts and percentages for adult Indian population. A multicentric study was conducted involving eight sites across the country. A total of 1206 (approximately 150 per/centre) healthy participants were enrolled in the study. The ratio of male (N = 645) to female (N = 561) of 1.14:1. The healthy status of the participants was assessed by a pre-decided questionnaire. At all centers the CD4+ T cell count, percentages and absolute CD3+ T cell count and percentages were estimated using a single platform strategy and lyse no wash technique. The data was analyzed using the Statistical Package for the Social Scientist (SPSS), version 15) and Prism software version 5. The absolute CD4+ T cell counts and percentages in female participants were significantly higher than the values obtained in male participants indicating the true difference in the CD4+ T cell subsets. The reference range for absolute CD4 count for Indian male population was 381-1565 cells/μL and for female population was 447-1846 cells/μL. The reference range for CD4% was 25-49% for male and 27-54% for female population. The reference values for CD3 counts were 776-2785 cells/μL for Indian male population and 826-2997 cells/μL for female population. The study used stringent procedures for controlling the technical variation in the CD4 counts across the sites and thus could establish the robust national reference ranges for CD4 counts and percentages. These ranges will be helpful in staging the disease progression and monitoring antiretroviral therapy in HIV infection in India.


Current evaluation of the contribution of self-examination to secondary prevention of breast cancer.
The "state of art" in the problem of BSE and its role in breast cancer early diagnoses in analysed. Advantages and disadvantages of this method and a complex of socio-psychologic problems arising in healthy population due to its introduction are discussed. The absence of scientifically grounded data on the importance of BSE for early diagnosis of breast cancer suggests the necessity of further investigations in order to identify its efficacy. Such data can be obtained only on the basis of randomized population study with estimation of efficacy by the decrease of breast cancer mortality in population. Under the auspices of the WHO such investigation has been conducted in Leningrad and in Moscow (USSR). Methods or investigation applied are described in short.


Rates of complete nonadherence among atypical antipsychotic drugs: A study using blood samples from 13,217 outpatients with psychotic disorders.
Nonadherence to antipsychotics may cause relapse and hospitalizations in patients with psychotic disorders. The purpose was to quantify and compare the outpatient's nonadherence rates of atypical antipsychotics by objective detection in blood samples. Totally, 13,217 outpatients with therapeutic drug monitoring (TDM) data of atypical antipsychotics were included. An event of complete nonadherence was defined as an occurrence of undetectable level of a prescribed antipsychotic in the blood sample submitted for TDM. Patients with such an event(s) were defined as nonadherent of the respective drug treatment (outcome). The rates of nonadherence patients were compared between the drugs by logistic regression. In the study population, 70.2% of the patients were prescribed doses compliant with a schizophrenia diagnosis. The mean olanzapine equivalent dose in the population was 13.4 mg (95% confidence interval (CI): 13.3, 13.6). The frequency of nonadherence patients, regardless of drug, was 3.7% (CI: 3.4-4.0). The nonadherence patient rate was lowest in clozapine-treated patients (2.2%; CI: 1.5-2.8), followed by aripiprazole (2.3%; 1.7-2.8), risperidone (2.4%; 1.6-3.0), quetiapine (2.8%; 2.3-3.2) and olanzapine (4.9%; 4.1-5.3). Users of olanzapine had significantly higher risk of complete nonadherence (Odds ratio: 1.9; CI: 1.6-2.3, p < 0.001) compared to patients treated with other antipsychotics as a group. In this study, complete nonadherence of atypical antipsychotics, measured as undetectable blood level, was disclosed for ~5% of outpatients with psychotic disorders. The rate of complete nonadherence was significantly higher during olanzapine treatment compared to other atypical antipsychotics. Further studies should investigate if this reflects drug differences in tolerability or other causal relationships.


Long-term follow-up of spinal cord injury patients with vesicoureteral reflux.
The medical records of 32 spinal cord injury patients with 43 vesicoureteral refluxes admitted to our hospital from 1970 to 1982 were retrospectively reviewed. These patients were followed yearly with pyelograms together with cystograms or cystourethrograms. Many of these individuals were on an indwelling Foley catheter at the time reflux was detected, indicating that free urinary drainage such as a Foley catheter did not prevent reflux formation. Further, the majority of refluxes developed 1-2 years post-injury, and some disappeared spontaneously without causing any damage to the urinary tract. However, the indwelling Foley catheter was ineffective for reflux treatment because in the long run it did not prevent progression of vesicoureteral reflux and did not protect the refluxing kidney from damage. We also noticed that the incidence of reflux was statistically higher in patients with complete spinal lesion than in those with incomplete neurological dysfunction. This incidence was also higher in individuals with an upper motor neuron lesion.


Pelvic tilt makes acetabular cup navigation inaccurate.
Modern navigation techniques allow precise positioning of the acetabular cup relative to the anterior pelvic plane. Variations in pelvic tilt will affect the resulting spatial orientation of the cup. We measured pelvic tilt in 30 volunteers with an inclinometer combined with an ultrasonographic position measurement system. A mathematical algorithm was developed to calculate the resulting cup position measured on standard radiographs, depending on pelvic tilt. Average pelvic tilt at rest was -4 degrees in the lying position and -8 degrees in the standing position, and ranged from -27 degrees to +3 degrees. Pelvic reclination of 1 degree will lead to functional anteversion of the cup of approximately 0.7 degree. Pelvic tilt makes navigation systems referring to the anterior plane inaccurate.


Implementation of ED I-PASS as a Standardized Handoff Tool in the Pediatric Emergency Department.
Communication, failures during patient handoffs are a significant cause of medical error. There is a paucity of data on standardized handoff tools for intershift transitions of care in pediatric emergency medicine (PEM). The purpose of this quality improvement (QI) initiative was to improve handoffs between PEM attending physicians (i.e., supervising physicians ultimately responsible for patient care) through the implementation of a modified I-PASS tool (ED I-PASS). Our aims were to: (1) increase the proportion of physicians using ED I-PASS by two-thirds and (2) decrease the proportion reporting information loss during shift change by one-third, over a 6-month period. After literature and stakeholder review, Expected Disposition, Illness Severity, Patient Summary, Action List, Situational Awareness, Synthesis by Receiver (ED I-PASS) was implemented using iterative Plan-Do-Study-Act cycles, incorporating: trained "super-users"; print and electronic cognitive support tools; direct observation; and general and targeted feedback. Implementation occurred from September to April of 2021, during the height of the COVID-19 pandemic, when patient volumes were significantly lower than prepandemic levels. Data from observed handoffs were collected for process outcomes. Surveys regarding handoff practices were distributed before and after ED I-PASS implementation. 82.8% of participants completed follow-up surveys, and 69.6% of PEM physicians were observed performing a handoff. Use of ED I-PASS increased from 7.1% to 87.5% ( p < .001) and the reported perceived loss of important patient information during transitions of care decreased 50%, from 75.0% to 37.5% ( p = .02). Most (76.0%) participants reported satisfaction with ED I-PASS, despite half citing a perceived increase in handoff length. 54.2% reported a concurrent increase in written handoff documentation during the intervention. ED I-PASS can be successfully implemented among attending physicians in the pediatric emergency department setting. Its use resulted in significant decreases in reported perceived loss of patient information during intershift handoffs.


Uptake, Persistence, and Performance of Weekly Home Monitoring of Visual Field in a Large Cohort of Patients With Glaucoma.
This study examines the short-term uptake, compliance, and performance of a tablet device used for home monitoring of visual field (VF-Home) by glaucoma patients. Single-center, observational, longitudinal, compliance study. Participants who were glaucoma suspects or had stable glaucoma in at least one eye were recruited during a regular clinic review. Baseline in-clinic visual field (VF) was recorded with the Humphrey Field Analyser (HFA, SITA standard) and repeated at 6 months. Participants were tasked with performing 6 VF examinations from home, at weekly intervals, using a loaned iPad tablet. Uptake was defined as returning at least 1 test from home. Reliability and global indices from VF-Home were compared to in-clinic outcomes. Data are shown as either mean ± [standard deviation] or median [quartile 1-3 range], and group comparisons were achieved with bootstrap. We recruited 186 eyes of 101 participants. VF-Home uptake was excellent, with 88% of participants successfully completing ≥1 home examination and 69% completing all 6 examinations. The median duration between tests was 7.0 [7.0-8.0] days. Barriers to uptake and compliance involved information technology (IT) logistical reasons, lack of motivation, or competing life demands. VF-Home gave greater fixation loss but a similar level of False Positives (FP) as the HFA. A high correlation was found for the mean defect between in-clinic and at-home outcomes (R = 0.85). VF-Home can return a high level of short-term compliance and results comparable to those found by in-clinic testing. IT logistical reasons and lack of motivation are barriers to uptake and compliance.