Disjunctive models of Boolean category learning.
Four connectionistic/neural models which are capable of learning arbitrary Boolean functions are presented. Three are probably convergent, but of differing generalization power. The fourth is not necessarily convergent, but its empirical behavior is quite good. The time and space characteristics of the four models are compared over a diverse range of functions and testing conditions. These include the ability to learn specific instances, to effectively generalize, and to deal with irrelevant or redundant information. Trade-offs between time and space are demonstrated by the various approaches.


Aflatoxin contamination in field mustard (Brassica juncea) cultivars.
7 varieties of mustards were cultivated in statistically designed field during 1988 through 1989 and 1989 through 1990 crops in order to ascertain the resistant or less susceptible varieties for aflatoxin elaboration. Under field condition, none of the varieties of mustard was found to be resistant. Maximum aflatoxin contamination was observed in the late planting time (15 th November) crops. Insect (Lipaphis erysime) incidence had significant negative correlation (r=-0.9354) with the yield (Q/hectare) while it had significant positive correlation (r=0.5705) with aflatoxin contamination.


Quasi-independent monitor unit calculation for intensity modulated sequential tomotherapy.
The number of linac monitor units (MU) from intensity modulated sequential tomotherapy (IMST) is substantially larger than the MU delivered in conventional radiation therapy, and the relation between MU and dose is obscure due to complicated variation of the beam intensities. The purpose of this work was to develop a practical method of verifying the MU and dose from IMST so that the MU of each arced beam could be double-checked for accuracy. MU calculations for 41 arced beams from 14 IMST patients were performed using the variables of vane open fraction time, field size, target depth, output factor, TMR, and derived intensity distribution. Discrepancy between planned and checked MU was quantified as 100 (MU(cal)-MU(plan))/MU(plan) percent. All 41 discrepancies were clustered between -5% to +4%, illustrated in a Gaussian-shaped histogram centered at -1.0+/-3.5% standard deviation indicating the present MU calculations are in agreement with the planned expectations. To confirm the correctness of the present calculated MUs of the IMST plans, eight of the calculated IMST plans are performed dose verifications using their hybrid plans, which are created by transporting patient's IMST plan beams onto a spherical polystyrene Phantom for dose distribution within the Phantom. The dose was measured with a 0.07 cc ionization chamber inserted in the spherical Phantom during the hybrid plan irradiation. Average discrepancy between planned and measured doses was found to be 0.6+/-3.4% with single standard deviation uncertainty. The spread of the discrepancies of present calculated MUs relative to their planned ones are attributed to uncertainties of effective field size, effective planned dose corresponding to each arc, and inaccuracy of quantification of scattered dose from adjacent arced beams. Overall, the present calculation of MUs is consistent with what derived from treatment plans. Since the MUs are verified by actual dose measurements, therefore the present MU calculation technique is considered adequate for double-checking planned IMST MUs.


Transcription inactivation through local refolding of the RNA polymerase structure.
Structural studies of antibiotics not only provide a shortcut to medicine allowing for rational structure-based drug design, but may also capture snapshots of dynamic intermediates that become 'frozen' after inhibitor binding. Myxopyronin inhibits bacterial RNA polymerase (RNAP) by an unknown mechanism. Here we report the structure of dMyx--a desmethyl derivative of myxopyronin B--complexed with a Thermus thermophilus RNAP holoenzyme. The antibiotic binds to a pocket deep inside the RNAP clamp head domain, which interacts with the DNA template in the transcription bubble. Notably, binding of dMyx stabilizes refolding of the beta'-subunit switch-2 segment, resulting in a configuration that might indirectly compromise binding to, or directly clash with, the melted template DNA strand. Consistently, footprinting data show that the antibiotic binding does not prevent nucleation of the promoter DNA melting but instead blocks its propagation towards the active site. Myxopyronins are thus, to our knowledge, a first structurally characterized class of antibiotics that target formation of the pre-catalytic transcription initiation complex-the decisive step in gene expression control. Notably, mutations designed in switch-2 mimic the dMyx effects on promoter complexes in the absence of antibiotic. Overall, our results indicate a plausible mechanism of the dMyx action and a stepwise pathway of open complex formation in which core enzyme mediates the final stage of DNA melting near the transcription start site, and that switch-2 might act as a molecular checkpoint for DNA loading in response to regulatory signals or antibiotics. The universally conserved switch-2 may have the same role in all multisubunit RNAPs.


A novel series of pyrazole derivatives toward biological applications: experimental and conceptual DFT characterization.
A new series of 13 pyrazole-derivative compounds with potential antifungal activity were synthetized with good yields. The series have the (E)-2-((1-(R)-3,5-dimethyl-1H-pyrazol-4-yl)diazenyl)phenol general structure and were characterized by means of X-ray diffraction, UV-Vis, FTIR, 1H-NMR, 13C-NMR, and two-dimensional NMR experiments. This experimental characterization was complemented by DFT simulations. A deep insight regarding molecular reactivity was accomplished employing a conceptual DFT approach. In this sense, dual descriptors were calculated at HF and DFT level of theory and GGV spin-density Fukui functions. The main reactive region within the molecules was mapped through isosurface and condensed representations. Finally, chemical descriptors that have previously shown to be close related to biological activity were compared within the series. Thus, higher values of chemical potential ω and electrophilicity χ obtained for compounds 10, 9, 8, 6 and 7, in this order, suggest that these molecules are the better candidates as biological agents.


Toluene in venous blood during and after work in rotogravure printing.
Toluene exposure was studied in 62 male rotogravure printers, employed in three plants. The exposure level as measured by personal sampling during a week ranged from 8 to 1080 mg/m3 (median 96). The concentration of toluene in venous blood sampled directly after work correlated significantly with the time-weighted average (TWA) for toluene in air during the preceding workshift (n = 57, Spearman's r = 0.84, P less than 0.00001). The post-shift toluene level in venous blood is usable for biological monitoring of exposure. An air level of 100 mg/m3 corresponds to an average blood toluene level of 2.9 mumol/l; an air level of 300 mg/m3 to 8.2 mumol/l. The elimination of toluene is slow. Thus, toluene was detected in most Monday pre-shift blood samples and the levels increased statistically significantly during the work week (median 0.21 versus 0.42 mumol/l, P less than 0.0001). The toluene level in venous blood sampled directly before work on Thursday/Friday was found to be a function of the estimated mean exposure during the work week. In a multiple linear regression analysis, the mean exposure during the week was a good predictor for the concentration of toluene in venous blood before work at the end of the week (n = 52, r = 0.71). Thus, pre-shift blood values at the end of the week can be used as a biological index for the weekly exposure, when the variation of the ambient toluene concentration is known. The slow decrease of toluene in venous blood was followed in six workers for two weeks after cessation of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)


Rapid one-pot synthesis of LiMPO4 (M = Fe, Mn) colloidal nanocrystals by supercritical ethanol process.
We report a rapid one-pot supercritical fluid approach to prepare the desired size and morphology controlled LiMPO(4) nanocrystals, using oleylamine as both capping and reducing agent.


The Role of Alpha Power in the Suppression of Anticipated Distractors During Verbal Working Memory.
As working memory (WM) is limited in capacity, it is important to direct neural resources towards processing task-relevant information while ignoring distractors. Neural oscillations in the alpha frequency band (8-12 Hz) have been suggested to play a role in the inhibition of task-irrelevant information during WM, although results are mixed, possibly due to differences in the type of WM task employed. Here, we examined the role of alpha power in suppression of anticipated distractors of varying strength using a modified Sternberg task where the encoding and retention periods were temporally separated. We recorded EEG while 20 young adults completed the task and found: (1) slower reaction times in strong distractor trials compared to weak distractor trials; (2) increased alpha power in posterior regions from baseline prior to presentation of a distractor regardless of condition; and (3) no differences in alpha power between strong and weak distractor conditions. Our results suggest that parieto-occipital alpha power is increased prior to a distractor. However, we could not find evidence that alpha power is further modulated by distractor strength.


Staff perceptions of the implementation of a trauma video review program at a level I trauma center.
Successful implementation of any new technology requires extensive engagement with front-line staff. We explored the perceptions of emergency department and trauma staff about a trauma video review program (TVR) prior to implementation of the first such program in Canada at our level I trauma center. We conducted semi-structured individual interviews and in situ small group interviews with 35 multidisciplinary ED and trauma staff members of a teaching and research hospital in Toronto, Canada. We sought maximum variation in the sample of purposively selected participants. Interviews were recorded with audiotapes or detailed field notes, transcribed verbatim, coded, and analyzed using standard thematic analysis techniques. Participants expressed overall support for the concept of TVR, but there is a core sense of unease that influenced overall staff perceptions. Despite several departmental presentations, very few participants actually had a solid understanding of how the TVR worked. Many were apprehensive about their own professional privacy, deeply concerned about vulnerable patients being filmed without consent, and questioned how video data would be used. Despite significant hesitancy, ED and trauma staff identified positive opportunities that TVR could bring, including providing an evidence base for quality improvement. TVR is an evolving approach to evaluate quality and patient safety in the trauma bay. As such it brings with it natural concerns and apprehension from staff regarding privacy, confidentiality, and how data will be captured and used. There is opportunity for these types of concerns to be addressed with a robust knowledge translation plan and engagement of staff throughout the implementation process.


[Adaptation capacity of elderly to new (or improved) dentures; use of a geriatric assessment subscale].
Elderly people's diminished adaptability is an important factor in their acceptance of new or improved dentures. This research project shows that a geriatric rating scale for infirmity may have a valuable predictive function for adaptability.


Review of guidelines for pediatric advanced life support.
Most of the 2000 Guidelines related to PALS remain unchanged. The changes that were made are based on a review of the literature and were made to simplify the overall management of the critically ill child. Despite these changes, the primary goals of PALS--early recognition of respiratory failure and shock and prevention of cardiopulmonary arrest--remain unchanged.


Risk factors for neck pain in college students: a systematic review and meta-analysis.
During the COVID-19 epidemic, the prevalence of neck pain among college students has increased due to the shift from offline to online learning and increasing academic and employment pressures. Therefore, this systematic review aimed to identify the personal, occupational, and psychological factors associated with the development of neck pain to promote the development of preventive strategies and early intervention treatment. Seven electronic databases were searched from inception to December 2022 for cross-sectional studies, cohort studies, case----control studies, and randomized controlled trials (RCTs) on neck pain. The quality of the selected studies were assessed by American Agency for Healthcare Research and Quality (AHRQ) or the Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the effects of the included risk factors on neck pain. Thirty studies were included, including 18,395 participants. And a total of 33 potentially associated risk factors were identified. Ultimately, 11 risk factors were included in the meta-analysis after assessing, and all results were statistically significant (P < 0.05). The factors supported by strong evidence mainly include the improper use of the pillow (OR = 2.20, 95% CI: 1.39 to 3.48), lack of exercise (OR = 1.88, 95% CI: 1.53 to 2.30), improper sitting posture (OR = 1.97, 95% CI: 1.39 to 2.78), history of neck and shoulder trauma (OR = 2.32, 95% CI: 1.79 to 3.01), senior grade (OR = 2.86, 95% CI: 2.07 to 3.95), staying up late (OR = 1.80, 95% CI: 1.35 to 2.41), long-time electronic product usage daily (OR = 1.53, 95% CI: 1.33 to 1.76), long-time to bow head (OR = 2.04, 95% CI: 1.58 to 2.64), and emotional problems (OR = 2.09; 95% CI: 1.66 to 2.63). Risk factors supported by moderate evidence were high stress (OR = 1.61, 95% CI: 1.02 to 2.52) and female gender (OR = 1.69, 95% CI: 1.52 to 1.87). This study obtained 11 main risk factors affecting college students neck pain, including improper use of the pillow, lack of exercise, improper sitting posture, history of neck and shoulder trauma, senior grade, staying up late, long-term electronic product usage daily, long time to bow head, high stress, emotional problems and female gender.


Store and restaurant advertising and health of public housing residents.
To determine relationships between food and beverage signs and health. In 12 public housing neighborhoods, food and alcohol signs were counted for stores and restaurants. Health and demographic data were from 373 adults. Multilevel modeling showed higher BMI was related to more store and restaurant alcohol signs, higher blood pressure, nonsmokers, and females. Higher dietary fat consumption was related to more store and restaurant alcohol and fewer low-calorie healthy signs, lower fruit consumption, fewer minutes walked, and white and Hispanic/Latino ethnicity. Signs in stores and restaurants are related to BMI and dietary fat consumption among residents.


PRCP regulates angiogenesis in vivo.
In this issue of Blood, Adams et al provide evidence for an important novel function of prolylcarboxypeptidase (PRCP), or angiotensinase C, in endothelial cell physiology and angiogenesis.


Anthropometric measurements as a risk for hypertensive disorders in pregnancy: a hospital based study in South Asian population.
To determine the relationship between pregnancy induced hypertensive diseases and obesity. A retrospective case controlled study was performed at Aga Khan University Hospital including records from July 2000 to June 2005. All women developing hypertension with or without proteinuria after 20 weeks of pregnancy (n = 218) were included. Categories of pregnancy induced hypertensive diseases (PIHD) were defined according to National high blood pressure working group and ACOG committee bulletin. Controls were selected randomly with a ratio of 1:1.7 between cases and controls. The estimated prevalence of pre-eclampsia in our institution is 1.9%. Earlier reports suggested mostly non-Asian women primigravida were more likely to develop gestational hypertension when compared with multigravidae (p-value = 0.004). Mean BMI of cases was significantly higher than controls (p = < 0.001). The risks of both non-protienuric hypertension (Mean BMI = 27.16 +/- 5.46) and preeclampsia (Mean BMI = 27.39 +/- 6.15) increased consistently with increasing BMI. This rise was significantly associated with severity of pre-eclampsia and early development of PIH, but not associated with complications like eclampsia. No significant association of height and hypertension was found as most women of both cases and control were 150-165 cm tall. High BMI in pregnant women serves as a significant risk factor for developing hypertension in pregnancy but failed to establish this association with height is the main findings of our study.


Periodontal Pathogens and Associated Intrathecal Antibodies in Early Stages of Alzheimer's Disease.
Recent studies suggest a link between periodontitis and Alzheimer's disease (AD). Verification of the presence of periodontal pathogens and the intrathecal generation of pathogen-specific antibodies in 20 patients with AD and 20 with other forms of dementia (DEM-noAD). Clinical periodontal indices were recorded. Cerebrospinal fluid (CSF) was analyzed for total tau protein (T-tau) and amyloid-β (Aβ1-42). In serum and CSF, antibody levels against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema species were quantified. The presence of selected bacteria and inflammatory biomarkers were determined in periodontium, serum, and CSF. In line with diagnoses, CSF-levels of Aβ1-42 were significantly lower in AD than DEM-noAD patients. Periodontal destruction and inflammation were omnipresent with no difference between groups. P. gingivalis, T. forsythia, and Treponema species were detected in more than 50% of subgingival biofilm samples, but neither in serum nor in the CSF. Elevated levels of anti-pathogen antibodies in CSF of 16 patients (7 AD; 9 DEM-noAD) compared to serum highlight a possibility of the intrathecal immune response to pathogens. There was no significant difference in antibodies levels against selected bacteria in CSF and serum between groups. Multivariate regression analysis and general linear models revealed an association of the T-tau level in AD group with both serum levels of anti-P. gingivalis antibodies and MCP-1/CCL-2. Periodontal pathogens may enter the brain and stimulate a local immune response. However, in patients with dementia at the age up to 70 years, periodontal pathogens do not act as a trigger for developing AD.


Emergent Management of Tandem Occlusions in Anterior Circulation Stroke: A Single-Centre Experience.
For anterior circulation tandem occlusions, the optimal management strategy for extracranial carotid lesions is controversial. We aimed to compare the efficacy and safety of acute stenting (AS) with balloon angioplasty (BA) only. Clinical data were collected from 98 patients with anterior circulation tandem occlusion who underwent endovascular treatment at our center. Of these patients, 64 and 34 were assigned to the AS and BA groups, respectively. The clinical characteristics and outcome data of the 2 groups were analyzed and compared. The proportion of patients with good outcomes was 59.2%. The AS group had a higher rate of successful recanalization (98.4% vs. 82.4%, P = 0.007) and a lower rate of occlusion of the responsible vessel at 90 days (14.1% vs. 32.4%, P = 0.039) than the BA group. The AS group was also significantly better than the BA group in terms of good outcomes (67.2% vs. 44.1%, P = 0.027), but there was no significant difference between the 2 groups in terms of 90-day mortality (6.3% vs. 8.8%, P = 0.691) and asymptomatic intracranial hemorrhage (6.3% vs. 5.9%, P = 1.000). Lower baseline National Institutes of Health Stroke Scale scores were associated with good outcomes (P < 0.001), and the presence of symptomatic intracranial hemorrhage was associated with 90-day mortality (P = 0.003). Acute stent placement in patients with acute ischemic stroke due to anterior circulation tandem occlusion may have a better outcome than BA alone, and the safety of both approaches is comparable.


Hairy-cell leukemia with hybrid B-T features: a study with a panel of monoclonal antibodies.
The peripheral blood of three patients with otherwise typical hairy-cell leukemia (HCL), but with a substantial number of circulating cells expressing both light chain restricted surface immunoglobulin (SIg) and sheep erythrocyte (E) receptor, was studied with a panel of monoclonal antibodies. The presence of hybrid B-T surface features was confirmed and, although as in previous studies of E+SIg+ proliferations, the precise phenotypes varied at different times of study, E+ non-T SIg+ and E+T+SIg+ populations were at times present in all three patients together with typical B hairy-cell (HC) and phenotypically normal T-cell populations. In one patient an E-OKT11+SIg+ population was also observed. Extensive precautions were taken to exclude spurious explanations for these hybrid phenotypes. These results are discussed in relation to the recent demonstration that both HCs and normal B cells can express T-cell features after appropriate in vitro stimulation.


Effect of alpha lipoic acid on intracerebroventricular streptozotocin model of cognitive impairment in rats.
In the present study, the effect of alpha lipoic acid, a potent free radical scavenger, was investigated against the intracerebroventricular streptozotocin model of cognitive impairment in rats, which is characterized by a progressive deterioration of memory, cerebral glucose and energy metabolism, and oxidative stress. Wistar rats were injected with intracerebroventricular streptozotocin bilaterally. The rats were treated chronically with alpha lipoic acid (50, 100 and 200 mg/kg) orally for 21 days starting from day 1 of streptozotocin injection in separate groups. The learning and memory behavior was evaluated and the rats were sacrificed for estimation of oxidative stress. The intracerebroventricular streptozotocin rats treated with alpha lipoic acid (200 mg/kg, p.o.) showed significantly less cognitive impairment as compared to the vehicle treated rats. There was also an insignificant increase in oxidative stress in the alpha lipoic acid treated groups. The study demonstrated the effectiveness of alpha lipoic acid in preventing cognitive impairment and oxidative stress induced by intracerebroventricular streptozotocin and its potential in dementia associated with age and age related neurodegenerative disorders where oxidative stress is involved such as Alzheimer's disease.


Identifying disrupted biological factors and patient-tailored interventions for chronic fatigue in adolescents and young adults with Q-Fever Fatigue Syndrome, Chronic Fatigue Syndrome and Juvenile Idiopathic Arthritis (QFS-study): study protocol for a randomized controlled trial with single-subject experimental case series design.
Chronic fatigue with a debilitating effect on daily life is a frequently reported symptom among adolescents and young adults with a history of Q-fever infection (QFS). Persisting fatigue after infection may have a biological origin with psychological and social factors contributing to the disease phenotype. This is consistent with the biopsychosocial framework, which considers fatigue to be the result of a complex interaction between biological, psychological, and social factors. In line, similar manifestations of chronic fatigue are observed in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and juvenile idiopathic arthritis (JIA). Cognitive behavioral therapy is often recommended as treatment for chronic fatigue, considering its effectiveness on the group level. However, not everybody benefits on the individual level. More treatment success at the individual level might be achieved with patient-tailored treatments that incorporate the biopsychosocial framework. In addition to biological assessments of blood, stool, saliva, and hair, the QFS-study consists of a randomized controlled trial (RCT) in which a single-subject experimental case series (N=1) design will be implemented using Experience Sampling Methodology in fatigued adolescents and young adults with QFS, CFS/ME, and JIA (aged 12-29). With the RCT design, the effectiveness of patient-tailored PROfeel lifestyle advices will be compared against generic dietary advices in reducing fatigue severity at the group level. Pre-post analyses will be conducted to determine relevance of intervention order. By means of the N=1 design, effectiveness of both advices will be measured at the individual level. The QFS-study is a comprehensive study exploring disrupted biological factors and patient-tailored lifestyle advices as intervention in adolescent and young adults with QFS and similar manifestations of chronic fatigue. Practical or operational issues are expected during the study, but can be overcome through innovative study design, statistical approaches, and recruitment strategies. Ultimately, the study aims to contribute to biological research and (personalized) treatment in QFS and similar manifestations of chronic fatigue. Trial NL8789 . Registered July 21, 2020.


Cr (VI) inhibits DNA, RNA and protein syntheses in hepatocytes: involvement of glutathione reductase, reduced glutathione and DT-diaphorase.
In patients with orthopaedic implants, metallic particles have been shown to be disseminated widely throughout the body, particularly in the liver, spleen and lymph nodes. Levels of metal particles and ions in distant organs were highest in patients with loose, corroded prostheses, and when stainless steel and cobalt chrome alloy corrode, chromium is released predominantly as Cr (VI), a toxic ion. This manuscript investigates the interaction of Cr (VI) with liver cells in terms of inhibition of macromolecular synthesis, and the contribution of reduced glutathione (GSH), DT-diaphorase and glutathione reductase (GRd) to the toxicity of Cr (VI). Cr (VI) caused concentration dependent inhibition of protein, DNA and RNA synthesis in hepatocytes. GRd and to a lesser extent DT-diaphorase activities were involved in the generation of toxic intermediates. GRd activity was markedly inhibited during the reduction of Cr (VI), and GSH levels decreased. The concentrations of Cr (VI) found to inhibit macromolecular syntheses in this study are clinically relevant: it is therefore important to develop implants with minimum wear potential.


Cloud point extraction coupled with HPLC-UV for the determination of phthalate esters in environmental water samples.
A method based on cloud point extraction was developed to determine phthalate esters including di-ethyl-phthalate (DEP), di-(2-ethylhexyl)-phthalate (DEHP) and di-cyclohexyl-phthalate (DCP) in environmental water samples using high-performance liquid chromatography separation and ultraviolet detection (HPLC-UV). The non-ionic surfactant Triton X-114 was chosen as extraction solvent. The parameters affecting extraction efficiency, such as concentrations of Triton X-114 and Na2SO4, equilibration temperature, equilibration time and centrifugation time were evaluated and optimized. Under the optimum conditions, the method can achieve preconcentration factors of 35, 88, 111 and detection of limits of 2.0, 3.8, 1.0 ng/ml for DEP, DEHP and DCP in 10-ml water sample, respectively. The proposed method was successfully applied to the determination of trace amount of phathalate esters in effluent water of the wastewater treatment plant and the lixivium of plastic fragments.


Modulation of antibody display on M13 filamentous phage.
Here we describe a phage vector for the display of single chain antibodies and polypeptides on the surface of filamentous M13 phage which permits facile manipulation of the valency of display. The gene encoding the polypeptide is fused to a synthetic copy of the major coat protein VIII gene (gpVIII) which permits incorporation into the phage during assembly of the filament. Here we examine the growth parameters of phage propagation on the subsequent selection of an anti-progesterone antibody fragment from a mixture of display phage. Our results suggest that the density of the polypeptides displayed on phage may be modulated by altering growth conditions. This ability to influence polypeptide display density on filamentous phage may provide a versatile approach for accessing complex libraries and the capture of weaker ligand receptor interactions by avidity, whilst the potential to access and discriminate between higher affinity interactions is not negated.


Effects of Atorvastatin (80 mg) Therapy on Quantity of Epicardial Adipose Tissue in Patients Undergoing Pulmonary Vein Isolation for Atrial Fibrillation.
Epicardial adipose tissue (EAT) has been recognized as a sensitive marker of cardiometabolic risk. Recent evidence suggests efficacy of long-term statin therapy in reducing EAT in patients with coronary artery disease. Whether short-term statin therapy is associated with changes in the volume of EAT is currently unknown. A cohort of patients with atrial fibrillation who underwent pulmonary vein isolation were randomized to receive either 80 mg/day of atorvastatin (n = 38, 32 men, age 56 ± 11 years) or placebo (n = 41, 33 men, age 56 ± 10 years) for a 3-month period. EAT volume was assessed by cardiac computed tomography at baseline and at follow-up. Patients randomized to statin treatment exhibited a modest but significant decrease in median EAT volume (baseline vs follow-up: 92.3 cm(3) [62.0 to 133.3] vs 86.9 cm(3) [64.1 to 124.8], p <0.05), whereas median EAT remained unchanged in the placebo group (81.9 cm(3) [55.5 to 110.9] vs 81.3 cm(3) [57.1 to 110.5], p = NS). Changes in median systemic inflammatory markers and lipid profile were also seen with statin treatment: C-reactive protein (2.4 mg/L [0.7 to 3.7] vs 1.1 mg/L [0.5 to 2.7], p <0.05), total cholesterol (186 mg/dL [162.5 to 201] vs 123 mg/dL [99 to 162.5], p <0.001), and low-density lipoprotein cholesterol (116 mg/dL [96.5 to 132.5] vs 56 [40.5 to 81] mg/dL, p <0.001) diminished, whereas median body mass index did not change (27.8 kg/m(2) [25 to 30] versus 27.6 kg/m(2) [25.7 to 30.5], p = NS). No variations occurred in the placebo group. In conclusion, short-term intensive statin therapy significantly reduced the volume of EAT in patients with atrial fibrillation.


Efficient transformation of wheat by using a mutated rice acetolactate synthase gene as a selectable marker.
Acetolactate synthase (ALS) is a target enzyme for many herbicides, including sulfonylurea and imidazolinone. We investigated the usefulness of a mutated ALS gene of rice, which had double point mutations and encoded an herbicide-resistant form of the enzyme, as a selectable marker for wheat transformation. After the genomic DNA fragment from rice containing the mutated ALS gene was introduced into immature embryos by means of particle bombardment, transgenic plants were efficiently selected with the herbicide bispyribac sodium (BS). Southern blot analysis confirmed that transgenic plants had one to more than ten copies of the transgene in their chromosomes. Adjustment of the BS concentration combined with repeated selection effectively prevented nontransgenic plants from escaping herbicide selection. Measurement of ALS activity indicated that transgenic plants produced an herbicide-resistant form of ALS and therefore had acquired the resistance to BS. This report is the first to describe a selection system for wheat transformation that uses a selectable marker gene of plant origin.


Randomized Study of Noninferiority Comparing Prosthetic and Autologous Vein Above-Knee Femoropopliteal Bypasses.
The main aim of this study was to compare the 5 years rates of secondary patency of above-knee femoropopliteal revascularizations with autologous veins or prosthetic grafts. The secondary objectives were to compare the rates of primary patency, limb salvage, morbidity, and mortality between the 2 groups. This was a single-blind randomized study of noninferiority (ratio 1:1), carried out in 11 centers of vascular surgery with 2 parallel groups between July 2002 and November 2005. Follow-up finished in May 2011. The monitoring protocol included a clinical examination and an ultrasound control at 1 month, 3 and 6 months, then annually. One hundred patients were included and randomized in the study, 52 in the prosthetic group and 48 in the autologous vein group. Four patients randomized in the vein group received a prosthetic graft. No patient was excluded from the analysis. In the in intent-to-treat analysis, the 5 years secondary patency was 84.6% in the prosthetic group (IC 95%, 71.9-93.1) and 70.8% in the autologous vein group (IC 95%: 55.9-83.1), and the difference in secondary patency between the prosthetic and the autologous vein groups was 13.8% (IC 95%, -4.4 to 32.0). In the under treatment analysis, the 5 years secondary patency was 96.2% among patients receiving a prosthesis (IC 95%, 80.4-99.9) and 90.5% among patients receiving an autologous vein (IC 95%, 66.9-98.9), and the difference in the rate of patency between prostheses and veins was 5.7% (IC 95%, -13.2 to 24.6). Although there was no significant difference at 5 years, the death rate and the rate of amputation were higher in the prosthetic group. Although it is impossible to conclude definitely to the noninferiority of prosthetic bypass compared with venous bypass because of the insufficient number of inclusions, this randomized study nevertheless showed at 5 years the satisfactory results obtained with prostheses compared with autologous vein for above-knee femoropopliteal bypasses.


Internal daughter formation of Toxoplasma gondii tachyzoites is coordinated by transcription factor TgAP2IX-5.
Toxoplasma gondii rapidly propagates through endodyogeny of tachyzoites, a process in which daughter parasites divide within the cell of the mother parasite. Recent studies have revealed that transcription factors with AP2-domain participate in the process of cell division in T. gondii. However, the concise regulation of the division cycles by AP2 proteins is poorly understood. In this study, we evaluated the effect of the transcription factor TgAP2IX-5 on the daughter cell formation in T. gondii. TgAP2IX-5 is a nuclear protein and is highly expressed during the S phase of the cell cycle of tachyzoites. TgAP2IX-5-disrupted strain showed a severe defect in replication and completely blocked lytic parasite growth. Following 3-indoleacetic acid treatment or without treatment of AP2IX-5-AID-3HA tagged strain for 30 min, 1 and 2 hr, the differentially expressed genes were 8, 54 and 202, respectively. Among these genes, the significantly downregulated ones were AP2 proteins, inner membrane complex (IMC) proteins and SAG-related proteins. Interestingly, loss of TgAP2IX-5 leads to a defect in internal daughter IMC formation and abnormalities in the morphology of organelles during cell division. Together, our study suggests that TgAP2IX-5 is crucial in regulating IMC formation of daughter cells in T. gondii.


Spontaneous ventricular fibrillation occurring immediately after institution of cardiopulmonary bypass: possible clinical implications.
Twenty-four patients developed spontaneous ventricular fibrillation (SVF), for no apparent reasons, immediately after the institution of cardiopulmonary bypass (CPB) and prior to aortic cross-clamping and cardioplegic arrest. These were compared to 76 similar patients who remained in normal sinus rhythm (NSR). The following observations were made: (1) SVF occurred more frequently in patients undergoing urgent coronary bypass and having unstable or crescendo angina with severe triple coronary artery disease and/or left main coronary artery stenosis; (2) in nonvented hearts the mean left atrial pressure increased to levels above 28 mm Hg during SVF and prior to cardioplegic arrest; (3) at the end of CPB, arrhythmias and episodes of ventricular fibrillation were common (48% SVF versus 8% NSR); (4) the overall myocardial infarction rate was 37% SVF versus 4% NSR; and (5) the mortality rates were 25% SVF versus 1.3% NSR. It is postulated that the occurrence of SVF at the start of CPB may be indicative of serious derangements in myocardial cellular metabolism and/or function and may have clinical and prognostic implications.


Computed tomography in hereditary ataxias.
Cranial CT in 39 patients (23 belonged to 8 families) with four different groups of hereditary ataxia (HA) showed mainly three combinations of atrophic findings: (1) cerebellar ataxia (CA, n = 17) had marked atrophy of the cerebellum and/or the brain stem combined with moderate cerebral atrophy; (2) an intermediate group consisting of hereditary spastic paraplegia (HSP, n = 10) and Friedreich's ataxia (FA, n = 7), both with moderate infra- and supratentorial atrophy; (3) atrophy was hardly demonstrated in the group of Charcot-Marie-Tooth disease (CMT, n = 5). HA cases with atrophy could be distinguished from multiple sclerosis (MS) by CT.


Development of a cell culture method for quantal assay of strain I-2 of Newcastle disease virus.
Repeated titrations of strains of Newcastle disease virus (NDV) are more conveniently undertaken in cell cultures rather than in embryonated eggs. This is relatively easy with mesogenic and velogenic strains that are cytopathic to various cell lines, but is difficult with avirulent Australian isolates that are poorly cytopathic. Strain V4 for example has been shown to be pathogenic iin vitro only to of chicken embryo liver cells. Strain I-2 was reported to produce cytopathic effect (CPE) on chicken embryo kidney (CEK) cells. The present studies confirmed this observation and developed a quantal assay. CEK cells infected with strain I-2 developed CPE characterized by degeneration, rounding, granularity and vacuolation, and the formation of synctia. End points were readily established by microscopic examination of fixed and stained cells. In virus infectivity studies on strain I-2, where multiple titrations are required and where large numbers of samples are used, titration using CEK cell grown in microtitre plates is recommended. Such studies may not be feasible in embryonated eggs.


Monitoring of MYD88 L265P mutation by droplet digital polymerase chain reaction for prediction of early relapse in a patient with Bing-Neel syndrome.
Bing-Neel syndrome (BNS) is a rare neurologic complication of lymphoplasmacytic lymphoma (LPL) characterized by direct infiltration of lymphoplasmacytic cells (LPCs). Although no standard treatment has yet been established, patients with BNS harboring the MYD88 L265P mutation have been reported to respond favorably to ibrutinib, which can cross the blood-brain barrier and trigger apoptosis of MYD88 L265P-positive LPCs. However, it is still unclear whether monitoring of MYD88 L265P mutation status would be useful for predicting relapse/progression or for assisting diagnosis and evaluating response to chemotherapy. Here, we report the case of a patient with BNS receiving ibrutinib in whom we detected relapse early by monitoring for molecular residual disease (MRD) based on the presence of the MYD88 L265P mutation in cerebrospinal fluid (CSF) on droplet digital polymerase chain reaction assay. Persistent MRD increased 2 weeks before the onset of relapse symptoms without any abnormal imaging findings or evidence of clonal LPCs on CSF cytology, flow cytometry analysis, or immunofixation electrophoresis. Our findings suggest that an increase in MRD levels is correlated with relapse in patients with BNS.


Rainfall and reproduction in females of the tropical lizard Mabuya striata striata.
The reproduction of females of the lizard Mabuya striata striata was studied at two sites in Central Africa in an area with distinct rainy and dry seasons. The two sites differed in the amount of rain received. At the wetter site, a high proportion of M. s. striata were reproductive at all seasons. At the drier site, a high proportion of females were reproductive during the rainy season, but fewer were reproductive during the dry season. In addition, clutch size was lower at the drier site in the dry season. At both sites, low rainfall during the dry season appeared to constrain reproduction, but this constraint was greater at the drier site. At both sites, abdominal fat bodies were large during the rainy season and the early dry season and much smaller in the late dry season. In the early dry season abdominal fat bodies were larger at the drier than the wetter site. Females at the drier site apparently channel energy differentially into adult survival rather than present reproduction.


Near-maximum microwave absorption in a thin metal film at the pseudo-free-standing limit.
Electromagnetic absorbers based on ultra-thin metallic film are desirable for many applications such as plasmonics, metamaterials, and long-wavelength detectors. A metallic film will achieve a maximum 50% of electromagnetic wave absorption, frequency independent, at a thickness defined by its conductivity, typically in the sub-Angstrom range for good metals if bulk conductivity is maintained throughout. This makes it extremely difficult to obtain substantial absorption from thin metal films, in contrast to 2D materials such as graphene. Luckily, however, from a practical point of view, metal conductivity is drastically reduced as the film becomes sub-100 nm, to make it a race between the thinnest possible metal thickness experimentally achievable vs the conductivity reduction. Here, we demonstrate a near-50% absorption at a gold film thickness of 6.5 nm, with conductivity much reduced from the bulk value, down to the range of 106 Siemens per meter. Studying the effect of the substrate thickness, we found that the common cover glass, with its thickness much smaller than the wavelength, achieves symmetric absorption of 44%, implying that a pseudo-free-standing limit is achieved. Our work may find applications in infrared sensing as in bolometers and biomedical sensing using microwaves.


Epiphyll deterrence to the leafcutter ant Atta cephalotes.
Epiphyll growth on leaves of the grapefruit Citrus paradisi and the understory cyclanth Cyclanthus bipartitus repelled the fungus-growing, leafcutter ant Atta cephalotes from harvesting leaves of these tropical plants. Experimental removal of epiphylls from leaves resulted in 2-3 times more herbivore damage by leafcutter ants as compared to matched leaves with epiphylls. Because of the protection from herbivore damage, host plants may derive a partial fitness benefit from association with epiphylls.


The relationship between lung fibrosis, the epidermal growth factor receptor, and disease outcomes in COVID-19 pneumonia: a postmortem evaluation.
The aim of this study was to examine the relationship between the severity of fibrosis in lung tissue and epidermal growth factor receptor (EGFR) positivity in patients who died due to COVID-19 pneumonia, demographic characteristics, comorbidities, biochemical values, and treatments received. Fifty patients who died from COVID-19 pneumonia were included in the study. Demographic data for the patients, laboratory tests, thorax computerized tomography findings, comorbidities, length of stay in the intensive care unit (ICU), intubation times, and treatments given were noted. Postmortem Tru-cut lung biopsy was performed. EGFR positivity was examined and grouped as negative, mild, moderate, and severe. Data were analyzed statistically. EGFR involvement was negative in 11 (22%), mild in 20 (40%), moderate in 13 (26%), and severe in 6 (12%) patients. The mean C-reactive protein (CRP) values, D-dimer values, and mean length of stay in the ICU were found to be significantly different between the groups (p = 0.024; p = 0.003; p = 0.016, respectively). Methylprednisolone dose and the presence of comorbidity did not differ significantly in EGFR involvement (p = 0.79; p = 0.98, respectively). CRP and D-dimer values can be used as a guide to assess the severity of pulmonary fibrosis that develops in severe COVID-19 pneumonia patients. The dose of methylprednisolone used does not make a significant difference in the severity of fibrosis.Trail registration: Clinical Trials.gov identifier date and number 01/13/2022 NCT05290441.


The role of the arginine-nitric oxide pathway in the pathogenesis of bipolar affective disorder.
There is a reciprocal regulation of arginase and nitric oxide synthase (NOS) in L-arginine-metabolizing pathways. Nitric oxide (NO) may be involved in some psychiatric disorders like schizophrenia, depression and bipolar affective disorder (BPAD). To our knowledge, there is no study in the literature in which the role of arginase, an important part of the arginine regulatory system affecting NOS activity, was investigated in BPAD. This study aims to investigate arginase, manganese (Mn) and total nitrite levels (a metabolite of NO) and their relationship to the arginine-NO pathway in patients with BPAD. Arginase activities, Mn and total nitrite levels were measured in plasma from forty-three patients with BPAD (Type one) and thirty-one healthy control subjects. Plasma arginase activities and Mn were found to be significantly lower and total nitrite level higher in patients with BPAD compared with controls. Our results suggest that the arginine-NO pathway is involved in the pathogenesis of BPAD.


Protective mechanism of demethylase fat mass and obesity-associated protein in energy metabolism disorder of hypoxia-reoxygenation-induced cardiomyocytes.
What is the central question of this study? What is the effect of fat mass and obesity-associated protein (FTO) on energy metabolism in hypoxia-reoxygenation (H/R)-induced cardiomyocytes? What is the main finding and its importance? FTO modification of N6 -methyladenosine (m6 A) is associated with myocardial cell energy metabolism disorder. FTO reduced the m6 A level of sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) mRNA through demethylation, thus promoting SERCA2a expression, maintaining calcium homeostasis, and improving energy metabolism of H/R cardiomyocytes. Energy metabolism disorder is the initial physiological link of myocardial ischaemia-reperfusion injury. Fat mass and obesity-associated protein (FTO) is an N6 -methyladenosine (m6 A) demethylase implicated in several cardiac defects. This study sought to investigate the effect of FTO on energy metabolism in hypoxia-reoxygenation (H/R)-induced cardiomyocytes. FTO and sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a) expression in H/R-induced cardiomyocytes were determined. Cardiomyocyte viability, cytotoxicity and apoptosis were measured. The total RNA and polyA+ RNA contents were isolated from cells. The m6 A level of RNA and the enrichment of m6 A of SERCA2a mRNA were calculated. Several indices such as the glycolytic potential, reactive oxygen species (ROS), mitochondrial activity and ATP content were evaluated. The concentration of calcium in cardiomyocytes was determined. FTO and SERCA2a were poorly expressed in H/R-induced cardiomyocytes. There was an elevated m6 A level in total RNA and enrichment of m6 A in SERCA2a mRNA. H/R treatment reduced the cell viability, mitochondrial membrane potential and ATP content in cardiomyocytes, but increased the cytotoxicity, apoptosis, ROS content and calcium concentration. Upregulation of FTO reversed the preceding findings with downregulation of the m6 A level of SERCA2a mRNA. Downregulation of SERCA2a annulled the promoting effect of FTO on calcium homeostasis and energy metabolism in H/R-induced cardiomyocytes. Collectively, the current study demonstrated that FTO reduced the m6 A level on SERCA2a mRNA through demethylation, thus promoting SERCA2a expression, maintaining calcium homeostasis and improving the energy metabolism of H/R cardiomyocytes.


The Junction Between the Peristaltic and Non-peristaltic Bowel (Shore Break) is Found in the Transition Zone in Hirschsprung's Disease.
The junction between the peristaltic and non-peristaltic bowel, which is named the "shore break" (SB), observed on endoscopy is thought to be the boundary between normal and abnormal motility in Hirschsprung's disease (HD). The transition zone (TZ), which is the histopathological border, does not have normal motility and should be resected. This study aimed to evaluate the histopathological findings of the SB and determine the association between the SB and TZ. A retrospective review of surgical specimens of patients with HD who underwent preoperative SB marking was conducted. The TZ was defined if nerve hypertrophy, myenteric hypoganglionosis, or partial circumferential aganglionosis was detected. Ten patients (9 boys and 1 girl) were studied. The median age at surgery was 30 days. The median distance from the anal verge to the marked SB site was 14 cm. No patients manifested any obstructive symptoms resulting from a residual TZ bowel. In eight patients, nerve hypertrophy was identified at the proximal margin and at the SB. Myenteric hypoganglionosis was identified in three patients at the proximal margin and SB. Partial circumferential aganglionosis was identified at the SB in two patients. As a result, in all patients, the pull-through site and SB site had histopathological features indicating TZ. The SB is located in the TZ. Our results suggest that the proximal part of the TZ has normal motility and that functional border points may be present in the TZ. IV.


Onchocerca fasciata: enzyme histochemistry and tissue distribution of various dehydrogenases in the adult female worm.
Histochemistry studies of key dehydrogenases in the glycolytic pathway and related enzymes and the tricarboxylic acid (TCA)-cycle enzymes were carried out on adult female Onchocerca fasciata. The distribution pattern and enzymatic activities of 6-phosphogluconate dehydrogenase (6-GPDH), lactate dehydrogenase (LDH), mitochondrial glycerol-3-phosphate dehydrogenase (GPDH), nicotinamide adenine dinucleotide (phosphate) [NAD+(P)]-linked isocitrate dehydrogenase (ICDH), and NAD+(P)-linked malate dehydrogenase (MDH) in various tissues of the worm were determined. Moderate to intense enzyme activities were localized in three main areas, namely, the hypodermis, body-wall muscle, and reproductive tissues. Activity of the formazan reaction product was very low, if at all present, in the intestinal epithelium and was completely absent in the cuticle. On the basis of the present results and earlier observations, it is suggested that glycolysis leading to the end product lactate is the main energy-generating pathway in O. fasciata. The presence of significant activity of 6-GPDH indicates that the pentose-phosphate pathway might be operative in O. fasciata. In light of the activity of some of the TCA-cycle enzymes, ICDH and MDH, demonstrable in O. fasciata, it is possible that an additional pathway (pyruvate-succinate) of glucose metabolism via a reverse sequence of the TCA cycle may also be operative in the worm. The possible functional significance of the enzymes detected is discussed with respect to their location.


Kinetic study on urea uptake with chitosan based sorbent materials.
A one-pot kinetic uptake study of urea in aqueous solution with various chitosan sorbent materials such as pristine chitosan, cross-linked chitosan with glutaraldehyde from low (C-1) to higher (C-2) glutaraldehyde content, and a Cu(II) complex of a glutaraldehyde cross-linked chitosan material (C-3) is reported herein. The kinetic uptake profiles were analyzed by the pseudo-first order (PFO) and pseudo-second-order (PSO) models, respectively. The uptake rate constant of urea and the sorption capacity (qe) of high molecular weight (HMW) chitosan, C-1, C-2, and C-3 were best described by the PFO model. The uptake rate constant of urea with the various sorbents is listed in ascending order: HMW chitosan<C-1<C-2≈C-3. The qe values (mg urea/g sorbent) for the sorbent/urea systems are listed in ascending order: HMW chitosan (48.1)≈C-1 (44.7)<C-2 (51.3)<C-3 (66.4mg/g), revealing good agreement with uptake values obtained independently at equilibrium conditions. Cross-linked chitosan displays relatively rapid urea uptake and greater adsorption capacity when compared with pristine chitosan. The observed trends are in agreement with the greater surface accessibility and pore structure properties of cross-linked chitosan based on scanning electron microscopy studies. These results further illustrate the rational design of chitosan-based materials for the controlled uptake of urea in aquatic environments.


Colorimetric determination of Listeria monocytogenes using aptamer and urease dual-labeled magnetic nanoparticles and cucurbit[7]uril-mediated supramolecular assembly of gold nanoparticle.
A host-guest colorimetric strategy is described for the detection of Listeria monocytogenes (L. monocytogenes). The optical probes were self-assembled based on the supramolecular interactions between the carbonyl groups of cucurbit[7]uril portals and gold nanoparticles (CB[7]-AuNPs). Aptamer and urease modified magnetic nanoparticles were used to specifically recognize and binding to L. monocytogenes, simultaneously hydrolyzing urea to produce ammonium ion (NH4+) that can reverse CB[7] induced AuNPs aggregation. In the presence of L. monocytogenes, the above-mentioned magnetic conjugates preferentially bind to the bacterial surface, which results in blocking the catalytic active sites, thus inhibiting the production of ammonium ions. The normalized absorbance ratio of A700 nm/A525 nm was proportional to the L. monocytogenes concentration ranging from 10 to 106 cfu·mL-1, and the visual determination can be done down to 10 cfu·mL-1. For spiked food samples analyzed without pre-enrichment, recoveries of 98.4% to 99.3% were achieved could be verified and RSD were less than 10%. This work may offer a broad prospect for sensitive and specific determination of pathogens.


Comprehensive analysis of 225 Castleman's diseases in the oral maxillofacial and neck region: a rare disease revisited.
The aim of the present study was to comprehensively summarize the epidemiological, clinicopathological characteristics, treatments as well as prognosis of Castleman's disease (CD) identified in the oral maxillofacial and neck region. Patients with CD in the oral maxillofacial and neck were retrieved from disease registry at our institution from Jan. 1990 to Dec. 2015. Systematic reviews from both English and Chinese literature were performed to collect the detailed information about the oral maxillofacial and neck CD. The epidemiological, clinicopathological data and treatment outcomes were further statistically analyzed. Four patients with the oral maxillofacial and neck CD were identified and histologically confirmed as hyaline-vascular type. They underwent surgical excision without recurrence during the follow-up. Systematic literature reviews identified 221 cases from 123 eligible articles which satisfied the inclusion criteria. In 225 patients, most patients were diagnosed as unicentric (207) or hyaline-vascular type (205) of CD and identified in the neck, and treated by surgical resection with good prognosis. In contrast, the minority of patients was multicentric or plasma-cell/mixed type and treated by chemotherapy with inferior outcomes. Kaplan-Meir analyses revealed that both clinical and pathological types were significantly associated with patients' overall survival. Although rare, most cases of the oral maxillofacial neck CD are found in adults and classified as unicentric and hyaline-vascular type of CD. Complete surgical excision is preferred with favorable prognosis for unicentric disease, whereas chemotherapy is usually exploited for multicentric disease with inferior outcomes. These data provide comprehensive information about the epidemiology, clinicopathological features, treatments, and outcomes of the oral maxillofacial and neck CD.


Zidovudine impairs adipogenic differentiation through inhibition of clonal expansion.
Lipoatrophy is a prevalent side effect of treatment with thymidine analogues. We wished to confine the time point of the antiadipogenic effect of zidovudine (AZT) during adipogenesis and to evaluate the antiproliferative effect of AZT on adipocyte homeostasis. We investigated the effects of AZT on adipogenesis in 3T3-F442A cells and studied their proliferation, differentiation, viability, and adiponectin expression. Cells were exposed to AZT (1 microM, 3 microM, 6 microM, and 180 microM), stavudine (d4T; 3 microM), or dideoxycytosine (ddC; 0.1 microM) for up to 15 days. Differentiation was assessed by real-time PCR and quantification of triglyceride accumulation. Proliferation and clonal expansion were determined by a [(3)H]thymidine incorporation assay. When they were induced to differentiate in the presence of AZT at the maximum concentration in plasma (C(max)) and lower concentrations, 3T3-F442A preadipocytes failed to accumulate cytoplasmic triacylglycerol and failed to express normal levels of the later adipogenic transcription factors, CCAAT/enhancer-binding protein alpha and peroxisome proliferator-activated receptor gamma. AZT exerted an inhibitory effect on the completion of the mitotic clonal expansion, which resulted in incomplete 3T3-F442A differentiation and, finally, a reduction in the level of adiponectin expression. In addition, AZT impaired the constitutive proliferation in murine and primary human subcutaneous preadipocytes. In contrast, incubation with d4T and ddC at the C(max) did not affect either preadipocyte proliferation or clonal expansion and differentiation. We conclude that the antiproliferative and antiadipogenetic effects of AZT on murine and primary human preadipocytes reveal the impact of the drug on fat tissue regeneration. These effects of the drug are expected to contribute to disturbed adipose tissue homeostasis and to be influenced by differential drug concentration and penetration in individual patients.


Application of NT-proBNP and BNP measurements in cardiac care: a more discerning marker for the detection and evaluation of heart failure.
Measurement of brain natriuretic peptide (BNP) has become a potent diagnostic aid as a means of identifying patients with systolic or diastolic dysfunction. Due to better stability in circulating blood, we reasoned that measurement of N-terminal proBNP (NT-proBNP) may be a more discerning marker for the detection and evaluation of chronic heart failure. The relationships between plasma concentrations of NT-proBNP and BNP, and aetiology, New York Heart Association (NYHA) classification, and left ventricular ejection fraction (LVEF) were analyzed in 105 patients with chronic heart failure. Sixty-seven healthy volunteers were studied as the controls. Both NT-proBNP and BNP showed progressive increases (P<0.001) in proportion to the NYHA classification; the increment of NT-proBNP was larger than that of BNP. Elevated NT-proBNP significantly correlated with BNP (r=0.737, P<0.001). Receiver operating characteristics analysis to detect LVEF<40% showed similar values (area under the curve, AUC: NT-proBNP 0.754 vs. BNP 0.770), however, AUC to detect LVEF<50% tended to be greater for NT-proBNP than that for BNP (NT-proBNP 0.820 vs. BNP 0.794). NT-proBNP may be a more discerning marker for the detection and evaluation of heart failure than BNP.


Lower molecular weight intravenous iron dextran for restless legs syndrome.
Various techniques used to assess brain iron concentrations have demonstrated the presence of low iron stores in patients with restless legs syndrome (RLS). Previous open-label and randomized studies generally support the value of iron treatment for RLS symptoms. Only one of these studies assessed iron therapy response to changes in brain iron status. The current study was designed to assess the effect of iron therapy on RLS symptoms and on CSF measures of brain iron status. Idiopathic RLS patients drawn from the Korean population received four weekly intravenous (IV) doses of 250 mg low-molecular weight iron dextran for a total dose of 1g. One week after the last dose, any subject on RLS medication tapered off the RLS medications. Blood and CSF samples were taken to measure iron parameters at baseline and again, three weeks after the last dose. We have been following their response to the drug for two years after treatment. Twenty-five patients (age 55.2 ± 9.3, 18 female) enrolled in this study without serious adverse reactions. Seventeen of the 25 patients (68%) showed moderate or complete improvement of all RLS symptoms after treatment based on the Korean-translated versions of the International RLS Severity scale (K-IRLS). Changes in the K-IRLS did not correlate significantly with changes in CSF ferritin. The response to IV iron could not be predicted by patients' demographics, or by blood or CSF iron baseline characteristics. RLS symptom improvement started between one and six weeks after treatment and the treatment benefits lasted from one month to 22 months. Fourteen patients, (56%) completely stopped all medications, for a mean duration of 31.3 ± 33.1 weeks. These results are comparable to those from a prior study with high molecular weight dextran. Intravenous low-molecular weight iron dextran produced significant improvement of RLS symptoms in a majority of patients without any significant adverse effects. Serious anaphylaxis occurs with high molecular weight, but rarely, if ever, with this low molecular weight dextran. Given apparent comparable efficacy the low molecular weight and not the high molecular weight iron dextran, should be considered for RLS treatment. Although changes in CSF ferritin were seen following therapy, these changes were not related to clinical improvements.


Endoscopic management of intracerebral hemorrhage.
Massive intracerebral and intraventricular hemorrhages require aggressive and rapid management to decrease intracranial hypertension. The amount of intraventricular blood is a strong prognostic predictor, and its fast removal is a priority. Neuroendoscopy may offer some advantages over more traditional surgical approaches. All relevant data described in our experience and in publications about minimally invasive treatment of intraventricular and intracerebral hemorrhage found through MEDLINE searches and related references are reviewed. We described the technical details of neuroendoscopic management, highlighting the potential pitfalls and advantages of the techniques. Early neuroendoscopic surgery is a feasible approach, allowing, in most instances, rapid clinical and radiological improvement.


Balance and sound conditions in adults with bilateral cochlear implants.
Determine if 1) balance is impaired in patients with bilateral cochlear implants compared to healthy controls; 2) the presence of sound, non-speech or speech, affects standing balance. Four patients with bilateral cochlear implants were tested on three balance conditions on Romberg tests on medium density compliant foam with eyes closed, with head stationary or moving in yaw or pitch, under 5 sound conditions: no sound, ambient background noise, pink noise, foreign language, English language. Dependent measure were duration of standing and kinematics. Three of four subjects performed well with head still and no sound, background noise, or pink noise. All subjects performed poorly during the head movement conditions in the presence of either a foreign language or English words. Subjects could not perform enough head movements during yaw and pitch conditions for accurate kinematic measurements. The no-sound condition did not influence standing balance skills. The addition of ambient or pink noise also did not affect their balance. When they were distracted by attending to words, however, regardless whether or not they understood the words, standing balance skills deteriorated. Thus, distracted attention in these patients leads to impaired balance, which may impair functional motor skills.


A perspective on color vision in platyrrhine monkeys.
Studies carried out over the past two decades show that many platyrrhine (New World) monkeys have polymorphic color vision. This condition results from the sorting of allelic versions of X-chromosome cone opsin genes at a single gene site, yielding a mixture of dichromatic and trichromatic phenotypes in the population. Two genera of platyrrhine monkey are known to deviate significantly from this pattern. Examination of color vision, photopigments, and photopigment genes of all of these monkeys have stimulated a renewed interest in understanding the evolution of primate color vision.


Inflammatory Studies of Dehydroandrographolide: Isolation, Spectroscopy, Biological Activity, and Theoretical Modeling.
Dehydroandrographolide (DA) was isolated and experimentally characterized utilizing FT-IR, UV-Vis, and NMR spectroscopy techniques along with detailed theoretical modelled at the DFT/B3LYP-D3BJ/6-311 + + G(d,p) level of theory. Substantially, molecular electronic property investigations in the gaseous phase alongside five different solvents (ethanol, methanol, water, acetonitrile and DMSO) were comprehensively reported and compared with the experimental results. The globally harmonized scale (GHS), which is used to identify and label chemicals, was also utilized to demonstrate that the lead compound predicted an LD50 of 1190 mg/kg. This finding implies that consumers can safely consume the lead molecule. Notable impacts on hepatotoxicity, cytotoxicity, mutagenicity, and carcinogenicity were likewise found to be minimal to nonexistent for the compound. Additionally, in order to account for the biological performance of the studied compound, in-silico molecular docking simulation analysis was examined against different anti-inflammatory target of enzymes (3PGH, 4COX, and 6COX). From the examination, it can be inferred that DA@3PGH, DA@4COX, and DA@6COX, respectively, showed significant negative binding affinities of -7.2 kcal/mol, -8.0 kcal/mol, and - 6.9 kcal/mol. Thus, the high mean binding affinity in contrast to conventional drugs further reinforces these results as an anti-inflammatory agent.


A 433-MHz surface acoustic wave sensor with Ni-TiO2-poly(L-lysine) composite film for dopamine determination.
A ternary hybrid material composed of Ni nanoparticles (NPs), TiO2 NPs, and poly(L-lysine) (Ply) was used as a sensing material. It was electrodeposited in situ onto a commercial 433-MHz surface acoustic wave (SAW) resonator to construct a Ni-TiO2-Ply/SAW sensor. The Ni-TiO2-Ply sensing layer fully covered the resonant cavity of the SAW resonator. As the sensing layer completely covers the interdigital transducer and piezoelectric substrate, the sensing area is significantly increased, and the resonator is protected from damage or contamination. To detect the level of dopamine (DA) in serum, the fabrication of the Ni-TiO2-Ply sensing layer, distributions of various components in the sensing layer, and responses of the SAW biosensor to DA were investigated in detail. In addition, an electric field-assisted liquid-phase oxidation technique was developed for loading analytes onto the SAW sensors. After optimizing the pH value and L-lysine content of the sensing layer electrolyte and the pH value of the DA solution, the SAW biosensor responded to DA with a linear concentration range of 1 to 1000 nM, sensitivity of 5.77 MHz nM-1 cm-2, and limit of detection of 0.067 nM. Moreover, the sensor exhibited good selectivity, reproducibility, and stability at ambient temperature.Graphical abstract.


[Ultrasound diagnostics for myotendinous injuries and insertion tendinopathies of the elbow joint].
Acute capsular injuries of the elbow joint and its ligaments predominantly occur after joint dislocation or subluxation. Together with lateral and medial epicondylitis they represent a common injury pattern in radiology, orthopedic and trauma surgery. Because of the complexity of the elbow joint, knowledge of the elbow dislocation and injury pattern as well as the anatomy is essential in order to adequately estimate the injury severity and joint stability. This is crucial for the correct diagnosis and choice of treatment. Systematic physical examination and careful radiographic evaluation are components of an adequate management of acute soft tissue elbow injuries. The cost-effective ultrasound has emerged as a useful imaging modality for the diagnosis of acute joint and soft tissue pathologies especially in the acute phase after injury. Ultrasound as a diagnostic tool enables visualization of motion sequences during dynamic examination and therefore a better understanding of pathologies. Ultrasound examinations of the most common injuries of the elbow joint are presented in this overview.


Mitochondrial dysfunction in the neuronal ceroid-lipofuscinoses (Batten disease).
There are at least eight genetic entities known as the ceroid-lipofuscinoses in humans which share clinical and pathological features that have caused them to be grouped together under the eponym of Batten disease. They present pathologically as lysosomal storage diseases but are also characterised by severe neurodegeneration. Although the biochemical defects appear primarily centred on lysosomes and defects in proteolysis, the link between this and pathogenesis of neuronal death is poorly understood. The pathogenesis of neurodegeneration has been studied particularly in two animal models these being the English setter dog and the New Zealand Southhampshire sheep (OCL6). In these, and some of the human entities, there is evidence of mitochondrial dysfunction. This includes the accumulation of subunit c of ATP synthase as a component of storage material in at least six of eight genetic forms of the disease; structural abnormalities of mitochondria and selective loss of neurons in areas of the brain that are particularly metabolically active. Direct evidence of dysfunction comes from mitochondrial function tests in fibroblasts and, in animal models, isolated liver mitochondria. Supporting evidence of mitochondrial dysfunction was shown by disturbances in proportions of energy-rich phosphates in fibroblasts in some of these diseases. If these various defects were reflected in neurons, then it would support the hypothesis that neuron death was associated with energy-linked excitotoxicity.


Selected metabolites profiling of Orthosiphon stamineus Benth leaves extracts combined with chemometrics analysis and correlation with biological activities.
Studies on selected metabolites profiling of Orthosiphon stamineus extracts using chromatographic and spectroscopic techniques combined with chemometric tools have not been fully elucidated. Thus present study was performed to profile selected metabolites in O. stamineus leaves extracts using HPLC and FTIR combined with chemometric tools and correlated with biological activities. Five different extracts were prepared using three methods; maceration, soxhlet and reflux. The extracts were analyzed using UV-Vis, HPLC and FTIR techniques. Analysis of selected primary and secondary metabolites was also evaluated. The antioxidant and cytotoxic activities of the extracts were evaluated. Chemometric tools were employed to classify the extracts based on HPLC analysis and FTIR fingerprints. The ethanolic extract using maceration characterized high content of phenolics and flavonoids, (rosmarinic acid and eupatorin) with high antioxidant activity. Ethanolic (50%) and methanolic extracts using soxhlet showed high proteins and glycosaponins. Water extracts using reflux and maceration showed high polysaccharides. Methanolic extract (50%) using soxhlet and methanolic extract using maceration showed strong cytotoxic effect against MCF7 and HCT116 cell lines, respectively. Antioxidant and cytotoxic activities showed significant correlation with selected primary and secondary metabolites. HPLC fingerprints combined with chemometrics showed the extracts have been clustered based on selected major peaks profile. FTIR fingerprints combined with chemometrics showed that the extracts have been clustered based on protein and polysaccharide contents. Ten different extracts of O. stamineus have showed significant differences in the content of selected primary and secondary metabolites as well as the biological activities. Chemometric tools were able to classify and discriminate the distinctive features of extracts thus can be correlated with the biological activities.


Structural-functional heterogeneity along the rabbit collecting tubule.
The possibility that the rabbit collecting tubule is heterogeneous with respect to electrical and morphologic properties was examined in isolated segments. Collecting tubules from rabbits treated with desoxycorticosterone acetate were dissected from various locations within the cortex and outer medulla, and the transepithelial potential was measured. The cortical collecting tubule always displayed a negative potential. In contrast, collecting tubules dissected from the inner stripe of the outer medulla displayed a positive potential. That this change is a function of position within the kidney is supported by the observation that some tubules generated a negative potential at the superficial (cortical) end and a positive potential at the deep (medullary) end of the same tubule. Histologic evaluation of tubules after perfusion resulted in a striking correlation between the existence of a negative potential and the presence of dark cells. The results of this study provide evidence that the collecting tubule is heterogeneous with respect to active transport processes and suggest that these functional differences may correlate with morphologic differences between the cortical segment and the medullary segment of the collecting tubule.


Cancer-associated 53BP1 mutations induce DNA damage repair defects.
TP53 binding protein 1 (53BP1) plays an important role in DNA damage repair and maintaining genomic stability. However, the mutations of 53BP1 in human cancers have not been systematically examined. Here, we have analyzed 541 somatic mutations of 53BP1 across 34 types of human cancer from databases of The Cancer Genome Atlas, International Cancer Genome Consortium and Catalogue of Somatic Mutations in Cancer. Among these cancer-associated 53BP1 mutations, truncation mutations disrupt the nuclear localization of 53BP1 thus abolish its biological functions in DNA damage repair. Moreover, with biochemical analyses and structural modeling, we have examined the detailed molecular mechanism by which missense mutations in the key domains causes the DNA damage repair defects. Taken together, our results reveal the functional defects of a set of cancer-associated 53BP1 mutations.


Heat stress affects breathing and metabolism of chicks incubated at high temperature.
Global warming poses serious implications to animal physiology and a gradual increase in ambient temperature affects all living organisms, particularly fast-growing selected species. We recorded ventilation (V̇E), body temperature (TB), oxygen consumption (V̇O2) and respiratory equivalent (V̇E/V̇O2) of 14-day-old (14d) male and female chicks at room air conditions, hypercapnia and hypoxia at heat stress (HS, 32 °C). These chicks had previously been exposed to control (CI, 37.5 °C) and high (HI, 39 °C) temperatures during the first 5 days of incubation. Under resting conditions, acute HS increased V̇E in HI females but not in HI males. Hypercapnia combined with heat promoted a potentiation of CO2-hyperventilatory response in HI females when compared with thermoneutral condition, whereas in HI incubated males a hypoventilation under hypercapnia and heat stress was observed compared to the CI group. Hypoxia associated with heat stress increased V̇E only in HI females. Our data indicates that females are more sensitive to thermal manipulation during incubation and it seems that the thermal embryonic manipulation, at least during the first days of development, does not improve the adaptive response of chicks to heat stress.


Well-Being Data Gathering during COVID-19: Exploring the Feasibility of a Contact Tracing and Community Well-Being Safeguarding Framework.
Given the need for real time data to aid in decision-making at the community level, contact tracing applications (apps) are explored as a potential method of gauging overall community well-being. The context of contact tracing effectiveness and integration with artificial intelligence is provided, as well as ideas and suggestions for how to expand for use as a community-wide data gathering approach. This commentary seeks to explore dimensions around the use of such apps to help manage in times of crisis given the widespread and destructive impacts the pandemic has on community well-being, including negative economic impacts and social declines. By connecting with community well-being, the idea of a contact tracing framework would enable communities to track data and make decisions to help foster well-being across public health, economic and social domains.


Effects of delayed cord clamping on neurodevelopment and infection at four months of age: a randomised trial.
To investigate the effect that delayed and early umbilical cord clamping have on neurodevelopment, immunoglobulin G (IgG) and symptoms of infection during the first 4 months of life. Full-term infants (n = 382) were randomised to delayed (≥180 sec) or early cord clamping (≤10 sec). The Ages and Stages Questionnaire (ASQ) was used to assess neurodevelopment at 4 months. Immunoglobulin G was measured at birth, 2-3 days and 4 months. Parents recorded any symptoms indicating infection during the first 4 months of life. The total scores from the ASQ did not differ between groups. However, the delayed cord clamping (DCC) group had a higher mean (SD) score in the problem-solving domain [55.3 (7.2) vs. 53.5 (8.2), p = 0.03] at 4 months and a lower mean (SD) score in the personal-social domain [49.5 (9.3) vs. 51.8 (8.1), p = 0.01]. The IgG level was higher in the DCC group at 2-3 days (11.7 vs. 11.0 g/L, p = 0.004), but did not differ between the groups at 4 months. Symptoms of infection were comparable between the groups. Delayed cord clamping did not affect overall neurodevelopment or symptoms of infection up to 4 months of age, but may have an impact on specific neurodevelopmental domains.


Effects of dissolved oxygen levels and the role of extra- and intracellular amino acid concentrations upon the metabolism of mammalian cell lines during batch and continuous cultures.
The effects of dissolved oxygen and the concentration of essential amino acids upon the metabolism of two mammalian cell lines (rCHO producing human active (t-PA) and a mouse-mouse hybridoma) were investigated in batch, chemostat, and perfusion cultures. Intracellular amino acid concentrations were measured for both cell lines during repeated batch cultures and the K(S)-values for the essential amino acids were calculated using Monod equations via computer simulation. The K(S)-values were in the range of 10 mmol L(-1) and the pool of most intracellular amino acids remained constant at about 10-100 fold higher in concentration than in the medium. No significant differences were observed between the hybridoma and CHO cell. The specific nutrient uptake rates corresponded with the cell specific growth rate and the effects of reduced dissolved oxygen concentrations only became evident when the DO dropped below 5% of air saturation (critical concentration below 1%). Nevertheless, a correlation between nutrient concentration and specific oxygen uptake was detected.


[Ocular malignancies of xeroderma pigmentosum: clinical and therapeutic features].
Our aim was to determine the epidemiological, clinical and histopathological features as well as the most suitable therapeutic management of malignant ocular tumours in xeroderma pigmentosum based on a retrospective study of 32 patients. Our study was conducted in the ophthalmology unit of the Charles-Nicolle hospital between January 2001 and January 2004. A complete bilateral ophthalmologic investigation was performed for all patients and the severity of photophobia was scored on a four-point scale. Thirty-two xeroderma pigmentosum patients were examined during this period. Photophobia was found in 66% of cases and 19 of 32 patients (59%) were presenting ocular and periocular malignancies. The mean age of patients was 19 years (four to 40 years). Thirty-three tumours were diagnosed in these 19 patients. Blindness was noted in 3/26 (12%) eyes in patients without malignant tumour and in 10/38 (26%) eyes in patients with malignant tumour. Various types of malignant ocular-cutaneous tumours relating to sunlight developed in xeroderma pigmentosum patients. These disorders are more prevalent in severe and moderate forms of xeroderma pigmentosum. Lesions occur almost exclusively in the eyelids, conjunctiva, limbus and/or cornea. The rapid regression of these tumours, particularly in the cornea and limbus, may cause blindness, emphasising the importance of early management and regular monitoring of patients in order to allow early diagnosis of this condition, thereby ensuring the least mutilant treatment possible.


Influence of pentifylline on brain metabolism of normal and anoxic rats.
1-Hexyl-3,7-dimethyl-xanthine (pentifylline) increases significantly (1 h after oral administration of 25 mg/kg) the adenosine triphosphate and the total adenine nucleotide pool in the brain of normal rats and rats subjected to nitrogen breathing for 30 s. An increase in glycogen and in pyridine nucelotides (NAD+ + NADH2) were also noted. The results indicate that pentifylline shows a tendency toward normalizing or "economizing" the brain metabolism.


Short Cycle, Intermittent Therapy: A Valuable Option in Selected, Virologically Suppressed People Living with HIV.
The use of long-acting antiretroviral regimens will not be suitable for all people living with HIV for various reasons (previous virological failure with drugs of the same class, side effects, logistic difficulties, and costs). We think that short-cycle therapies could represent a feasible and valuable option for antiretroviral treatment optimization in selected individuals. So here we review clinical evidence about efficacy of short-cycle therapy in suppressed HIV-infected patients.


Changing the patterns of hospitalized diabetic foot ulcer (DFU) over a 5-year period in a multi-disciplinary setting in Thailand.
After years of decline, the rate of amputations was reported to increase by 50% in the U.S. population between 2009 and 2015. Few studies have examined the most recent trends in hospitalized diabetic foot ulcer (DFU) in Asian patients. This study aimed to examine recent trends and outcomes in hospitalized DFU at a tertiary diabetes center in Bangkok. We conducted a retrospective study from consecutive hospitalized DFU admissions from 2014 to 2018 at Theptarin Hospital, a multi-disciplinary diabetes center, led by diabetologists. During the study period, 290 patients (male 57.4%, age 65.5 ± 13.3 years, T2DM 99.4%, DM duration 18.8 ± 11.5 years, A1C 8.6 ± 2.3%) with 350 admissions were included. DFU were classified into neuropathic wounds (38.0%), ischemic wounds (2.6%), and mixed-type wounds (59.4%). The median length of stay was 8 days. Severe DFU (Wagner grade 3-5) composed 68.3% of all DFU and one-third of patients had prior history of amputations. Complete healing was achieved in 73.5% of the patients. Major amputation was performed in 16 (4.6%) and minor amputation was performed in 78 (22.3%) of all DFU. The mortality rate at 1 year after discharge was 12.0%. Advanced diseases with higher co-morbidities were associated with worse outcomes. When compared with our previous published data from 2009 to 2013, the annual rate of ischemic wounds from peripheral arterial diseases (PAD) and severity of DFU were increased in this study period. The major amputation rate slightly decreased from 6.0 to 4.6% but the minor amputation rate increased from 18.7 to 22.3%. The changing trend of DFU provides an excellent outlook into the inadequacies of our current diabetes care systems and global trend of aging population. After considerable successes in reducing major amputations over the past decade, the current analysis revealed a discouraging change in the healing rate of DFU and a stable pattern of major amputation. The prevalence of PAD among Thai patients with DFU increased significantly and affected the results of DFU treatments. Redefined organization of care with multidisciplinary team approach and coordination with referral centers are urgently required to improve outcomes of DFU.


Influence of incisional complications on infrainguinal vein bypass graft outcome.
Incisional complications following infrainguinal vein bypass remain a formidable challenge to the vascular surgeon. A retrospective analysis of 250 infrainguinal vein bypass grafts (214 patients) was undertaken to identify risk factors for the development of incisional complications and determine the impact of incisional complications on outcome. Incisional complications occurred in 47 (19%) of the bypasses. The mean age was 67.8 years and 155 (62%) of the bypasses were performed in men. The patients were divided into two groups based on the presence or absence of an incisional complication. By univariate analysis, the contributing factors for an incisional complication were: veteran hospital status, dialysis dependence, anemia, obesity, leukocytosis, and hypoalbuminemia (p < 0.05). By multivariate analysis, veteran hospital status, female gender, leukocytosis, and prior ipsilateral bypass were independent risk factors for incisional complications (p < 0.05). The increased incidence of incisional complications in the veteran's hospital group was associated with anemia, leukocytosis, decreased lymphocyte count, and increased incidence of tissue loss (p < 0.05). By life-table analysis, incisional complications did not influence primary patency (p = 0.73), secondary patency (p = 0.91), limb salvage (p = 0.69), or survival (p = 0.92). However, a significant suppurative soft-tissue infection ultimately resulted in a high rate of major amputation.


Treatment of incarceration of the penis by tempered steel bushings.
A case of penile incarceration secondary to a tempered steel ball bearing compromising the penile vascular supply is presented. The management of this case is described and guidelines for the management of similar cases reviewed.


Studies on the brush border membrane on mouse duodenum: lipids.
Lipids were extracted from purified mouse duodenal brush border membranes. Lipid: protein ratios in different membrane preparations varied from 0.58 to 0.68. Both the chloroform and non-chloroform phases were quantitatively analysed for lipids. Chloroform extracts were composed of cholesterol, triglycerides and phospholipids. The major neutral lipid was cholesterol. Rechromatrography of the phospholipid spot showed sphingomyelin (7.9%), phosphatides of ethanolamine (61.7%), inositol (14.2%) and serine (16.2%). The average molar ratio of cholesterol to phospholipid was 1.39. Lipids in the non-chloroform phase were all glycosylated, being cerebrosides (69.3%), cerebroside sulphates (28.8%) and galgliosides (1.9%). Overal membrane lipid composition was neutral lipid 24%, phospholipid 33%, and glycolipid 43%.


Converting mouse epiblast stem cells into mouse embryonic stem cells by using small molecules.
The derivation of mouse embryonic stem cells (mESCs) from the inner cell mass (ICM) of mouse preimplantation blastocysts has provided tremendous opportunities in exploring mammalian development and pluripotent stem cell biology (Martin, Proc Natl Acad Sci U S A 78(12):7634-7638, 1981; Evans and Kaufman, Nature 292(5819):154-156, 1981). The progresses of mESC studies also enabled the subsequent establishment of human ESCs (hESCs) from human embryos (Thomson et al., Science 282(5391):1145-1147, 1998). However, it had been a long-standing mystery why mESCs and hESCs exhibit distinct differences in terms of self-renewal signaling dependence and cell culture behaviors, such as colony morphology and response to single-cell dissociation, although both of them are pluripotent. Recently, a novel type of pluripotent stem cells were isolated from the postimplantation egg cylinder-stage epiblasts of mouse and rat (Tesar et al., Nature 448(7150):196-199, 2007; Brons et al., Nature 448(7150):191-195, 2007), and were named epiblast stem cells (EpiSCs). Interestingly, mouse EpiSCs (mEpiSCs) closely resemble hESCs in respect of the colony morphology and self-renewal dependence. These results suggest that different pluripotent states exist during mammalian development: the mESC-like state representing the preimplantation ICM and hESC/mEpiSC-like state representing later epiblast cells. This chapter introduces methods of converting mEpiSCs back to mESCs through chemical approaches.


Structural changes in the SL5 and SL6 leader sequences of HIV-1 RNA following interactions with the viral mGag protein.
We previously identified sequences downstream of the SL4 region of HIV-1 RNA that are involved in the recognition of the 5' leader region of HIV-1 RNA by a minimal version of the HIV-1 Gag protein (mGag). These sequences increase the affinity of this interaction, promote Gag multimerization, and enhance formation of an early mGag-RNA complex. Now, we provide protein footprinting results on the +350 to +500 nucleotide region of viral RNA, based on use of different single-stranded and base-paired ribonucleases. Use of the mfold program confirmed the existence of both a stem-loop 5 (SL5), downstream of SL4, and a more complex multi-stem-loop structure (SL6). Footprinting analysis using mGag and single-stranded-specific nucleases showed almost complete protection of the single-stranded region. In contrast, results obtained with RNase V1, a double-stranded-specific nuclease, suggest that the RNA structure is changed upon protein binding, presumably because of formation of novel and longer stems. Furthermore, RNA footprinting, using viral nucleocapsid protein (NC) and RNase VI, indicate a highly double-stranded structure in several regions. These findings show that viral RNA structure is modified by interaction with proteins, and that NC may possess different chaperone activity in the context of the Gag precursor than in its mature form.


Nursing Management in Pediatric Patients Undergoing Chimeric Antigen Receptor T (CAR-T) Cell Therapy: A Systematic Literature Review.
This systematic review aims to describe an overview of the overall care, patient and parent education, staff training, and management of complications from a nursing perspective of pediatric patients undergoing chimeric antigen receptor T (CAR-T) cell infusion in order to provide an updated summary of the approach to the management of these patients. CAR-T cellular therapy represents an innovation within pediatric hematology and oncology used to treat relapse and refractory leukemias, solid tumors, and lymphomas when standard therapy has not worked. However, this type of therapy could lead to the onset of some clinical complications that must be managed appropriately and promptly. Although their use is constantly increasing, the knowledge and resources in the literature are still limited. The review was conducted from January 2022 to July 2022 in PubMed, CINAHL, Scopus, and Cochrane and produced 502 articles. Based on the selection criteria and after removing duplicate articles, 26 articles were included in the study. From these analyzed articles, it was possible to have an overview regarding the management, patient and parent education, staff training, and management of complications from a nursing perspective of pediatric patients undergoing CAR-T cell infusion. The management of hematology-oncology patients undergoing CAR-T cell therapy from a nursing perspective is not simple. We hope this review can be used as a tool to guide nursing staff. In this regard, we have developed a summary table with the actions to be taken in the case of assisting a pediatric patient being treated with CAR-T.


A simple method for eyelid reconstruction with an advancement flap after resection of a minor nevus on the eyelid margin.
We developed a simple and effective method for eyelid reconstruction after resection of a minor nevus on the eyelid margin. With a vertical advancement flap to repair the defect, all patients were satisfied with the cosmetic and functional results of the eyelids, and no significant complications occurred.


Investigation on the occurrence and contamination of multi-mycotoxin in chestnut and jujube (red date).
A rapid and efficient QuEChERS-based preparation method was established for the simultaneous determination of 43 mycotoxins in chestnut and jujube (Chinese date). The contaminants were extracted using acetonitrile and subjected to dispersive solid-phase extraction for further clean-up. Central composite design was conducted to overcome the limitations of conventional optimization methods, and assess the interaction effects between variables and reach the true optimal conditions. Quantitative analysis was performed on UHPLC-MS/MS with the aid of stable isotope internal standards and matrix-matched curves, whereas qualitative identification was carried out by using high-resolution MS based on exact masses and fragmentation patterns. In addition to the mycotoxins that are routinely monitored (like aflatoxins, ochratoxin A, etc.), this study also revealed a non-negligible contamination of zearalenone (56/170), beauvericin (52/170), enniatin B (43/170), and alternariol monomethyl ether (42/170) in chestnut and jujube, especially the chestnut flour.


Bone mass and beyond: risk factors for fractures.
Numerous prospective studies have demonstrated a strong relationship between bone mass and fracture risk. The fact that the bone mass distributions of fracture and nonfracture cases overlap does not necessarily indicate a shortcoming of bone mass, but might instead be due to the sporadic nature of falls and the influence of other fracture risk factors. The recent finding that prevalent fractures are strong predictors of fracture risk, independent of bone mass, suggests (but does not prove) that there may be other, potentially measurable fracture risk factors that complement, and act independently of, bone mass. This paper reviews possible mechanisms by which prevalent fractures might serve as etiologic risk factors, or as surrogate indicators of other risk factors. Potential risk factors other than bone mass and prevalent fractures are also considered. Whether or not etiologic fracture risk factors other than bone mass can be identified, it appears that treatments that influence bone will be most effective if begun early, before bone strength becomes impaired and fractures begin to occur.


Influence of glygerol on ATP and 2,3-DPG levels of human erythrocytes.
Glycerolization of freshly collected human erythrocytes leads to a reduction in ATP levels which return to their original values following deglycerolization. The reduction in ATP levels is largely prevented by pyruvate but not by inosine and glucose, singly or in combination. This implies that the ATP lesion associated with glycerolization reflects mainly a decrease in the NAD/NADH ratio and accordingly a reduced glyceraldehyde-3-phosphate dehydrogenase activity. 2,3-DPG levels were not influenced by glycerolization and deglycerolization. Erythrocytes depleted of ATP in the presence of glycerol can have their ATP levels repleted by either pyruvate or inosine, but require the presence of both compounds for maintenance during a post-rejuvenation incubation period. This indicates that the prolonged presence of glycerol influences both the NAD/NADH ratio and the carbon-containing intermediates of glycolysis. Glycerol did not influence ATP repletion of erythrocytes stored at 4 degrees C for 20 days by inosine in combination with pyruvate, but substantially decreased the repletion of their 2,3-DPG levels.


Deproteination of serum samples for LC-MS/MS analyses by applying magnetic micro-particles.
Investigation of the practicability and performance of a magnetic micro-particle based method for protein depletion of serum samples, preceding the quantitative analysis of small molecules by LC-MS/MS. A commercially available kit including a protein denaturation reagent and functionalized magnetic particles together with a magnetic separator device was tested by addressing the quantification of amiodarone in serum as an exemplary analyte by LC-MS/MS with on-line SPE. A standard method validation protocol was applied. The sample preparation protocol was found to be convenient, straightforward and robust. Validation data characterized the entire analytical method - combining particle-based protein depletion and two-dimensional chromatography - as compatible with the analytical needs regarding selectivity, accuracy (102-106%), linearity (r(2)≥0.99), reproducibility (CV<7%), and control of ion suppression. Since this novel approach of sample preparation does neither require centrifugation nor the technically demanding application of positive or negative pressure, as in conventional solid phase extraction protocols, it seems highly attractive for developing fully automatized preparation systems for LC-MS/MS analyzers.


Cushing's syndrome associated with galactorrhea, amenorrhea, and hypothyroidism: a primary hypothalamic disorder.
A 19-year-old woman presented with a unique constellation of endocrinopathies, including Cushing's disease, post-partum galactorrhea, hypothalamic hypothyroidism and hypothalamic amenorrhea. There was no evidence of granulomatous or neoplastic disease in pituitary or hypothalamus. The potential role of excess glucocorticoids and disturbances in normal hypothalamic regulation of anterior pituitary function in the pathophysiology of this syndrome is discussed.