Chronically ill patients' self-management abilities to maintain overall well-being: what is needed to take the next step in the primary care setting?
Although widespread problems in patient-professional interaction and insufficient support of patients' self-management abilities have been recognized, research investigating the relationships among care quality, productive interaction, and self-management abilities to maintain overall well-being is lacking. Furthermore, studies have revealed differences in these characteristics among certain groups (e.g., less-educated and older patients). This longitudinal study thus aimed to identify relationships among background characteristics, quality of care, productivity of patient-professional interaction, and self-management abilities to maintain overall well-being in chronically ill patients participating in 18 Dutch disease management programs. This longitudinal study included patients participating in 18 Dutch disease management programs. Surveys were administered in 2011 (T1; n = 2191 (out of 4693), 47 % response rate) and 2012 (T2: n = 1722 (out of 4350), 40 % response rate). A total of 1279 patients completed questionnaires at both timepoints (T1 and T2) (27 % response rate). Self-management abilities to maintain well-being were measured using the short (18-item) version of the Self-Management Ability Scale (SMAS-S), patients' perceptions of the productivity of interactions with health care professionals were assessed with the relational coordination instrument and the short (11-item) version of the Patient Assessment of Chronic Illness Care (PACIC-S) was used to assess patients' perceptions of the quality of chronic care delivery. Perceived and objective quality of care and the productivity of patient-professional interaction were found to be related to patients' self-management abilities to maintain overall well-being. These abilities were related negatively to and significantly predicted by low educational level, single status, and older age, despite the mediating role of productive interaction in their relationship with patients' perceptions of care quality. These findings suggest that patient-professional interaction is not yet sufficiently productive to successfully protect against the deterioration of self-management abilities in some groups of chronically ill patients, although such interaction and high-quality care are important factors in such protection. Improvement of the quality of chronic care delivery should thus always be accompanied by investment in high-quality communication and patient-professional relationships.


Effects of hypothermia on excitatory amino acids and metabolism in stroke patients: a microdialysis study.
The objective of this study was to assess the effect of therapeutic moderate hypothermia on excitatory amino acids and metabolism by applying cerebral microdialysis in patients suffering from space-occupying middle cerebral artery infarction. This was an open, prospective, observational study of 12 patients undergoing moderate hypothermia (33 degrees C) as rescue therapy for large, life-threatening middle cerebral artery infarction. Microdialysis probes were placed concomitantly with intracranial pressure (ICP) measuring devices in the frontal lobe of the infarcted and/or noninfarcted hemisphere. Using the CMA 600 Microdialysis Autoanalyzer, we analyzed glutamate, glycerol, pyruvate, and lactate. According to follow-up cranial CT scans, 3 different compartments of microdialysis measurements could be defined. First, noninfarcted brain tissue had stable dialysate concentrations but a significant effect of hypothermia on glutamate (2.6 versus 3.6 micromol/L), lactate (1.8 versus 3 mmol/L), and pyruvate (50 versus 95.8 micromol/L). Second, measurements from peri-infarct tissue had a significant effect of hypothermia on glutamate (4.8 versus 12.6 micromol/L), glycerol (58 versus 82 micromol/L), lactate (0.7 versus 1.3 mmol/L), and pyruvate (13.3 versus 36.8 micromol/L). Third, dialysate concentrations obtained from irreversibly damaged tissue were excessive for glutamate (453 micromol/L), glycerol (1187 micromol/L), lactate (12 micromol/L), and pyruvate (4 micromol/L). In this extreme compartment, no effect of hypothermia was observed. Cerebral microdialysis is a safe and feasible bedside method for neurochemical monitoring indicating normal brain tissue, potentially salvageable brain tissue, and irreversibly damaged areas in stroke. We could demonstrate that hypothermia decreases glutamate, glycerol, lactate, and pyruvate in the "tissue at risk" area of the infarct but not within the infarct core. Thus, future treatment strategies for life-threatening stroke should be guided by close neurochemical monitoring.


Superhydrophilicity boron-doped cobalt phosphide nanosheets decorated carbon nanotube arrays self-supported electrode for overall water splitting.
Transition metal borides (TMBs) or phosphides (TMPs) have attracted great attention to the design of bifunctional electrocatalysts for energy storage. The superaerophobicity and superhydrophilicity of the catalytic electrode surface are crucial factors to determine the reaction process of the gas electrode. Herein, we report a self-supported electrode of carbon nanotube (CNTs) array grown on carbon cloth (CC) modulated together by boron-doped cobalt phosphide (CoP-B/CNTs/CC). The electrode requires the overpotential of 73.8 mV and 189.5 mV at the current density of ±10 mA cm-2 for hydrogen and oxygen evolution reactions in an alkaline electrolyte (1.0 M KOH), respectively, meanwhile maintaining outstanding long-term durability for more than 300 h. The excellent activity of CoP-B/CNTs/CC is attributed to boron doping regulating its electronic structure and further enriching active sites. The attractive stability of CoP-B/CNTs/CC is due to the unique geometric structure of the self-supported electrode. Furthermore, the superaerophobicity and superhydrophilicity of the electrode surface also accelerate the reaction process of the gas electrode. Expectedly, water splitting cells assembled using CoP-B/CNTs/CC electrodes as cathode and anode, respectively, require a cell voltage of 1.54 V at 10 mA cm-2, which is lower than that of the Pt/C/CC||RuO2/CC couple (1.69 V at 10 mA cm-2). Importantly, CoP-B/CNTs/CC||CoP-B/CNTs/CC achieve stable cell voltage under the step current changes (10 mA cm-2, 50 mA cm-2, and 100 mA cm-2) over 300 h. This work highlights a new path to understanding the effects of the static and dynamic behavior of bubbles on the surface of self-supporting electrodes on catalytic performance.


Transport of organic anions through the erythrocyte membrane as K+-valinomycin complexes.
K+, Rb+, or Cs+ complexes of valinomycin form ion pair complexes with picric acid and trinitrobenzenesulfonate (TNBS). The formation of a picrate-K+-valinomycin complex is supported by spectral evidence. These complexes have zero net charge and readily permeate the intact erythrocyte membrane. The K+-valinomycin complex has been used to convert the nonpenetrating TNBS into a penetrating covalent probe, making it as useful vectorial probe to measure accessible amino groups of proteins and phospholipids on both sites of the erythrocyte membrane. The enhanced transport of TNBS into the cell by valinomycin is dependent on external K+ in the medium. The entry of TNBS into the cell is manifested by an increased labeling of hemoglobin and membrane phosphatidylethanolamine (PE). Stilbeneisothiocyanatedisulfonate (SITS) and anilinonaphthalenesulfonate (ANS) inhibit both the basal and K+-valinomycin stimulated labeling of PE and hemoglobin by TNBS. The data suggest two independent effects of ANS and SITS, one mediated by an inhibition of the anion transport protein and another by the incorporation of these hydrobic anions into the cell membrane with an increase in negative charge on the membrane which leads to an inhibition of TNBS permeation into the cell by electrostatic repulsion.


Transcriptomic, proteomic and metabolomic profiling unravel the mechanisms of hepatotoxicity pathway induced by triphenyl phosphate (TPP).
Triphenyl phosphate (TPP) has been found in various environmental media and in biota suggesting widespread human exposure. However, there is still insufficient information on the hepatotoxicity mechanisms of health risk exposed to TPP. In this study, TPP could induce human normal liver cell (L02) apoptosis, injury cell ultrastructure and elevate the levels of reactive oxygen species (ROS). The integrated multi-omic (transcriptomic, proteomic, and metabolomic) analysis was used to further investigate the mechanisms. Transcriptomic analysis revealed that TPP exposure markedly affected cell apoptosis, oncogene activation, REDOX homeostasis, DNA damage and repair. Additionally, proteomic analysis found that the related proteins associated with apoptosis, oxidative stress, metabolism and membrane structure were affected. And metabolomic analysis verified that the related metabolic pathways, such as glycolysis, citrate cycle, oxidative phosphorylation, lipid and protein metabolism, were also significantly disrupted. Based on the multi-omic results, a hypothesized network was constructed to discover the key molecular events in response to TPP and illustrate the mechanism of TPP-induced hepatotoxicity in L02 cells. Therefore, molecular responses could be elucidated at multiple biological levels, and multi-omic analysis could provide scientific tools for exploring potential mechanisms of toxicity and chemical risk assessment.


Expression of c-sis/platelet-derived growth factor B, insulin-like growth factor I, and transforming growth factor alpha messenger RNAs and their respective receptor messenger RNAs in primary human gastric carcinomas: in vivo studies with in situ hybridization and immunocytochemistry.
In situ hybridization and immunocytochemistry have been applied to investigate the expression of c-sis/platelet-derived growth factor (PDGF)-B, insulin-like growth factor (IGF)-I, and transforming growth factor alpha mRNAs and their respective receptor mRNAs in three primary human gastric carcinomas and in their adjacent nonmalignant mucosas. Expression of c-sis/PDGF-B mRNA and PDGF-receptor beta mRNA was seen in the tumor cells of the three gastric cancer specimens but not in their adjacent nonmalignant mucosa. The mRNA expression was accompanied by the expression of their respective protein products. IGF-I, IGF-I receptor, and epidermal growth factor receptor mRNAs were seen in both the tumor cells of the gastric cancer specimens and in nonmalignant mucosa. Transforming growth factor alpha mRNA was expressed in gastric tumor cells but not in nonmalignant mucosa. The coexpression of a potent "competence" growth factor, PDGF, and "progression" growth factors, IGF-I and transforming growth factor alpha, in the tumor cells of gastric carcinomas may contribute to their growth and maintenance.


Factors affecting place of death in Washington State, 1968-1981.
A study was carried out to determine factors affecting place of death (home, hospital, nursing home or "other places") among all 426,115 resident deaths in Washington State during 1968-1981, using death certificate information. Sixteen percent of deaths occurred at home, 74% in institutions (51% in hospitals, 23% in nursing homes) and 9% at "other places." Age, marital status and cause of death all strongly affect place of death. Further, the effect of each factor was strongly dependent on the others. Sex had no effect on place of death after controlling for other factors. Elderly people died relatively more frequently in nursing homes, infants and middle aged people in hospitals and young adults in "other places." The frequency of deaths at home was quite constant by age. Hospitals were the most common place of death following both vascular disease (including heart attack) and neoplasms, and nursing homes were the most common place of death following cerebrovascular disease (including "stroke"). Race, socioeconomic status and urban or rural residents affected the place of death only slightly or not at all. The place of death pattern changed little during the time period 1968-1981, except for a slight increase in frequency of home deaths and a corresponding decrease in the frequency of deaths in other places. Among cancer patients, the likelihood of death at home was positively associated with longer periods of survival after diagnosis. Cancer patients of hospitals serving targeted populations, such as veterans, were relatively more likely to die in a hospital and less likely to die in a nursing home compared to other cancer patients, suggesting that the "targeted" hospitals are sometimes serving a nursing home function. There was a marked difference in the terminal cancer caseload by hospital. The number of cancer deaths per cancer diagnosis varied widely across hospitals (0.1 to 1.6) and was unrelated to size of the hospital or level of services offered. Intervention aimed at affecting place of death, such as increasing the number of deaths at home, will need to take account of the joint effect of age, marital status and disease.


Expression and cellular localization of classic NADPH oxidase subunits in the spontaneously hypertensive rat kidney.
Phagocytes generate superoxide anion (O(2)(-)) by a classic, 5-component NADPH oxidase. O(2)(-) contributes to hypertension in spontaneously hypertensive rats (SHR). Therefore, we tested the hypothesis that NADPH oxidase expression is enhanced in the SHR kidney. We also analyzed the localization of NADPH oxidase components in SHR kidney. Renal NADPH oxidase was quantified by reverse transcription-polymerase chain reaction and Western blotting and was localized in SHR and Wistar Kyoto rat (WKY) kidney by immunohistochemistry. The mRNA for 5 subunits of phagocyte NADPH oxidase, and also for MOX1 and RENOX (NOX4), was detected in adult rat kidney. Kidneys of adult (10 weeks old) SHR had a significantly (P<0.01) greater mRNA for p47phox (SHR 0.81 +/- 0.05 versus WKY 0.37 +/- 0.01, arbitrary unit), which was confirmed by Western blotting (SHR 0.58 +/- 0.04 versus WKY 0.42 +/- 0.04, arbitrary unit; P<0.05) and by immunohistochemistry. This higher p47phox protein expression was also detected in young prehypertensive SHR (SHR 0.61 +/- 0.05 versus WKY 0.39 +/- 0.04, arbitrary unit; P<0.01). The 10-week-old SHR contained more modest but significantly (P<0.05) greater protein for p67phox (SHR 0.54 +/- 0.02 versus WKY 0.46 +/- 0.02). Immunostaining localized p47phox, p67phox, and p22phox in vasculature, macula densa, distal convoluted tubule, cortical collecting duct, and outer and inner medullary collecting ducts. The kidney of SHR expresses genes for all the main components of phagocyte NADPH oxidase, RENOX, and MOX1. There is a prominent increase in the SHR kidney of the mRNA, and protein expression of p47phox in the vasculature, macula densa, and distal nephron, which precedes development of hypertension.


Veverimer: An Emerging Potential Treatment Option for Managing the Metabolic Acidosis of CKD.
Sodium bicarbonate is the mainstay treatment of the metabolic acidosis of chronic kidney disease but associated concerns center on administering sodium to patients with hypertension and sodium-retentive states. Veverimer (formerly referred to as TRC101), a drug candidate for which Tricida, Inc is seeking approval from the US Food and Drug Administration, is a novel nonabsorbable polymer that binds hydrogen cations and chloride anions in the gastrointestinal tract and then is excreted fecally, thereby increasing serum bicarbonate concentration without administering sodium. We examine the published evidence on the investigational use of veverimer in patients with chronic kidney disease and metabolic acidosis. We highlight the achieved increase in serum bicarbonate concentration without coadministering sodium, effects on physical functioning, and the safety record of the drug. We also scrutinize certain unanticipated findings: a lack of dose dependency in the increase in serum bicarbonate concentration observed and that despite the presumed large hydrogen chloride losses in feces, veverimer induces an isochloremic increase in serum bicarbonate concentration that is accompanied by a decrease in serum anion gap. We propose likely explanations for these puzzling findings and raise questions about veverimer's mode of action and its potential interaction with colonic bacterial flora. Additional work is required to fill these knowledge gaps that could have important clinical implications.


Analysis of Infections Caused by Influenza Viruses and Influenza-Like Viruses in the Population of People over 65 Years of Age in the 2019-2020 Epidemic Season in Poland.
BACKGROUND Influenza can be the most dangerous for people in risk groups, for example for seniors, in whom it can lead to serious and life-threatening complications. The aim of this research was to analyze the activity of influenza viruses and influenza-like viruses in patients over 65 years of age in the 2019-2020 epidemic season in Poland. MATERIAL AND METHODS A total of 1269 samples collected from patients over 65 years of age with suspected influenza or other respiratory viruses in the 2019-2020 epidemic season (from October 1, 2019, to September 30, 2020) were analyzed. The test material was nose and throat swabs collected during the 2019-2020 epidemic season. Quantitative polymerase chain reaction was used to determine the influenza virus type and subtype for positive samples. RESULTS Among the confirmed infections with influenza viruses, cases due to influenza A were dominant, and the dominant subtype was influenza A subtype A/H1N1/pdm09. Infections with influenza-like viruses were also confirmed in the patients participating in the study, with the presence of genetic material of respiratory syncytial viruses confirmed most often. CONCLUSIONS Seasonal vaccinations can significantly reduce the number of cases and thus the risk of post-influenza complications and deaths among seniors. This is very important, especially now, due to the current epidemiological situation related to the ongoing SARS-CoV-2 respiratory virus pandemic.


Outcomes of corneal transplantation for irreversible corneal decompensation secondary to corneal endotheliitis in Asian eyes.
To describe outcomes of corneal transplantation for irreversible corneal decompensation from corneal endotheliitis in Asian eyes. Retrospective, observational case series. We reviewed consecutive patients with corneal endotheliitis (32 eyes of 31 subjects) who underwent keratoplasty (January 1, 2008-December 1, 2009). All eyes had preoperative aqueous polymerase chain reaction (PCR) analysis for viruses, including cytomegalovirus (CMV). CMV-positive patients were treated preoperatively with topical corticosteroids and anti-CMV treatment (oral valganciclovir 900 mg twice daily, topical ganciclovir 0.15% 5 applications per day, for 6 weeks) with complete resolution of ocular inflammation, and quiescence for at least 6 months before corneal transplantation. Our main outcome measure was recurrence of endotheliitis within 1 year after corneal transplantation. Five eyes were CMV positive; the remaining 27 eyes were negative for all viruses on PCR analysis. CMV-positive patients had a higher rate of recurrence of endotheliitis within 1 year after corneal transplantation, compared with CMV-negative eyes (60% vs 7.4%, P = .01). The CMV-positive eyes had recurrent endotheliitis at a median of 10 months (range 3-11 months) after corneal transplantation. After successful anti-CMV treatment, all 5 CMV-positive eyes then continued to have clear grafts for a median duration of 21 months (range 13-44 months). Our study suggests that Asian patients with corneal endotheliitis may benefit from preoperative aqueous PCR analysis before corneal transplantation. Such patients were more likely to have a recurrence of endothelial inflammation if they were CMV positive preoperatively, despite successful anti-CMV treatment before surgery.


Nutrition support and clinical outcomes following allogeneic stem cell transplantation.
Nutrition support is frequently required post allogeneic stem cell transplantation (SCT) and while there is some evidence on the benefits of enteral nutrition (EN), parenteral nutrition (PN) is widely used in practice. The study aimed to examine the impact of EN versus PN on early outcomes following SCT. All patients who underwent allogeneic SCT over 2.5 years were included in the analysis. Data was retrospectively collected on mode of nutrition support with clinical outcome data obtained from an existing database. Clinical outcomes were compared between groups by logistic, poisson and negative binomial regression, with adjustment for baseline confounders as appropriate. Patients who received EN then changed to PN had a longer length of hospital stay compared to those who received EN only (IR 1.24, 95% CI: 1.11-1.38, p < 0.001). Compared to those who received EN only, patients who received EN that changed to PN or PN only had a longer time to neutrophil engraftment (IR 1.11, 95% CI: 1.02-1.20, p = 0.016 and IR 1.16, 95% CI: 1.03-1.30, p = 0.017) and platelet engraftment (IR 1.20, 95% CI 1.08-1.33, p < 0.001 and IR 1.24, 95% CI 1.08-1.42, p = 0.002). Enteral nutrition should be first line nutritional support for patients undergoing allogeneic SCT.


A glycoengineered anti-CD19 antibody with potent antibody-dependent cellular cytotoxicity activity in vitro and lymphoma growth inhibition in vivo.
Human cluster of differentiation (CD) antigen 19 is a B cell-specific surface antigen and an attractive target for therapeutic monoclonal antibody (mAb) approaches to treat malignancies of B cell origin. MEDI-551 is an affinity-optimized and afucosylated CD19 mAb with enhanced antibody-dependent cellular cytotoxicity (ADCC). The results from in vitro ADCC assays with Natural Killer cells as effector cells, demonstrate that MEDI-551 is effective at lower mAb doses than rituximab with multiple cell lines as well as primary chronic lymphocytic leukaemia and acute lymphoblastic leukaemia samples. Targeting CD19 with MEDI-551 was also effective in several severe combined immunodeficiency lymphoma models. Furthermore, the combination of MEDI-551 with rituximab resulted in prolonged suppression of tumour growth, demonstrating that therapeutic mAbs with overlapping effector function can be combined for greater tumour growth inhibition. Together, the data demonstrate that MEDI-551 has potent antitumour activity in preclinical models of B cell malignancies. The results also suggest that the combination of the ADCC-enhanced CD19 mAb with an anti-CD20 mAb could be a novel approach for the treatment of B cell lymphomas.


Cerebellar top-of-the-basilar syndrome.
We present a patient with unusual cerebrovasculature due to the absence of anastomosis between anterior and posterior circulations and bilateral fetal posterior cerebral arteries. This resulted in an atypical 'cerebellar' top-of-the-basilar syndrome, with bilateral superior cerebellar artery infarctions. We review the clinical presentation and radiologic findings and explain the embryologic origin of this vascular anatomy.


Faculty of Prehospital Care, Royal College of Surgeons Edinburgh guidance for medical provision for wilderness medicine.
To support leaders and those involved in providing medical care on expeditions in wilderness environments, the Faculty of Pre-Hospital Care (FPHC) of The Royal College of Surgeons of Edinburgh convened an expert panel of leading healthcare professionals and expedition providers. The aims of this panel were to: (1) provide guidance to ensure the best possible medical care for patients within the geographical, logistical and human factor constraints of an expedition environment. (2) Give aspiring and established expedition medics a 'benchmark' of skills they should meet. (3) Facilitate expedition organisers in selecting the most appropriate medical cover and provider for their planned activity. A system of medical planning is suggested to enable expedition leaders to identify the potential medical risks and their mitigation. It was recognised that the scope of practice for wilderness medicine covers elements of primary healthcare, pre-hospital emergency medicine and preventative medicine. Some unique competencies were also identified. Further to this, the panel recommends the use of a matrix and advisory expedition medic competencies relating to the remoteness and medical threat of the expedition. This advice is aimed at all levels of expedition medic, leader and organiser who may be responsible for delivering or managing the delivery of remote medical care for participants. The expedition medic should be someone equipped with the appropriate medical competencies, scope of practice and capabilities in the expedition environment and need not necessarily be a qualified doctor. In addition to providing guidance regarding the clinical competencies required of the expedition medic, the document provides generic guidance and signposting to the more pertinent aspects of the role of expedition medic.


Fatigue is a prevalent and severe symptom associated with uncertainty and sense of coherence in patients with chronic heart failure.
Fatigue is a common symptom in patients with chronic heart failure (CHF) and has a major impact on their daily life activities. The purpose of this study was to examine the prevalence and severity of fatigue, conceptualized as a multiple dimensional symptom, and to determine the influence of sense of coherence and uncertainty on the fatigue experience in patients with CHF. Ninety-three consecutive patients, hospitalized with a diagnosis of CHF, completed the Multidimensional Fatigue Inventory Scale (MFI-20), Cardiovascular Population Scale (CPS), and Sense of Coherence Scale (SOC) and were classified according to the New York Heart Association (NYHA) functional classification criteria. Associations between selected variables were explored with multiple regression analysis. The patients reported high prevalence and severity in the physical dimensions of fatigue. Uncertainty was associated positively with tiredness and reduced functional status. High age predicted reduced motivation and the ability to concentrate were affected by low SOC. Fatigue is a prevalent and distressing experience in patients with CHF, where a variety of factors influence different dimensions of the fatigue experience. Recognising this, symptom management must be directed towards comprehensive assessment and a broad approach in interventions aimed at alleviating fatigue.


Comparison of methods to assess visual impairment from glare and light scattering with posterior capsule opacification.
To compare 2 glare tests to determine their relative usefulness in the assessment of posterior capsule opacification (PCO) and to evaluate the potential benefits of combined visual, acuity, contrast sensitivity, and glare testing. Teaching hospital ophthalmology department. Sixteen patients had glare, visual acuity, and contrast sensitivity testing before and after neodymium:YAG (Nd:YAG) capsulotomy. Results with the Brightness Acuity Tester (BAT, Mentor), which measures disability glare, and the Straylightmeter (Foundation for Eye Research, The Netherlands), which quantifies forward scatter by direct compensation techniques, were compared. The correlation between glare, ETDRS visual acuity, and Pelli-Robson contrast sensitivity was determined. Pretreatment visual acuity was significantly correlated with contrast sensitivity (P < .01). However, visual acuity and contrast sensitivity were poorly correlated with both the BAT and Straylightmeter (P > .05), indicating that visual acuity is predictive of contrast sensitivity but a poor predictor of glare. Glare was significantly improved (Straylightmeter, P < .0001; BAT, P < .05) following capsulotomy. While the Straylightmeter consistently measured precapsulotomy forward scatter that improved with treatment, corresponding BAT disability glare was unmeasurable in 18.8% of patients with PCO, as their visual acuities improved rather than deteriorated with glare testing. Glare testing provided more information than contrast sensitivity when combined with visual acuity in the evaluation of PCO. Glare related to PCO is better assessed using the Straylightmeter because the BAT may yield aberrant disability glare results.


Characteristics of psychiatric hospitals associated with length of stay in Japan.
Average length of inpatient stay at psychiatric hospitals in Japan has been consistently longer than that in any other developed country, and was 330 days in 1996. Although some reforms have been implemented with the intention of decreasing length of stay (LOS), appreciable reductions have not been achieved. The present study examined hospital characteristics associated with length of stay in regional psychiatric hospitals in Japan, in order to identify variables that might help to reduce LOS. This cross-sectional study analysed the complete database of one district in Japan. Analyses were conducted using aggregate data from 24 hospitals. Multiple regression analysis was performed to determine hospital characteristics influencing LOS in psychiatric hospitals. Significant positive associations were identified between LOS and two hospital characteristics: inpatient capacity; proportion of involuntary admissions. Negative associations were observed for three variables: number of outpatients; human resources in terms of healthcare professionals available in each hospital; community activity. Multiple linear regression analysis for the 24 hospitals revealed that number of outpatients and proportion of patients receiving public aid were independently associated with shorter LOS, while proportion of involuntary admissions was independently associated with longer LOS. A negative association between human resources in terms of number of healthcare professionals and LOS was suggested. Several hospital characteristics are associated with LOS in psychiatric hospitals. Factors identified in this study offer insights into directions for effective psychiatric health policy to reduce LOS.


Coexistent bronchogenic carcinoma and active pulmonary tuberculosis.
Sixty-four cases of coexistent bronchogenic carcinoma and active pulmonary tuberculosis were diagnosed between 1969 and 1976. The majority were male chronic cigarette smokers in their fifth and sixth decades. Human bacilli were isolated in 48 patients (88.9 percent) and atypical bacilli in six patients (11.1 percent). All of the atypical bacilli and 8.3 percent of the human bacilli were found to be resistant to the first line antituberculous drugs. All patients, except two who died following resection, were given a course of antituberculous drugs with 93.8 percent successful sputum conversion. Uncontrolled or disseminated tuberculous infection was not observed. Forty-five patients (70.3 percent) underwent pulmonary resection. Median survival time of those who had curative resection was 14.3 months with a 5 year survival rate of 13.2 percent. Median survival times of those treated by palliative resection plus anticancer chemotherapy and by anticancer chemotherapy alone were 8.3 months and 11.1 months, respectively. None of these patients survived more than 30 months. It appears that, clinically, each disease runs its own course with little effect on the other.


Carbohydrates detected by lectins in the vestibular organ.
In the vestibular organ the presence of carbohydrates in the cupula and otoconia of young (6-day-old) and adult rats was investigated using fluorescent lectins. The following sugars have been identified in both young and adult rats: N-acetyl-glucosamine, galactose, mannose and fucose. In contrast, N-acetyl-galactosamine was not detected. In order to demonstrate the specificity of the reaction, control experiments were performed after preincubation of the lectin with its specific inhibitory sugar. The same sugars were identified in calcified (i.e. otoconia) and non-calcified (i.e. cupula) structures. The role of these sugars in the mineralization and fusion process of otoconia is discussed.


Characters available in photoplethysmogram for blood pressure estimation: beyond the pulse transit time.
The continuous and noninvasive blood pressure (BP) measurement based on pulse transit time (PTT) doesn't need cuff and could monitor BP in real time for a long period. However, PTT is just a time index derived from electrocardiogram (ECG) and photoplethysmogram (PPG), while BP-related information within the PPG waveform has seldom been taken into consideration. We hypothesized that PPG waveform feature might be useful for BP estimation. Nine healthy subjects took part in an exercise stress test, including baseline resting, exercise on bicycle ergometry and recovering resting. ECG of lead V5 and PPG from left finger were collected simultaneously, and systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded from a cuff sphygmometer on the right wrist. The correlation coefficients were obtained between BP (SBP, DBP and pulse pressure (PP)) and PPG morphological indices (total 15 indices in terms of waveform amplitude, time span and area ratio). Five PPG indices were correlated with both SBP and PP (absolute value of correlation coefficient |r| > 0.6) and were further tested for the capability to BP estimation, which were: (1) PTTA, time delay between the R peak of ECG and the foot point of PPG; (2) RSD, time ratio of systole to diastole; (3) RtArea, area ratio of systole to diastole; (4) TmBB, time span of PPG cycle; (5) TmCA, diastolic duration. Comparisons were made between the measured BP and the estimated BP by regression lines and quadratic curve fitting, respectively. As a result, the mean errors of SBP liner fitting with RSD, RtArea, TmBB and TmCA respectively were 5.5, 5.4, 5.2, 5.1 mmHg, which were smaller than that with PTTA of 5.8 mmHg. And the mean errors of SBP quadratic curve fitting with RSD, RtArea, TmBB and TmCA were all 5.1 mmHg, which were smaller than that with PTTA of 5.7 mmHg. The mean errors of multiple regression for SBP, PP and DBP was 4.7, 4.7, 3.5 mmHg respectively, which were more accurate than the regression with single PTTA of 5.8, 5.3, 5.2 mmHg respectively. However, PPG-based SBP and DBP could under estimate cuff pressure by 8 mmHg and over estimate by 10 mmHg respectively, which is a clinically significant error. In conclusion, the combination of time span (PTT, time ratio of systole to diastole, time span of PPG cycle and diastolic duration) and waveform morphology (area ratio of systole to diastole) could improve the performance of PPG-based BP estimation.


Microbial production of (2R,3S)-isocitric acid: state of the arts and prospects.
(2R,3S)-isocitric acid has long been used only as a specific biochemical reagent. However, there is ever increasing evidence that it can also be used as an original promising substance for prevention and treatment of some diseases. The review considers the results of longtime research in our laboratory and the data of other researchers related to microbial synthesis of (2R,3S)-isocitric acid, derivation and selection of active microbial producers, development of their cultivation conditions, as well as the results of study of the mechanism of acid overproduction, and regulation of enzymes involed in this process. The efficient processes of (2R,3S)-isocitric acid production with the aid of natural, mutant, and recombinant strains of Yarrowia lipolytica and methods of product isolation and purification to pharmacopeial standarts are also reviewed.


The pharmacology of drug abuse--a novel approach to drug education at San Quentin.
A novel and successful undergraduate-level course in pharmacology has been established as part of the drug education program at California's San Quentin State Prison. The program was designed to create a two-way teaching--learning experience between former drug abusers and their teachers, all of whom were doctoral candidates and post-doctoral scholars in pharmacology at a nearby university medical center. In reviewing the pharmacology of psychoactive drugs, the emphasis was on the principles of drug action in the central nervous system, with additional attention to those factors that contribute a potential for abuse. An attempt was made to present information in a strictly objective and non-prejudical manner. An initial analysis has shown a possible change in attitude among the student-inmates toward drugs of abuse. It is likely that courses following a similar design would be well received and successful in any type of undergraduate program that addresses the subject of drug abuse.


Systemic saturated lysophosphatidylcholine is associated with hepatic function in patients with liver cirrhosis.
Serum lysophosphatidylcholine (LPC) is described to decline in patients with chronic liver diseases. Here it was evaluated which of the LPC species are associated with liver function. LPC species were quantified by direct flow-injection electrospray ionization tandem mass spectrometry in serum of 45 patients with mainly alcoholic liver cirrhosis. Saturated LPC is 52.1 (31.7-110.0) μmol/l in serum of patients with CHILD-PUGH score C (decompensated liver cirrhosis) and significantly lower compared to patients with well-compensated disease (CHILD-PUGH score A) with 114.1 (12.3-401.4) μmol/l. Mono- and polyunsaturated LPC are not changed in these groups. Saturated LPC is negatively correlated with the model for end-stage liver disease score, bilirubin and galectin-3 and positively with Quick prothrombin time. Ascites and varices are complications of liver cirrhosis. Saturated LPC does, however, not correlate with hepatic venous pressure gradient, ascites volume and variceal size. Unexpectedly, saturated LPC measured in serum of 42 patients declines from 88.4 (27.8-177.5) μmol/l to 72.4 (27.6-141.8) μmol/l shortly after transjugular intrahepatic portosystemic shunt implantation. Hepatic vein saturated LPC (82.3 (12.4-161.7) μmol/l) is higher than portal vein levels (78.8 (10.1-161.0) μmol/l) suggesting hepatic release of this lipid species. Current data demonstrate that systemic saturated LPC species are reduced in patients with decompensated liver cirrhosis and associated with mortality risk.


Neurologic considerations in worker fitness evaluation.
This chapter focuses on neurological conditions that may seriously change work performance or risk, as well as considerations in neurological evaluation of the asymptomatic worker.


Juxtaglomerular apparatus hyperplasia under dual angiotensin blockade. A footprint of adequate RAS inhibition or a concern for renal fibrosis?
Dual renin-angiotensin system blockade with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been advocated to minimize proteinuria. However, recent trials have questioned the renal safety of this approach. Our understanding on the molecular effects of dual blockade in humans is incomplete. We present a patient with corticoid resistant nephrotic syndrome who developed marked juxtaglomerular apparatus hyperplasia and renin expression in the context of dual angiotensin system blockade. Although renin may have profibrotic effects mediated by (pro)renin receptor activation, this report raises questions on the potential consequences of local renin activation on chronic kidney disease in patients with dual angiotensin blockade.


A simple LC-ESI-MS/MS method for quantification of bacopaside I in rat plasma and its application to a pharmacokinetic study.
Bacopaside I is one of the main pseudojujubogenin glycosides isolated from Bacopa monniera. In the present study, a rapid and robust LC-ESI-MS/MS method was developed and validated to quantify bacopaside I in rat plasma. After plasma samples were deproteinized by methanol, the post-treatment samples were analyzed on a Zorbax Eclipse Plus C18 (2.1×50mm, 1.8μm) column using a mobile phase of acetonitrile and water (65:35, v/v). Detection was performed on a triple-quadrupole tandem mass spectrometer with selected reaction monitoring (SRM) mode via electrospray ionization source. This method covered a linearity range of 10-2000ng/mL with the lower limit of quantification of 10ng/mL. The intra- and inter-day precisions of analysis were less than 10.2%, and the accuracies were between -11.1% and 8.4% at the concentrations of 25, 150 and 1800ng/mL. The total run time was 6.0min. This method was successfully applied to the preclinical pharmacokinetic study of bacopaside I following intravenous or oral administration to rats.


Left pleural effusion in a young woman with genital tuberculosis.
Disseminated tuberculosis is a rare form of tuberculosis that can cause severe illness if diagnosed and treated late. We present the case of a young Senegalese woman who had a miscarriage due to a pelvic inflammatory disease, followed by the development of a left pleural effusion. Despite laparoscopic findings and a salpinx biopsy that revealed necrotizing granulomas, only microbiological examinations of pleural biopsies revealed the final diagnosis of disseminated, drug-sensitive tuberculosis.


Comparative genomics of Archaea: how much have we learned in six years, and what's next?
Archaea comprise one of the three distinct domains of life (with bacteria and eukaryotes). With 16 complete archaeal genomes sequenced to date, comparative genomics has revealed a conserved core of 313 genes that are represented in all sequenced archaeal genomes, plus a variable 'shell' that is prone to lineage-specific gene loss and horizontal gene exchange. The majority of archaeal genes have not been experimentally characterized, but novel functional pathways have been predicted.


Sonography of epididymal cystadenoma.
Noninflammatory, epididymal masses are unusual. A patient with von Hippel-Lindau disease and sonographically demonstrated cystadenoma of the epididymis is presented.


Depolarization of brain synaptosomes activates opposing factors involved in regulating levels of cytoskeletal actin.
Depolarization of mouse brain synaptosomes elicits transmitter release and modifies factors that regulate cytoskeletal actin (C-actin) levels. We previously reported (Bernstein and Bamburg, J. Neurosci. 1985. 5:2565-2569) that depolarization causes a release of about 25% of the actin associated with the cytoskeleton of synaptosomal lysates. From our current studies we conclude that depolarization only transiently perturbs the balance in opposing factors which regulate C-actin levels in lysates. Prolonged incubation of the lysates permits the actin to reequilibrate so that no difference between C-actin levels of resting and depolarized synaptosomes is observed. Both the initial transient release of actin from the cytoskeleton and its reassociation with the cytoskeleton during prolonged incubation are calcium dependent and involve factors in both the cytoskeletal and soluble fractions. Depolarization initiates modifications that both increase and decrease the C-actin level probably through mechanisms involving calcium sensitive actin binding proteins.


Investigation of antioxidant compounds in commercial pomegranate molasses products using matrix-solid phase dispersion extraction coupled with HPLC.
Pomegranate is a well known fruit for its unique flavor, taste and health benefits. The medicinal properties of this fruits directly associated with the phenolic content present, with great anti-oxidant potential. The research is intended to develop matrix solid phase dispersion method (MSPD) and HPLC quantification of four major anti-oxidant marker constituents (vitamin C, gallic acid, rutin & ellagic acid) in pomegranate molasses samples. The effects of several important experimental parameters like type of dispersant, sample-dispersant ratio, solvents and its volume, time of extraction were investigated. A C18 column with the specification (5 µm, 250 × 4.0 mm) was used for the separation. A gradient flow of mobile phase was selected after many trials containing 0.1%, v/v solution of orthophosphoric acid and acetonitrile. The flow rate was 1.0 mL/min; and the chromatograms were recorded at 254 nm. The validation parameters, like linearity (r2 = 0.9985, 0.9965, 0.9925 & 0.9986), accuracy (100.3, 99.5, 100.9 & 101.9%), intra-day precision (%RSD = 1.09, 1.02, 1.26 & 0.97), inter-day precision (%RSD = 1.32, 0.83, 1.07, & 1.15) LOD (0.07, 4.50, 0.45 & 0.40 µg/mL), LOQ (0.095, 9.50, 0.85 & 9.5 µg/mL) and robustness (% RSD = 0.92, 0.76, 0.81 & 0.83) respectively for vitamin C, gallic acid, rutin & ellagic acid, were found satisfactory as per ICH guidelines.


An ode to owlsWhat an Owl Knows: The New Science of the World's Most Enigmatic Birds Jennifer Ackerman Penguin, 2023. 352 pp.
New tools and techniques offer insight into the lives of these secretive birds.


Gait characterization for osteoarthritis patients using wearable gait sensors (H-Gait systems).
The objective of this work was to investigate the possibilities of using the wearable sensors-based H-Gait system in an actual clinical trial and proposes new gait parameters for characterizing OA gait. Seven H-Gait sensors, consisting of tri-axial inertial sensors, were attached to seven lower limb body segments (pelvis, both thighs, both shanks and both feet). The acceleration and angular velocity data measured were used to estimate three-dimensional kinematic parameters of patients during level walking. Three new parameters were proposed to assess the severity of OA based on the characteristics of these joint center trajectories in addition to conventional gait spatio-temporal parameters. The experiment was conducted on ten subjects with knee OA. The kinematic results obtained (hip, knee and ankle joint angles, joint trajectory in the horizontal and sagittal planes) were compared with those from a reference healthy (control) group. As a result, the angle between the right and left knee trajectories along with that of the ankle joint trajectories were almost twice as large (21.3° vs. 11.6° and 14.9° vs. 7.8°) compared to those of the healthy subjects. In conclusion, it was found that the ankle joints during stance abduct less to avoid adduction at the knee as the severity of OA increases and lead to more acute angles (less parallel) between the right and left knee/ankle joints in the horizontal plane. This method was capable to provide quantitative information about the gait of OA patients and has the advantage to allow for out-of-laboratory monitoring.


Effect of growth factors with dexamethasone on healing of rabbit corneal stromal incisions.
Treatment of rabbit corneal wounds with topical corticosteroid retards both epithelial regeneration and healing of penetrating stromal wounds. Currently, no clinical agent is available which accelerates the rate of stromal wound healing. Epidermal growth factor (EGF, 0.5 mg ml-1), fibroblast growth factor (FGF, 20 micrograms ml-1), and insulin (0.5 mg ml-1) were tested for their ability to accelerate healing of totally penetrating wounds in rabbit corneas when the hormones were administered alone or in combination with dexamethasone (1 mg ml-1). After 5 days of treatment with eye drops, the tensile strengths of corneal wounds treated with EGF (54 +/- 4 g mm-1) or treated with EGF and dexamethasone (32 +/- 9 g mm-1) were significantly higher than the tensile strengths of corneal wounds treated with only saline vehicle (3 +/- 1 g mm-1) or dexamethasone (1 +/ 0 g mm-1) (P less than 0.001). The combination of dexamethasone with EGF significantly (P less than 0.025) reduced the strength of corneal wounds compared to treatment with EGF alone. Similarly, the tensile strength of corneal wounds after 5 days of insulin treatment alone (28 +/- 8 g mm-1) or in combination with dexamethasone (25 +/- 7 g mm-1) was significantly increased compared with saline- or dexamethasone-treated corneas (P less than 0.001). In the absence of dexamethasone, EGF increased the tensile strength of corneal wounds significantly better than insulin (P less than 0.01). However, when EGF or insulin were given in combination with dexamethasone there was no significant difference between the tensile strength produced by the peptide hormones. In comparison to the tensile strength of corneal wounds treated by EGF or insulin, treatment with FGF alone (5 +/- 4 g mm-1) or in combination with dexamethasone (2 +/- 1 g mm-1) produced poor wound healing. The in vitro actions of EGF or FGF alone or in combination with dexamethasone were tested for ability to stimulate [3H]-thymidine incorporation into pure cultures of human corneal fibroblasts (HCF) in defined culture medium. EGF (5 mM) or FGF (100 ng ml-1) alone stimulated [3H]-thymidine incorporation approximately 2.5-fold compared to control cultures, whereas in combination with dexamethasone (10 nM), the stimulatory action of FGF, but not EGF, was abolished. Dose-response curves indicated that HCF in culture were very sensitive to EGF, insulin, and FGF with maximum stimulation of [3H]-thymidine incorporation occurring at approximately 1 nM for EGF and insulin and at 100 micrograms ml-1 for FGF. Binding of 125I-EGF to HCF reached maximum after 2 hr at 37 degrees C and was specific, saturable, and of high affinity (half saturation at 1 nM). (ABSTRACT TRUNCATED AT 400 WORDS)


Association Between Antidiabetic Medications and Prostate-Specific Antigen Levels and Biopsy Results.
Diabetic men appear to have a lower risk of prostate cancer. Whether antidiabetic medications are protective or potentially mask prostate cancer by lowering prostate-specific antigen (PSA) levels is unclear. To examine the associations of antidiabetic medication use with (1) PSA levels, (2) frequency of PSA testing, (3) receipt of biopsy following elevated PSA results, and (4) prostate cancer detection at biopsy. Population-based cohort study using data from the Stockholm PSA and Biopsy Register. Participants were all prostate cancer-free men aged 40 to 79 years residing in Stockholm County, Sweden, between January 1, 2006, and December 31, 2015. Data were analyzed from November 2018 to March 2019. One or more prescription for metformin, sulfonylurea, or insulin, as recorded in Sweden's National Prescribed Drug Register. Levels of PSA following first exposure to antidiabetic medications were assessed using multivariable linear regression. Frequency of PSA testing was assessed via multivariable Poisson regression. Biopsy following elevated PSA (≥3.0 ng/mL) and prostate cancer detection at biopsy were assessed via multivariable logistic regression. The cohort of 564 666 men (median [range] age, 65 [40-79] years) consisted of 4583 men initially exposed to metformin, 1104 exposed to sulfonylurea, and 978 exposed to insulin who were age matched with unexposed men (1:5). Exposed men had lower median (interquartile range) PSA levels before starting antidiabetic medications compared with unexposed men (1.2 [0.7-2.5] vs 1.6 [0.8-3.2] ng/mL). After accounting for baseline differences, PSA levels did not vary from those of unexposed men following exposure to antidiabetic medications. Frequency of PSA testing was higher for those receiving metformin (rate ratio, 1.07; 95% CI, 1.06-1.09) and sulfonylurea (rate ratio, 1.06; 95% CI, 1.03-1.08) but was lower for those receiving insulin (rate ratio, 0.79; 95% CI, 0.77- 0.81). Likelihood of biopsy after elevated PSA was lower among men receiving metformin (odds ratio, 0.87; 95% CI, 0.80-0.96) and insulin (odds ratio, 0.83; 95% CI, 0.74-0.93). There were no differences in prostate cancer detection at biopsy, regardless of PSA levels that triggered the biopsy. This study's findings do not support the hypothesis that the inverse association between diabetes and prostate cancer is mediated through antidiabetic medications lowering PSA levels to mask prostate cancer. They do suggest potential detection bias due to fewer biopsies among men receiving antidiabetic medications, which may explain the lower prostate cancer risk in men with diabetes.


Valgus intertrochanteric osteotomy for neglected femoral neck fractures in young adults.
Twenty cases of neglected (more than 1 month old) displaced femoral neck fractures in young adults were treated with a valgus intertrochanteric osteotomy. A fracture union rate of 85% (17 cases) was achieved. Two of the healed cases developed avascular necrosis. After 30 months 15 patients (75%) had achieved good to excellent results. We believe that intertrochanteric osteotomy provides good alternative management for neglected femoral neck fractures.


Complete Genome Sequence of a Colombian Zika Virus Strain Obtained from BALB/c Mouse Brain after Intraperitoneal Inoculation.
A Zika virus (ZIKV) strain was isolated from an acute febrile patient during the Zika epidemics in Colombia. The strain was intraperitoneally inoculated into BALB/c mice, and 7 days postinoculation, neurological manifestations and ZIKV infection in the brain were demonstrated. The reported genome sequence is highly related to strains circulating in the Americas.


Release of neurotensin by selective perfusion of the jejunum with oleic acid in dogs.
Plasma neurotensin concentrations are rapidly elevated after oral ingestion or intraduodenal infusion of fat, apparently before fat reaches the ileum where neurotensin is highly concentrated. The purpose of this study was to investigate the site of neurotensin release and to determine whether neurotensin is released by direct luminal stimulation by fat in conscious dogs. Dogs were prepared with isolated jejunal or ileal segments and portal vein catheters. Release of neurotensin into the portal venous blood was examined by selective perfusion of each intestinal segment with sodium oleáte. The results of this study show that selective perfusion of the jejunum, but not the ileum, with sodium oleate, caused a significant release of neurotensin. We speculate that release of ileal neurotensin is not due to direct luminal stimulation, but is mediated by local neural or humoral intermediates.


Is 18F-FDG PET accurate to predict neoadjuvant therapy response in breast cancer? A meta-analysis.
Clinical evidence regarding the value of (18)F-FDG PET for therapy responses assessment in breast cancer is increasing. The objective of this study is to evaluate the accuracy of (18)F-FDG PET in predicting responses to neoadjuvant therapies with meta-analysis and explore its optimal regimen for clinical use. Articles in English language relating to the accuracy of (18)F-FDG PET for this utility were retrieved. Methodological quality was assessed by QUADAS tool. Pooled estimation and subgroup analysis data were obtained by statistical analysis. Nineteen studies met the inclusion criteria and involved 920 pathologically confirmed patients in total (mean age 49.8 years, all female). Methodological quality was relatively high. To predict histopathological response in primary breast lesions by PET, the pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio were 84% (95% CI, 78-88%), 66% (95% CI, 62-70%), 50% (95% CI, 44-55%), 91% (95% CI, 87-94%), and 11.90 (95% CI, 6.33-22.36), respectively. In regional lymph nodes, sensitivity and NPV of PET were 92% (95% CI, 83-97%) and 88% (95% CI, 76-95%), respectively. Subgroup analysis showed that performing a post-therapy (18)F-FDG PET early (after the 1st or 2nd cycle of chemotherapy) was significantly better than later (accuracy 76% vs. 65%, P = 0.001). Furthermore, the best correlation with pathology was yielded by employing a reduction rate (RR) cutoff value of standardized uptake value between 55 and 65%. (18)F-FDG PET is useful to predict neoadjuvant therapy response in breast cancer. However, the relatively low specificity and PPV still call for caution. It is suggested to perform PET in an earlier course of therapy and use RR cutoff value between 55 and 65%, which might potentially identify non-responders early. However, further prospective studies are warranted to assess this regimen and adequately position PET in treatment management.


Improving disease resistance of butternut (Juglans cinerea), a threatened fine hardwood: a case for single-tree selection through genetic improvement and deployment.
Approaches for the development of disease-resistant butternut (Juglans cinerea L.) are reviewed. Butternut is a threatened fine hardwood throughout its natural range in eastern North America because of the invasion of the exotic fungus, Sirococcus clavigignenti-juglandacearum Nair, Kostichka and Kuntz, which causes butternut canker. Early efforts were made to identify and collect putatively resistant germ plasm, identify vectors and to characterize the disease. More recently, molecular techniques have been employed to genetically characterize both the pathogen and the resistant germ plasm. Much of the host resistance may originate from hybridization with a close Asian relative, Japanese walnut (Juglans ailanthifolia Carr.), and from a few natural phenotypic variants. Further genetic characterization is needed before classical breeding or genetic modification can be used to produce canker-resistant trees.


Retracted: Study on the Predictive Value of P53 Protein Expression in Brain Metastasis in NSCLC and the Mechanism of miR-424 Reversing Platinum Resistance in NSCLC.
[This retracts the article DOI: 10.1155/2022/5273772.].


Chronic lymphocytic leukemia developing in a patient with chronic myeloid leukemia: evidence of distinct lineage-associated genomic events.
We describe the cytogenetic, fluorescence in situ hybridization (FISH), and molecular findings in a patient who developed a typical chronic lymphocytic leukemia (CLL) 20 months after the diagnosis of a Philadelphia (Ph)-positive chronic myeloid leukemia. Unstimulated bone marrow culture showed a 46,XX,t(9;22)(q34;q11) karyotype, and interphase FISH detected the presence of a BCR/ABL fusion signal in 13% of cells. On stimulated bone marrow culture, a normal karyotype and a 13q14 deletion by interphase FISH with D13S319 probe in 14% of the cells were found. Molecular studies detected the chimeric BCR/ABL messengers by nested reverse-transcriptase polymerase chain reaction. The B-cellular clone was documented by the presence of a clonal heavy chain immunoglobulin rearrangement. The coexistence of these two hematologic malignancies leads to questions about their cell(s) of origin. We provide evidence that CLL arose in a Ph-negative clone. The implications of these findings are discussed.


Recent advancements in nanotechnological strategies in selection, design and delivery of biomolecules for skin regeneration.
Skin is a very complex organ and hence designing a bioengineered skin model replicating the essential physiological characteristics for replacing the diseased or damaged parts has been a challenging goal for many. Newer technologies for satisfying most of the criteria are being attempted with the copious efforts of biologists, engineers, physiologists, using multitude of features in combination. Amongst them nanotechnology based biomaterials have gained prominence owing to the enhanced pharmacokinetics, bio-distribution profile, extended half-life and reduced side effects. Designing a matrix that can be assimilated into the body during the regeneration and delivering the essential pharmacological agents in a temporal and spatially specific manner is a tremendous goal. This review essentially deals with the various approaches for designing a multidisciplinary translational smart matrix for addressing the various skin related ailments.


Long-term outcome in endometrial carcinoma favors a two- instead of a three-tiered grading system.
Endometrial carcinoma is the most common malignancy of the female genital tract. Recognized prognostic factors include FIGO stage, histologic grade, depth of myometrial invasion, and age. Although determination of these factors may seem clear and reproducible, the histologic grade has recently been the subject of debate. A retrospective analysis of long-term outcome and predictive factors in endometrial carcinoma was conducted, focusing on the prognostic value of tumor grade. The study included 253 patients with endometrial carcinoma Stages I to III, who were treated between 1984 and 1993. The histologic slides were reviewed and the prognostic value of stage, age, myometrial invasion (depth and pattern), tumor grade, and histologic subtype was analyzed. The end point was cancer-specific death; the median follow-up time was 11.7 years. The actuarial 5- and 10-year cancer-specific survival rates (CSS) were 85% and 82%, respectively. Five-year vaginal and/or pelvic recurrence and distant relapse rates were 7% and 15%. In multivariate analysis, stage, pattern of myometrial invasion, tumor grade, and age were independent prognostic factors. At pathology review, a shift from Grade 2 to Grade 1 was seen in 112 of the original 144 Grade 2 (78%). There was no difference in CSS between Grade 1 and Grade 2 (94 vs. 90% for original grade and 92 vs. 95% for grade after review), whereas Grade 3 was found to be a significant adverse prognostic factor (p < 0.001). The independent prognostic factors for patients with endometrial cancer were stage, pattern of myometrial invasion, tumor grade, and age. Systematic grading led to a considerable shift from Grade 2 to Grade 1. However, there was no difference in prognostic significance between Grade 1 and 2, whereas Grade 3 was a major adverse prognostic factor. A two-tiered grading system, instead of the currently used three-tiered system seems preferable, because it has a better correlation with clinical outcome and is expected to have less interobserver variability.


Isolated and multisystem hepatic trauma in children: the true role of non-operative management.
We retrospectively reviewed children with hepatic injuries (HI) admitted to our institutions from January 1982 to December 1999. Specific comparison was made of isolated (IHT) and multisystem hepatic trauma (MHT). Over the 18-year period 127 patients were identified with HI, 91 (71%) with MHT and 36 with IHT. The median age was 8 years (range 13 months to 14 years). Motor vehicle injury was the most common mechanism in both groups, but bicycle injuries were more common in IHT ( P<0.001). Shock ( P=0.02), the requirement for blood transfusion ( P<0.001), and operative intervention for the HI ( P=0.001) were all significantly more common in MHT. The distribution of liver injury grades was similar between the two groups. Twenty-two (17.3%) children died and in 18 the HI was the main cause or contributed significantly. There were 19 and 3 deaths in the MHT and IHT groups, respectively, a difference that was not significant. After excluding children with minor HI, 27 (39%) required operative intervention within 24 h of their injury. This suggests that the high success rate for non-operative management of HIs in the literature may have been biased by the inclusion of a significant proportion of subclinical injuries.


Endothelial glycocalyx and coronary vascular permeability: the fringe benefit.
Current concepts of vascular permeability are largely still based on the Starling principle of 1896. Starling's contribution to understanding vascular fluid homeostasis comes from realising that the transport of fluid to and from the interstitial space of peripheral tissues follows the balance between opposing oncotic and hydrostatic pressures. It is presumed that in peripheral tissues fluid is readily filtered from blood to tissues at the arterial/arteriolar side of the circulation and largely reabsorbed at the venular/venous aspect, excess fluid being removed from the tissue by the lymphatic system. This balance is determined particularly by the properties of the vascular barrier. Recent studies have shown that the endothelial glycocalyx, located with a thickness of at least 200 nm on the luminal side of healthy vasculature, plays a vital role in vascular permeability by constituting the vascular barrier together with the endothelial cells themselves. While water and electrolytes can freely pass through the glycocalyx, plasma proteins, especially albumin, interact strongly. Binding and intercalating plasma constituents with the structural elements of the glycocalyx creates the so-called endothelial surface layer. This is the actual interface between flowing blood and the endothelial cell membrane in vivo. The oncotic pressure difference pertinent to fluid homeostasis is not built up between the intravascular and the interstitial tissue spaces, but within a small protein-free zone beneath the glycocalyx surface layer. This explains why perturbation of the glycocalyx leads to a breakdown of both fluid and protein handling in the coronary vascular bed. Preventing damage to the glycocalyx seems to be a promising goal in cardioprotection in many clinical scenarios, including acute ischaemia, hypoxia and inflammation, and chronic vascular disease as in atherosclerosis, diabetes and hypertension.


Photodynamic therapy using glycol chitosan grafted fullerenes.
Glycol chitosan (GC)-grafted fullerene (GC-g-C(60)) conjugates were developed for use in photodynamic therapy of tumor cells. GC-g-C(60) was synthesized in anhydrous benzene/dimethylsulfoxide (DMSO) co-solvent via the chemical conjugation of free amine groups of GC to CC double bonds of C(60). The GC-g-C(60) with 5×10(-4) C(60) molecules per one repeating unit of GC was soluble in water. As C(60) molecules conjugated to GC increased to 0.16 molecules per one repeating unit of GC, GC-g-C(60) started to form supramolecular assemblies (∼30 nm) stabilized in phosphate buffer saline (PBS, 150 mM, pH 7.4). Upon 670 nm light illumination, photo-responsive properties of GC-g-C(60) allowed tremendous singlet oxygen generation in tumor cells for super phototoxicity. GC-g-C(60) also showed highly increased tumor accumulation ability for in vivo tumor of KB tumor-bearing nude mice. It is expected that our GC-g-C(60) conjugate may be a good candidate for in vivo photodynamic therapy in various malignant tumor cells.


Infant's apnea, bradycardia and tachycardia monitor based on the Z-80 microprocessor.
Home monitoring has been increasingly adopted by pediatricians to help in the prevention of sudden infant death syndrome. The home monitor can be made reliable, easy to operate, inexpensive, and capable of data storage. This can be done by using a microprocessor and a minimum number of integrated circuit chips. Simple real-time algorithm's and digital hardware have been developed to achieve this goal.


Effect of procainamide on pulmonary thromboembolism and platelet malondialdehyde in mice.
To study the effect of procainamide (PA) on pulmonary thromboembolism, platelet malondialdehyde (MDA) level and platelet aggregation induced by collagen and adrenaline. Pulmonary thromboembolism, 2-thiobarbituric acid fluorescence micro-determination, conventional microscopic counting, and platelet aggregation test were used. PA (10-20 mg.kg-1) and mannitol (200 mg.kg-1) reduced thrombosis by 30%-75% and 75%, respectively. Thrombocytopenia followed thrombosis increased after the pretreatment of PA and mannitol. MDA decreased by both of them in vivo. In vitro, PA inhibited platelet aggregation and MDA production induced concentration-dependently by collagen and adrenaline. Inhibition of PA on pulmonary thromboembolism is involved in the decrease of platelet aggregation and MDA production.


Sequence-Based analysis of the HLA-DRB1 polymorphism in Metalsa Berber and Chaouya Arabic-speaking groups from Morocco.
To examine the genetic diversity in Morocco, the polymorphism at the HLA-DRB1 locus was investigated in two populations: the Metalsa group consisting of Berbers from north Morocco (who speak the Tarifit language and live in the Nador area), and the Chaouya group who are Arabic-speaking people from west Morocco (Atlantic coast) living in the Settat area. The DRB1 alleles of 197 healthy unrelated individuals were identified by direct DNA sequencing of exon 2 using fluorescently-labeled primers. A total of 28 and 29 alleles at DRB1 locus were identified in the Metalsa and Chaouya groups, respectively. The most frequent alleles in the Metalsa group are DRB1*03011 (20.2%), DRB1*0701 (12.12%), and DRB1*1302 (11.11%). In the Chaouya group, DRB1*0701 (16.33%), DRB1*15011 (12.76%), and DRB1*03011 (11.73%) are most common. Each population exhibits some specific variants and some uncommon alleles. The frequency of the DRB1*03011 allele differs significantly between the two populations (p = 0.0311). The DRB1 frequency distributions in the two groups suggest the effects of balancing selection. The interpopulation analysis highlighted a strong relatedness, based on genetic distances, between the two Moroccan groups and the other north Africans (the Moroccans from El Jadida area, Moroccan Souss Berbers, Algerians, and Tunisians), and to a lesser extent with the Iberians, French, and Ethiopians.


Surface modification of poly(propylene carbonate) by aminolysis and layer-by-layer assembly for enhanced cytocompatibility.
Poly(propylene carbonate) (PPC) is a biodegradable polymer with desirable mechanical properties for bone and cartilage repair. However, the poor biocompatibility impedes its applications in tissue engineering. The aim of this study was to evaluate the effect of surface modification of PPC on the improvement of its cytocompatibility. The combination of aminolysis and layer-by-layer (LBL) assembly techniques was used to modify the PPC surface. The results of ATR-FTIR measurement demonstrated that PPC was aminolyzed by polyethylenimine (PEI) at specific reaction conditions and the degree of aminolyzation was quantitatively determined by ninhydrin method. Positively charged PEI and negatively charged gelatin were alternatively deposited on the aminolyzed PPC membranes at pH 7.4, which formed polyelectrolyte multilayers surface with gelatin as the outermost layer. The presence of amino groups on the aminolyzed PPC and gelatin on the multilayers had significant impact on enhancing the hydrophilicity of PPC. Fibroblast and primary human osteoblasts (HOBs) were used to assess the cytocompatibility of PPC. The deposition of PEI and gelatin bilayers on PPC remarkably promoted both fibroblast and HOBs cell attachment, spreading and growth. In particular, the osteogenic gene expression of HOBs cultured on the multilayers modified PPC was substantially increased. The aminolysis followed by LBL assembly is a convenient and cost effective technique for enhancing cell attachment and proliferation. The product has high potential for musculoskeletal tissue engineering applications due to its desirable mechanical strength and tunable cytocompatibility.


Detection of secretion from pancreatic islets using chemically modified electrodes.
Secretion of insulin from pancreatic islets was monitored indirectly by detecting zinc. Anodic stripping voltammetric measurements of zinc were done on a bismuth-modified electrode. Comparison of the performance of bismuth-modified electrodes and mercury film electrodes showed that bismuth is an appropriate alternative for Zn detection. The bismuth-coated electrode was used to detect zinc in insulin samples and insulin secreted from pancreatic islets upon stimulation with high concentrations of K(+). Detection of zinc released from pancreatic islets was done in the culture medium without any further cleanup. This detection method can be used to monitor secretion from pancreatic islets in their native environment.


Evaluation of the efficacy and tolerability of alendronate versus denosumab in kidney transplant patients with reduced bone mineral density.
To compare the effect of denosumab and alendronate on bone mineral density (BMD) in renal transplant recipients (RTRs) with low bone mass. Patients were randomized to receive either denosumab subcutaneously (60 mg/6 months), oral alendronate (70 mg/week), or no treatment for 1 year. The three groups were prescribed daily calcium and vitamin D. Primary outcome was BMD assessed at lumbar spine, hip, and radius and measured by dual-energy X-ray absorptiometry (DEXA) at baseline and after 6 and 12 months. Adverse events and laboratory assessments (calcium, phosphate, vitamin D, renal functions, and intact parathyroid hormone) were monitored for all patients. Quality of life was assessed at baseline and after 6 and 12 months for all patients. Ninety RTRs were included in the study (30 in each group). Baseline clinical characteristics and BMD values were comparable in the three groups. After 12 months, lumbar spine T-score of patients treated with denosumab and alendronate showed a median increase of 0.5 [95% confidence interval (CI): 0.4-0.6] and 0.5 (95% CI: 0.4-0.8), respectively, and patients in the control group showed a decrease of -0.2 (95% CI: -0.3 to -0.1), p < 0.001. Denosumab and alendronate showed a significant comparable gain in T-scores at hip and radius versus a significant decrease in the control group. Adverse events and laboratory values were similar in the three groups. Both treatments resulted in comparable significant improvement in physical functioning, physical role limitations, vitality, and pain scores. Denosumab and alendronate showed comparable efficacy in improving BMD at all measured skeletal sites and were safe and well-tolerated, with no serious adverse effects reported in RTRs with low bone mass. The study was registered on ClinicalTrials.gov, number NCT04169698.


Should we recruit trainees into the Oral and Maxillofacial Surgery pathway at the beginning of the second degree to ensure the long term viability of the specialty?
There has been a sustained decline in the number of trainees applying for entry into the Oral and Maxillofacial Surgery (OMFS) training program, which has sparked further debate on the issue of OMFS training and the future of the specialty in the United Kingdom. Here I discuss the option of recruiting the trainees into the program at the beginning of their second degree to streamline the training, and to improve the recruitment drive to ensure long term viability of the specialty.


Modulation of Na+/K+- ATPase activity by triterpene 3β, 6β, 16β-trihidroxilup-20 (29)-ene (TTHL) limits the long-term secondary degeneration after traumatic brain injury in mice.
Traumatic brain injury (TBI) is a public health problem characterized by a combination of immediate mechanical dysfunction of the brain tissue, and secondary damage. Based on the hypothesis that selected targets, such as Na+ K+-ATPase are involved in the secondary damage after TBI and modulation of this enzyme activity by triterpene 3β, 6β, 16β-trihidroxilup-20 (29)-ene (TTHL) supports the ethnomedical applications of this plant, we decided to investigate whether previous TTHL treatment interrupts the progression of pathophysiology induced by TBI. Statistical analyses revealed that percussion fluid injury (FPI) increased Na+,K+-ATPase activity in all isoform (α1 and α2/3) 15 min after neuronal injury. The FPI protocol inhibited Na+,K+-ATPase activity total and α1 isoform, increased [3H]MK-801 binding but did not alter Dichloro-dihydro-fluorescein diacetate (DCFH-DA) oxidation, carbonylated proteins and free -SH groups 60 min after injury. The increase of immunoreactivity of protein PKC and state of phosphorylation of at Ser16 of Na+,K+-ATPase 60 min after FPI suggest the involvement of PKC on Na+,K+-ATPase activity oscillations characterized by inhibition of total and α1 isoform. Our experimental data also revealed that natural product rich in compounds such as triterpenes (TTHL; 30 mg/kg) attenuates [3H]MK-801 binding increase, phosphorylation of the PKC and the Na+,K+-ATPase alpha 1 subunit (Ser16) induced by FPI. The previous TTHL treatment had not effect on motor disability but protected against spatial memory deficit, BDNF, TrKB expression decrease, protein carbonylation and hippocampal cell death 7 days after FPI. These data suggest that TTHL-induced reduction on initial damage limits the long-term secondary degeneration and supports neural repair or behavioral compensation after neuronal injury.


Extracellular calcium level is crucial for aortic contractile response in pregnant rat.
Studies of vascular reactivity during late pregnancy were performed to investigate the previously described hyporeactivity to vasopressors. Two groups of seven control (nonpregnant) and seven late pregnant (day 20) Wistar rats were used. Rubbed (E-) segments from thoracic aorta were studied for contractile studies in a Krebs solution containing either 1.25 or 2.50 mmol/L Ca concentration. Norepinephrine (NE; 10-9-3 x 10-5) or depolarization induced (KCl, 100 mmol/L) contractions are given as mN/mm2. With 2.50 mmol/L Ca, the maximal contraction to NE in E-segments is decreased in late pregnant rats compared with nonpregnant rats. However, this difference disappears when calcium concentration is set to 1.25 mmol/L Ca, the physiological value for free calcium concentration in extracellular fluid. For the contraction induced by opening of voltage operated calcium channels (KCl depolarization), a decreased maximal tension is also obtained in the pregnant rats compared with nonpregnant only with 2.50 mmol/L Ca concentration. It appears that aortic response to vasoconstrictors is modulated by extracellular calcium concentration in a different way between pregnant and nonpregnant rats.


A snapshot of chronic obstructive pulmonary disease management in general practice in Ireland.
Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability. Its diagnosis, classification and management are complex. There is a paucity of data on the standard of COPD management in Irish general practice. We studied whether COPD diagnosis and management was in accordance with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. We investigated if patients who were smokers had received smoking cessation advice. We examined whether influenza and pneumococcal vaccination had been given. Ten general practices affiliated with the Irish Mid-West Specialist Training Programme in General Practice (GP) were searched, to determine which patients had a diagnosis of COPD. A data-collection audit tool was developed using GOLD 2019 guidelines. Results were tabulated in SPSS. Descriptive statistics were used. Of 482 patients studied, 91.7% were eligible for free GP care. In 49.4%, the diagnosis of COPD had been made appropriately. In 56.2%, there was no evidence that the stage of COPD had been formally assessed. Of the patients studied, 33.2% were deemed to be receiving appropriate therapy. Smoking status was documented in 99.6% of cases studied and 59.9% were ex-smokers, while 25.9% were current smokers. Appropriate smoking cessation advice had been offered to 71% of eligible patients. Influenza vaccine had been given to 66.2% in the previous 12 months. A total of 53.9% had ever received pneumococcal vaccination. This study provides a comprehensive snapshot of care in Irish general practice for patients with COPD prior to introduction of the Chronic Disease Management programme (CDM).


Effectiveness of Leg Elevation to Prevent Spinal Anesthesia-Induced Hypotension during Cesarean Delivery in the Resource-Limited Area: Open Randomized Controlled Trial.
Postspinal hypotension is the most common complication after spinal anesthesia for cesarean section (CS). Hypotension mainly occurs due to the reductions of vascular tone leading to decreased systemic vascular resistance and decreased venous return. The aim of this study was to assess the effectiveness of leg elevation (LE) as a method of prevention of postspinal hypotension in patients who undergo cesarean section under spinal anesthesia. This is a single-center parallel-randomized controlled trial study, and 52 full-term parturients scheduled for elective cesarean section who meets inclusion criteria were included in the study. The randomization sequence was created by a researcher not participating in patient management using a computer random generator. The participant was randomly assigned to the leg elevation group (n = 26) or to the control group (n = 26) of usual perioperative care. The proportions of patients who develop hypotension are lower (8 (33.3%)) in the leg elevation group than the control group (15 (62.5%)) with an X 2 (1, N = 48) = 4.09, P=0.043. The relative risk of developing postspinal hypotension in the leg elevation group compared to the control group was 0.47 (95% CI, 0.28-1.00). The proportion of severe hypotension was significantly decreased in the leg elevation group at a P value of 0.02. Performing leg elevation immediately after spinal anesthesia reduced the incidence of hypotension. The trial is registered with PACTR201908713181850.


Comparison of the efficacy and cost-effectiveness of an immunologically targeted low-dose rituximab protocol with the conventional rheumatoid arthritis protocol in severe pemphigus.
Various dosing protocols of rituximab have been used in pemphigus. B-cell repopulation following rituximab treatment can be considered a forerunner of clinical relapse. Immunologically guided dosing may remove the need for fixed timepoint maintenance dosing, hence being more cost-effective and perhaps safer. To compare the overall efficacy and cost-effectiveness of a low-dose rituximab regimen (500 mg, 2 weeks apart) with immunologically guided, ultralow-dose (200 mg) top-up infusions on immunological relapse vs. the use of a rheumatoid arthritis (RA) protocol with rituximab 500 mg repeat infusion to treat clinical relapse in severe pemphigus, over a 1-year period, METHODS: In total, 23 patients with severe pemphigus were randomized into Group A (RA protocol: 1000 mg given as two doses, 2 weeks apart) and Group B (low-dose rituximab 500 mg given as two doses, 2 weeks apart). Both groups also received short-term oral corticosteroids, and underwent clinical and immunological (3-monthly flow cytometry assessments of B-cell subtypes) monitoring. Group A received a top-up dose of rituximab 500 mg upon clinical relapse, while Group B received an ultralow top-up dose (200 mg) following detection of B-cell repopulation, which was intended to prevent clinical relapse. Outcome parameters [complete remission off treatment (CROT), relapse (clinical and immunological), total corticosteroid dose and direct cost of therapy] were compared. The mean ± SD time to CROT (Group A, 27.1 ± 1.6 weeks; Group B, 26 ± 1.2 weeks, P = 0.09) and the cumulative prednisolone dose (P = 0.28) were comparable between the two groups. In Group A, 3 of 9 (33.3%) patients had clinical relapse (mean ± SD time of 9.3 ± 0.4 months). In Group B, B-cell repopulation was seen in 10 of 11 (90.9%) patients within a mean time of 8.4 ± 2.4 months, and a single top-up dose of 200 mg successfully prevented clinical relapse. The overall cost of therapy was 37.4% cheaper in Group B. An immunologically guided low-dose rituximab regimen can be an equally effective but more affordable alternative to conventional rituximab regimens in pemphigus.


Clinical features of subungual melanoma according to the extent of Hutchinson's nail sign: a retrospective single-centre study.
Hutchinson's nail sign (HS) is among the diagnostic criteria for subungual melanoma (SUM). However, there is minimal evidence supporting the overall clinical significance of HS in SUM. To identify clinicopathological features of SUM according to the extent of HS. Retrospective cohort study was performed with consecutive SUM patients at a single centre from January 2006 to December 2017. The extent of HS was defined by the number of affected nail folds (range 0-4). Comparison groups were organized as follows: patients with HS (affecting ≥1 nail folds) vs. without HS; patients with HS affecting ≥2 nail folds vs. HS affecting <2 nail folds; patients with HS affecting ≥3 nail folds vs. HS affecting <3 nail folds. Clinicopathological characteristics of SUM were compared between the groups. Sixty-one SUM patients were included. Forty-six (75.4%) exhibited HS; 22 (47.8%) on a toe and 24 (52.2%) on a finger. In multivariate analysis, nail destruction [hazard ratio (HR), 10.00; 95% confidence interval (CI), 2.61-38.30; P = 0.001] was significantly associated with the presence of HS and amputation was significantly associated with HS affecting ≥2 nail folds (HR, 4.75; 95% CI, 1.36-16.61; P = 0.015). High T stage (HR, 1.85; 95% CI, 1.20-2.85; P = 0.005, Fig. 2) was significantly associated with HS appearing in ≥3 nail folds. Besides its value of detecting SUM, HS provides useful clinical information. The number of nail folds exhibiting HS could be a useful clinical clue for planning therapeutic strategies for SUM.


Antibiotic-associated gastrointestinal symptoms in general pediatric outpatients.
As part of an intensive program of surveillance for adverse drug reactions in general pediatric outpatients, 2,714 courses of oral antibiotic therapy were monitored for the occurrence of gastrointestinal (GI) adverse drug reactions. Using a recently developed algorithm to establish a causal link between drugs and adverse symptoms, the risks of diarrheal or upper GI tract adverse drug reactions were found to vary considerably with different antimicrobial agents and, for several agents, according to the administered dosage. For diarrhea, the risk was lowest with sulfasoxazole and trimethoprim/sulfamethoxazole and was highest with cloxacillin. A significant dose-response effect was found with both amoxicillin and trimethoprim/sulfamethoxazole. For upper GI tract adverse drug reactions, the risk was again lowest with sulfasoxazole and trimethoprim/sulfamethoxazole and was highest with erythromycin. Knowledge of the risks of gastrointestinal adverse drug reactions with different agents and different doses should be clinically helpful in assessing risks and benefits when oral antibiotics are prescribed for children.


Investigation of multiaxial molecular dynamics by 2H MAS NMR spectroscopy.
The technique of 2H MAS NMR spectroscopy is presented for the investigation of multiaxial molecular dynamics. To evaluate the effects of discrete random reorientation a Lie algebraic formalism based on the stochastic Liouville-von Neumann equation is developed. The solution to the stochastic Liouville-von Neumann equation is obtained both in the presence and absence of rf irradiation. This allows effects of molecular dynamics to be evaluated during rf pulses and extends the applicability of the formalism to arbitrary multiple pulse experiments. Theoretical methods are presented for the description of multiaxial dynamics with particular emphasis on the application of vector parameters to represent molecular rotations. Numerical time and powder integration algorithms are presented that are both efficient and easy to implement computationally. The applicability of 2H MAS NMR spectroscopy for investigating molecular dynamics is evaluated from theoretical spectra. To demonstrate the potential of the technique the dynamics of thiourea-2H4 is investigated experimentally. From a series of variable temperature MAS and quadrupole echo spectra it has been found that the dynamics can be described by composite rotation about the CS and CN bonds. Both experiments are sensitive to the fast CS rotation which is shown to be described by the Arrhenius parameters E(CS) = 46.4 +/- 2.3 kJ mol(-1) and ln(A(CS))= 32.6 +/- 0.9. The MAS experiment represents a significant improvement by simultaneously allowing the dynamics of the slow CN rotation to be fully characterized in terms of E(CN) = 56.3 +/- 3.4 kJ mol(-1) and ln(A(CN)) = 25.3 +/- 1.1.


Association of Hb Q-Thailand with heterozygous Hb E in a Chinese patient.
We describe a Chinese patient who was heterozygous for both Hb Q-Thailand [alpha74(EF3)Asp-->His] and Hb E [beta26(B7)Gly-->Asp, GAG-->GTG]. Interaction of the alpha(Q-Thailand) and beta(E) chains leads to a hemoglobin (Hb) variant, namely Hb QE, which differs in electrophoretic mobility and high performance liquid chromatography (HPLC) profiles and in the amount of the Hb Q-Thailand variant present in the blood.


Intraparotid Ganglioneuroma: A rare case report.
Introduction: Ganglioneuromas (GNs) are slow-growing, benign tumors arising from Schwann cells, gangliocytes, and neuronal tissues. Case Presentation: We report a rare intraparotid ganglioneuroma in a 42-year-old female presented with a parotid mass. The onset of the lesion dated back to 2021, but the growth was remarkable only in November 2022. The FNA suggested a plexiform neurofibroma. The post-surgical microscopic examination of the excised lesion revealed neoplastic large, rounded cells with abundant, finely granular eosinophilic cytoplasm and a large, eccentric nucleus with a prominent nucleolus as well as fasciculated, with an elongated cytoplasm with fine fibrillar extensions. No mitosis or tumor necrosis was observed. The periphery of the tumor showed perineural entrapment. The immunohistochemical staining for S100 protein, synaptophysin, and chromogranin A were positive. However, the neoplastic cells showed no immunoreactivity for cytokeratin (CK5/6, CK7, AE1/AE3), epithelial membrane antigen, HMB45, Melan A, CD30, CD117 and p40. The case was signed out as mature intraparotid ganglioneuroma. Conclusion: The treatment of choice was surgical resection without adjuvant radiotherapy. No recurrence or post-surgical complications were hitherto reported. To the best of our knowledge, this is the first reported case of intraparotid ganglioneuroma. Caution should be taken not to diagnose this benign neoplasm as a metastasis (e.g. metastatic neuroblastoma) or to request unnecessary overtreatment (e.g., postoperative chemotherapy and radiotherapy).


Vaginal mucositis in measles.
Measles (rubeola), a common childhood exanthema, occurs infrequently in adults. Vaginal mucositis in association with measles is not commonly described. During a recent measles epidemic, 2 female patients presented with high fever, myalgia, exanthema, and prostration. On examination, each patient had marked inflammation and tenderness of the vaginal mucosa, prompting the presumptive diagnosis of toxic shock syndrome. The evolution of the illness was consistent with measles. Cervicovaginal cultures were negative for pathogens. Acute and convalescent antibody titers for Rocky Mountain spotted fever, rubella, leptospirosis, and Proteus Ox-19 were not consistent with a recent infection. The sera also were negative for anti-toxic shock toxin-1 and anti-streptolysin. Measles antibody titers were consistent with a recent infection. Vaginal mucositis is an unusual manifestation of measles that may mimic toxic shock syndrome.


Distribution of Peyer's patches in the distal ileum.
Peyer's patches play a major role in intestinal immunity, are portals of entry for significant pathogens, and may be important in Crohn's disease. Whereas their microscopic anatomy and immune function are well described, surprisingly little is known of their macroscopic anatomy and distribution. Our aim was to assess their number, area, and distribution in the normal distal ileum, with particular reference to patient age. Distal ilea (200 cm) obtained at autopsy from 55 adults without intestinal disease were opened along the mesenteric border, fixed in acetic acid, and transilluminated. Peyer's patches were counted, and the length, breadth, and distance from the ileocecal valve were recorded. Patches were most numerous in the terminal 10-15 cm where they formed a lymphoid ring. More proximal patches were oval, antimesenteric, and irregularly spaced. By area, 46% of patch tissue occurred in the terminal 25 cm. The mean number of patches ranged from 29.4 +/- 5.4 in the youngest group studied, to 19.0 +/- 3.0 in the oldest. Total patch area was greatest in the group aged 21-30 (47.4 +/- 1.0 cm2). Peyer's patches are concentrated in the distal 25 cm of ileum but extend proximally for 200 cm. The variation in their size, shape, and distribution in different individuals is greater than often appreciated and may influence the presentation of diseases centered on these structures.


Alterations of Tear Film and Ocular Surface in Children with Type 1 Diabetes Mellitus.
Purpose: To investigate whether diabetes mellitus (DM) affects ocular surface of children with well-controlled type 1 DM.Methods: Sixty-five diabetic patients and 55 age-matched controls enrolled to study. Detailed ocular surface assessment including, ocular surface disease index (OSDI) questionnaire, tear film break-up time (TBUT) analysis, Schirmer test, and conjunctival impression cytologic analysis were performed.Results: Schirmer test and TBUT results were significantly lower in DM group than controls (p = 0.001, for all). OSDI scores of all participants were within normal range. Impression cytology analysis showed grade 0 changes in all participants and there was no difference between groups for goblet cell density (p > 0.05). The TBUT results were significantly associated with duration of DM (r = -0.309, p = 0.036).Conclusion: Diabetic children without symptoms, signs, and definite diagnosis of dry eye still had lower TBUT and Schirmer test results than controls; however, impression cytology analysis was similar in both groups.


Vasodilator drugs in the treatment of hypertension.
Vasodilator drugs counteract the major haemodynamic abnormality of hypertension, namely, arteriolar constriction. As a group, they tend to cause tachycardia and fluid retention, but these side-effects are variable within the group. Vasodilator drugs are effective in the treatment of the whole range of hypertensive diseases, from severe refractory hypertension to mild hypertension. With increasing recognition of the necessity of treatment in mild asymptomatic hypertension, those vasodilator drugs which can be used on their own, such as prazosin and calcium antagonists, are attractive as initial therapy, because they do not have adverse effects on the levels of atherogenic lipids and other risk factors for vascular disease. The major current use of vasodilator drugs in combination with a thiazide and a beta-adrenoreceptor-blocking drug is in the treatment of moderate-to-severe hypertension.


Inhibition of acetylcholinesterase by TX-100.
At high detergent concentrations, approximately the equivalent of 2 micelles of TX-100 reversibly bind to acetylcholinesterase and fully inhibit the enzyme. This result suggests that the appropriate lipid environment might regulate this neuronal enzyme's function.


Universality in the viscous-to-inertial coalescence of liquid droplets.
We present a theory on the coalescence of 2 spherical liquid droplets that are initially stationary. The evolution of the radius of a liquid neck formed upon coalescence was formulated as an initial value problem and then solved to yield an exact solution without free parameters, with its 2 asymptotic approximations reproducing the well-known scaling relations in the inertially limited viscous and inertial regimes. The viscous-to-inertial crossover observed in previous research is also recovered by the theory, rendering the collapse of data of different viscosities onto a single curve.


[Clinical indications for radiotherapy of the mediastinum (author's transl)].
The clinical and radiobiological problems associated with radiotherapy of the mediastinum are discussed with reference to the efficacy of such treatment on various forms (therapeutical and palliative management and its indications) and the damage caused to normal organs.


Formation in professional education: an examination of the relationship between theories of meaning and theories of the self.
Being formed through learning a practice is best understood within a constitutive theory of meaning as articulated by Charles Taylor. Disengaged views of the person cannot account for the formative changes in a person's identity and capacities upon learning a professional practice. Representational or correspondence theories of meaning cannot account for formation. Formation occurs over time because students actively seek and take up new concerns and learn new knowledge and skills. Engaged situated reasoning about underdetermined practice situations requires well-formed skillful clinicians caring for particular patients in particular situations.


[Effect of high-power pulse laser radiation on experimental tumor metastasis].
Under study was the effect of the energy density and pulse duration of laser radiation on metastasization of Lewis carcinoma and melanoma B16. It was shown that laser irradiation of blastomas, the energy density of the former not exceeding 400 joule/cm2 and the pulse duration being 1 msec, not only fails to contribute to tumor proliferation but, on the contrary, somewhat reduces the number of pulmonary metastases. The phenomenon of such kind is observed in simultaneous rise of the energy density up to 800 joule/cm2 and lengthening of the pulse up to 6 msec.


Methyleugenol protects against t-BHP-triggered oxidative injury by induction of Nrf2 dependent on AMPK/GSK3β and ERK activation.
Methyleugenol (Mlg), a natural ingredient of many herbs and used as a flavoring substance in dietary products, inhibits inflammation and oxidative stress. The aim of the study is to explore the antioxidative potential of Mlg against tert-butyl hydroperoxide (t-BHP)-triggered oxidative injury and the involvement of antioxidative mechanisms. Our findings indicated that Mlg exposure significantly alleviated t-BHP-stimulated cytotoxicity, suppressed reactive oxygen species (ROS) generation, and increased superoxide dismutase (SOD) and glutathione (GSH) levels, which were related to the induction of the glutamate-cysteine ligase catalytic/modifier (GCLC/GCLM) subunit, heme oxygenase-1 (HO-1), and NAD (P) H: quinone oxidoreductase (NQO1) largely dependent upon upregulating the nuclear factor-erythroid 2-related factor 2 (Nrf2) induction, inhibiting the Keap1 protein expression, and heightening the antioxidant response element (ARE) activity. Additionally, Mlg exposure obviously induced AMP-activated protein kinase (AMPK), glycogen synthase kinase 3β (GSK3β) and extracellular signal-regulated kinase (ERK) phosphorylation, but AMPK and ERK inhibitors treatment exhibited effectively reduced levels of Mlg-enhanced Nrf2 nuclear translocation, respectively. Furthermore, Mlg exposure significantly lessened t-BHP-induced cytotoxicity and ROS production which were evidently abolished by treatment with AMPK and ERK inhibitors and Nrf2 siRNA. Accordingly, Mlg might exhibit a protective role against t-BHP-triggered cytotoxicity via the activation of the AMPK/GSK3β- and ERK-Nrf2 signaling pathways.