Chemical availability of fallout radionuclides in cryoconite.
Atmospheric deposition on glaciers is a major source of legacy fallout radionuclides (FRNs) accumulating in cryoconite, a dark granular material with surface properties that efficiently bind FRN contaminants (specifically 137Cs; 210Pb; 241Am). Cryoconite-bound FRNs in glaciers can be released when they interact with and are transported by glacial meltwater, resulting in the discharge of amassed particulate contaminants into aquatic and terrestrial environments downstream. The environmental consequences of FRN release from the cryosphere are poorly understood, including impacts of cryoconite-sourced FRNs for alpine food chains. Consequently, there is limited understanding of potential health risks to humans and animals associated with the consumption of radiologically-contaminated meltwater. To assess the chemical availability of cryoconite-adsorbed FRNs we used a three-stage sequential chemical extraction method, applied to cryoconite samples from glaciers in Sweden and Iceland, with original FRN activity concentrations up to 3300 Bq kg-1 for 137Cs, 10,950 Bq kg-1 for unsupported 210Pb (210Pbun) and 24.1 Bq kg-1 for 241Am, and orders of magnitude above regional backgrounds. Our results demonstrate that FRNs attached to cryoconite are solubilized to different degrees, resulting in a stage-wise release of 210Pbun involving significant stepwise solubilization, while 137Cs and 241Am tend to be retained more in the particulate phase. This work provides an insight into the vulnerability of pristine glacial environments to the mobilization of FRN-contaminated particles released during glacier melting, and their potential impact on glacial-dependent ecology.


The effect of dopamine administration on the activity of the renin-angiotensin-aldosterone system in sick preterm infants.
Nine premature infants with birth weight of 1150 to 2500 g and gestational age of 28 to 35 weeks were given dopamine in a dose of 2-4 micrograms/kg/min to treat cardiopulmonary distress. In addition to monitoring of blood gases, blood pressure, acid-base balance, urine flow and urinary sodium excretion, plasma renin activity (PRA) and plasma aldosterone concentration (PA) was also determined prior to and during dopamine therapy. The dopamine-induced increase in urine flow and urinary sodium excretion was associated with a significant increase of PRA from 18.2 +/- 5.1 ng/ml/h to 33.0 +/- 5.6 ng/ml/h (P less than 0.025), while PA and blood pressure remained unaltered by dopamine administration. It is suggested that the angiotensin II-stimulated aldosterone production is overridden by the inhibitory effect of dopamine.


Complications of endovascular treatment of cerebral aneurysms.
The number of neuroendovascular treatments of both ruptured and unruptured aneurysms has increased substantially in the last two decades. Complications of endovascular treatments of cerebral aneurysms are rare but can potentially lead to acute worsening of the neurological status, to new neurological deficits or death. Some of the possible complications, such as vascular access site complications or systemic side effects associated with contrast medium (e.g. contrast medium allergy, contrast induced nephropathy) can also be encountered in diagnostic angiography. The most common complications of endovascular treatment of cerebral aneurysms are related to acute thromboembolic events and perforation of the aneurysm. Overall, the reported rate of thromboembolic complications ranges between 4.7% and 12.5% while the rate of intraprocedural rupture of cerebral aneurysms is about 0.7% in patients with unruptured aneurysms and about 4.1% in patients with previously ruptured aneurysms. Thromboembolic and hemorrhagic complications may occur during different phases of endovascular procedures and are related to different technical, clinical and anatomic reasons. A thorough knowledge of the different aspects of these complications can reduce the risk of their occurrence and minimize their clinical sequelae. A deep understanding of complications and of their management is thus part of the best standard of care.


Immunoenzymatic assay that measures the expression of murine histocompatibility antigens in macrophages and lymphocytes.
A convenient--simple, sensitive, rapid and reproducible--enzyme immunoassay to measure H-2 particulated and solubilized cellular antigens is described. Cellular antigens were measured by ELISA through the binding of specific biotinylated antibodies and streptoavidin-peroxidase conjugate to cells in suspension. Endogenous peroxidase activity of activated cells was inhibited by addition of sodium azide and H2O2 in acid conditions. The assay proved capable of distinguishing between two cell lines (EL-4/H-2b and P815/H-2d) and even between the cells of three congenic mouse strains (BALB/B, H-2b, BALB/c, H-2d, and BALB/K, H-2k) and was sensitive to as few as 2.5 x 10(4) cells/well. Results were comparable to those obtained with FACS. An inhibition version of this assay was found to be very useful for the detection of H-2 antigens present in whole antigen cells extracts.


Predatory potential of Euseius alatus (Phytoseiidae) on different life stages of Oligonychus ilicis (Tetranychidae) on coffee leaves under laboratory conditions.
This study evaluated the predatory capacity of Euseius alatus (DeLeon) as a biological control agent of the pest mite Oligonychus ilicis (McGregor) on coffee leaves under laboratory conditions, using arenas containing 25 O. ilicis per coffee (Coffea arabica) leaf to one specimen of each stage of the predator mite. The functional response and oviposition rate of adult females of E. alatus were evaluated on coffee leaf arenas and offered from 1 to 125 immature stages of O. ilicis per arena. The number of preys killed and the number of eggs laid by the predator were evaluated every 24 h during 8 days. The preys consumed were daily replaced. Male and female adults of E. alatus were the most efficient in killing all developmental stages of O. ilicis. Larvae and nymphs of O. ilicis were the most consumed by all stages of the predatory mite. The functional response and oviposition rates of E. alatus increased as the prey density increased, with a positive and highly significant correlation. Regression analysis suggested a type II functional response, with a maximum predation of 22 O. ilicis/arena and a maximum oviposition rate of 1.7 eggs/day at a density of 70 O. ilicis/arena.


LC-APCI-MS/MS analysis of urinary 8-hydroxy-2'-deoxyguanosine.
8-Hydroxy-2'-deoxyguanosine (8OHdG) is regarded as an important biomarker of oxidative DNA damage and it may be estimated by using different techniques in various biological matrices, most notably DNA and urine. In the case of DNA, artifactual oxidation may take place during the isolation of DNA, its hydrolysis and possible derivatization (as for GC-MS), invalidating the measurement of 8OHdG. Therefore, the direct analysis of 8OHdG excreted into urine was preferred. Interferences from the urine matrix were excluded by applying LC-APCI-MS/MS in the multiple reaction monitoring (MRM) mode. The abundant fragment ion at m/z 168 arising from 8OHdG was monitored in the urine sample of volunteers supplemented with tomato concentrate for different times. The procedure allowed the detection of levels of 8OHdG as low as 1 ng/ml in urine sample.


Silent meningioma - a rare cause of stroke in post-cardiopulmonary bypass patients.
Stroke in cardiac patients undergoing surgery is usually attributed to the use of cardiopulmonary bypass. In this report, we present an unusual cause of cerebral dysfunction: a meningioma leading to stroke, following coronary artery bypass grafting in a 62-year-old patient. Diagnosis and treatment options of the pathology are discussed with the guidance of the literature.


Protocatechuate overproduction by Corynebacterium glutamicum via simultaneous engineering of native and heterologous biosynthetic pathways.
Protocatechuic acid (3, 4-dihydroxybenzoic acid, PCA) is a natural bioactive phenolic acid potentially valuable as a pharmaceutical raw material owing to its diverse pharmacological activities. Corynebacterium glutamicum forms PCA as a key intermediate in a native pathway to assimilate shikimate/quinate through direct conversion of the shikimate pathway intermediate 3-dehydroshikimate (DHS), which is catalyzed by qsuB-encoded DHS dehydratase (the DHS pathway). PCA can also be formed via an alternate pathway extending from chorismate by introducing heterologous chorismate pyruvate lyase that converts chorismate into 4-hydroxybenzoate (4-HBA), which is then converted into PCA catalyzed by endogenous 4-HBA 3-hydroxylase (the 4-HBA pathway). In this study, we generated three plasmid-free C. glutamicum strains overproducing PCA based on the markerless chromosomal recombination by engineering each or both of the above mentioned two PCA-biosynthetic pathways combined with engineering of the host metabolism to enhance the shikimate pathway flux and to block PCA consumption. Aerobic growth-arrested cell reactions were performed using the resulting engineered strains, which revealed that strains dependent on either the DHS or 4-HBA pathway as the sole PCA-biosynthetic route produced 43.8 and 26.2 g/L of PCA from glucose with a yield of 35.3% and 10.0% (mol/mol), respectively, indicating that PCA production through the DHS pathway is significantly efficient compared to that produced through the 4-HBA pathway. Remarkably, a strain simultaneously using both DHS and 4-HBA pathways achieved the highest reported PCA productivity of 82.7 g/L with a yield of 32.8% (mol/mol) from glucose in growth-arrested cell reaction. These results indicated that simultaneous engineering of both DHS and 4-HBA pathways is an efficient method for PCA production. The generated PCA-overproducing strain is plasmid-free and does not require supplementation of aromatic amino acids and vitamins due to the intact shikimate pathway, thereby representing a promising platform for the industrial bioproduction of PCA and derived chemicals from renewable sugars.


Three-dimensional echoventriculography.
A method of generating a three-dimensional image of the human left ventricle by computer techniques is described. The volume of each image was estimated by a modification of Simpson's rule. The method was applied to nine suitable patients and estimations of end-diastolic and end-systolic volumes were compared to volumes determined by cineangiography. Significant linear correlation coefficients of 0.95 and 0.94 were obtained for end-diastolic and end-systolic volumes, respectively. The standard errors of estimate were 9 ml for end-diastolic volumes and 7 ml for end-systolic volumes. The value of this methodology lies in the ability to estimate left ventricular volumes with accuracy, using an imaging technique of little inconvenience and no risk to the patient and computer hardware that is readily available at most clinical institutions.


A modified lecithin/sphingomyelin ratio test for fetal maturity.
Several desirable techniques (rapid chromatogram development, planimetry, acetone precipitation of lecithin, and copper molybdate staining) used in other published lecithin/sphingomyelin (L/S) ratio procedures were integrated into a single L/S ratio test. The resulting test requires only 2 ml of amniotic fluid, can be performed within 75 minutes, and is semiquantitative. Methodology tests showed a high degree of reproducibility without the need for a densitometer: Coefficients of variation for the standards and amniotic fluid samples were 11% and 4%, respectively. Also, a linear relationship was observed between the L/S weight ratios in synthetic mixtures and the corresponding area ratios up to the mature value of 2.5. Clinical evaluation on a normal and high-risk patient population showed excellent reliability: The accuracy in predicting fetal lung maturity and immaturity was 100% and 85%, respectively. Moreover, the numerical value of the L/S ratio in the immature range was found to be indicative of the severity of respiratory distress syndrome. Finally, the relationship between the L/S ratio and gestational age in a normal population was described mathematically by an approximating curve. We concluded from our methodologic and clinical data that the L/S ratio may be determined simply and reliably by means of the procedure described in this report.


Systemic therapy in metastatic renal cell carcinoma (mRCC): an evidence-based recommendation of the German interdisciplinary RCC guidelines group.
The treatment landscape in metastatic renal cell carcinoma (mRCC) has evolved dramatically in recent years. Within the German guideline committee for RCC we evaluated current medical treatments and gave recommendations. A systematic review of published evidence for medical treatment of mRCC was performed (July 2016-August 2019) to cover the duration from last guideline update in 2016. Evidence was graded according to SIGN ( http://www.sign.ac.uk/pdf/sign50.pdf ). Recommendations were made on the basis of a nominal group work with consensus approach and included patient advocates and shareholder of the German RCC treatment landscape. Each recommendation was graded according to its strength as strong recommendation (A) or recommendation (B). Expert statements were given, where appropriate. Strong first-line recommendations (IA) exist for axitinib + pembrolizumab (all risk categories) and ipilimumab + nivolumab (intermediate or poor risk only). Axitinib + avelumab is a recommended first-line treatment across patients with any risk category (IB). In patients who are not candidates for immune check point inhibitor (ICI) combinations, targeted agents should be offered as an alternative treatment. Subsequent treatment after ICI-based combinations remain ill-defined and no standard of care can be formulated. ICI-based combinations are the first-line standard of care and should be considered accordingly. There is an unmet medical need for pivotal studies that define novel standards in patients with failure of ICI-based combinations.


A study of segment weight optimization with the CMS XiO step-and-shoot IMRT technique for prostate cancer.
The aim of this study was to compare IMRT optimization in the CMS XiO radiotherapy treatment planning system, with and without segment weight optimization. Twenty-one prostate cancer patients were selected for this study. All patients were initially planned with step-and-shoot IMRT (S-IMRT). A new plan was then created for each patient by applying the segment weight optimization tool (SWO-IMRT). Analysis was performed on the (SWO-IMRT) and (S-IMRT) plans by comparing the total number of segments, monitor units, rectal and bladder dose. The study showed a statistically significant reduction in the total number of segments (mean: 25.3%; range: 16.8%-31.1%) with SWO-IMRT as compared to S-IMRT (p < 0.0001). Similarly, a mean reduction of 3.8% (range: 0.4%-7.7%) in the total MU was observed with SWO-IMRT (p < 0.0001). The study showed an average rectal dose decrease of 13.7% (range: 7.9%-21.4%) with SWO-IMRT (p < 0.0001). We also observed a statistically significant reduction of 26.7% (range: 16.0%-41.4%; p < 0.0001) in the mean dose to the posterior one-third rectum and an overall reduction in mean bladder dose of 2.2% (range: 0.1%-6.1%) for SWO-IMRT (p < 0.0001). This study shows that the segment weight optimization method significantly reduces the total number of segments and the dose to the rectum for IMRT prostate cancer. It also resulted in fewer monitor units for most of the prostate cases observed in this study.


Clinical Profile, Patterns of Care & adherence to Guidelines in Patients with Hepatocellular Carcinoma: Prospective multi-center Study.
Increasing incidence of hepatocellular carcinoma (HCC) in India is a matter of concern and need for adequate profiling and streamlining management strategies cannot be over-emphasized. This is a prospective multi-centric observational cohort study comprising of an oncology center, one university tertiary hospital with specialized hepatology service, one public hospital with gastroenterology service, and a private liver transplant center located within a 3-km radius. The demographic and clinical parameters were recorded on a prospectively maintained database. The clinical profile, demographics, characteristics of HCC and the allocated treatment were noted and compared among the four centers. In total, 672 patients were enrolled from June 2016 till January 2020. Abdominal pain (64.3%) and weight loss (47.3%) were the most common symptoms. Most common identified etiology was hepatitis B (39%). The cancer center received lesser patients with hepatitis C and those with advanced stage of HCC. The private transplant center reported the highest proportion of NASH, which was also significantly higher in those belonging to higher socioeconomic strata, and lowest proportion of alcoholic cirrhosis. Metastasis was seen in almost one-fifth (19%) cases at diagnosis. Portal vein thrombosis was evident in 40%. Adherence to treatment guidelines was seen in three-fourth cases (76%). Hepatitis B is the most common underlying cause for HCC, whereas other causes like NASH are on the rise. Etiologic profile may vary with selective specialization of centers catering to patients with HCC. Adherence to guideline while allocating treatment was high among all centers with highest non-adherence in BCLC A.


Gorham-Stout disease affecting both hands: stabilisation during biphosphonate treatment.
The Gorham-Stout syndrome is a rare condition in which spontaneous, progressive resorption of bone occurs. The aetiology is poorly understood. We report a patient with osteolysis of the metacarpal bones in both hands due to an increased number of stimulated osteoclasts. This suggests that early potent antiresorptive therapy with bisphosphonates may prevent local progressive osteolysis.


Translation, cultural adaptation and validation of the Chinese Multimorbidity Treatment Burden Questionnaire(C-MTBQ): a study of older hospital patients.
Due to an ageing population, multimorbidity is becoming more common. Treatment burden (the effort required of patients to look after their health and the impact this has on their wellbeing) is prevalent in patients with multimorbidity. The Multimorbidity Treatment Burden Questionnaire (MTBQ) is a patient-reported outcome measure of treatment burden that has been validated amongst patients with multimorbidity in the UK. The aim of this study was to translate and culturally adapt the MTBQ into Chinese and to assess its reliability and validity in elderly patients with multimorbidity in hospital. The original English version of the MTBQ was translated into Chinese using Brislin's model of cross-culture translation. The C-MTBQ was piloted on a sample of 30 elderly patients with multimorbidity prior to being completed by 156 Chinese elderly patients with multimorbidity recruited from a hospital in Zhengzhou, China. We examined the proportion of missing data, the distribution of responses and floor and ceiling effects for each question. Factor analysis, Cronbach's alpha, intraclass coefficient and Spearman's rank correlations assessed dimensional structure, internal consistency reliability, test-retest reliability and criterion validity, respectively. The average age of the respondents was 73.5 years (range 60-99 years). The median C-MTBQ global score was 20.8 (interquartile range 12.5-29.2). Significant floor effects were seen for all items. Factor analysis supported a three-factor structure. The C-MTBQ had high internal consistency (Cronbach's alpha coefficient, 0.76) and test-retest reliability (the intraclass correlation coefficient, 0.944), the correlations between every item and global scores scored > 0.4. The scale content validity index(S-CVI) was 0.89, and the item level content validity index(I-CVI)was 0.83 ~ 1.00. The criterion validity was 0.875. The Chinese version of MTBQ showed satisfactory reliability and validity in elderly patients with multimorbidity, and could be used as a tool to measure treatment burden of elderly patients with multimorbidity in hospital.


New extraction procedure to improve the determination of quinolones in poultry muscle by liquid chromatography with ultraviolet and mass spectrometric detection.
The present article aims to develop a new extraction procedure to improve the determination of quinolones in chicken muscle. This new determination method was validated using liquid chromatography-ultraviolet detection (LC-UV) and liquid chromatography-mass spectrometry detection (LC-MS), which has special bearing on stability studies. The results obtained by using the method were compared with the results obtained with a previous methodology. The new extraction procedure presents a sensitivity low enough to determine concentration of these drugs below the permissible maximum residue limits (MRL) in chicken muscle and is less time consuming than the previous methodology.


Rapid and efficient removal of Ni(2+) from aqueous solution by the one-pot synthesized EDTA-modified magnetic nanoparticles.
A facile one-pot process has been proposed to prepare the novel ethylenediaminetetraacetic acid (EDTA)-modified magnetite nanoparticles (EDTA-MNPs). The bared Fe3O4 magnetite nanoparticles and EDTA-MNPs were characterized using FTIR spectroscopy, TEM, VSM, and X-ray diffraction. The application of the modified magnetite nanoparticles for metal ion uptake was studied using Ni(2+) as a model. The adsorption was fast and the equilibrium was established within 5 min, and the adsorption kinetics of Ni(2+) onto EDTA-MNPs followed the pseudo second-order chemisorption mechanism. Maximum adsorption capacity for Ni(2+) reached as high as 41.3 mg/g at pH 6. The successive adsorption-desorption studies indicated that the EDTA-MNPs kept the adsorption and desorption efficiencies constant over ten cycles. Importantly, EDTA-MNPs were able to remove nearly 100 % of Ni(2+) from real water.


The smile in anencephalic infants.
During the period 1947-1959 twelve new-born mero-anencephalics were observed, who survived for more than 1 day after birth. Two even lived for 20 and 237 days, respectively. In 4 of the 12 children studied touching or slight pressure, and also faradic stimulation of various spots of the cerebro-vascular area were invariably followed by a facial expression which was very similar to smiling. Movies of it were shown to groups of impartial observers. In 78% the facial expression was judged to be a smile, a laugh or a grin. The neuroanatomical finding of a largely intact pontine tegmentum as being the most rostrally situated identifiable structure of the brainstem, has led to the hypothesis that the neural mechanisms underlying the smile are localized in the pontine tegmentum.


A new method of magnification cerebral angioautotomography for the analysis of intracranial aneurysms.
The authors have developed a new method of magnification cerebral angioautotomography which is performed by the use of a special head-swing apparatus. From the results of experiences of 24 intracranial aneurysms in 15 patients, the method has proved useful for the intracranial aneurysms in detecting the shape and the stalk of aneurysms which were obscured or hidden on conventional magnification cerebral angiography.


The integrity of liver protein synthesis in male rats treated with 1,2-dibromo-3-chloropropane.
Male rats treated with a single dose of 1,2-dibromo-3-chloropropane (DBCP) were tested for their ability to carry out the synthesis of liver proteins. In animals treated for 12 h, we found no changes in the uptake of [14C]orotic acid into liver RNA or the uptake of [3H]leucine into liver or serum protein. Uptake of [3H]leucine into the soluble fraction of the enlarged liver increased in proportion to liver size, while the uptake of [14C]orotic acid was unchanged. Examination of the ultrastructure of liver cells from rats treated for 12, 24, or 48 h revealed that the structure of the rough and smooth endoplasmic reticulum (RER; SER) were modified. An absence of ordered stacks of the RER and the presence of tangled nets of SER were noted.


Morphine and gabapentin decrease mechanical hyperalgesia and escape/avoidance behavior in a rat model of neuropathic pain.
A behavioral test paradigm that measures the aversive quality of stimulus-evoked pain in an animal model of neuropathic pain (L5 ligation) was tested for sensitivity to (1) different forces (476 and 202 mN) and frequencies (once every 15 or 30 s) of mechanical stimulation to the hyperalgesic paw and (2) different doses of the common antinociceptive compounds morphine (1 and 10 mg/kg) and gabapentin (30 and 90 mg/kg). Compared to non-ligated controls, the greater force (476 mN) and frequency (every 15 s) of mechanical stimulation of the hyperalgesic paw was associated with the greatest degree of escape/avoidance behavior. There was not a significant degree of escape/avoidance behavior at the lowest force (202 mN) and frequency (every 30 s) of mechanical stimulation. Compared to ligated vehicle treated controls, morphine (1 mg/kg) and gabapentin (90 mg/kg) decreased mechanical hyperalgesia and also attenuated the escape/avoidance behavior. The antinociceptive and antiaversive effects were found at doses that did not produce evidence of decreased motor activity. It is concluded that the behavioral test paradigm used to measure the aversiveness of stimulus-evoked nociceptive behavior is sensitive to different degrees of evoked pain and traditional analgesic compounds.


Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia: The Randomized RAIN-FLOW Study.
Background ST-segment-elevation myocardial infarction complicated with no reflow after primary percutaneous coronary intervention is associated with adverse outcomes. Although several hyperemic drugs have been shown to improve the Thrombolysis in Myocardial Infarction flow, optimal treatment of no reflow remains unsettled. Saline infusion at 20 mL/min via a dedicated microcatheter causes (flow-mediated) hyperemia. The objective is to compare the efficacy of pharmacologic versus flow-mediated hyperemia in patients with ST-segment-elevation myocardial infarction complicated with no reflow. Methods and Results In the RAIN-FLOW (Treatment of Slow-Flow After Primary Percutaneous Coronary Intervention With Flow-Mediated Hyperemia) study, 67 patients with ST-segment-elevation myocardial infarction and no reflow were randomized to receive either pharmacologic-mediated hyperemia with intracoronary adenosine or nitroprusside (n=30) versus flow-mediated hyperemia (n=37). The angiographic corrected Thrombolysis in Myocardial Infarction frame count and the minimal microcirculatory resistance, as assessed with intracoronary pressure-thermistor wire, dedicated microcatheter, and thermodilution techniques, were compared after study interventions. Both Thrombolysis in Myocardial Infarction frame count(40.2±23.1 versus 39.2±20.7; P=0.858) and minimal microcirculatory resistance (753.6±661.5 versus 993.3±740.8 Wood units; P=0.174) were similar between groups. Thrombolysis in Myocardial Infarction 3 flow was observed in 26.7% versus 27.0% (P=0.899). Flow-mediated hyperemia showed 2 different thermodilution patterns during saline infusion indicative of the severity of the no reflow phenomenon. In-hospital death and nonfatal heart failure were observed in 10.4% and 26.9%, respectively. Conclusions Both treatments showed similar (and limited) efficacy restoring coronary flow. Flow-mediated hyperemia with thermodilution pattern assessment allowed the simultaneous characterization of the no reflow degree and response to hyperemia. No reflow was associated with a high rate of adverse outcomes. Further research is warranted to prevent and to treat no reflow in patients with ST-segment-elevation myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04685941.


APA Health CARE: A Student-Led Initiative Addressing Health Care Barriers Faced by the Asian and Pacific Islander American Immigrant Population in Los Angeles.
Asian and Pacific Islander Americans face cultural, linguistic, and financial barriers to accessing health care. APA Health CARE (APAHC), a UCLA student-led organization, attempts to bridge these disparities through free community health screenings, health education seminars, and follow-up procedures. From 2011 to 2018, participants' demographic and health-related information were recorded during health fairs and follow-up phone calls. Trends in participant characteristics were analyzed over time. Health fair data were compared to data from follow-up phone calls to assess the effectiveness of health fair education and referral practices. 5635 participants from 69 health fairs were screened over the 8-year period. Follow-up contact was attempted for 2258 participants, of which 555 responded. Over time, a greater proportion of participants reported higher income, health insurance, and access to a regular doctor. Of those contacted at follow-up, 32.3% reported visiting a doctor, 50.2% reported making lifestyle changes, and 68.0% of those who were uninsured at health fairs reported obtaining health insurance within 1 month of attendance. Despite an observed increase in the proportion of participants having insurance and a regular doctor, health fair attendance remained consistent, possibly due to Asian American immigrants' preference for services that are convenient and linguistically and culturally accessible. Attendees reported visiting a physician, making lifestyle changes, and obtaining health insurance based on health fair referrals, suggesting measurable success with referral uptake and follow through. Student-led initiatives similar to APAHC can serve as catalysts to increase health literacy and motivate communities to seek health insurance and care.


The Perception, Level of Safety Satisfaction and Safety Feedback on Occupational Safety and Health Management among Hospital Staff Nurses in Sabah State Health Department.
This study aimed to determine the perception and level of safety satisfaction of staff nurses with regards to Occupational Safety and Health (OSH) management practice in the Sabah Health Department, and to associate the OSH management dimensions, to Safety Satisfaction and Safety Feedback. A cross-sectional study using a validated self-administered questionnaire was conducted among randomly respondents. 135 nurses responded the survey. Mean (SD) score for each dimension ranged from 1.70 ± 0.68-4.04 ± 0.65, with Training and Competence dimension (mean [SD], 4.04 ± 0.65) had the highest while Safety Incidence was the least score (mean [SD], 1.70 ± 0.68). Both mean (SD) scores for Safety Satisfaction and Safety Feedback was high, 3.28 ± 0.51 and 3.57 ± 0.73, respectively. Pearson's correlation analysis indicated that all OSH dimensions had significant correlation with Safety Satisfaction and Safety Feedback (r coefficient ranged from 0.176-0.512) except for Safety Incidence. The overall perception of OSH management was rather low. Significant correlation between Safety Satisfaction and Safety Feedback and several dimensions, suggest that each organization to put in place the leaders who have appropriate leadership and supervisory skills and committed in providing staff training to improve staff's competency in OSH practice. In addition, clear goals, rules, and reporting system will help the organization to implement proper OSH management practice.


QuickStats: Age-Adjusted Prevalence*(,)(†) of Hypertension Treatment(§) Among Adults Aged ≥18 Years with Hypertension,(¶) by Sex and Race/Ethnicity - National Health and Nutrition Examination Survey, United States, 2011-2014.
During 2011-2014, 74.6% of adults aged ≥18 years with hypertension reported taking antihypertensive medication. Overall, a smaller percentage of non-Hispanic Asian adults (63.8%) with hypertension reported taking antihypertensive medication compared with non-Hispanic white (75.8%), non-Hispanic black (77.3%), and Hispanic (70.7%) adults with hypertension. This pattern was found for both men and women with one exception: the difference between non-Hispanic Asian men and Hispanic men was not significant. A larger percentage of non-Hispanic white, non-Hispanic black, and Hispanic women reported taking antihypertensive medication than did their male counterparts.


Gene expression profiling for the prediction of therapeutic response to docetaxel in patients with breast cancer.
Systemic chemotherapy for operable breast cancer substantially decreases the risk of death. Patients often have de novo resistance or incomplete response to docetaxel, one of the most active agents in this disease. We postulated that gene expression profiles of the primary breast cancer can predict the response to docetaxel. We took core biopsy samples from primary breast tumours in 24 patients before treatment and then assessed tumour response to neoadjuvant docetaxel (four cycles, 100 mg/m2 daily for 3 weeks) by cDNA analysis of RNA extracted from biopsy samples using HgU95-Av2 GeneChip. From the core biopsy samples, we extracted sufficient total RNA (3-6 microg) for cDNA array analysis using HgU95-Av2 GeneChip. Differential patterns of expression of 92 genes correlated with docetaxel response (p=0.001). Sensitive tumours had higher expression of genes involved in cell cycle, cytoskeleton, adhesion, protein transport, protein modification, transcription, and stress or apoptosis; whereas resistant tumours showed increased expression of some transcriptional and signal transduction genes. In leave-one-out cross-validation analysis, ten of 11 sensitive tumours (90% specificity) and 11 of 13 resistant tumours (85% sensitivity) were correctly classified, with an accuracy of 88%. This 92-gene predictor had positive and negative predictive values of 92% and 83%, respectively. Correlation between RNA expression measured by the arrays and semiquantitative RT-PCR was also ascertained, and our results were validated in an independent set of six patients. If validated, these molecular profiles could allow development of a clinical test for docetaxel sensitivity, thus reducing unnecessary treatment for women with breast cancer.


Cone-beam Computed Tomography for Detecting Vertical Root Fractures in Endodontically Treated Teeth: A Systematic Review.
A vertical root fracture (VRF), commonly found in teeth with endodontic treatment, is challenging to diagnose and has poor treatment outcomes. Cone-beam computed tomography (CBCT) has become an increasingly popular imaging modality in endodontics, but image artifacts arising from root-filling materials may hinder VRF detection. The aim of this investigation was to conduct a systematic review to assess the diagnostic ability of CBCT for detecting VRFs in endodontically treated teeth. A systematic review of in vivo clinical diagnostic literature (initial search December 2014, updated August 2015) was conducted. Assessment of methodological quality was performed by using the modified Quality Assessment of Diagnostic Accuracy Studies tool. Four studies with a total of 130 patients were included. The reported ranges of values were 40%-90% for VRF prevalence, 84% (0.64-0.95) to 100% (0.83-1.00) for sensitivity, 64% (0.35-0.87) to 100% (0.03-1.00) for specificity, 71% (0.51-0.87) to 100% (0.63-1.00) for positive predictive value, and 50% (0.01-0.99) to 100% (0.84-1.00) for negative predictive value. All 4 studies revealed multiple items at high risk or unclear risk of bias. Because of the significant imprecision in the range of reported estimates and the biases observed in the included studies, there is currently insufficient evidence to suggest that CBCT is a reliable test in detecting VRFs in endodontically treated teeth.


Mineral utilization of malted sorghum and corn with added crayfish in rats.
Forty adult rats were used to study the mineral balances of malted and unmalted wet- or dry-milled sorghum and corn combined with crayfish and fed rats for 12 days. Five out of the twelve days were for adjustment and the rest for balance period. These mixtures each was calculated to provide 1.6 g N daily for the entire study period. Malting and wet milling produced increases in crude protein content of the cereal grains. However, the increases were much more evident in sorghum. Wet milling caused increases in calcium retention in corn groups. It produced the same effect on phosphorus balance only in sorghum groups. On the other hand, it produced positive iron balances only in unmalted corn and malted sorghum groups. The results suggest improved mineral nutriture due to malting except for the Fe retention of the MDC:CR group.


Charge conversion enables quantification of the proximity between a normally-neutral mu-conotoxin (GIIIA) site and the Na+ channel pore.
mu-Conotoxin (mu-CTX) inhibits Na+ flux by obstructing the Na+ channel pore. Previous studies of mu-CTX have focused only on charged toxin residues, ignoring the neutral sites. Here we investigated the proximity between the C-terminal neutral alanine (A22) of mu-CTX and the Na+ channel pore by replacing it with the negatively charged glutamate. The analog A22E and wild-type (WT) mu-CTX exhibited identical nuclear magnetic resonance spectra except at the site of replacement, verifying that they have identical backbone structures. A22E significantly reduced mu-CTX affinity for WT mu1 Na+ channels (90-fold), as if the inserted glutamate repels the anionic pore receptor. We then looked for the interacting partner(s) of residue 22 by determining the potency of block of Y401K, Y401A, E758Q, D762K, D762A, E765K, E765A and D1241K channels by WT mu-CTX and A22E, followed by mutant cycle analysis to assess their individual couplings. Our results show that A22E interacts strongly with E765K from domain II (DII) (deltadeltaG=2.2 +/- 0.1 vs. <1 kcal/mol for others). We conclude that mu-CTX residue 22 closely associates with the DII pore in the toxin-bound channel complex. The approach taken may be further exploited to study the proximity of other neutral toxin residues with the Na+ channel pore.


Synthesis of rat muscle carbonic anhydrase III in a cell-free translation system.
Carbonic anhydrase III (CA III) was identified in the products of rat soleus muscle RNA translation in vitro by both a radioimmunoassay and a specific immunoprecipitation technique followed by SDS--polyacrylamide gel electrophoresis analysis of the precipitated antigen. The primary translation product has the same Mr-value as the native isoenzyme. CA III mRNA was found to represent approximately 0.55% of the total mRNA present in rat soleus muscle.


Coumarin-benzimidazole hybrids: A review of developments in medicinal chemistry.
Coumarin and benzimidazole are privileged structures in medicinal chemistry and are widely used in drug discovery and development due to their vast biological properties. The pharmacokinetic and pharmacodynamic properties of the individual scaffolds can be improved by developing coumarin-benzimidazole chimeric molecules via molecular hybridization approach. The three major classes of coumarin-benzimidazole hybrids are merged, fused and spacer-linked hybrids. Depending on the substitution position, fused hybrids and spacer-linked hybrids can be further classified as coumarin-C3 hybrids, coumarin-C4 hybrids and coumarin-C5/6/7/8 hybrids. Most of the coumarin-benzimidazole hybrid molecules exhibited potent anticancer, antiviral, antimicrobial, antitubercular, anthelmintic, anti-inflammatory, antioxidant, anticonvulsant and carbonic anhydrase inhibitory activities. The fused coumarin-C3 hybrid (2), thiomethylene-linked coumarin-C3 hybrid (45), N-glucoside substituted thiomethylene-linked coumarin-C3 hybrid (37c), amide-linked coumarin-C3 hybrid (50a), and sulfonylmethylene-linked coumarin-C4 hybrid (63) were identified as the representative potent anticancer, antimicrobial, antiviral, antioxidant and antitubercular agents respectively. The biological properties of the different classes of coumarin-benzimidazole hybrids with their structure-activity relationship studies and the mechanism of action studies were presented in this review, aiming to help the researchers across the globe to generate future hybrid molecules as potential drug candidates.


Repair of ochratoxin A-induced DNA damage and modulation of OTA-related genotoxicity by co-incubation with bile acids and methotrexatein vitro.
The mycotoxin ochratoxin A (OTA) induced DNA strand breaks in porcine urinary bladder epithelial cells (PUBEC) and in Madin Darby canine kidney (MDCK) cells. A co-incubation with bile acids or methotrexate reduced or even prevented this adverse effect of OTAin vitro. The protective effect is possibly attributable to a decreased OTA uptake in cells, since bile acids and methotrexate are known to share common transport systems such as organic anion transporters (OAT) and/or organic anion transporting polypeptides (OATP) with the mycotoxin. OTA uptake in cells and its modulation can be one factor which determines the extent of adverse effects in different cell types. Another aspect of interest in this regard relates to repair of DNA damage: PUBEC cells are sensitive to OTA-induced damage which is more pronounced when DNA repair is blocked (by cytosine β-D-arabino-furanosid/hydroxyurea). On the other hand, when cells are kept in fresh (toxin-free) medium for 3 h, OTA-induced DNA damage decreased to control levels.


Recontacting subjects in mutagen-exposure-monitoring studies: II. Results of a questionnaire study of mutagenesis researchers, with review of the pertinent literature.
A questionnaire on the attitudes of mutagenesis researchers regarding the health significance of and the use of data from tests of human mutagen exposure or genetic damage was completed by 71 of 312 (23%) individuals who had been participants in meetings or organizations concerned with mutagenesis research. On a point scale of 0 to 10, with 0 indicating strong disagreement, 5 indicating uncertainty, and 10 indicating strong agreement, the average respondent felt (8.31 +/- 2.27) that data indicating a probable health hazard should be shared automatically with the subjects, but was also moderately concerned about psychological distress of subjects learning of study results indicating abnormally high mutagen exposure (6.14 +/- 2.57) or genetic damage (6.94 +/- 2.48). The average respondent felt that follow-up of subjects could improve the quality of mutagen-exposure-monitoring studies (8.33 +/- 1.49), disagreed that subjects whose laboratory data suggested unusually severe exposure or damage should not be asked about possible sources of exposure (1.15 +/- 1.32), and disagreed that it was ethical to follow up but not discuss results with subjects having laboratory evidence of abnormal mutagen exposure (3.78 +/- 3.43) or genetic damage (3.06 +/- 3.17) to see how many developed cancer relative to a control group. Fifteen specific tests for measuring mutagen exposure or genetic damage were rated on a scale of 0 to 10, with 0 being "totally experimental" and 10 being "absolutely diagnostic of degree of exposure or genetic damage." Values ranged from 6.13 +/- 2.67 for karyotyping leukocytes to 3.43 +/- 2.43 for quantifying frequency of rare red cells with mutant protein. This study may help in decision making regarding follow-up of mutagen-exposed subjects.


Over-expression of genes coding for proline oxidase, riboflavin kinase, cytochrome c oxidase and an MFS transporter induced by acriflavin in Trichophyton rubrum.
Acriflavin (3,6-acridinediamine) and other acridine derivatives act in both prokaryotic and eukaryotic cells at the level of DNA-coiling enzymes (topoisomerases) causing the stabilization of the enzyme-DNA cleavable complex. In order to better understand the mode of action of acriflavin, Differential Display RT-PCR was used to isolate transcripts specifically over-expressed during exposure of Trichophyton rubrum mycelia to this drug. Five transcripts, whose differential expressions were confirmed by Northern blotting, revealed genes not previously described in this dermatophyte. Functional grouping identified putative enzymes possibly involved in the mitochondrial respiratory electron-transport chain and in iron transport. These results may be relevant to our understanding of the molecular events involved in the stress response of T. rubrum to acriflavin.


Dermolipoma in an Unusual Location: A Case Report and Literature Review.
A healthy nine-year-old Japanese male presented with a history of inferonasal conjunctival mass that was noted to increase in size in a few years' time. Initial examination revealed a 10-mm soft yellowish inferonasal conjunctival mass with a whitish surface. The rest of the examination findings were unremarkable. A computed tomographic scan was done and showed a conjunctival mass that was not connected posteriorly to the orbital fat but had the same density as the orbital fat. Complete surgical excision was performed, and pathologic evaluation of the excised specimen revealed a dermolipoma. The patient was subsequently followed up to monitor for any postoperative complications. Three months following the operation, there was no recurrence of the tumor, and the patient had an excellent cosmetic outcome.


Investigation of Aerobic and Muscular Fitness and Concussion Among Service Academy Cadets at the United States Air Force Academy: Results from the CARE Consortium.
Concussion has become the signature injury facing the U.S. military. However, little is understood about the relationship between military fitness and concussion recovery. The current study examined the recoveries of cadets at a U.S. Service Academy to determine whether preinjury physical fitness improved recovery and whether recovery was associated with post-injury physical fitness measures. Participants were enrolled in a longitudinal study of concussion. Aerobic Fitness Test (AFT) and Physical Fitness Test (PFT) data were used to estimate cadet fitness. Survival analysis evaluated significant estimators of concussion recovery time. Linear regression models were used to explore the relationship between recovery duration and change in physical fitness scores. Between 2014 and 2017, 307 (n = 70; 22.80% Women) cadets who had sustained a concussion were enrolled. Preinjury physical fitness was not significantly associated with recovery duration (P > .05). Men and intercollegiate cadets took fewer days to reach recovery milestones. Compared to women, men had greater decrements in the Aerobic Fitness Test total score (P < .05) and increased 1.5-mile time postconcussion (P < .05). Women had greater decreases in push-ups postconcussion compared to males (P < .05). There was a trend for a negative association between days until asymptomatic and change in the Physical Fitness Test score (P = .07). Preconcussion physical fitness levels do not appear to impact concussion recovery time among a highly physically fit cohort. Possible methods to reduce the effect of symptom duration on strength-related physical fitness should be investigated along with evaluating reductions in strength as a possible mechanism for postconcussion injury risk.


Retracted: The Performance of Artificial Intelligence Translation App in Japanese Language Education Guided by Deep Learning.
[This retracts the article DOI: 10.1155/2022/7962722.].


Sex difference in polyethylenglycol-induced thirst.
The polyethylenglycol-induced thirst in male and female castrated rats has been studied. The polyethylenglycol (PG) increases the water intake more in females than in males. Estradiol benzoate and testosterone P. diminishes the amount of water drunk after PG treatment in the females, but not in the males.


Neuronal regulation of innate lymphoid cell responses.
The immune system and the peripheral nervous system are distributed throughout the body and surveil vital organs utilizing various sensory mechanisms. Previous studies have demonstrated that tissue-resident innate lymphoid cells (ILCs) and neurons are heavily enriched in the body's barrier surfaces, where it is critical to detect and rapidly adapt to the changes in dietary, microbial and other environmental stimuli. However, our understanding of how these two sensory systems cooperatively integrate these diverse signals to orchestrate host responses remains incomplete. Recent research has provided insights into how neurotrophic and neuronally derived factors regulate the functions of ILCs, establishing the neuro-ILC axis as a crucial component of broader neuro-immune interactions. Further, neurons express receptors for many cytokines produced by ILCs, opening the possibility for bidirectional neuro-immune interactions in regulating tissue homeostasis and inflammation. This review highlights recent advances in the cellular and molecular mechanisms of neuro-ILC interactions and their potential therapeutic implications.


Pharmaceutical virtue.
In the early history of psychopharmacology, the prospect of developing technologically sophisticated drugs to alleviate human ills was surrounded with a fervor that could be described as religious. This paper explores the subsequent history of the development of psychopharmacological agents, focusing on the ambivalent position of both the industry and its employees. Based on interviews with retired pharmaceutical employees who were active in the industry in the 1950s and 1960s when the major breakthroughs were made in the development of MAOIs and SSRIs, the paper explores the initial development of educational materials for use in sales campaigns. In addition, based on interviews with current employees in pharmaceutical sales and marketing, the paper describes the complex perspective of contemporary pharmaceutical employees who must live surrounded by the growing public vilification of the industry as rapacious and profit hungry and yet find ways to make their jobs meaningful and dignified. The paper will contribute to the understudied problem of how individuals function in positions that require them to be part of processes that on one description constitute a social evil, but on another, constitute a social good.


Synthesis of a "Butterfly Cage" Based on a Double-Decker Silsesquioxane.
Novel polyhedral structures were prepared with a butterfly-shape composed of oligosiloxane wings and a double-decker silsesquioxane (DDSQ) body. The compounds were synthesized in two steps from commercially available alkoxysilanes, and their structures were confirmed using spectroscopic methods and X-ray crystallography. Not like other phenyl-substituted cage silsesquioxanes, these butterfly cages show very good solubility in common organic solvents. The crystal structures clearly showed their unique features: a larger space with longer siloxane chains and a very flexible framework. Moreover, these compounds are thermally stable with a Td5 (5 % weight loss temperature) over 320 °C.


Why the Central Dogma: on the nature of the great biological exclusion principle.
The Central Dogma of molecular biology posits that transfer of information from proteins back to nucleic acids does not occur in biological systems. I argue that the impossibility of reverse translation is indeed a major, physical exclusion principle that emerges due to the transition from the digital information carriers, nucleic acids, to analog information carriers, proteins, which involves irreversible suppression of the digital information.


Rat memory T lymphocytes. II. Differences in macrophage-dependent activation shown by Actinomyces viscosus antigens and by mitogens, using silica in vitro.
Protein-coated silica, a macrophage toxin, was used to assess the requirement for accessory cells in the induction of an in vitro proliferative response to (i) antigens from Actinomyces viscosus and (ii) the mitogens conconavalin A (Con A) and phytohaemagglutinin (PHA). T cells were obtained from RIC-Sprague-Dawley rats primed in vivo with A. viscosus Nyl by splenectomy and filtering the spleen cell suspensions through Degalan Ig-anti-IgG columns. In the presence of 100 microgram silica/ml during 4 days of culture, the proliferative response of T lymphocytes was not diminished. In contrast, when the T cells were precultured with silica for 24 h, washed, and subsequently cultured with the antigen fractions, antigen-induced proliferation was abolished. This procedure, however, had no influence on mitogen-induced proliferation was abolished. This procedure, however, had no influence on mitogen-induced T-cell activation. It is therefore concluded that the antigen-dependent anamnestic in vitro response (but not activation by mitogens) of rat T lymphocytes needs help from silica-sensitive macrophages.


Post-cone biopsy traumatic neuroma of the uterine cervix.
Traumatic neuroma rarely occurs in the female genital tract and is probably the rarest complication of cone biopsy. A traumatic neuroma of the cervix found incidentally in the hysterectomy specimen of a 40-year-old woman who had previous conization for cervical squamous intraepithelial neoplasia grade 3 is presented. Significance of the finding is described.


Thermodynamic properties of the binding of alpha-, omega-amino acids to the isolated kringle 4 region of human plasminogen as determined by high sensitivity titration calorimetry.
The binding of alpha-, omega-amino acids, which are important effectors of human plasminogen activation, to the isolated kringle 4 (K4) peptide region of this protein has been investigated by high sensitivity titration calorimetry. The titration curve of the heat changes accompanying binding of the widely employed ligand, epsilon-aminocaproic acid (EACA), to K4 were deconvoluted to yield the following binding characteristics: n = 0.87 +/- 0.08 mol/mol; Ka = 3.82 +/- 0.37 x 10(4) M-1; delta H = -4.50 +/- 0.22 kcal/mol; delta S = 6.01 +/- 0.7 entropy units; and delta G = 6.29 +/- 0.06 kcal/mol. Here, both delta H and delta S provide the driving force of the interaction, with both hydrogen bonds and hydrophobic interactions, the latter which may result from an induced conformational change in K4 upon ligand binding, as well as possible alterations in peptide-bound water structure, providing the stabilizing forces for complex formation. The thermodynamic binding parameters were not greatly influenced by pH between the values of 5.5 and 8.2, suggesting that titratable groups on K4 in this pH region did not influence the binding. Investigations of the binding properties of structural analogues of EACA to K4 demonstrated that definable steric requirements existed for a maximal interaction, with spacing between the functional groups on EACA, as well as a hydrophobic region of this molecule, being important. This rapid and reliable method for measuring all thermodynamic parameters of formation of this complex at a given temperature can now be employed to investigate this important interaction with a wide variety of kringles and modified kringles to provide a more complete understanding of the necessary factors for this binding to occur.


Crossover interference underlies sex differences in recombination rates.
In many organisms, recombination rates differ between the two sexes. Here we show that in mice, this is because of a shorter genomic interference distance in females than in males, measured in Mb. However, the interference distance is the same in terms of bivalent length. We propose a model in which the interference distance in the two sexes reflects the compaction of chromosomes at the pachytene stage of meiosis.


The significance of heat shock proteins in breast cancer therapy.
The evalutionary conserved heat shock proteins are involved basically life protecting mechanisms against harmful extracellular effects such as primarily heat shock response. Normally, the expression of these proteins is increased for cellular adaptation to high temperature. This increase is also important in the etiology of breast cancer. Overexpression of heat shock proteins is associated with reduced disease-free survival in breast cancer. However, increased expression of these proteins is related to acquired resistance of traditional chemotherapeutic drugs in use in breast cancer treatment. In this review, we discuss the multiple roles of heatshock proteins in resistance and where we are to overcome this in clinical practice.


Spacer-elongated cell wall fusion proteins improve cell surface expression in the yeast Saccharomyces cerevisiae.
Fusion proteins for cell surface expression in the yeast Saccharomyces cerevisiae were constructed that consisted of the N-terminal leader sequence of Kre1p, followed by the nine amino acid viral epitope hemagglutinin (HA), and the carboxyterminal anchoring domain of either Cwp2p or Flo1p. All fusions were constitutively expressed under transcriptional control of the phosphoglycerate kinase promoter and immunofluorescence analysis indicated that in each construct the HA peptide was correctly anchored to the outer yeast cell surface. Successful solubilization of the cell wall fusions by laminarinase treatment indicated that the fusions are covalently linked to cell wall beta-1,3- D-glucans in vivo. FACS analyses further demonstrated that 70% of the yeast cell population expressed the corresponding cell wall fusion. Neither the number of positive cells within the population nor the distribution of the fusion at the single-cell level were negatively affected by replacing the "heterologous" Kre1p leader by the "native" Cwp2p leader. Insertion of a 350 amino acid Ser/Thr-rich spacer sequence into the fusions led to a dramatic increase in HA peptide accessibility on the yeast cell surface. Our data show that FACS analyses represent a valuable means for investigating cell surface expression, and indicate that artificial-spacer-elongated cell wall fusions might raise novel possibilities for cell surface expression of heterologous proteins in yeast.


Developmental aspects of normal EEG.
In pediatrics recording of EEG can range from premature infants aged just 25 weeks of gestation to young adults. Recording EEG in pediatrics ranges from 25 weeks of gestation premature in the incubator to young adults. Hence, recording conditions need to be adapted to very different situations, not only of age but also of environment, asepsis, and behavior.This requires that recording conditions be adapted to very different situations, not only of age but also of environment, asepsis and behavior. The two major determinants of EEG features are the level of vigilance and age. Standard examination includes spontaneous sleep until the age of 5 years, and hyperventilation and intermittent light stimulation in older children. Hyperventilation may modify the tracing in a physiological way until adolescence. One of the major characteristics of a child's EEG recording is its course over time that parallels rapid brain maturation. EEG changes are particularly rapid in early age and they involve both temporal and spatial organization. In premature babies modifications appear by two 2 weeks, in infancy by 1 month and in childhood by 1 year, before reaching the adult patterns at an age varying between 8 and 12 years of age. Apart from being aware of the normal EEG patterns according to thein children of different ages, it is important to recognize unusual patterns that are not linked to a pathological situation. Most important are the interpretation and the conclusion of the EEG tracing and any conclusions reached, for which and a precise knowledge besides clinical information is mandatory for this purpose is essential.


Eosinophilic esophagitis: A relevant entity for the otolaryngologist.
Eosinophilic esophagitis (EE) is a recently recognised pathologic entity whose prevalence has risen significantly since it was first described. Its diagnosis represents a challenge for different medical specialties, among which ENT specialists play an important role. Clinical suspicion in a patient with recurrent food impaction or a child with eating disorders and history of hypersensitivity constitutes the first warning sign of a possible EE. The purpose of this review is to highlight EE as a possible differential diagnosis in patients with deglutition disorders and describe the possible clinical symptoms that should alert the ENT specialist to perform appropriate diagnostic tests and procedures. The transnasal esophagoscopy, performed in-office by the ENT, is ideal for reducing possible underdiagnosed cases. Given the fact that an ENT specialist will evaluate a great many patients with deglutition disorders, it is paramount for possible EE cases to be suspected and recognised so that a correct multidisciplinary approach involving not only ENT specialists but also paediatricians, gastroenterologists, allergologists and pathologists can be established. Identifying the dietary component responsible for the esophageal inflammation and removing that food from the patient's diet is the key in the treatment of this immune-mediated disease.


Bivalent inhibition of beta-tryptase: distance scan of neighboring subunits by dibasic inhibitors.
Based on bifunctional diketopiperazines as templates and m-aminomethyl-phenylalanine as arginine mimetic, we have synthesized a new class of structurally related dibasic tryptase inhibitors with systematically increasing spacer length. These compounds were used to scan the distance between the active sites of two neighboring subunits of the beta-tryptase tetramer. The K(i)-values obtained are a function of the distance between the terminal amino groups and indicate optimal binding of inhibitors with 29-31 bonds between the amino groups. These experimental data are in full agreement with predictions derived from a novel modeling program that allows the docking of bivalent ligands.


High-frequency data reveal differential dissolved and suspended solids behavior from a mixed restored prairie and agricultural catchment.
Quantifying temporal variability and fluxes within hydrologic catchments is critical to understanding the underlying chemical and physical processes leading to material transport. Measuring variability and fluxes requires sampling at time scales similar to the time scale of process occurrence. This demand has led to the development of automated sampling systems designed to sample at high frequencies, on the order of minutes. While widely deployed in a variety of systems, we installed two high-frequency sampling devices in a single drainage comprised of restored prairie and agricultural land uses in temperate Eastern Nebraska. The sampling systems determined flow rate, conductivity, and turbidity at 15-minute intervals for a twelve-month period. Conductivity was used as a proxy for total dissolved solids (TDS) concentrations and turbidity was used as a proxy for total suspended solids (TSS) concentrations. Using the high-frequency data, estimates of solids flux were calculated, error on the estimates was constrained, the effects of sample timing were considered, and conductivity and turbidity changes during precipitation events were examined. Overall, TDS fluxes were about three times higher than TSS fluxes from the catchment as a whole. However, the TSS fluxes were higher in the agricultural section of the catchment than from the restored prairie. Sheet and rill soil loss estimates from both the restored prairie and agricultural settings were low (<0.060 mm/yr). For TDS flux calculations, sampling at a monthly frequency gave a value that was only 11% lower than sampling every 15 min. For TSS flux calculations, sampling only during precipitation events (0.7% of the time) would capture 67% of the annual flux. Thus, minimizing error in sampling strategies depends on the constituent being analyzed.


Glia in development, function, and neurodegeneration of the adult insect brain.
Glial cells have long been viewed as a passive framework for neurons but in the meanwhile were shown to play a much more active role in brain function and development. Several reviews have described the function of glia in the insect embryo. The focus of this review is the role of glial cells in the development and function of the normal and diseased adult brain. In different insect species, a considerable variety of central nervous system glia has been described indicating adaptation to different functional requirements. In the development of the adult visual and olfactory system, glial cells guide incoming axons acting as intermediate targets. Glia are part of the insect blood-brain barrier, provide nourishment for neurons, and help to regulate the extracellular concentration of ions and neurotransmitters. To fulfill these tasks insect glial cells, like vertebrate glia, interact with each other and with neurons, thus influencing neural activity. The examples presented suggest that crosstalk between all brain cells is necessary not only to develop and maintain the complex insect brain but also to endow it with the capacity to respond and adapt to the changing environment.


High expression of TIMP-1 in human breast cancer tissues is a predictive of resistance to paclitaxel-based chemotherapy.
For breast cancer patients with lymph node metastasis, paclitaxel is the first-line chemotherapy drug. Clinical studies showed that some patients with breast cancer were insensitive to paclitaxel, which led to chemotherapy failure. Today, no validated markers exist for the prediction of chemotherapy sensitivity in this patient group. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been shown to protect against apoptosis. Epidemiological studies have also associated elevated tumor tissue TIMP-1 levels with a poor response to cyclophosphamide/methotrexate/5-fluorouracil and anthracycline-based chemotherapy. Additionally, our previous study proved that TIMP-1 significantly decreased the sensitivity of breast cancer cells to paclitaxel-induced apoptosis by enhancing degradation of cyclin B1. These data imply that TIMP-1 may be a useful predictive biomarker for chemotherapy resistance. In this retrospective study, we investigated the association between expression levels of TIMP-1 protein in the primary tumor and objective response to paclitaxel-based chemotherapy in 99 patients with breast cancer. With Kaplan-Meier survival analysis, the patients with high TIMP-1 levels were found to have significantly worse 5-year DFS (71.1 %) than the patients with low levels (88.5 %; P = 0.020). Similarly, the patients with high TIMP-1 levels had significantly worse 5-year OS (78.9 %) than patients with low levels (96.7 %; P = 0.004). In Cox's univariate and multivariate analyses, TIMP-1 was prognostic for both DFS and OS. Our data showed that elevated tumor tissue TIMP-1 levels were significantly associated with a poor response to paclitaxel-based chemotherapy, and TIMP-1 might be a potential biomarker for predicting response of breast cancer patients to paclitaxel-based chemotherapy.


Vitamin K-dependent blood coagulation proteins form hetero-dimers.
The later stages of the blood coagulation cascade are characterized by the presence of vitamin K-dependent proteins and their involvement in membrane-bound, multi-protein converting complexes with an essential requirement for calcium ions. Specific interactions between zymogens and activating enzymes have not yet been identified. Here we describe a crystallographic study of prothrombin fragment 1 (residues 1-156 of prothrombin) which indicates that vitamin K-dependent coagulation proteins have specific association sites that allow them to form hetero-dimers. The calcium-induced formation of a hetero-dimer between fragment 1 and factor X is demonstrated by cross-linking. Such hetero-dimers of vitamin K-dependent proteins could be significant in the coagulation system.


2-Amino-5-chloro-pyrimidin-1-ium hydrogen maleate.
In the title salt, C(4)H(5)ClN(3) (+)·C(4)H(3)O(4) (-), the 2-amino-5-chloro-pyrimidinium cation is protonated at one of its pyrimidine N atoms. In the roughly planar (r.m.s. deviation = 0.026 Å) hydrogen malate anion, an intra-molecular O-H⋯O hydrogen bond generates an S(7) ring. In the crystal, the protonated N atom and the 2-amino group of the cation are hydrogen bonded to the carboxyl-ate O atoms of the anion via a pair of N-H⋯O hydrogen bonds, forming an R(2) (2)(8) ring motif. The ion pairs are connected via further N-H⋯O hydrogen bonds and a short C-H⋯O inter-action, forming layers lying parallel to the bc plane.


Proliferation pattern of capillary endothelial cells in chorioallantoic membrane development indicates local growth control, which is counteracted by vascular endothelial growth factor application.
The density and distribution of whole mount BrdU-anti-BrdU labeled endothelial cells (days 6-15) in the chick chorioallantoic membrane (CAM) was analyzed with computer-assisted microscopy. A significant loss of proliferative activity was noted after day 10: the density of labeled nuclei (in 10(-2) mm-2) decreased from a median 7.78 (days 6, 8, 10) to 2.42 (days 12, 14, 15). CAMs initially showed random patterns of labeled endothelial cells, but changed to clearly focal patterns after day 12. A regular arrangement of labeled nuclei was never seen. After application of vascular endothelial growth factor (VEGF) to the day 13 CAM, a significant increase in proliferative activity (11.50) and a random distribution of labeled endothelial cells was observed on day 15. Development of CAM precapillary vessels was assessed in terms of length density (in mm-1, mean +/- standard deviation), which was augmented three-fold from day 6 (1.22 +/- 0.05) to day 14 (3.54 +/- 0.23) and then remained nearly constant. VEGF application from day 13 to 15 raised arterial length per unit area to 4.53 +/- 0.77. It is concluded that normally a local regulation of endothelial proliferation and differentiation develops in the CAM, which doubles capillary endothelial cell density but simultaneously adapts to the decreasing need for endothelial cells, and thus maintains the quasi two-dimensional vessel pattern. However, proliferative foci persist in the capillary layer after day 10, and precapillary vessel density continues to increase until day 14. VEGF enhances DNA synthesis in all capillary endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)


High-performance hydrophobic interaction chromatography of estrogen receptors and magnesium dependent protein kinase(s): detection of two molecular forms of estrogen receptors in the presence and absence of sodium molybdate.
The separation characteristics of estrogen receptors (ER) from human breast cancer were evaluated based on their hydrophobic properties. Results show that (1) two distinct hydrophobic isoforms of ER exist either in the presence of sodium molybdate (peaks MI and MII with retention times of 15-17 min and 24-26 min) or in its absence (peaks I and II with retention times of 25-27 min and 34-36 min respectively); (2) this is observed whether molybdate (MoO2-4) is added to prepared cytosol or to the buffer prior to homogenization; (3) isoform MII and I separated with similar retention times suggesting they are the same ER species; and (4) isoform MI (Rt = 15-17 min) is a distinct ER species from either MII/I (Rt = 25-28 min) or II (Rt = 34-36 min). The latter isoform represents a highly hydrophobic species seen only in the absence of MoO2-4. Finally, (5) MoO2-4 ions appear to interconvert the most hydrophobic species (II) into the least hydrophobic isoform (MI) with virtually no change in the quantity of isoform(s) MII/I. However, it cannot be ascertained if the II----MI interconversion proceeds via isoform MII/I. Isoform II may result from the interaction with the stationary phase via its DNA binding site since MoO2-4, which is suggested to directly interact with this site, selectively interacts with peak II. These results imply the usefulness of inclusion of receptor stabilizing reagents in the mobile phase for preserving receptor integrity and in elucidating the interrelationships of ER isoforms and associated macromolecules.


Management of proximal interphalangeal joint injuries.
Injuries about the PIP joint of the finger are commonly encountered by primary care physicians and are associated with significant morbidity, including pain, stiffness, instability, premature degenerative arthritis, and residual deformities. An accurate understanding of the regional anatomy and appreciation of the mechanism of injury allows for classification so that a treatment protocol can be formulated for each injury pattern. Emphasis on careful consideration of the implications of open reduction, rational splinting, and early, active, protected motion provides for the most favorable outcome.


Methicillin-resistant Staphylococcus aureus infections.
Methicillin-resistant Staphylococcus aureus (MRSA) is an increasingly common multidrug-resistant clinical pathogen responsible for increasing health costs and for patient morbidity and mortality. Presented in this review, the definition, cell and molecular biology, epidemiology, prevention, diagnosis, and treatment of MRSA infections, including skin and soft tissue infections, bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system infections, are addressed. In the treatment of MRSA, this article highlights several common antibiotics that retain activity against different strains of MRSA.


Synthesis of 5-[1-hydroxy(or methoxy)-2-bromo(or chloro)ethyl]-2'-deoxyuridines and related halohydrin analogues with antiviral and cytotoxic activity.
A series of new 5-(1-hydroxy-2-haloethyl)-2'-deoxyuridines (3, 6, 8) were synthesized in 60-70% yields by addition of HOX (X = Br, Cl, I) to the vinyl substituent of the respective 5-vinyl-2'-deoxyuridines (2, 5, 7). Treatment of 3a,b with methanolic sulfuric acid afforded the corresponding 5-(1-methoxy-2-haloethyl)-2'-(deoxyuridines (4a,b). The 5-(1-hydroxy-2-chloroethyl) (3b), 5-(1-methoxy-2-bromoethyl) (4a), 5-(1-hydroxy-2-bromo-2-(ethoxycarbonyl)ethyl) (6a), and 5-(1-hydroxy-2-iodo-2-(ethoxycarbonyl)ethyl) (6b) derivatives exhibited in vitro antiviral activity (ID50 = 0.1-1 microgram/mL range) against herpes simplex virus type 1 (HSV-1). 5-(1-Hydroxy-2-bromo-2-(ethoxycarbonyl)-ethyl)-2'-deoxyuridine (6a) was the most active cytotoxic agent in the in vitro L1210 screen exhibiting an ED50 of 11 micrograms/mL relative to melphalan (ED50 = 0.15 micrograms/mL).


Antitumour activity of pembrolizumab in advanced mucosal melanoma: a post-hoc analysis of KEYNOTE-001, 002, 006.
Mucosal melanoma is an aggressive melanoma with poor prognosis. We assessed efficacy of pembrolizumab in patients with advanced mucosal melanoma in KEYNOTE-001 (NCT01295827), -002 (NCT01704287), and -006 (NCT01866319). Patients received pembrolizumab 2 mg/kg every 3 weeks (Q3W) or 10 mg/kg Q2W or Q3W. Response was assessed by independent central review per RECIST v1.1. 1567 patients were treated and 84 (5%) had mucosal melanoma. Fifty-one of 84 were ipilimumab-naive. In patients with mucosal melanoma, the objective response rate (ORR) was 19% (95% CI 11-29%), with median duration of response (DOR) of 27.6 months (range 1.1 + to 27.6). Median progression-free survival (PFS) was 2.8 months (95% CI 2.7-2.8), with median overall survival (OS) of 11.3 months (7.7-16.6). ORR was 22% (95% CI 11-35%) and 15% (95% CI 5-32%) in ipilimumab-naive and ipilimumab-treated patients. Pembrolizumab provides durable antitumour activity in patients with advanced mucosal melanoma regardless of prior ipilimumab.


Apoptotic death in an in vitro model of neuronal oxidative stress.
1. Oxidative stress is believed to be an important mediator of neuronal cell death but the precise mechanism by which this occurs is unknown. 2. We have developed an in vitro model of neuronal oxidative stress to study the pathways by which free radicals kill neurones. 3. We have shown that oxidative stress, cystine deprivation and glutathione depletion results in cell death with the morphological and biochemical features of apoptosis. 4. Neuronal apoptosis induced by oxidative stress can be inhibited by macromolecular synthesis inhibitors. 5. This in vitro model will be a valuable tool for defining the molecular targets of toxic free radicals in neurones and, in turn, in designing rational new therapies for free radical mediated diseases.


The TPR domain of BepA is required for productive interaction with substrate proteins and the β-barrel assembly machinery complex.
BepA (formerly YfgC) is an Escherichia coli periplasmic protein consisting of an N-terminal protease domain and a C-terminal tetratricopeptide repeat (TPR) domain. We have previously shown that BepA is a dual functional protein with chaperone-like and proteolytic activities involved in membrane assembly and proteolytic quality control of LptD, a major component of the outer membrane lipopolysaccharide translocon. Intriguingly, BepA can associate with the BAM complex: the β-barrel assembly machinery (BAM) driving integration of β-barrel proteins into the outer membrane. However, the molecular mechanism of BepA function and its association with the BAM complex remains unclear. Here, we determined the crystal structure of the BepA TPR domain, which revealed the presence of two subdomains formed by four TPR motifs. Systematic site-directed in vivo photo-cross-linking was used to map the protein-protein interactions mediated by the BepA TPR domain, showing that this domain interacts both with a substrate and with the BAM complex. Mutational analysis indicated that these interactions are important for the BepA functions. These results suggest that the TPR domain plays critical roles in BepA functions through interactions both with substrates and with the BAM complex. Our findings provide insights into the mechanism of biogenesis and quality control of the outer membrane.


Spirituality as a core domain in the assessment of quality of life in oncology.
This study investigated including spiritual wellbeing as a core domain in the assessment of quality of life (QOL) in an Australian oncology population. Four hundred and ninety consecutive cancer patients with mixed diagnoses completed the Functional Assessment of Chronic Illness Therapy--Spiritual Well-Being (FACIT-Sp) and the Mental Adjustment to Cancer (MAC) scale. Overall, 449 patients completed assessments. Spiritual wellbeing demonstrated a significant, positive association with QOL (r=0.59), fighting spirit (r=0.49) and a significant, negative relationship with helplessness/hopelessness (r=-0.47) and anxious preoccupation (r=-0.26). A hierarchical multiple regression showed spiritual wellbeing to be a significant, unique contributor to QOL beyond the core domains of physical, social/family, and emotional wellbeing (R(2) change=0.08, p=0.000). However, high levels of meaning/peace or faith did not appear to significantly impact patients' ability to enjoy life despite chronic symptoms of pain or fatigue, making the current results inconsistent with other findings. Results lend further support to the biopsychosocialspiritual model. By failing to assess spiritual wellbeing, the 'true' burden of cancer is likely to be miscalculated. However, at this stage, the exact clinical utility of spirituality assessment is unclear.


[Endobronchial ultrasound (EBUS): the state of the art].
Endobronchial ultrasound (EBUS) is a technique which allows the endoscopist to sample mediastinal and/or hilar lymph nodes for complete staging of thoracic malignancy without recourse to surgery. Originally developed at the beginning of the 21st century, EBUS has become a well developed practice within France in recent years. As the technique requires high tech, expensive and fragile equipment, it has been important to develop an approach that is appropriate for the specific features and constraints of the French health system, including access to anaesthesia, imaging modalities and costing. The first centers to adopt EBUS had to adapt quickly and develop their own practices for its use. Training seminars were carried out in order to pass on this experience. After the passage of several years, it seems helpful to give a progress report on this technique through the stages of its development, taking account of the specificities of the French system and thus to transmit this accumulated experience. In this article, the authors review the literature concerning all the essential aspects needed to apply this technique under the best conditions in the French health system.


Data on energy, exergy analysis and optimisation for a sugar factory.
A huge amount of energy is consumed during sugar production in the food industry. The large amount of steam used and the power of the turbine power plant are key factors. This makes energy and exergy analysis important in sugar factories. The data given in the following paper are related to input and output information of the paper entitled Energy - exergy analysis and optimisation of a model sugar factory in Turkey by Taner and Sivrioglu (2015) [1]. Factory total energy efficiency and exergy efficiency are found to be η enT=72.2% and η exT=37.4%, respectively, and according to these results, the total energy quality ∅ T=0.64. These results indicate higher efficiency than similar studies (Vuckovic et al., 2014; Pellegrini and Oliviera Junior, 2011; Deshmukh et al., 2013; Palacios-Bereche et al., 2015) [2], [3], [4], [5]. This study can be a model for these similar factories by Taner and Sivrioglu (2015) [1].


Could transesophageal echocardiography be useful in selected cases during liver surgery resection?
Although only limited scientific evidence exists promoting the use of transesophageal echocardiography (TEE) in non cardiac surgery, several recent studies have documented its usefulness during liver surgery. In the present case study, through the use of color Doppler TEE, compression of the inferior vena cava and the right hepatic vein was clearly evident, as was their restoration after surgery. TEE should be encouraged in patients undergoing liver resection, not only for hemodynamic monitoring, but also for its ability to provide information about the anatomy of the liver, its vessels, and inferior vena cava patency.


A randomized controlled trial on using predictive algorithm to adapt level of psychological care for community college students: STAND triaging and adapting to level of care study protocol.
There is growing interest in using personalized mental health care to treat disorders like depression and anxiety to improve treatment engagement and efficacy. This randomized controlled trial will compare a traditional symptom severity decision-making algorithm to a novel multivariate decision-making algorithm for triage to and adaptation of mental health care. The stratified levels of care include a self-guided online wellness program, coach-guided online cognitive behavioral therapy, and clinician-delivered psychotherapy with or without pharmacotherapy. The novel multivariate algorithm will be comprised of baseline (for triage and adaptation) and time-varying variables (for adaptation) in four areas: social determinants of mental health, early adversity and life stressors, predisposing, enabling, and need influences on health service use, and comprehensive mental health status. The overarching goal is to evaluate whether the multivariate algorithm improves adherence to treatment, symptoms, and functioning above and beyond the symptom-based algorithm. This trial will recruit a total of 1000 participants over the course of 5 years in the greater Los Angeles Metropolitan Area. Participants will be recruited from a highly diverse sample of community college students. For the symptom severity approach, initial triaging to level of care will be based on symptom severity, whereas for the multivariate approach, the triaging will be based on a comprehensive set of baseline measures. After the initial triaging, level of care will be adapted throughout the duration of the treatment, utilizing either symptom severity or multivariate statistical approaches. Participants will complete computerized assessments and self-report questionnaires at baseline and up to 40 weeks. The multivariate decision-making algorithm will be updated annually to improve predictive outcomes. Results will provide a comparison on the traditional symptom severity decision-making and the novel multivariate decision-making with respect to treatment adherence, symptom improvement, and functional recovery. Moreover, the developed multivariate decision-making algorithms may be used as a template in other community college settings. Ultimately, findings will inform the practice of level of care triage and adaptation in psychological treatments, as well as the use of personalized mental health care broadly. ClinicalTrials.gov NCT05591937, submitted August 2022, published October 2022.


Preoperative splenic artery embolization for splenic ectopic pregnancy.
Primary splenic pregnancy is an extremely rare form of extra tubal ectopic pregnancy. Trans-arterial embolization is emerging as an effective treatment for ectopic pregnancy. Here, we present a 34-year-old G4P3003 woman who presented with vaginal bleeding and elevated serum quantitative human chorionic gonadotropin (beta-hCG). After initial workup showed no intrauterine pregnancy, MRI of the abdomen showed an ectopic gestational sac at the splenic hilum. A preoperative splenic artery embolization was performed successfully prior to open splenectomy for removal of the ectopic pregnancy to minimize operative blood loss. By sharing our experience in this case, we contribute to the validation of trans-arterial embolization as an effective adjunctive measure in treating ectopic pregnancy.


Intramedullary arachnoid cyst: 3-year follow up after bilateral dorsal root entry zone myelotomy.
Spinal arachnoid cysts are relatively uncommon an intramedullary location is believed to be extremely rare. A 35 year old woman, admitted with progressive weakness in the lower limbs, was diagnosed as having a thoracic intramedullary arachnoid cyst. After bilateral dorsal root entry zone myelotomy procedures and wide fenestration was performed, there was a dramatic and immediate recovery. This is the first intramedullary arachnoid cyst reported to be treated by this approach and the long term outcome discussed.


The CPEB-family of proteins, translational control in senescence and cancer.
Cytoplasmic elongation of the poly(A) tail was originally identified as a mechanism to activate maternal mRNAs, stored as silent transcripts with short poly(A) tails, during meiotic progression. A family of RNA-binding proteins named CPEBs, which recruit the translational repression or cytoplasmic polyadenylation machineries to their target mRNAs, directly mediates cytoplasmic polyadenylation. Recent years have witnessed an explosion of studies showing that CPEBs are not only expressed in a variety of somatic tissues, but have essential functions controlling gene expression in time and space in the adult organism. These "new" functions of the CPEBs include regulating the balance between senescence and proliferation and its pathological manifestation, tumor development. In this review, we summarize current knowledge on the functions of the CPEB-family of proteins in the regulation of cell proliferation, their target mRNAs and the mechanism controlling their activities.


Preclinical pharmacology of F-98214-TA, a novel potent serotonin and norepinephrine uptake inhibitor with antidepressant and anxiolytic properties.
Serotonin (5-HT) and norepinephrine (NE) re-uptake inhibitors (SNRIs) have been proposed to have a higher efficacy and/or faster onset of action than previously available antidepressants. We examined in biochemical, electrophysiological and behavioural assays the antidepressant properties of (S)-(-)-4-[(3-fluorophenoxy)-phenyl]methyl-piperidine (F-98214-TA), a compound that displays very high affinity for 5-HT and NE transporters. F-98214-TA potently inhibited the uptake of both 5-HT and NE into rat brain synaptosomes (IC50 = 1.9 and 11.2 nM, respectively) and decreased the electrical activity of dorsal raphe serotonergic neurones (ED50 = 530.3 microg/kg i.v.), an effect completely abolished by the 5-HT(1A) antagonist WAY100,635. In acute behavioural assays in mice, the orally administered compound potentiated the 5-hydroxy-tryptophan (5-HTP)-induced syndrome [minimal effective dose (MED) = 10 mg/kg], antagonized the hypothermia induced by a high dose of apomorphine (ED50 = 2 mg/kg) and reduced the immobility in the tail suspension test (MED = 10 mg/kg). Moreover, it also decreased the immobility in the forced swimming test in mice and rats (30 mg/kg, p.o.). Chronic administration of F-98214-TA (14 days, 30 mg kg(-1) day(-1), p.o.) attenuated the hyperactivity induced by olfactory bulbectomy in rats, confirming its antidepressant-like properties. Interestingly, the same dosage regimen significantly increased the social interaction time in rats, suggesting an additional potential anxiolytic activity. In most assays the compound was more potent than fluoxetine, venlafaxine and desipramine. F-98214-TA is a novel SNRI that displays greater potency than other reference antidepressants in animal models predictive of antidepressant and anxiolytic activities.


Biomechanical function of surgical procedures for acromioclavicular joint dislocations.
Surgical procedures for treatment of acromioclavicular (AC) joint dislocation replace the coracoclavicular (CC) ligaments to minimize motion, allow scarring, and increase the subsequent stability of the joint. The purpose of this study was to evaluate the biomechanical function of the surgically repaired or reconstructed (CC Sling, Rockwood Screw [DePuy Orthopaedics, Warsaw, IN], and Coracoacromial [CA] Ligament Transfer Construct) AC joint after AC joint dislocation. A cadaver study using a convenience sample. Twelve cadaveric shoulders were tested using a robotic/UFS testing system. Three external loading conditions (anterior, posterior, or superior load of 70 N) were applied to intact and surgically repaired or reconstructed AC joint. The resulting kinematics of the AC joint and in situ forces in the CC ligaments or surgical constructs was determined. For the CC Sling, anterior and posterior translation significantly increased by 110% and 330% in response to an anterior and posterior load, respectively. However, the posterior translation for the Rockwood Screw significantly decreased by 60%. Anterior, posterior, and superior translation for the CA Ligament Transfer Construct significantly increased by 110%, 360%, and 100%, respectively. The coupled translations also significantly increased for the CC Sling and CA Ligament Transfer Construct in response to all loading conditions. In contrast, the coupled translations for the Rockwood Screw tended to decrease. Furthermore, the in situ forces increased significantly for all 3 surgical constructs compared with the intact CC Ligaments in response to an anterior and posterior load. At time zero, increases in the primary and coupled motion for the CC Sling and CA Ligament Transfer Construct could comprise the initial healing period prescribed for AC joint dislocation. Our findings also suggest that the Rockwood Screw provides a highly rigid fixation and may explain the complications frequently seen in clinical practice. Current surgical procedures do not have the appropriate stiffness to restore the stability of the intact joint before healing. Therefore, our results may lead to the design and development of new repairs, reconstructions, and rehabilitation protocols for AC joint dislocation.


Antigen specific and nonspecific modulation of the immune response by aminolevulinic acid based photodynamic therapy.
Photosensitizers used normally in treating cancers have considerable potential for treatment of other diseases. One such photosensitizer is the endogenously synthesized photosensitizer protoporphyrin IX (PpIX). To better understand how protoporphyrin might be used in transplantation or in treating autoimmune diseases, information must be obtained on how the photosensitizer affects all immune cells. We used a combination of flow cytometry and in vitro activation assays (recall assays and mixed-lymphocyte reactions) to examine the effects of PpIX on the antigen specific component, lymphocytes and the non-antigen specific component, the macrophages/monocytes and dendritic cells of the immune system. Whereas, lymphocytes accumulate PpIX only when activated, both macrophages and dendritic cells accumulated PpIX immediately, without in vitro activation, as measured by flow cytometry. ALA-PDT (aminolevulenic acid-photodynamic therapy) treated adherent cells in the recall assay had a decreased capability to activate lymphocytes. By increasing the light dose in the recall assay, antigen primed lymphocytes were selectively eliminated from a population of cells. Stimulator cells in an MLR had a decreased stimulatory capacity following ALA-PDT treatment. Functional alterations are seen in both the antigen specific


Grasping an object naturally or with a tool: are these tasks guided by a common motor representation?
The aim of the present study was to determine whether kinematic parameters of the grasping motor act are controlled independently of the biomechanical features of the grasping effector. With this purpose in mind, we compared grasping movements performed naturally or using a tool. The tool consisted of two mechanical fingers whose opening and closing phases required squeezing (flexion of the biological fingers) and releasing (extension of the biological fingers) of a handle, respectively. The forces required for opening and closing the mechanical fingers were, respectively, greater and smaller than those used to grasp the objects naturally. In a control experiment the participants grasped with their thumb and index finger the same objects grasped with the tool. The kinematics of the mechanical and biological fingers as well as those of the arm in the two experiments were compared with each other. Grasping an object with the tool showed some kinematic characteristics strikingly similar to those of the natural grasp, whereas others were different. Like the natural grasp, the tool grasp consisted of a finger opening and closing phase. The scaling of both peak velocity of aperture and maximal aperture of the mechanical fingers as a function of object size was the same as that of the biological fingers. In contrast, the tool grasp differed from the natural one for the temporal aspects of the movement. Finally, the initial reach (i.e. the acceleration phase) was poorly influenced by the tool use whereas the final reach (i.e. the deceleration phase) was lengthened and more sensitive to object size. We discuss the results of the present study as being in favour of the hypothesis that some features of the grasp motor representation are coded in cortical areas independently of the used effector. In addition, they suggest a partial independence between the reach and the grasp components.


Biological properties and mechanism of action of ibandronate: application to the treatment of osteoporosis.
Bisphosphonates, with their proven efficacy and safety, are the most commonly prescribed treatment for women with postmenopausal osteoporosis; however, optimal efficacy is often not achieved due to poor patient adherence to medication. Poor adherence leads to an increased risk of fracture, which itself results in morbidity, elevated healthcare costs and potentially, mortality. Although weekly rather than daily dosing of bisphosphonates has improved adherence, there remains a significant problem, and dosing less frequently than weekly has been suggested as a possible means for further improving adherence. Ibandronate is a new bisphosphonate that has a specific structure and set of characteristics that enable less frequent dosing than currently available bisphosphonates. This review provides details of the general structural features of all bisphosphonates and how these are understood to contribute to their functions in osteoporosis treatment. From this, the unique structure of ibandronate is described, along with how this translates into the high antiresorptive potency, favorable bone-binding, persistence in bone, and good tolerability that permits less frequent dosing. Finally, the clinical evidence for ibandronate is briefly presented, demonstrating the viability of less frequent dosing, with its potential benefits for patient convenience and adherence to therapy.


Complex and Potentially Harmful Medication Patterns in Heart Failure with Preserved Ejection Fraction.
Complex medication regimens, often present in heart failure with preserved ejection fraction, may increase the risk of adverse drug effects and harm. We sought to characterize this complexity by determining the prevalence of polypharmacy, potentially inappropriate medications, and therapeutic competition (where a medication for 1 condition may worsen another condition) in 1 of the few dedicated heart failure with preserved ejection fraction programs in the United States. We conducted chart review on 231 patients with heart failure with preserved ejection fraction seen in the University of Michigan's Heart Failure with Preserved Ejection Fraction Clinic between July 2016 and September 2019. We recorded: 1) standing medications to determine the presence of polypharmacy, defined as ≥10 medications; 2) potentially inappropriate medications based on the 2016 American Heart Association Scientific Statement on drugs that pose a major risk of causing or exacerbating heart failure, the 2019 Beers Criteria update, or a previously described list of medications associated with geriatric syndromes; and 3) competing conditions and subsequent medications that could create therapeutic competition. The prevalence of polypharmacy was 74%, and the prevalence of potentially inappropriate medications was 100%. Competing conditions were present in 81% of patients, of whom 49% took a medication that created therapeutic competition. In addition to confirming that polypharmacy was highly prevalent, we found that potentially inappropriate medications and therapeutic competition were also frequently present. This supports the urgent need to develop patient-centered approaches to mitigate the negative effects of complex medication regimens endemic to adults with heart failure with preserved ejection fraction.