Safety profiles of methylphenidate, amphetamine, and atomoxetine: analysis of spontaneous reports submitted to the food and drug administration adverse event reporting system.
Background: Methylphenidate, atomoxetine, and Amphetamine are the three most commonly used medications approved by the United States Food and Drug Administration (FDA) for the treatment of attention deficit/hyperactivity disorder (ADHD). However, a comprehensive analysis of their safety profiles across various age groups and genders in real-world contexts has yet to be conducted. In this study, a pharmacovigilance analysis was performed using the FDA Adverse Event Reporting System (FAERS) database to examine differences in adverse events between methylphenidate, atomoxetine, and Amphetamine. Methods: From January 2014 to September 2022, FAERS reports listing "Methylphenidate," "Dexmethylphenidate," "Atomoxetine," "Amphetamine," "Lisdexamfetamine," "Dextroamphetamine," and "Methamphetamine" as primary suspects were analyzed after removing duplicate reports. We used the standardized Medical Dictionary for Regulatory Activities (MedDRA) query generalized search for adverse events at the preferred term level based on case reports. After filtering duplicate reports, disproportionality analysis was used to detect safety signals according to the proportional reporting ratio (PRR). In order to delve into potential safety concerns, we undertook a two-step analysis of the data. Initially, the data was segmented based on age cohorts: 0-5 years, 6-12 years, 13-18 years, and individuals aged ≥19 years. Following this, after partitioning the data into males and females within the 0-18 years age group, and similarly for those aged ≥19 years, further analysis was conducted. Results: The pharmacovigilance analysis uncovered substantial safety signals in the standardized MedDRA queries. Methylphenidate was associated with dyskinesia (PRR = 21.15), myocardial infarction (PRR = 12.32), and hypertension (PRR = 8.95) in children aged 0-5, 6-12, and 13-18 years, respectively, as well as neonatal exposures via breast milk (PRR = 14.10) in adults aged ≥19 years. Atomoxetine was linked to hostility/aggression (PRR = 15.77), taste and smell disorders (PRR = 6.75), and hostility/aggression (PRR = 6.74) in children aged 0-5, 6-12, and 13-18 years, respectively, as well as hostility/aggression (PRR = 14.00) in adults aged ≥19 years. Amphetamine was associated with psychosis and psychotic disorders (PRR = 16.78), hostility/aggression (PRR = 4.39), and Other ischaemic heart disease (PRR = 10.77) in children aged 0-5 years, 6-12 years, and 13-18 years, respectively, and hostility/aggression in adults aged ≥19 years (PRR = 9.16). Significant and noteworthy adverse event signals were also identified at the preferred term level. Specifically, methylphenidate was associated with myocardial infarction, acute myocardial infarction, coronary artery dissection, electrocardiogram QT prolonged, growth retardation, self-destructive behavior, suicidal ideation, and completed suicide. Atomoxetine was linked to electrocardiogram QT prolonged, growth retardation, and tic. Amphetamine was recorded for coronary artery dissection, suicidal ideation, and completed suicide. It was observed that male patients, including both children and adults, showed a more significant and frequent occurrence of adverse events compared to females, particularly in terms of cardiac disorders. The intensity and quantity of adverse event signals were distinctly different between the two genders, with males having a higher number of signals. All detected safety signals were confirmed using signals obtained from the disproportionality analysis. Conclusion: This pharmacovigilance analysis demonstrated significant variations in the safety profiles of methylphenidate, atomoxetine, and Amphetamine across different age groups and between different genders. Following an in-depth analysis of the FAERS database, we discerned prominent safety signals. Notably, the strength of the signals associated with coronary artery dissection induced by methylphenidate and amphetamine, as well as those related to suicide, demand particular attention. Consequently, it remains imperative to persist in monitoring these medications, assessing the associated risks, and carrying out comparative studies particularly geared towards ADHD drugs.


[The effect of the carnitine biosynthesis inhibitor mildronate on the lipid metabolic indices of rats].
The course administration of a carnitine biosynthesis inhibitor mildronate (100 mg/kg, orally, for 10 and 30 days) was shown to increase the rat blood serum concentration of free fatty acids. By the 30th day of the treatment no changes in the rat myocardium contents of free fatty acids, triglycerides and cholesterol were found that along with the prevention of the accumulation of long chain metabolites of fatty acids in the heart under conditions of adrenergic actions indicated the pathogenetically right approach to the treatment of ischemic heart disease with mildronate.


Idiopathic calcium nephrolithiasis.
Calcium nephrolithiasis (CaNL) accounts for more than 70% of all renal stones, and its prevalence has increased in the last decades. Under this definition are included patients passing stones, composed of calcium oxalates and/or calcium phosphates. Current views of the pathogenesis of CaNL are based on the role of metabolic abnormalities which concur to render urines more conducive to crystallization. Therefore, the diagnostic approach is aimed at detecting these abnormalities, and the medical treatment assumes that a decrease in the risk of lithogenesis will result in remission or improvement of recurrences. The workup of the patients with CaNL begins with the analysis of passed stones and X-ray, sonography or other imaging techniques. Eligible patients, that is, both recurrent active stone formers and single-stone formers with individual risk factors, are considered for a metabolic evaluation, by which a number of blood and urine parameters are measured and others calculated. These include estimates of urine state of saturation with calcium and uric acid salts, net gastrointestinal alkali absorption, renal threshold of phosphate and other renal clearances and net acid and total nitrogen excretions. Basically, this screening is informative on renal function, metabolic abnormalities and their pathophysiology, risk of stone formation and dietary habits. During treatment it gives information about patient compliance and adverse effects of therapy. The cost of a comprehensive screening in Piedmont is 192,000 ITL (100 Euro) and rises to 300,000 ITL (154 Euro) if hormones and hydroxyproline are measured. In individual patients second- and third-level studies are performed, in order to detect systemic diseases which account for about 20% of CaNL in our series. Cost-to-benefit analysis has shown that the medical procedures for CaNL yield considerable saving in terms of difference between expenditure for drugs and testing and reduction of stone events. However, the current workup cannot be considered exhaustive, because misleading events may hamper the relation between laboratory findings and clinical outcome, and factors other than urine composition have appeared on the scenario of nephrolithiasis. These represent our challenge for the third millennium.


[Extracapsular cataract extraction for highly myopic patients].
Extracapsular cataract extraction was performed on 54 cataract cases with high myopia. During a follow-up of 5-18 months, the corrected visual acuity was 0.1-0.2 in 18 cases (33%), 0.3-0.5 in 16 cases (30%), 0.6-0.9 in 8 cases (15%), and 1.0 or over in 7 cases (13%). The major complications included intraoperative posterior capsular tear in 3 cases, secondary glaucoma due to residual cortex in 2 cases, posterior capsular opacity in 7 cases, cystoid macular edema in 1 case, and retinal detachment in 1 case. The study indicated that ECCE was safe and desirable for highly myopic patients.


The reaction of fully reduced cytochrome c oxidase with oxygen studied by flow-flash spectrophotometry at room temperature. Evidence for new pathways of electron transfer.
Absorption changes during the O2 reaction of reduced bovine cytochrome c oxidase were investigated by the rapid-reaction technique of flow-flash spectrophotometry in the Soret, visible and near-i.r. spectral regions. New features in the time courses of absorption change were observed relative to the earlier findings reported by Greenwood & Gibson [(1967) J. Biol. Chem. 242, 1782-1787]. These new features arise in the Soret and near-i.r. regions and allow the reaction to be described at all wavelengths as a composite of three exponential processes. There is a rapid O2-sensitive phase detectable in the Soret and visible region. The second phase has a rate that is somewhat less dependent on O2 concentration than is the fastest phase rate and is detectable in all three spectral regions. The rate of the third phase is almost independent of the O2 concentration and is also detectable in all spectral regions. Analysis of the three phases gives their rates and absorption amplitudes. The fast phase reaches a rate of 2.5 X 10(4) s-1 at the highest O2 concentration available at 20 degrees C, whereas the phase of intermediate rate is limited at a value of 7 X 10(3) s-1 and the slow phase rate is limited at 700 s-1. The ratios of the kinetic difference spectra for the fast phase and the slow phase do not correspond to the spectra of the individual haem centres. A branched mechanism is advanced that is able to reconcile the kinetic and static difference spectra. This mechanism suggests that some of the cytochrome a is oxidized along with cytochrome a3 in the initial O2-sensitive phase. In addition, the model requires that CuA is oxidized heterogeneously. This fits with the complex time course of oxidation observed at 830 nm while retaining CuA as virtually the sole contributor to absorbance at this wavelength.


Processing of the encephalomyocarditis virus capsid precursor protein studied in rabbit reticulocyte lysates incubated with N-formyl-[35S]methionine-tRNAfMet.
Translation of encephalomyocarditis virus RNA in rabbit reticulocyte lysates in the presence of N-formyl-[(35)S]methionine-tRNA(f) (Met) revealed that a small polypeptide is cleaved from the N-terminus of the capsid protein precursor, preA, by virus-coded protease activity. Therefore, this N-terminal segment comprising the translation initiation site is not conserved in any of the mature capsid proteins.


Assessing Time of Full Renal Recovery Following Minimally Invasive Partial Nephrectomy.
To assess renal function in the operated kidney at different time points post partial nephrectomy (PN) and establish the time in which optimal recovery occurs. Recovery of renal function post-PN has received significant attention. However, the optimal time to determine full recovery has not been clearly established. Renal function following minimally invasive (laparoscopic and robotic) PNs performed between 2002 and 2015 was reviewed. Patients included in this study had renal function assessed preoperatively as well as 3 days, 6-12 weeks, and 1 year post-PN, using a combination of estimated glomerular filtration rate (eGFR) from serum creatinine and relative renal uptake (RRU) from Tc99m-MAG3 renal scintigraphy. Together, eGFR and RRU provide the ipsilateral renal function (IRF) of the operated organ. At 6-12 weeks postoperatively, percent preserved eGFR, RRU, and IRF (relative to preoperative baselines) were 92.1%, 83.3%, and 77.4% respectively. %IRF at 6-12 weeks was significantly improved from %IRF at 3 days postoperatively, but did not differ significantly from 1 year postoperatively. Furthermore, 89% of patients had RRU values at 6-12 weeks which differed by less than 5% from RRU values at 1 year. Our data suggest that renal function recovery at 6-12 weeks was equivalent to long-term recovery at 1 year in the majority of post-PN patients. This has important implications for post-PN follow-up, particularly in assessing the functional outcomes utilizing novel minimally invasive PN strategies, as well as in planning staged procedures for bilateral synchronous renal masses.


Interactions of host APOBEC3 restriction factors with HIV-1 in vivo: implications for therapeutics.
Restriction factors are natural cellular proteins that defend individual cells from viral infection. These factors include the APOBEC3 family of DNA cytidine deaminases, which restrict the infectivity of HIV-1 by hypermutating viral cDNA and inhibiting reverse transcription and integration. HIV-1 thwarts this restriction activity through its accessory protein virion infectivity factor (Vif), which uses multiple mechanisms to prevent APOBEC3 proteins such as APOBEC3G and APOBEC3F from entering viral particles. Here, we review the basic biology of the interactions between human APOBEC3 proteins and HIV-1 Vif. We also summarise, for the first time, current clinical data on the in vivo effects of APOBEC3 proteins, and survey strategies and progress towards developing therapeutics aimed at the APOBEC3-Vif axis.


Charting a roadmap for heart failure biomarker studies.
Heart failure is a syndrome with a pathophysiological basis that can be traced to dysfunction in several interconnected molecular pathways. Identification of biomarkers of heart failure that allow measurement of the disease on a molecular level has resulted in enthusiasm for their use in prognostication and selection of appropriate therapies. However, despite considerable amounts of information available on numerous biomarkers, inconsistent research methodologies and lack of clinical correlations have made bench-to-bedside translations rare and left the literature with countless publications of varied quality. There is a need for a systematic and collaborative approach aimed at definitively studying the clinical benefits of novel biomarkers. In this review, on the basis of input from academia, industry, and governmental agencies, we propose a systematized approach based on adherence to specific quality measures for studies looking to augment current prediction model or use biomarkers to tailor therapeutics. We suggest that study quality, rather than results, should determine publication and propose a system for grading biomarker studies. We outline the need for collaboration between clinical investigators and statisticians to introduce more advanced statistical methodologies into the field of biomarkers that would allow for data from a large number of variables to be distilled into clinically actionable information. Lastly, we propose the creation of a heart failure biomarker consortium that would allow for a comprehensive list of biomarkers to be concomitantly analyzed in a pooled sample of randomized clinical trials and hypotheses to be generated for testing in biomarker-guided trials. Such a consortium could collaborate in sharing samples to identify biomarkers, undertake meta-analyses on completed trials, and spearhead clinical trials to test the clinical utility of new biomarkers.


Contrast media and pain in patients with acute ureteral stone obstruction. A comparative study with iohexol and metrizoate.
A randomized study was conducted in 43 patients who were in pain due to acute ureteral obstruction. Emergency urography was performed in all patients, using either a low osmolar non-ionic (iohexol) or a high osmolar ionic (metrizoate) contrast medium. Increase of pain following injection of contrast media was found in 56 percent of all patients. Increase of pain occurred with both contrast media without any difference between the degree of pain nor the number of patients who experienced an increase of pain. Delayed excretion was considered the only reliable indicator of the degree of obstruction in the present study. Nineteen (68%) of the 28 patients with a delayed excretion greater than 10 min experienced increased pain while the incidence of pain increase was significantly lower (33%) in patients without that sign of ureteral obstruction (p less than 0.05). The increase of pain was not associated with a simultaneous increase of the mean arterial blood pressure.


Human immunodefeciency virus associated cryptococcal meningitis at a tertiary care centre: diagnostic tools and antifungal susceptibility testing.
Cryptococcal meningitis has emerged as a leading cause of the infectious morbidity and mortality in HIV sero-reactive subjects and it is the second most common cause of the opportunistic neuroinfections in it. As this is a indistinguishable from other causes of meningitis, its early diagnosis is the key to the therapeutic success. This study was undertaken to know the incidence of Cryptococcal meningitis in HIV sero-reactive individuals and to assess the role of the microbiological parameters in its specific diagnosis, with a perspective of evaluating the anti-fungal resistance. A total of 66 CSF samples from suspected cases of meningoencephalitis were subjected to standard microbiological procedures. The Cryptococcal isolates were identified by microscopy, the cultural characteristics, melanin production on Niger Seed agar, urea hydrolysis, the Nitrate assimilation test and by capsular antigen detection by latex agglutination. The Cryptoccal isolates were further biotyped by using Canavanine-Glycine-Bromothymol blue agar. The Minimum Inhibitory Concentrations (MIC) of Amphotericin B and Fluconazole for the isolates were detected. The incidence of Cryptococcal meningitis in our study group was 18.2% (12/66). The Cryptococcal antigen was detected in all the 12 cases, whereas microscopy was positive only in 9 cases and Cryptococcus was isolated by culture in 10 cases. All the isolates were sensitive to Amphotericin B and 90% of the isolates were sensitive to Fluconazole. The CD4counts ranged between 22-138 cells /μl. A high incidence of Cryptococcal meningitis in HIV sero-reactive subjects necessitates the importance of a precise and an early microbiological diagnosis for better management of such subjects. Due to the growing concern of emerging drug resistance, the testing for the anti-fungal susceptibility has to be encouraged in all the cases.


Human absorption and metabolism of oleuropein and hydroxytyrosol ingested as olive (Olea europaea L.) leaf extract.
Phenolic compounds derived from the olive plant (Olea europaea L.), particularly hydroxytyrosol and oleuropein, have many beneficial effects in vitro. Olive leaves are the richest source of olive phenolic compounds, and olive leaf extract (OLE) is now a popular nutraceutical taken either as liquid or capsules. To quantify the bioavailability and metabolism of oleuropein and hydroxytyrosol when taken as OLE, nine volunteers (five males) aged 42.8 ± 7.4 years were randomized to receive either capsulated or liquid OLE as a single lower (51.1 mg oleuropein, 9.7 mg hydroxytyrosol) or higher (76.6 mg oleuropein, 14.5 mg hydroxytyrosol) dose, and then the opposite strength (but same formulation) a week later. Plasma and urine samples were collected at fixed intervals for 24 h post-ingestion. Phenolic content was analyzed by LC-ESI-MS/MS. Conjugated metabolites of hydroxytyrosol were the primary metabolites recovered in plasma and urine after OLE ingestion. Peak oleuropein concentrations in plasma were greater following ingestion of liquid than capsule preparations (0.47 versus 2.74 ng/mL; p = 0.004), but no such effect was observed for peak concentrations of conjugated (sulfated and glucuronidated) hydroxytyrosol (p = 0.94). However, the latter peak was reached earlier with liquid preparation (93 versus 64 min; p = 0.031). There was a gender effect on the bioavailability of phenolic compounds, with males displaying greater plasma area under the curve for conjugated hydroxytyrosol (11,600 versus 2550 ng/mL; p = 0.048). All conjugated hydroxytyrosol metabolites were recovered in the urine within 8 h. There was wide inter-individual variation. OLE effectively delivers oleuropein and hydroxytrosol metabolites to plasma in humans.


Thoracotomy and thoracoscopy: postoperative pulmonary function, pain and chest wall complaints.
Two different surgical accesses combined with standard pain management procedures are compared regarding early and intermediate pulmonary function and pain relief. In a prospective study, 15 consecutive patients undergoing video-thoracoscopy for pulmonary wedge resection (group 1) were matched to 15 patients undergoing standard postero-lateral thoracotomy for lobectomy (group 2) according to age, gender and preoperative pulmonary function. Postoperative pain control consisted of patient controlled analgesia in group 1 and epidural analgesia in group 2. Pain intensity was scored from 0-4. The predicted postoperative pulmonary function (FVC and FEV 1) after lobectomies was calculated from the preoperative value according to the extent of resection. A clinical measurement was obtained after a mean follow-up time of 4.2 months. The ratios of postoperative measured to predicted values of FVC and FEV1 for group 1 compared with group 2 were 0.64 +/- 0.15 and 0.65 +/- 0.14 compared with 0.60 +/- 0.19 and 0.59 +/- 0.13, resp. (both n.s.) at the first day postoperative; 0.92 +/- 0.18 and 0.95 /- 0.17 compared with 0.76 +/- 0.20 (P < 0.05) and 0.83 +/- 0.23 (n.s.), resp. at hospital discharge; 0.98 +/- 0.10 and 0.94 +/- 0.14 compared with 1.01 +/- 0.17 (n.s.) and 1.10 +/- 0.17 (P < 0.05), resp. at follow-up. Pain intensity score one day after surgery ranged from 0.4 (resting position) to 1.6 (coughing) for group 1, and from 0.3 to 1.2 for group 2. Thirty-six percent of the thoracoscopy patients and 33% of the thoracotomy group complained of persistent pain or discomfort on the site of the operation after 3-18 months. Post-thoracotomy pain can be effectively controlled with epidural analgesia and pain intensity is no higher than in patients after thoracoscopy who are managed with patient controlled analgesia. FVC is slightly more decreased after thoracotomy during the early postoperative period. FVC and FEV 1 approach the predicted values after four months in both groups. The rate of persistent pain is similar after thoracoscopy and thoracotomy.


Butorphanol tartrate: an intravenous analgesic for outpatient surgery.
Many surgical procedures in otolaryngology, particularly those in the areas of facial plastic surgery, are best performed under a local anesthetic. The majority of these procedures may be done on an outpatient basis and require an intravenous analgesic of some form. This analgesic must be safe, predictable, easy to administer, have a rapid onset, and provide good amnesia. A short recovery period is imperative. Diazepam has been widely used in the outpatient setting, since it generally fulfills the requirements listed. However, the recovery time is often prolonged and unpleasant for the patient. Butorphanol tartrate, a synthetic narcotic, provides rapid analgesia in an intravenous dose, fulfills the other requirements for an analgesic agent suitable for outpatient use, and has a relatively short duration. Butorphanol tartrate has been used in an intravenous drip form for outpatient surgical procedures for the past 18 months. Its use in 400 cases representing a broad spectrum of facial plastic procedures has been closely monitored in both the operative and postoperative periods and the results tabulated. We have found butorphanol tartrate to be an excellent agent for local anesthetic procedures in the outpatient setting.


Yng1p modulates the activity of Sas3p as a component of the yeast NuA3 Hhistone acetyltransferase complex.
The mammalian ING1 gene encodes a tumor suppressor required for the function of p53. In this study we report a novel function for YNG1, a yeast homolog of ING1. Yng1p is a stable component of the NuA3 histone acetyltransferase complex, which contains Sas3p, the yeast homolog of the mammalian MOZ proto-oncogene product, as its catalytic subunit. Yng1p is required for NuA3 function in vivo but surprisingly is not required for the integrity of the complex. Instead, we find that Yng1p mediates the interaction of Sas3p with nucleosomes and is thus required for the ability of NuA3 to modify histone tails. These data, and the observations that other ING1 homologs are found in additional yeast complexes that posttranslationally modify histones, suggest that members of the ING1 class of proteins may have broad roles in enhancing or modifying the activities of chromatin-modifying complexes, thereby regulating their activities in transcription control.


Diminished Returns in Europe: Socioeconomic Status and Ethno-Racial Health Disparities Across 30 Countries in the European Social Survey.
Ethnic and racial minorities in many countries experience worse relative health outcomes and earlier mortality compared to national averages or outcomes of the majority population. Although socioeconomic status often contributes to a portion of ethno-racial health disparities, there are many unanswered questions about the relationship between socioeconomic status and ethno-racial health disparities across contexts. Recent scholarship in the USA has found support for a "diminished returns" effect in which the socioeconomic health gradient is systematically smaller for marginalized groups, yet it is unclear whether this pattern exists in other national contexts. This study tests the interaction between socioeconomic status and ethno-racial minority status in 30 countries across six waves of the European Social Survey. The results include evidence of the diminished returns pattern, particularly for populations with origins in Sub-Saharan Africa and the Middle East. Multilevel mixed-effects models find variation across countries in the interaction between socioeconomic status and ethno-racial minority status. The findings suggest racism and socioeconomic status interact to affect health and health disparities in multiple contexts and highlight the importance of cross-national comparison to further understand variation across countries.


Effects of adrenocorticotropic hormone on low density lipoprotein receptors of human fetal adrenal tissue.
In the present investigation, the mechanism(s) whereby ACTH stimulates low density lipoprotein (LDL) metabolism in human fetal adrenal was evaluated. Plasma membrane fractions were prepared from fetal adrenal tissue fragments incubated in lipoprotein-poor serum with or without ACTH, and the binding of [125I]iodo-LDL to such membrane fractions was examined. The mean specific binding capacity for [125I]iodo-LDL by membrane fractions prepared from four separate fresh human fetal adrenal glands was 1370 +/- 168 ng mg-1 protein (mean +/- SE), and the concentration of [125I]iodo-LDL producing half-maximal binding was 20.8 +/- 1.2 ng ml-1. Thus, the presence of high affinity, low capacity binding sites for LDL in human fetal adrenal tissue was confirmed. When human fetal adrenal tissue was maintained in organ culture for 2 days in medium containing lipoprotein-poor serum in the absence of ACTH, and plasma membrane fractions were subsequently prepared, the binding capacity for LDL in such membrane fractions was the same as or slightly greater than that in membrane fractions prepared from fresh tissue. When ACTH was present in the culture medium, the binding capacity for LDL was doubled compared to that in membrane fractions prepared from tissues incubated in the absence of ACTH. The rate of [125I]iodo-LDL degradation by human fetal adrenal tissue maintained in medium containing ACTH was also twice that of tissue maintained in the absence of ACTH. These results demonstrate that ACTH causes an increase in the number of LDL-binding sites in human fetal adrenal tissue in vitro. This is one mechanism whereby ACTH stimulates LDL metabolism in this tissue.


Deadly dozen: dealing with the 12 types of thoracic injuries.
Although most thoracic trauma may be treated non-operatively, major thoracic trauma accounts for 25% of trauma deaths. Except for provision of a definitive airway and/or relief of a tension pneumothorax with a needle decompression, the vast majority of thoracic trauma is best served with "load and go," high-flow oxygen, placement of an IV line and administration of crystalloid solutions as the clinical scenario would indicate. Understanding the mechanism of injury is helpful in establishing both prehospital and in-hospital management priorities. Patients who sustain a single penetrating wound to the chest have the best survivability after a resuscitative thoracotomy. Practicing chest assessment skills is vital to being a good prehospital provider. Ultrasound, NIRS tissue oxygenation and telemedicine will likely become more commonly employed as prehospital monitoring options. PEEP, or "over bagging," may exacerbate a simple or open pneumothorax, converting it to a tension pneumothorax.


Protein-bound polysaccharide-K induces IL-1β via TLR2 and NLRP3 inflammasome activation.
Inflammasome activation has been shown to regulate both innate and adaptive immune responses. It is important to investigate whether immune-enhancing natural products can also activate inflammasome. The current study examined the potential of protein-bound polysaccharide-K (PSK), a hot water extract from Trametes versicolor, to activate inflammasome. Using THP-1 cells, we have demonstrated that PSK induces both pro-IL-1β and mature IL-1β in THP-1 cells in a caspase 1- and NLRP3-dependent manner. PSK also induces IL-1β and IL-18 in human PBMC. Cathepsin B is required for PSK-induced inflammasome activation as CA-074-Me, a cathepsin B inhibitor, significantly decreased PSK-induced IL-1β. PSK induces NLRP3 at both mRNA and protein level. Comparison of PSK-induced IL-1β in bone marrow-derived macrophages from wild type C57BL/6 mice, TLR2(-/-), P2X7R(-/-) and NLRP3(-/-) mice demonstrated that PSK-induced IL-1β is dependent on both TLR2 and NLRP3. P2X7R is not required for PSK-induced inflammasome activation, but enhances PSK-induced caspase-1 activation and IL-1β induction. Altogether, these results demonstrated that PSK induces inflammasome activation and production of IL-1β in a TLR2- and NLRP3-dependent mechanism. These results provide novel insights into the mechanisms of the immune modulatory effects of PSK.


Production of sugars from wood using high-pressure hydrogen chloride.
Saturating wood particles with HCl gas under pressure was found to be an effective pretreatment prior to subjecting wood to dilute acid hydrolysis. Pretreament is necessary to release sugars from wood because of the tight lattice structure of cellulose. The HCl gas makes the cellulose more susceptible to subsequent acid hydrolysis and the glucose yield is doubled when dilute acid hydrolysis is preceded by HCl saturation at high pressure. The saturation was most effectively performed in a fluidized bed reactor, with pure HCl gas fluidizing an equal volume of ground wood plus inert particles. The fluidized bed effectively dissipated the large amount of heat released upon HCl absorption into the wood. Batch reaction times of 1 h at 315 psia gave glucose yields of 80 degrees and xylose yields of 95 degrees after dilute acid hydrolysis. A model was developed which proposed gas diffusing through the solid as limiting the reaction rate and this was found to effectively describe the HCl-wood reaction in the fluidized bed. The HCl was found to form a stable adduct with the lignin residue in the wood, in a ratio of 3.33 mole of lignin monomer. The adduct was broken upon the addition of water.


[Effects of the exposure to polycyclic aromatic hydrocarbons or toluene on thiobarbituric acid reactive substance level in elementary school children and the elderly in a rural area].
Polycyclic aromatic hydrocarbons (PAH) and toluene have been reported to induce reactive oxygen species and oxidative stress. This study was performed to investigate the effects of low level exposure to PAHs or toluene on the lipid peroxidation level in elementary school children and the elderly in a rural area. Forty seven elementary school children and 40 elderly people who were living in a rural area and not occupationally exposed to PAH or toluene were the subjects of this study. Information about active or passive smoking and diet was obtained using a self-administered questionnaire. The urinary 1-hydroxypyrene (1-OHP), 2-naphthol, hippuric acid and thiobarbituric acid reactive substance (TBARS) concentrations were measured, and these values were corrected with the urinary creatinine concentration. In school children, the geometric means of the urinary 1-OHP, 2-naphthol, hippuric acid and TBARS levels were 0.02 micromol/mol creatinine, 0.47 micromol/mol creatinine, 0.14 g/g creatinine and 0.95 micromol/g creatinine, respectively. Those values for the elderly were 0.07 micromol/mol creatinine, 1.87 micromol/mol creatinine, 0.11 g/g creatinine and 1.18 micro mol/g creatinine, respectively. The mean levels of urinary 1-OHP, 2-naphthol and TBARS were significantly higher in the elderly subjects than in the children. The urinary TBARS level was not correlated with the urinary 1-OHP, 2-naphthol and hippuric acid, but they were correlated with the age of the subjects. These results suggest that low level inhalation exposure to PAH or toluene does not markedly increase lipid peroxidation, and age is a significant determinant of lipid peroxidation.


Low doses of CPS49 and flavopiridol combination as potential treatment for advanced prostate cancer.
Prostate cancer (PCa) still ranks as the second most frequently diagnosed cancer and metastatic castration resistant prostate cancer (CRPC) is a foremost cause of men cancer death around the world. The aim of this work was to investigate the selectivity and efficacy of new drug combinations for CRPC. We combined three compounds: paclitaxel (PTX: taxane that inhibits microtubule polymerization); 2-(2,4-Difluoro-phenyl)-4,5,6,7-tetrafluoro-1H-isoindole- 1,3(2H)-dione (CPS49; redox-reactive thalidomide analog with anti-angiogenic properties) and flavopiridol (flavo: semisynthetic flavonoid that inhibits cyclin dependent kinases). We assessed CPS49-flavo or -PTX combinations cytotoxicity in a panel of PCa cell lines and PC3 xenografts. We found that CPS49 enhanced flavo or PTX cytotoxicity in human PCa cell lines while showed resistance in a non-tumor cell line. Furthermore, xenografts generated by inoculation of human prostate carcinoma PC3 cells in nu/nu mice showed that CPS49/flavo administration reduced tumor growth both after 2 weeks of co-treatment and after 1 week of pretreatment with a low dose of flavo followed by 2 weeks of co-treatment. PTX and CPS49 combination did not significantly reduce tumor growth in PC3 xenografts. Histological analysis of xenograft PC3 tumor samples from CPS49/flavo combination showed extensive areas of necrosis induced by the treatment. RT-qPCR array containing 23 genes from PC3 cells or PC3 xenografts exposed to CPS49/flavo combination showed that this treatment shut down the expression of several genes involved in adhesion, migration or invasion. In summary, the antitumor activity of CPS49 or flavopiridol was improved by the combination of these compounds and using half dose of that previously reported. Hence, CPS49-flavo combination is a promising new alternative for PCa therapy.


The Significance of Oxidized Low-Density Lipoprotein in Body Fluids as a Marker Related to Diseased Conditions.
Oxidatively modified low-density lipoprotein (oxLDL) is known to be involved in various diseases, including cardiovascular diseases. The presence of oxLDL in the human circulatory system and in atherosclerotic lesions has been demonstrated using monoclonal antibodies. Studies have shown the significance of circulating oxLDL in various systemic diseases, including acute myocardial infarction and diabetic mellitus. Several different enzyme-linked immunosorbent assay (ELISA) procedures to measure oxLDL were utilized. Evidence has been accumulating that reveals changes in oxLDL levels under certain pathological conditions. Since oxLDL concentration tends to correlate with low-density lipoprotein (LDL)-cholesterol, the ratio of ox-LDL and LDL rather than oxLDL concentration alone has also been focused. In addition to circulating plasma, LDL and oxLDL are found in gingival crevicular fluid (GCF), where the ratio of oxLDL to LDL in GCF is much higher than in plasma. LDL and oxLDL levels in GCF show an increase in diabetic patients and periodontal patients, suggesting that GCF might be useful in examining systemic conditions. GCF oxLDL increased when the teeth were affected by periodontitis. It is likely that oxLDL levels in plasma and GCF could reflect oxidative stress and transfer efficacy in the circulatory system.


Response of substances co-expressed in hypothalamic magnocellular neurons to osmotic challenges in normal and Brattleboro rats.
The intention of this review is to emphasize the current knowledge about the extent and importance of the substances co-localized with magnocellular arginine vasopressin (AVP) and oxytocin (OXY) as potential candidates for the gradual clarification of their actual role in the regulation of hydromineral homeostasis. Maintenance of the body hydromineral balance depends on the coordinated action of principal biologically active compounds, AVP and OXY, synthesized in the hypothalamic supraoptic and paraventricular nuclei. However, on the regulation of water-salt balance, other substances, co-localized with the principal neuropetides, participate. These can be classified as (1) peptides co-localized with AVP or OXY with unambiguous osmotic function, including angiotensin II, apelin, corticotropin releasing hormone, and galanin and (2) peptides co-localized with AVP or OXY with an unknown role in osmotic regulation, including cholecystokinin, chromogranin/secretogranin, dynorphin, endothelin-1, enkephalin, ferritin protein, interleukin 6, kininogen, neurokinin B, neuropeptide Y, vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, TAFA5 protein, thyrotropin releasing hormone, tyrosine hydroxylase, and urocortin. In this brief review, also the responses of these substances to different hyperosmotic and hypoosmotic challenges are pointed out. Based on the literature data published recently, the functional implication of the majority of co-localized substances is still better understood in non-osmotic than osmotic functional circuits. Brattleboro strain of rats that does not express functional vasopressin was also included in this review. These animals suffer from chronic hypernatremia and hyperosmolality, accompanied by sustained increase in OXY mRNA in PVN and SON and OXY levels in plasma. They represent an important model of animals with constantly sustained osmolality, which in the future, will be utilizable for revealing the physiological importance of biologically active substances co-expressed with AVP and OXY, involved in the regulation of plasma osmolality.


Serum Neuregulin-1beta as a Biomarker of Cardiovascular Fitness.
PURPOSE: Neuregulins (NRG) are growth factors that bind to receptors of the erbB family, and are known to mediate a number of processes involved in diverse tissues. Neuregulin-1beta is expressed in skeletal muscle and is activated by exercise. We hypothesized that NRG-1beta might circulate in the bloodstream and increase as a consequence of physical activity. A study was conducted in healthy subjects to determine if NRG-1beta is immunodetectable in human serum, and if so whether levels relate acutely or chronically to exercise. METHODS: Nine healthy men underwent three bouts of exercise of varying degrees of intensity on a bicycle ergometer over a period of three weeks. Cardio-respiratory fitness was determined by measurement of maximal oxygen uptake (VO(2)max). Serum was sampled prior to and immediately after each session (up to 30 minutes post) and serum NRG-1beta was quantified utilizing an indirect sandwich ELISA assay developed in our lab. RESULTS: Across subjects, mean serum NRG-1beta levels ranged from 32 ng/mL to 473 ng/mL. Individual subjects showed relatively stable levels during the study period that did not change acutely after exercise. Serum NRG-1beta demonstrated a positive correlation with VO(2)max (r2=0.49, p =.044). CONCLUSIONS: These preliminary observations suggest that at least in healthy men, serum NRG-1beta is an indicator of cardio-respiratory fitness and does not change acutely with exercise.


Free-zone electrophoresis in glass capillaries.
A simple theory of zone electrophoresis in open-tubular capillaries is developed. According to this theory, to achieve the highest resolution of zones, tubes with as small an inside diameter as possible should be used in combination with as high an applied voltage as feasible. To test this approach, we performed electrophoresis in glass capillaries with an internal diameter of 75 micron and a length of 100 cm. A special fluorescence detector was used to detect fluorescent zones while they migrated inside the capillary. With the application of 30 kV potentials to this system, rapid and efficient separations of amino acids, peptides, and urinary amines were demonstrated. In all cases fluorescent derivatives were necessary for detection. Preliminary results are encouraging, and with further development of sensitive detection devices, applications in clinical analyses may be feasible.


Non-alcoholic fatty liver disease: An early mediator predicting metabolic syndrome in obese children?
To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome, and if liver B-ultrasound can be used for its diagnosis. We classified 861 obese children (6-16 years old) into three subgroups: group 0 (normal liver in ultrasound and normal transaminases); group 1 (fatty liver in ultrasound and normal transaminases); and group 2 (fatty liver in ultrasound and elevated transaminases). We measured the body mass index, waist and hip circumference, blood pressure, fasting blood glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), whole-body insulin sensitivity index (WBISI), lipid profile and transaminases in all the participants. The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination. Among the 861 obese children, 587 (68.18%) were classified as having NAFLD, and 221 (25.67%) as having MS. The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587), which was much higher than that in non-NAFLD group (group 0, 12.04%) (P < 0.01). There were significantly higher incidences concerning every component of MS in group 2 compared with group 0 (P < 0.05). The incidence of NAFLD in MS patients was 84.61% (187/221), which was significantly higher than that of hypertension (57.46%, 127/221) and glucose metabolic anomalies (22.62%, 50/221), and almost equal to the prevalence of dyslipidemia (89.14%, 197/221). Based on the B-ultrasound scales, the presence of moderate and severe liver fatty infiltration carried a high risk of hypertension [odds ratio (OR): 2.18, 95% confidence interval (95% CI): 1.27-3.75], dyslipidemia (OR: 7.99, 95% CI: 4.34-14.73), impaired fasting glucose (OR: 3.65, 95% CI: 1.04-12.85), and whole MS (OR: 3.77; 95% CI: 1.90-7.47, P < 0.01). The state of insulin resistance (calculated by HOMA-IR and WBISI) deteriorated as the degree of fatty infiltration increased. NAFLD is not only a liver disease, but also an early mediator that reflects metabolic disorder, and liver B-ultrasound can be a useful tool for MS screening.


Applying service-learning through a community-academic partnership: depression screening at a federally funded community health center.
Increasingly, health care facilities worldwide, particularly those that comprise the safety-net, are finding themselves understaffed and challenged to meet patients' needs. Identifying additional sources of support and resources is critical for facilities to be able to sustain current and develop new initiatives to improve patients' health. We present one community health center's reliance on a partnership with an academic medical/nursing institution to develop and initiate a depression screening and treatment project. Incorporating students to help implement or pilot a needed clinical service for a high prevalence condition presents significant rewards as well as challenges. Nevertheless, an academic-community partnership has the potential to initiate systems change at the clinical level. Using a service-learning modality, medical and nursing students worked with health center providers to initiate a pilot depression screening and treatment program based on the chronic disease model. Implementation of this initiative succeeded in poising the health center for participation in a large, federally supported collaborative on depression in primary care. While students gained insight into some of the challenges faced by safety net providers and their patients, discontinuity in student availability led to uneven pacing in project implementation. Curricula that employ a service-learning framework can enable health care facilities world-wide to gain additional resources for needed initiatives. Students' learning experiences can provide an excellent mutually beneficial opportunity as a "jumpstart" for new evidence-based clinical initiatives and demonstration projects. Such programs can help meet the needs of patients while enhancing students' education. However, students can neither make up for staffing shortages nor be expected to maintain programs. In order to be successful for the long term, service-learning projects must skirt the pitfalls of the inherent logistical incompatibilities e.g. schedules and length of commitment, between academic institutions and health care facilities.


Body Image, Food Addiction, Depression, and Body Mass Index in University Students.
The relationship between body image, depression, food addiction and body mass index (BMI) and differences in these variables due to gender and field of education have not been studied extensively. This study was conducted on a total of 793 university students (20.19 ± 1.90 years). The Beck Depression Inventory, Yale Food Addiction, and Body Image Scale were used. It was determined that body image scores of females and individuals enrolled in health sciences programs were lower compared to those of males and those enrolled in the social sciences. There was a negative relationship between body image and depression and food addiction scores. There was a positive relationship between food addiction and depression scores, in addition to a positive relationship between food addiction and BMI.


Improving on transfer entropy-based network reconstruction using time-delays: Approach and validation.
Transfer entropy constitutes a viable model-free tool to infer causal relationships between two dynamical systems from their time-series. In an information-theoretic sense, transfer entropy associates a cause-and-effect relationship with directed information transfer, such that one may improve the prediction of the future of a dynamical system from the history of another system. Recent studies have proposed the use of transfer entropy to reconstruct networks, but the inherent dyadic nature of this metric challenges the development of a robust approach that can discriminate direct from indirect interactions between nodes. In this paper, we seek to fill this methodological gap through the cogent integration of time-delays in the transfer entropy computation. By recognizing that information transfer in the network is bound by a finite speed, we relate the value of the time-delayed transfer entropy between two nodes to the number of walks between them. Upon this premise, we lay out the foundation of an alternative framework for network reconstruction, which we illustrate through closed-form results on three-node networks and numerically validate on larger networks, using examples of Boolean models and chaotic maps.


Addition and expansion theorems for complete orthonormal sets of exponential-type orbitals in coordinate and momentum representations.
Analytical properties of new complete orthonormal sets of Psi(alpha) exponential-type orbitals (Psi(alpha)-ETOs where alpha=1, 0, -1, -2, em leader ), introduced by the author as finite linear combinations of Slater-type orbitals (STOs), are studied. Addition and expansion theorems for Psi(alpha)-ETOs are obtained in both coordinate and momentum representations. Using expressions of Psi(alpha)-ETOs in terms of STOs, the new methods are suggested to calculate multicenter multielectron integrals over STOs.


Genome-wide identification of Diacylglycerol Acyltransferases (DGAT) family genes influencing Milk production in Buffalo.
The diacylglycerol acyltransferases (DGAT) are a vital group of enzymes in catalyzing triacylglycerol biosynthesis. DGAT genes like DGAT1 and DGAT2, have been identified as two functional candidate genes affecting milk production traits, especially for fat content in milk. Buffalo milk is famous for its excellent quality, which is rich in fat and protein content. Therefore, this study aimed to characterize DGAT family genes in buffalo and to find candidate markers or DGAT genes influencing lactation performance. We performed a genome-wide study and identified eight DGAT genes in buffalo. All the DGAT genes classified into two distinct clades (DGAT1 and DGAT2 subfamily) based on their phylogenetic relationships and structural features. Chromosome localization displayed eight buffalo DGAT genes distributed on five chromosomes. Collinearity analysis revealed that the DGAT family genes were extensive homologous between buffalo and cattle. Afterward, we discovered genetic variants loci within the genomic regions that DGAT genes located in buffalo. Seven haplotype blocks were constructed and were associated with buffalo milk production traits. Single marker association analyses revealed four most significant single nucleotide polymorphisms (SNPs) mainly affecting milk protein percentage or milk fat yield in buffalo. Genes functional analysis indicated that these DGAT family genes could influence lactation performance in the mammal through regulating lipid metabolism. In the present study, we performed a comprehensive analysis for the DGAT family genes in buffalo, which including identification, structural characterization, phylogenetic classification, chromosomal distribution, collinearity analysis, association analysis, and functional analysis. These findings provide useful information for an in-depth study to determine the role of DGAT family gens play in the regulation of milk production and milk quality improvement in buffalo.


A balancing act: investigations on the impact of altered signal sensitivity in bacterial quorum sensing.
Quorum sensing (QS) is a widespread form of cell-cell signaling that regulates group behaviors important for competition and cooperation within bacterial communities. The QS systems from different bacterial species have diverse properties, but the functional consequences of this diversity are largely unknown. Taking advantage of hyper- and hypo-sensitive QS receptor variants in the opportunistic pathogen Pseudomonas aeruginosa, we examine the costs and benefits of altered signal sensitivity. We find that the sensitivity of a model QS receptor, LasR, impacts the timing and level of quorum gene expression, and fitness during intra- and interspecies competition. These findings suggest competition with kin and with other bacterial species work together to tune signal sensitivity.


HoLEP: the gold standard for the surgical management of BPH in the 21(st) Century.
For many years, transurethral resection of the prostate (TURP) has been accepted as the gold standard to surgically alleviate obstructive voiding dysfunction in men with benign prostatic hyperplasia (BPH). This historical standard has been challenged repeatedly over the last decade by consistent data demonstrating the superiority of Holmium enucleation of the prostate (HoLEP). This review summarizes the literature comparing HoLEP and traditional therapies for BPH that are widely used and have long term efficacy data, primarily TURP, open prostatectomy (OP), and alternative laser therapies (PVP, ThuLEP, etc). Patients undergoing HoLEP have greater improvements in post-operative Qmax, greater reduction in post-operative subjective symptom scores, and lower rates of repeat endoscopic procedures for recurrent symptoms at 5-10 year follow up compared with TURP, OP, and other laser therapies. Furthermore, patients undergoing HoLEP benefit from significantly shortened catheterization times, decreased length of hospital stay (LOS), and fewer serious post-operative complications. In particular, randomized controlled trials (RCT) have demonstrated that HoLEP can be used to resect adenomas greater than 100 grams with equivalent efficacy to open prostatectomy, but with radically decreased morbidity. Numerous large, RCTs demonstrate HoLEP to be objectively superior to other surgical therapies for BPH. The urologic community should embrace HoLEP as the new gold standard for surgical BPH therapy, especially in men with large prostates who would otherwise be considered for an OP or staged TURP. The only obstacle to widespread implementation of HoLEP remains its difficult learning curve when compared with traditional transurethral resection. Further allocation of resources towards appropriate mentoring and teaching of HoLEP is warranted, particularly in residency training programs.


Large body size in an island-dwelling bird: a microevolutionary analysis.
Island races of passerine birds display repeated evolution towards larger body size compared with their continental ancestors. The Capricorn silvereye (Zosterops lateralis chlorocephalus) has become up to six phenotypic standard deviations bigger in several morphological measures since colonization of an island approximately 4000 years ago. We estimated the genetic variance-covariance (G) matrix using full-sib and 'animal model' analyses, and selection gradients, for six morphological traits under field conditions in three consecutive cohorts of nestlings. Significant levels of genetic variance were found for all traits. Significant directional selection was detected for wing and tail lengths in one year and quadratic selection on culmen depth in another year. Although selection gradients on many traits were negative, the predicted evolutionary response to selection of these traits for all cohorts was uniformly positive. These results indicate that the G matrix and predicted evolutionary responses are consistent with those of a population evolving in the manner observed in the island passerine trend, that is, towards larger body size.


Acute moderate hyponatraemia and its rapid correction: effects on striatal and pontine ultrastructure in an animal model of the TURP syndrome.
To investigate the effects of moderate hyponatraemia, induced by intravenous application of an electrolyte-free irrigation fluid, as a model of the human transurethral prostate resection syndrome and of its rapid correction by hypertonic saline infusion in rats. Experimental animals received irrigation fluid (Purisole SM) 20 mL kg(-1) body weight, intravenously. In one group, hyponatraemia was subsequently rapidly corrected by infusion of hypertonic saline (NaCl 5.85%), while rats of group two were 'sham-corrected' by infusion of a balanced salt crystalloid solution. Plasma sodium concentrations were analysed during and at the end of the experiments. After 10 days, experimental and untreated control animals were killed humanely, fixed by perfusion and the brains were prepared for electron microscopic investigation of myelin sheets and glial cell numbers in the striatum and pons. The myelin appearance was unaltered in experimental groups compared to controls, but glial cell numbers were distinctly altered in the pons but not in the striatum. In the pons, oligodendrocytes were significantly reduced in number upon rapid correction of hyponatraemia, while astrocyte numbers were increased in rats with uncorrected hyponatraemia. Our electron microscopic data demonstrate that the effects of hyponatraemia and of its rapid correction are multifarious in animals. This may also apply for human patients during transurethral prostate resection.


Focusing on Sodium Glucose Cotransporter-2 and the Sympathetic Nervous System: Potential Impact in Diabetic Retinopathy.
The prevalence of diabetes is at pandemic levels in today's society. Microvascular complications in organs including the eye are commonly observed in human diabetic subjects. Diabetic retinopathy (DR) is a prominent microvascular complication observed in many diabetics and is particularly debilitating as it may result in impaired or complete vision loss. In addition, DR is extremely costly for the patient and financially impacts the economy as a range of drug-related therapies and laser treatment may be essential. Prevention of microvascular complications is the major treatment goal of current therapeutic approaches; however, these therapies appear insufficient. Presently, sodium glucose cotransporter-2 (SGLT2) inhibitors may offer a novel therapy beyond simple glucose lowering. Excitingly, the EMPA-REG clinical trial, which focuses on the clinically used SGLT2 inhibitor empagliflozin, has been extremely fruitful and has highlighted beneficial cardiovascular and renal outcomes. The effects of SGLT2 inhibitors on DR are currently a topic of much research as outlined in the current review, but future studies are urgently needed to fully gain mechanistic insights. Here, we summarize current evidence and identify gaps that need to be addressed.


The complete DNA sequence and analysis of R27, a large IncHI plasmid from Salmonella typhi that is temperature sensitive for transfer.
Salmonella typhi, the causative agent of typhoid fever, annually infects 16 million people and kills 600 000 world wide. Plasmid-encoded multiple drug resistance in S. typhi is always encoded by plasmids of incompatibility group H (IncH). The complete DNA sequence of the large temperature-sensitive conjugative plasmid R27, the prototype for the IncHI1 family of plasmids, has been compiled and analyzed. This 180 kb plasmid contains 210 open reading frames (ORFs), of which 14 have been previously identified and 56 exhibit similarity to other plasmid and prokaryotic ORFs. A number of insertion elements were found, including the full Tn 10 transposon, which carries tetracycline resistance genes. Two transfer regions, Tra1 and Tra2, are present, which are separated by a minimum of 64 kb. Homologs of the DNA-binding proteins TlpA and H-NS that act as temperature-regulated repressors in other systems have been located in R27. Sequence analysis of transfer and replication regions supports a mosaic-like structure for R27. The genes responsible for conjugation and plasmid maintenance have been identified and mechanisms responsible for thermosensitive transfer are discussed.


Do minimum wage laws affect employer-sponsored insurance provision?
Employers may respond to minimum wage increases by adjusting their health benefits. We examine the impact of state minimum wage increases on employer health benefit offerings using the 2002-2020 Medical Expenditure Panel Survey - Insurance/Employer Component data. Our primary regression specifications are difference-in-differences models that estimate the relationship between within-state changes in employer-sponsored insurance and minimum wage laws over time. We find that a $1 increase in minimum wages is associated with a 0.92 percentage point (p.p.) decrease in the percentage of employers offering health insurance, largely driven by small employers and employers with a greater share of low-wage employees. A $1 increase is also associated with a 1.83 p.p. increase in the prevalence of plans with a deductible requirement, but we do not find consistent evidence that other benefit characteristics are affected. We find no consequent change in uninsurance, likely explained by an increase in Medicaid enrollment.


Extent of Cell Confinement in Microtracks Affects Speed and Results in Differential Matrix Strains.
During metastasis, cancer cells navigate through a spatially heterogeneous extracellular matrix (ECM). Physical properties of ECM, including the degree of confinement, influence cell migration behavior. Here, utilizing in vitro three-dimensional collagen microtracks, we demonstrate that cell-ECM interactions, specifically the degree of spatial confinement, regulate migratory behavior. We found that cells migrate faster when they are fully confined, contacting all four walls (top, bottom, and two sides) of a collagen microtrack, compared with cells that are partially confined, contacting less than four walls. When fully confined, cells exhibit fewer but larger vinculin-containing adhesions and create greater strains in the surrounding matrix directed toward the cell body. In contrast, partially confined cells develop a more elongated morphology with smaller but significantly more vinculin-containing adhesions and displace the surrounding matrix less than fully confined cells. The resulting effect of increasing cell contractility via Rho activation is dependent on the number of walls with which the cell is in contact. Although matrix strains increase in both fully and partially confined cells, cells that are partially confined increase speed, whereas those in full confinement decrease speed. Together, these results suggest that the degree of cell-ECM contact during confined migration is a key determinant of speed, morphology, and cell-generated substrate strains during motility, and these factors may work in tandem to facilitate metastatic cell migration.


The susceptibility effect of matrix material on the g value of any radical.
The susceptibility effect of matrix material on g value of any radical has theoretically been investigated. An equation which yields the relationship between the g value of radical and the magnetic susceptibility of matrix material has been deduced. Based on this equation, it has been concluded that if the matrix material is paramagnetic the g value of the radical becomes smaller than the g value of the same radical in vacuum while it becomes higher if the matrix material is diamagnetic. These statements have been found to be in good agreement with the experimental results.


Concizumab: a novel anti-TFPI therapeutic for hemophilia.
Concizumab is a novel subcutaneous prophylactic therapy for hemophilia. It is a hemostatic rebalancing agent that binds to the Kunitz-2 domain of tissue factor pathway inhibitor (TFPI), one of the molecules that contributes to downregulation of coagulation thereby preventing TFPI from binding to and blocking the factor Xa (FXa) active site. When the TFPI inhibitory activity is decreased, sufficient FXa is produced by the FVIIa-tissue factor complex to achieve hemostasis. On the basis of this mechanism of action, concizumab is expected to be equally effective in hemophilia A and B, regardless of inhibitor status. Moreover, the concizumab mechanism of action does not interfere with the regulation of coagulation downstream of TFPI. Results from 2 phase 2 trials in patients with hemophilia A or B with and without inhibitors demonstrated that concizumab had a favorable safety profile, with no deaths, no thromboembolic events, and no adverse events leading to withdrawal. Clinical proof of concept in prevention of bleeding episodes was confirmed in both concizumab phase 2 trials across all hemophilia subtypes assessed, with a statistically significant and clinically relevant reduction in annualized bleeding rates observed in inhibitor patients compared to those who received on-demand treatment. On the basis of phase 2 results, the US Food and Drug Administration granted concizumab Breakthrough Therapy designation for hemophilia B with inhibitor patients, a rare and vulnerable patient subgroup that currently has the highest unmet medical need. In the ongoing concizumab phase 3 trials, an optimized dosing regimen will be administered in patients with hemophilia A or B with and without inhibitors.


Metabolism of vitamin K and prothrombin synthesis: anticoagulants and the vitamin K--epoxide cycle.
Vitamin K is primarily located in hepatic microsomes, where the vitamin K-dependent carboxylation in prothrombin synthesis occurs. Recent evidence supports the idea that the carboxylation is linked to the metabolism of the vitamin--specifically the cyclic interconversion of vitamin K and vitamin K epoxide. The primary site of action of coumarin and indandione anticoagulants appears to be an inhibition of the epoxide-to-vitamin K conversion in this cycle. There is a correlation between the inhibition of prothrombin synthesis and the regeneration of vitamin K from the epoxide by anticoagulants. In hamsters and warfarin-resistant rats prothrombin synthesis and the epoxide-K conversion are less sensitive to warfarin than in the normal rat. The epoxide-K conversion is impaired in resistant rats, which may explain their high vitamin K requirement. There is also a correlation between vitamin K epoxidation and vitamin K-dependent carboxylation, but the apparent link may be because vitamin K hydroquinone is an intermediate in the formation of the epoxide and also the active form in carboxylation. The vitamin K-epoxide cycle is found in extrahepatic tissues such as kidney, spleen, and lung and is inhibited by warfarin.


Safety and effectiveness of zero antimicrobial prophylaxis protocol for outpatient cystourethroscopy.
To examine compliance and clinical outcomes after implementation of a zero antimicrobial prophylaxis protocol for outpatient cystoscopy in an academic centre. Medical records of all patients who underwent diagnostic cystoscopy in the year preceding and year following protocol implementation were evaluated for urinary tract infection (UTI) diagnosis within 30 days of cystoscopy. Variables compared between groups included age, sex, smoking history, benign prostatic hyperplasia (BPH) diagnosis, diabetes mellitus, immunosuppression, catheter use (indwelling, suprapubic, or intermittent), and previous lower urinary tract reconstruction (augmentation cystoplasty or neobladder). UTI was defined using the National Surgical Quality Improvement Program definition. Rates were compared between groups, and statistical analyses were performed using chi-squared and Fisher's exact tests and multivariable logistic regression, with significance defined as α < 0.05. In total, 941 patients were included in the analysis (72% men), 513 before protocol initiation, and 427 after. Groups were similar with regard to demographic variables and potential risk factors for infection. After protocol implementation, there was a significant reduction in patients receiving procedural antimicrobial prophylaxis (30% vs 15%; P < 0.001). The incidence of UTI after cystoscopy was slightly higher in the post-protocol group (2.9-3.7%), but the difference was not statistically significant (chi-squared = 0.56, P = 0.45). The incidence of UTI did not significantly differ with procedural antibiotic prophylaxis or with other antibiotic use at time of cystoscopy. Five out of a total of 31 UTIs (16%) over the study period resulted in fever, and four (13%) resulted in urosepsis. The probability of neither complication differed significantly between pre- and post-protocol groups. The only significant patient-level predictor of post-cystoscopy UTI was catheter use (odds ratio 1.48, 95% confidence interval 1.06-2.06). Protocol implementation led to a significant decrease in procedural antimicrobial prophylaxis, indicating protocols may be effective tools in promoting antibiotic stewardship. UTI incidence did not change significantly under the protocol, and antibiotic prophylaxis did not decrease infection rate. Our results support catheter use as a risk factor for post-cystoscopy infection, but other patient variables, including those present in the American Urological Association Best Practice statement, were not predictive. In total, this analysis suggests that decreasing antibiotic prophylaxis for cystourethroscopy is safe and can be effective in the outpatient setting.


Molecular differences between the rostral and caudal halves of the sclerotome in the chick embryo.
It is known that both neural crest cell migration and motor axon outgrowth in most vertebrate embryos are segmented because of restrictions imposed upon their distribution by the neighbouring sclerotomes, each of which is divided into a rostral and a caudal half. The caudal half does not allow crest migration or axon outgrowth, while the rostral half does. In this paper, we investigate the expression of proteins and glycoproteins in the two halves of the sclerotome of the chick embryo at stages between 20 and 32 pairs of somites by two-dimensional SDS-polyacrylamide gel electrophoresis. We find that the patterns of expression are complex, and that polypeptides and glycoproteins vary both spatially and temporally: of those that are expressed differentially by the sclerotome, some differ quantitatively and others qualitatively. Some macromolecules change their spatial distribution with developmental age, and some appear or disappear as the embryos become older.


Application of telethermography in the evaluation of preterm premature rupture of the fetal membranes.
The development of chorioamnionitis is a serious complication associated with preterm premature rupture of the fetal membranes (PPROM). There is no reliable early indicator of this infection. The objective of this study was to determine the sensitivity of telethermography (TTG) in the detection of subclinical chorioamnionitis in women with PPROM. Fourteen pregnant women with PPROM between 23 and 34 weeks' gestation were the subjects of the study. Serial frontal-abdominal TTG scans were obtained up to the time of delivery using the MARK-1026 telethermography imager. Following delivery, placental cultures and pathology results were obtained and infant sepsis evaluation was performed. Images were analyzed for temperature differences between umbilical, inguinal, four-quadrant average, and abdominal-wall hot spots. Data were compared with norms obtained from 12 pregnant women with intact membranes who served as gestational age-matched controls. Of five patients with pathology-proven chorioamnionitis and TTG scans within three days of delivery, four demonstrated significant increases in temperature differences between umbilical and abdominal-wall hot spots versus inguinal and four-quadrant averages (z-scores > or = 2.0). All three patients with negative pathology and cultures as well as scans within three days of delivery showed no increase in temperature differences of the above variables. No patient had any overt clinical sign of chorioamnionitis. This limited but consistent evidence demonstrates that telethermography is a sensitive, noninvasive diagnostic method for detecting subclinical chorioamnionitis in pregnant women with preterm rupture of the fetal membranes.


Navigating communication with families during withdrawal of life-sustaining treatment in intensive care: a qualitative descriptive study in Australia and New Zealand.
To explore how nurses navigate communication with families during withdrawal of life-sustaining treatment in intensive care. Death in the intensive care unit is seldom unexpected and often happens following the withdrawal of life-sustaining treatment. A family-centred approach to care relies on the development of a therapeutic relationship and understanding of what is happening to the patient. Whilst previous research has focused on the transition from cure to palliation and the nurse's role in supporting families, less is known about how nurses navigate communication with families during treatment withdrawal. A qualitative descriptive approach was used. Semi-structured focus groups were conducted with adult critical care nurses from four intensive care units, two in Australia and two in New Zealand. Twenty-one nurses participated in the study. Inductive content analysis revealed five key themes relating to how nurses navigate family communication: (1) establishing the WHO; (2) working out HOW; (3) judging WHEN; (4) assessing the WHAT; and (5) WHERE these skills were learnt. Navigating an approach to family communication during treatment withdrawal is a complex and multifaceted nursing activity that is known to contribute to family satisfaction with care. There is need for support and ongoing education opportunities that develop the art of communication in this frequently encountered aspect of end-of-life care. How nurses navigate communication with families during treatment withdrawal is just as important as what is communicated. Nurses need access to supports and education opportunities in order to be able to perform this vital role.


Mechanisms of tobacco smoke toxicity on pulmonary macrophage cells.
The enhanced morbidity from nonspecific respiratory infections found in smokers may be attributable to chemically-induced defects in the respiratory tract defense mechanisms that are organized around the alveolar macrophage. We have isolated by filtration and gas chromatography several cytotoxic components and single chemicals of the vapor phase of tobacco smoke and studied their cytotoxic effects on pulmonary alveolar macrophages. The filtered gas phase of cigarette smoke or acrolein suppresses phagocytic uptake and intracellular digestion of staphylococci when exposed in vitro; produces marked morphologic changes in the cytoplasmic membrane; inhibits cellular adhesion; disturbs glycolysis and arachidonic metabolism; inhibits calcium and magnesium ATPase, glyceraldehyde 3-phosphate dehydrogenase, and probably endoperoxide E-isomerase, but not sodium and potassium ATPase, glucose 6-phosphate dehydrogenase or lactic dehydrogenase in a dose-response fashion. Furthermore, in vivo studies show that acrolein exposure suppresses antibacterial defenses of the lung. These cellular deficiencies may be responsible for a significant component of altered host resistance in smokers who suffer increased morbidity from nonspecific respiratory infections.


MS-CleanR: A Feature-Filtering Workflow for Untargeted LC-MS Based Metabolomics.
Untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) is currently the gold-standard technique to determine the full chemical diversity in biological samples. However, this approach still has many limitations; notably, the difficulty of accurately estimating the number of unique metabolites profiled among the thousands of MS ion signals arising from chromatograms. Here, we describe a new workflow, MS-CleanR, based on the MS-DIAL/MS-FINDER suite, which tackles feature degeneracy and improves annotation rates. We show that implementation of MS-CleanR reduces the number of signals by nearly 80% while retaining 95% of unique metabolite features. Moreover, the annotation results from MS-FINDER can be ranked according to the database chosen by the user, which enhance identification accuracy. Application of MS-CleanR to the analysis of Arabidopsis thaliana grown in three different conditions fostered class separation resulting from multivariate data analysis and led to annotation of 75% of the final features. The full workflow was applied to metabolomic profiles from three strains of the leguminous plant Medicago truncatula that have different susceptibilities to the oomycete pathogen Aphanomyces euteiches. A group of glycosylated triterpenoids overrepresented in resistant lines were identified as candidate compounds conferring pathogen resistance. MS-CleanR is implemented through a Shiny interface for intuitive use by end-users (available at https://github.com/eMetaboHUB/MS-CleanR).


An on-line approach to monitor ethanol fermentation using FTIR spectroscopy.
Fermentation process control is currently limited by its inability to measure parameters such as substrate, product, and biomass concentrations rapidly for consistent on-line feedback. Physical and chemical parameters, such as temperature and pH, currently can be obtained on-line using appropriate sensors. However, to obtain information on the concentration of the substrate, product, and biomass, samples must be taken off-line for measurement. With the use of spectroscopic techniques, real-time monitoring of process constituents such as product and substrate is possible. Spectroscopic techniques are rapid and nondestructive, require minimal or no sample preparation, and can be used to simultaneously assess several constituents in complex matrices. The production of ethanol is the largest fermentation process in terms of production volume and economic value as a result of its prominence in the food, agricultural, and fuel industries. This study attempts to develop an on-line ethanol fermentation monitoring technique using Fourier transform infrared (FTIR) spectroscopy with a flow-through ATR capability. Models developed using multivariate statistics, employed to obtain on-line FTIR measurements, were successfully validated by off-line HPLC analysis and spectrophotometry data. Standard errors of prediction (SEP) values of 0.985 g/L (R2 = 0.996), 1.386 g/L (R2 = 0.998), and 0.546 (R2 = 0.972) were obtained for ethanol, glucose, and OD, respectively. This work demonstrates that FTIR spectroscopy could be used for rapid on-line monitoring of fermentation.


Studies on cell lines developed from the tissues of patients with galactosemia.
Cell lines were developed from biopsies on galactosemic and non-galactosemic patients. It was shown that one can discriminate between lines from the two types of donors by their relative growth in glucose and galactose and by their ability to oxidize galactose-1-C(14). The latter method was successful in distinguishing a heterozygous cell line from the normal ones. Sensitivity of galactosemic cells to galactose was suggested by some of the experiments. The kinetics of growth were in some ways reminiscent of a similar phenomenon in the transferase mutants of E. coli, though in the human cells the effect was much less marked.


Na+/I- symporter expression, function, and regulation in non-thyroidal tissues and impact on thyroid cancer therapy.
For the past 80 years, radioiodine (131I) has been used to ablate thyroid tissue not removed by surgery or to treat differentiated thyroid cancer that has metastasized to other parts of the body. However, the Na+/I- symporter (NIS), which mediates active iodide uptake into thyroid follicular cells, is also expressed in several non-thyroidal tissues. This NIS expression permits 131I accumulation and radiation damage in these non-target tissues, which accounts for the adverse effects of radioiodine therapy. We will review the data regarding the expression, function, and regulation of NIS in non-thyroidal tissues and explain the seemingly paradoxical adverse effects induced by 131I, the self-limited gastrointestinal adverse effects in contrast to the permanent salivary dysfunction that is seen after 131I therapy. We propose that prospective studies are needed to uncover the time-course of pathological processes underlying development and progression or ultimate resolution of 131I-induced salivary ductal obstruction and nasolacrimal duct obstruction. Finally, preventive measures and early therapeutic interventions that can be applied potentially to eliminate or alleviate long-term radioiodine adverse effects will be discussed.


In vitro and in vivo anti-MRSA activities of nosokomycins.
The anti-methicillin-resistant Staphylococcus aureus (MRSA) activity of nosokomycins A to D discovered in the silkworm-MRSA infection screening was investigated. The minimum inhibitory concentration (MIC) values of nosokomycins for authentic MRSA and S. aureus strains were calculated to be 0.06 to 2.0 μg/mL. They also showed potent inhibitory activity against 54 clinically isolated MRSA strains. Furthermore, nosokomycin A proved effective in the mouse-MRSA infection model.


Does Ethnic Diversity Impact on Risk Perceptions, Preparedness, and Management of Heat Waves?
Detrimental health impacts of heatwaves, including excess mortality, are increasing worldwide. To assess risk perceptions, protective knowledge and behaviors concerning heatwaves in Israel, a study was initiated, comparing attitudes of majority (Jewish) and minority (Arab) populations. A quantitative survey was disseminated through an internet panel, to a representative sample of 556 individuals (79% Jews; 21% Arabs). Overall, 74% consider heatwaves a problem, 93% believe that heatwaves' frequencies will increase, 27% are very concerned about the effects of heatwaves. Higher levels of awareness to heatwaves were found among Jewish compared to Arab respondents; 90 vs. 77% (respectively) could name heatwaves' symptoms (p < 0.001); 81 vs. 56% (respectively) reported knowing how to protect themselves (p < 0.001); 74 vs. 47% (respectively) reported knowing what to do when someone suffers from heat stroke (p < 0.001). Arab compared to Jewish respondents presented higher levels of concern about heatwaves' effects (3.22 vs. 3.09 respectively; t -2.25, p = 0.03), while knowledge of protective measures was higher among Jews compared to Arabs (3.67 vs. 3.56 t = 2.13 p = 0.04). A crucial component of enhancing preparedness to heatwaves is empowerment of minority as well as majority groups, to strengthen their capacity to implement protective behavior and elevate their self-belief in their individual ability and fortitude.


Selective Sweeps.
For almost 20 years, many inference methods have been developed to detect selective sweeps and localize the targets of directional selection in the genome. These methods are based on population genetic models that describe the effect of a beneficial allele (e.g., a new mutation) on linked neutral variation (driven by directional selection from a single copy to fixation). Here, I discuss these models, ranging from selective sweeps in a panmictic population of constant size to evolutionary traffic when simultaneous sweeps at multiple loci interfere, and emphasize the important role of demography and population structure in data analysis. In the past 10 years, soft sweeps that may arise after an environmental change from directional selection on standing variation have become a focus of population genetic research. In contrast to selective sweeps, they are caused by beneficial alleles that were neutrally segregating in a population before the environmental change or were present at a mutation-selection balance in appreciable frequency.


Characterization of a macaque recombinant monoclonal antibody that binds to a CD4-induced epitope and neutralizes simian immunodeficiency virus.
A potent neutralizing Fab fragment from a long-term survivor of simian immunodeficiency virus (SIVsm) infection was used to construct a recombinant macaque immunoglobulin G1kappa (IgG1kappa) molecule, designated IgG1-201. A Chinese hamster ovary cell line expressing IgG1-201 was derived by stable transfection and optimized for antibody secretion by methotrexate selection and dihydrofolate reductase gene amplification. IgG1-201 effectively neutralized the homologous, molecularly cloned SIVsmH4 virus but had no activity against the heterologous SIVmac251/BK28 virus. The previously characterized, neutralization-resistant SIVsmE543-3 virus was also not neutralized by IgG1-201. Binding to SIVsmH4 gp120 was enhanced in the presence of recombinant soluble CD4, suggesting that IgG1-201 bound a CD4-induced epitope. IgG1-201 immunoprecipitated the SIVsmH4 but not the SIVsmE543-3 envelope despite a close relationship between these two clones. Immunoprecipitation of a panel of SIVsmH4/SIVsmE543-3 chimeric viruses tentatively assigned the neutralization epitope to the third constant domain, immediately C terminal to the V3 loop. These findings suggest the presence of at least one CD4-induced neutralization epitope on SIV, as is the case with human immunodeficiency virus type 1.


Laundry Hygiene and Odor Control: State of the Science.
Laundering of textiles-clothing, linens, and cleaning cloths-functionally removes dirt and bodily fluids, which prevents the transmission of and reexposure to pathogens as well as providing odor control. Thus, proper laundering is key to controlling microbes that cause illness and produce odors. The practice of laundering varies from region to region and is influenced by culture and resources. This review aims to define laundering as a series of steps that influence the exposure of the person processing the laundry to pathogens, with respect to the removal and control of pathogens and odor-causing bacteria, while taking into consideration the types of textiles. Defining laundering in this manner will help better educate the consumer and highlight areas where more research is needed and how to maximize products and resources. The control of microorganisms during laundering involves mechanical (agitation and soaking), chemical (detergent and bleach), and physical (detergent and temperature) processes. Temperature plays the most important role in terms of pathogen control, requiring temperatures exceeding 40°C to 60°C for proper inactivation, while detergents play a role in reducing the microbial load of laundering through the release of microbes attached to fabrics and the inactivation of microbes sensitive to detergents (e.g., enveloped viruses). The use of additives (enzymes) and bleach (chlorine and activated oxygen) becomes essential in washes with temperatures below 20°C, especially for certain enteric viruses and bacteria. A structured approach is needed that identifies all the steps in the laundering process and attempts to identify each step relative to its importance to infection risk and odor production.


The Unique Challenges Faced by Assisted Living Communities to Meet Federal Guidelines for COVID-19.
This perspective addresses the challenges that assisted living (AL) providers face concerning federal guidelines to prevent increased spread of COVID-19. These challenges include restriction of family visitation, use of third-party providers as essential workers, staffing guidelines, transfer policies, and rural AL hospitalizations. To meet these challenges we recommend that AL providers incorporate digital technology to maintain family-resident communication. We also recommend that states adopt protocols that limit the number of AL communities visited by home health care workers in a 14-day period, appeal to the federal government for hazard pay for direct care workers, and to extend the personal care attendant program to AL. It is further recommended that states work with AL communities to implement COVID-19 comprehensive emergency management plans that are well-coordinated with local emergency operation centers to assist with transfers to COVID-19 specific locations and to assist in rural areas with hospital transfers. Together, these recommendations to AL providers and state and federal agencies address the unique structure and needs of AL and would enable AL communities to be better prepared to care for and reduce those infected with COVID-19.


Upper stratospheric photolysis of NaCl and KCl.
Sodium chloride has been postulated to be formed in the stratosphere by the reaction of NaOH with HCl, and an analogous reaction should occur also for KOH, with the formation of KCl. Photodissociation rates have been calculated for both NaCl and KCl using the published ultraviolet absorption cross sections below 300 nm. Both molecules absorb strongly and have photodissociation lifetimes of only a few minutes in the upper stratosphere. Neither molecule is an effective sink for chlorine above an altitude of about 35 km.


The quality in the radiology department.
In the last three years, the Spanish juridical ordinance has regulated (mostly the radiologic protection area) the essential quality that every radiodiagnostic and dentistry unit should comply with. This quality, as in every service, rests on the competence of the professional's who perform it. This means that in advanced countries much time and effort is dedicated to forming these people and therefore the academic charge for teaching dentistry radiology in Venezuela results 15 times higher than what is dedicated in our environment. Also, the supply of graduates or specialized radiologists is very poor; for example, it does not exist in Barcelona while in Merida the radiology service staff has 4 licentiates exclusively dedicated to oral radiology assistance and teaching (apart from two other people who work as technicians). This wealth influences positively in the quality of the service. Among other things, it allows the readjustment of the incoming petitions and also to justify them better and makes possible that all the explorations go out with the corresponding judgment. The academic quality in this discipline is also high due to the fact that it is a university teaching service. Our goal, through this work, is to show the situation of the problem comparing 2 different university services of oral radiology and reveal the lacks found with its solutions.


[Local unscheduled DNA synthesis following irradiation of a portion of mitotic chromosomes or interphase nucleus with UV microbeam].
Part of mitotic chromosome sets of the metaphase or anaphase SPEW mammalian cells were irradiated with an ultraviolet microbeam, and the subsequent incorporation of H3-thymidine into the postmitotic daughter nuclei was studied by autoradiography. The located areas of the unscheduled DNA synthesis were detected in these nuclei. This synthesis was likely to be due to repair process at the sites of postmitotic localization of the irradiated chromosomes. It is suggested that the selective chromosomal labeling induced by microirradiation could be employed in studying patterns of chromosome localization in the interphase nuclei. Local inhibition of the replicative DNA synthesis and local stimulation of the unscheduled DNA synthesis were observed after a partial microirradiation of the interphase nuclei. This unscheduled DNA synthesis was unaffected by hydroxyurea at concentration which inhibited normal DNA synthesis.


Sliding adhesion confers coherent motion to hair cell stereocilia and parallel gating to transduction channels.
When the tip of a hair bundle is deflected by a sensory stimulus, the stereocilia pivot as a unit, producing a shearing displacement between adjacent tips. It is not clear how stereocilia can stick together laterally but still shear. We used dissociated hair cells from the bullfrog saccule and high-speed video imaging to characterize this sliding adhesion. Movement of individual stereocilia was proportional to height, indicating that stereocilia pivot at their basal insertion points. All stereocilia moved by approximately the same angular deflection, and the same motion was observed at 1, 20, and 700 Hz stimulus frequency. Motions were consistent with a geometric model that assumes the stiffness of lateral links holding stereocilia together is >1000 times the pivot stiffness of stereocilia and that these links can slide in the plane of the membrane-in essence, that stereocilia shear without separation. The same motion was observed when bundles were moved perpendicular to the tip links, or when tip links, ankle links, and shaft connectors were cut, ruling out these links as the basis for sliding adhesion. Stereocilia rootlets are angled toward the center of the bundle, tending to push stereocilia tips together for small deflections. However, stereocilia remained cohesive for deflections of up to +/-35 degrees, ruling out rootlet prestressing as the basis for sliding adhesion. These observations suggest that horizontal top connectors mediate a sliding adhesion. They also indicate that all transduction channels of a hair cell are mechanically in parallel, an arrangement that may enhance amplification in the inner ear.


Improving the efficiency of individually randomized clinical trials by staggering the introduction of the intervention.
In cluster randomized trials, the introduction of the intervention can be staggered in different clusters, leading to a stepped wedge design. This strategy can lead to gains in efficiency, which might also translate to the context of individually randomized trials, though this has been relatively unexplored. Here, we present one illustrative example. We consider trials in which participants start in a control condition such as routine care and can cross over at any stage to the active intervention. We make the assumption that the effect of the intervention is the same however long the delay before a participant crosses over to the intervention condition. We consider designs for a trial with three repeated assessments, including a baseline, and show that a three-sequence design with staggered introduction of the intervention in two of the sequences estimates the treatment effect after one period more efficiently than a parallel groups design.


Psychiatric treatment of eczema: a controlled trial.
Seventy-two patients with eczema were randomly allotted to one of two treatment groups: A, those receiving dermatological treatment only, and B, those receiving the same dermatological treatment plus psychiatric treatment, limited where possible to four months. Cases were followed up at six-monthly dermatological assessments, 57 (79%) for 18 months. The findings suggest that in the presence of overt emotional disturbance, of new psychological or psychophysiological symptoms preceding the rash by up to a year, and of high motivation for it, brief psychiatric treatment improves the outcome in eczema (the proportion clear at 18 months was about doubled), whereas in their absence such treatment may worsen it, especially in the short term.


[Foods native to indigenous and afro-descendents in Colombia].
For social programs in Colombia, like those administered by the Instituto Colombiano de Bienestar Familiar (ICBF), it's important to know what native foods minority groups consume. This research obtained information on native foods consumed by indigenous and afro-descendents living in 10 Colombian departments: Cauca, Nariño, Amazonas, Chocó, Guainia, Vichada, Magdalena, Guajira, Cesar y Vaupés. A questionnaire was applied to key informants (individually or in groups), addressing the following topics: personal information on the informant, name and type of food, if consumed by indigenous and/or afro-Colombians, climate where produced, time of year when harvested, if consumed raw or cooked, preparations, properties ascribed to the food, and current production, use and availability. Key informants included participants in ICBF's programs, indigenous authorities, teachers, traditional healers, and others, under the supervision of professionals from ICBF's mobile unit in each department. Bibliography (n = 123 documents) was compiled and reviewed. In the departments selected, 13 municipalities were visited, 139 individuals were interviewed and at least 92 new foods (i.e., not currently included in the Colombian Food Composition Table) were identified. Among the 92, the scientific name was obtained for 62 foods. Of these, 2 were classified as other, 18 as meats, 3 as insects, and 39 as plants. Among the plants, informants mentioned fruit (n=29), leaves (n=4), seed (n=3) and roots (n=3). Indigenous and afro-descendent communities in Colombia report consuming dozens of foods that are not currently in the Colombian Food Composition Table.


Relationship between antioxidant intakes and class I sarcopenia in elderly men and women.
The effect of nutritional intake on sarcopenia has been mostly examined in class II sarcopenia, i.e. when muscle mass has sufficiently decreased to induce a loss in physical capacity. Although this provides important information regarding the treatment of sarcopenia, it may not help highlight mechanisms involved at the very beginning of its development. We hypothesized that class I sarcopenia is associated with differences in antioxidant intakes (vitamins A, C, E and selenium) and status in healthy, older white men and women when physical activity and protein intake are taken into account. Fat-free mass and total appendicular skeletal muscle mass was determined by dual-energy X-ray absorptiometry in 50 healthy, older white men (n = 16) and women (n = 34) aged 60-75 yrs. Physical activity energy expenditure (PAEE) was determined using a Caltrac accelerometer over a 3-d period. Dietary protein and antioxidant intakes were estimated from a 3-d food record and serum total antioxidant activity (TAA) was measured by a ferrylmyoglobin- ABTS assay. The prevalence of class I sarcopenia was 23.5 % in women and 25.0 % in men; 12 participants were thus considered sarcopenic (4 men and 8 women) and 38 participants were considered nonsarcopenic (12 men and 26 women). Our results showed that PAEE, serum albumin concentrations, TAA, and the four antioxidants intake levels were similar between groups. On the other hand, our results showed that total protein intake was significantly higher (P < 0.01) in the non-sarcopenic group than in the sarcopenic group. Also, the number of Recommended Dietary Allowances (RDAs) reached for the antioxidant nutrients and protein intakes by the non-sarcopenic group was significantly higher (P < 0.01) than in the sarcopenic group. Although there were no significant differences between the sarcopenic and the non-sarcopenic group when antioxidant intakes were considered individually, we observed that the number of RDAs reached for antioxidant micronutrients and protein in healthy, older white men and women was lower in sarcopenic than nonsarcopenic individuals. Our results also suggest that a higher total dietary protein intake is associated with the preservation of muscle mass loss although both groups displayed values above actual RDAs. Obviously, prospective studies are needed to determine the minimum amount of protein in the diet needed to prevent class I sarcopenia and to examine the utility of antioxidant intake to combat the age-related loss in skeletal muscle mass.