Relations between parental metacognitive talk and children's early metacognition and memory.
After decades of research suggesting that metacognition-that is, processes whereby people monitor and regulate their cognitive performance-did not emerge and is not related to children's performance until late childhood, recent studies have provided evidence that even preverbal infants can access their internal states. The existence of this basic metacognition raises the question of the variables influencing its development at such a young age and whether such early skills could predict successful cognitive performance. The current study had two main goals: (a) exploring the relation between parental metacognitive style and children's early metacognition and (b) determining whether these early metacognitive skills can predict children's memory performance. To this end, 2.5- to 4.5-year-old children (N = 72) and their parents were recruited. To assess parental metacognitive style, parent-child dyads were invited to participate in a 15-min session during which they played memory games. The parents' speech during this session was later coded for metacognitive content. Children's memory was assessed using cued recall and recognition tests. During one of these recognition tests, participants had the opportunity to ask for a cue to help them decide whether their response was correct (i.e., metacognitive measure). Results revealed that parental metacognitive style predicted both children's metacognitive accuracy and memory performance. Interestingly, a mediation effect of children's metacognitive skills on the relation between parental style and memory performance was found. These findings suggest that environmental factors such as parental metacognitive style are related to children's early metacognition, which in turn is linked to children's memory development.


A review of hospital-based interventions to improve inpatient influenza vaccination uptake for high-risk adults.
Despite positive steps towards transforming immunisation understanding and practice to better incorporate adults, coverage, especially those at higher risk, is not where it should be. One way to increase uptake is to take advantage of environments outside of primary care which present easy opportunities for vaccination. This study provides a narrative review of hospital-based strategies in acute care settings aimed at improving influenza vaccination rates for adult inpatients. A search was conducted using Scopus, Embase and PubMed databases for articles reporting on hospital-based interventions aimed at improving influenza vaccination for adults. Studies published in English were included and descriptively analysed. A total of 31 articles were included. Tested interventions included 7 standing order protocols (SOP); 4 reminders; 4 assessment/administration programs; 1 patient education program; 1 organisational-based program; 7 multi-component strategies and 8 studies comparing SOPs with other strategies. One article was included in both SOPs and reminders categories. Studies were published between 1983 and 2017 and conducted in the USA, Canada, or Australia. 18 studies reported statistical significance. Individually, each type of intervention showed success. SOPs were significantly more effective than other individual interventions, but multi-component interventions (which included an SOP) were more effective than SOPs alone. Three articles reported no significant increase in uptake attributed mainly to patient refusals, even with a strategy involving patient education. Only three studies tested provider-level strategies including hospital campaigns, hospital reward programs and interdepartmental competitions, and showed success. Hospital-based interventions are an effective means of improving opportunistic inpatient vaccination. Suggestions for future research include organisational or system-based interventions; qualitative review of barriers and enablers to inpatient vaccination programs; and re-examination of outpatient settings for vaccine delivery. Most studies were not randomised or controlled; therefore, we also recommend additional RCT studies to confirm existing findings on individual strategies.


Incidence of HCV infection in French hemodialysis units: a prospective study.
A large prospective study was carried out from 1997 to 2000 in 25 French hemodialysis units including 1,323 patients to determine the incidence of hepatitis C virus (HCV) infection. Monthly testing of alanine aminotransferase (ALT) activity, and assessment of HCV RNA and anti-HCV antibodies if the ALT activity was elevated, identified 14 new infections in 7 different units, giving an incidence of 0.4% new HCV infections per year. Molecular analyses and epidemiological data indicated that five patients became infected with HCV outside the unit where they were dialyzed, while the nine remaining patients acquired HCV from infected patients on dialysis during the same shift at the same unit. HCV was cleared in six of the seven (85.7%) patients with acute hepatitis C who were given standard doses of alpha-interferon (alpha-IFN). The persistence of nosocomial transmission of HCV in hemodialysis units emphasizes the need to implement infection control practices. Identifying new infections is crucial because alpha-IFN treatment results in long term clearance of HCV RNA in a large proportion of patients.


Thrombolytic therapy followed by stenting for renal artery dissection secondary to blunt trauma.
A 18-year-old man presented at our clinic with pain in the right flank following a motorbike accident. The diagnosis of renal artery dissection followed by thrombosis was made by computed tomography and confirmed by angiography. Successful revascularization was performed by means of repeated transcatheter injection of small doses of thrombolytic agents within the vessel, followed by deployment of a self-expandable stent. There were no complications, and the patient recovered well. Six months after stent placement, a selective renal angiogram showed excellent flow through the stented portion of the artery and normal parenchyma enhancement in the right kidney.


Isolated calf deep venous thrombosis: frequency on venous ultrasound and clinical characteristics.
It remains controversial whether to include calf veins in the initial ultrasound evaluation of suspected deep venous thrombosis (DVT). We sought to investigate the frequency and clinical characteristics of isolated calf DVT. In this retrospective analysis, we investigated a cohort of 596 patients (median age 69 years, 52.3% women) who had been imaged with complete lower extremity venous duplex ultrasound for suspected acute DVT. Radiology reports were analyzed for the presence and localization of DVT. Clinical information was collected from patients' electronic charts. DVT was found in 157 patients (26.3%), of which 74 patients (47.1%) had isolated calf DVT. Isolated calf DVTs were located in the posterior tibial veins (22 patients, 29.7%), peroneal veins (41 patients, 55.4%) and muscle veins (19 patients, 25.7%). There were no differences in age or sex between patients with isolated calf DVT and patients with proximal DVT. Isolated calf DVT was more commonly associated with leg pain (52.7% vs. 33.7%, p = 0.0234) and less commonly associated with subjective leg swelling (35.1% vs. 55.4%, p = 0.0158) and objectively measured difference in leg circumference (23% vs. 39.8%, p = 0.0268). D-Dimers were significantly lower in patients with isolated lower leg DVT (median 2.3 vs. 6.8 mg/L, p < 0.0001) compared to patients with proximal DVT. Isolated calf DVT represents approximately half of DVT cases and has different clinical characteristics than proximal DVT.


[Experimental tear fractures of the tendinous insertion of the os calcis (author's transl)].
Tear fractures of the os calcis are rare. If they do occur, the cause may be osteoporosis. This could be proved in an experimental study rupturing the achilles tendon. Usually, the tendon is the weakest link in the muscle-tendon-bone-chain. In case of osteoporosis, the insertion of the tendon is more vulnerable.


Effect of cycloheximide on RNA synthesis in Chironomus polytene chromosomes.
Modifications in the synthesis of salivary gland RNA were induced by treatments with 10 microgram/ml cycloheximide (CHM) on 4th instar larvae of Chironomus pallidivitattus. After 3, 6 and 24 h CHM treatment, RNA was labeled "in vitro", by incubating the salivary glands in a medium containing H3-uridine. The electrophoretical analyses corresponding to the 3 and 6 h treatment showed a stimulation of the non-ribosomal components of the newly synthesized RNA, while preribosomal RNA synthesis appeared depressed. This fact was also confirmed at cytological level, since autoradiograms made after 3 h of CHM treatment showed a reduced H3-uridine label over the nucleolus and an increase of diffuse labeling over the chromosomes. Longer treatments (24 h) causes a considerable inhibition of the synthesis of all RNA species. The role played by protein synthesis inhibition in the aforementioned effects is discussed.--Some of the morphological implications of CHM treatment, such as modifications of the nucleolar structure (nucleolar segregation) are also reported. The use of a squash technique based on glutaraldehyde fixation of the salivary glands, considerably facilitates such studies.


Endoscopic carpal surgery in carpal tunnel syndrome: A systematic review.
Endoscopic carpal tunnel release has become increasingly popular and has shown the advantage of early recovery of hand function with minimal morbidity. In this systematic review, we aimed to summarize the currently available data and describe the reported advantages and disadvantages of endoscopic carpal tunnel surgery for treating carpal tunnel syndrome. In this study, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, which is a set of reporting requirements for systematic reviews and meta-analyses. The search strategy with MeSH terms was "MeSH (carpal tunnel syndrome) AND (endoscopic)" Filters: in the last 5 years, English-on February 27th, 2022. A total of 131 articles fulfilled the first screening criteria. A detailed analysis of those articles identified 39 that matched the criteria, of which 14 were considered appropriate for this analysis after applying the complete inclusion and exclusion criteria. A total of 14 studies met the eligibility criteria. Analysis of those studies found that all types of portals in endoscopic carpal tunnel release reduced postoperative pain at a short-term follow-up. There was no evidence to suggest the superiority of the single- or two-portal techniques in terms of outcomes. In terms of pain relief, symptom resolution, patient satisfaction, duration to return to work, and adverse events, this early use of endoscopic carpal tunnel release produced satisfactory outcomes. Further studies comparing the number of portals are needed. Endoscopic carpal tunnel surgery for treating carpal tunnel syndrome is effective and both single- and dual-portal techniques provide advantages in terms of early recovery and minimal morbidity.


A new electroanalytical approach for sunset yellow monitoring in fruit juices based on a modified sensor amplified with nano-catalyst and ionic liquid.
The determination of food additives is one of the major points in the food industry that directly is relative to human health. This research work focused on sensing and monitoring sunset yellow as azo additive dyes in fruit juices using an electrochemical sensor amplified with Ni doped Pt decorated carbon nanotubes (NiO/Pt/CNTs) as nano-catalyst and 1-hexyl-3-methylimidazolium chloride ([HMIM][Cl]) as an ionic liquid binder. Carbon paste electrode (CPE) amplified with NiO/Pt/CNTs and [HMIM][Cl] (CPE/([HMIM][Cl])/NiO/Pt/CNTs) improved the sensitivity of sunset yellow sensing in aqueous solution in acidic condition and successfully monitored this azo dye in concentration range 1.0 nM-280 μM with detection limit 0.4 nM. On the other hand, the CPE/([HMIM][Cl])/NiO/Pt/CNTs was used for sensing and analysis of sunset yellow in different fruit juices, and recovery data between 98.65% and 103.66% confirmed the powerful ability of sensor for monitoring of sunset yellow in food samples.


Excitatory amino acid binding sites in the trigeminal principal sensory and spinal trigeminal nuclei of the rat.
Quantitative autoradiography was used to examine the density and distribution of excitatory amino acid (EAA) binding site subtypes in the principal sensory and spinal trigeminal nuclei of the rat trigeminal complex. The highest densities of N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate and metabotropic receptors were found in the superficial laminae (I and II) of subnucleus caudalis, a region known to be densely innervated by primary afferent nociceptive terminals. Lower densities of EAA binding sites were observed in spinal subnuclei interpolaris and oralis and within the principal sensory nucleus. These results are consistent with the hypothesis that EAAs are involved in primary afferent nociceptive neurotransmission.


Kingella kingae, a rare cause of bacterial meningitis.
A male adolescent with a history of pharyngitis developed meningitis due to Kingella kingae. This is a Gram-negative coccobacillus belonging to the family of Neisseriaceae. It is a rarely reported human pathogen, from which only 2 cases of meningitis have been described up to the present day. Our patient developed ophthalmoplegia, suggestive of basal meningitis. He was treated with penicillin G and recovered completely.


Muscle coordination patterns in regulation of medial gastrocnemius activation during walking.
The ankle plantar flexion in the late stance phase is referred to as the ankle push-off. When the ankle push-off force is enhanced, compensatory adjustments occur in the adjacent phases. The muscle control that achieves these compensatory movements remains unknown, although they are expected to be coordinately regulated across multiple muscles and phases. Muscle synergy is used as a quantification technique for muscle coordination, and this analysis enables the comparison of synchronized activity between multiple muscles. Therefore, this study aimed to elucidate the tuning of muscle synergies in muscle activation adjustment of push-off. It is hypothesized that muscle activation adjustment of push-off is performed in the muscle synergy related to ankle push-off and in the muscle synergy that activates during the adjacent push-off phase. Eleven healthy men participated, and participants manipulated the activity of the medial gastrocnemius during walking through visual feedback. Two conditions were compared as experimental conditions: increasing the muscle activity to 1.6 times that during normal walking (High) and matching it with that during normal walking (Normal). Twelve muscle activities in the trunk and lower limb and kinematic data were recorded. Muscle synergies were extracted by the non-negative matrix factorization. No significant difference was observed in the number of synergies (High: 3.5 ± 0.8, Normal: 3.7 ± 0.9, p = 0.21) and muscle synergy activation timing and duration between the High and Normal conditions (p > 0.27). However, significant differences were observed in the peak muscle activity during the late stance phase of the rectus femoris (RF), biceps femoris (BF) between conditions (RF at High: 0.32 ± 0.21, RF at Normal: 0.45 ± 0.17, p = 0.02; BF at High: 0.16 ± 0.01, BF at Normal: 0.08 ± 0.06 p = 0.02). Although the quantification of force exertion has not been conducted, the modulation of RF and BF activation could have occurred due to the attempts to help knee flexion. Muscle synergies during normal walking are therefore maintained, and slight adjustments in the amplitude of muscle activity occurred for each muscle.


Serum activin A does not predict ectopic pregnancy as a single measurement test, alone or as part of a multi-marker panel including progesterone and hCG.
To evaluate the diagnostic accuracy of activin A alone or in a multi-marker panel for the prediction of ectopic pregnancy (EP). A retrospective analysis was performed on a cohort of 289 women who presented to the emergency department (ED) with vaginal bleeding and/or abdominal pain/cramping and were diagnosed with EP, spontaneous abortion, or viable intrauterine pregnancy. Serum progesterone, hCG, and activin A concentrations were measured on the samples obtained in the ED. Statistical analysis was performed to determine the clinical utility of these biomarkers as single measurement and as a multi-marker panel test for ectopic pregnancy. Women ≥18 y with vaginal bleeding or abdominal pain/cramping. Progesterone (<10 ng/ml), hCG (<6,699 IU/l), and activin A (<0.26 ng/ml) cutoffs were optimized by ROC analysis. These demonstrated sensitivities of 62.9%, 74.2%, and 59.6%, and specificities of 60.5%, and 63.0%, and 61.0% respectively for detecting EP. The multi-marker panel utilizing all three biomarkers had a sensitivity of 70% and specificity of 69%. Serum activin A cannot be used as a single measurement or in a multi-marker panel with progesterone and hCG to predict EP.


Peer-led team learning in an undergraduate biology course: Impacts on recruitment, retention, and imposter phenomenon.
The data presented in this note were collected during a multi-year project conducted in the context of large-enrollment introductory biology course at a large private R-1 research institution in the Northeastern United States. The project aimed to examine the impact of Peer-Led Team Learning (PLTL) on the recruitment and retention of marginalized groups in Science, Technology, Engineering, and Mathematics (STEM) majors. While several results from the project have been published, additional data of interest have yet to be reported. This data note reports on additional associations between PLTL participation and improved outcomes for students from groups that have historically been excluded in STEM. Additional data reported herein were collected to determine if students in the course experienced imposter phenomenon, and whether PLTL may be associated with reduced levels of imposter feelings. The data in this note includes academic information such as final course grades and academic level; socio-demographic information such as gender identity, minority status, and first-generation status; and information on student recruitment, retention, imposter feelings, and participation in Peer-Led Team Learning (PLTL). These data might be useful and of value to education researchers and undergraduate STEM instructors who are interested in improving equity in STEM education.


Bird feathers as bioindicators in areas of the German Environmental Specimen Bank--bioaccumulation of mercury in food chains and exogenous deposition of atmospheric pollution with lead and cadmium.
Feathers of selected bird species are used as pollution integrating biomonitors in areas of the German Environmental Specimen Bank. Lead, cadmium and mercury are analysed by Zeeman Solid Sampling AAS in feather vanes of selected bird species with different ecologies. In feather vanes there are quite different distribution patterns of lead and cadmium on the one hand and mercury on the other: lead and cadmium show strong gradients with respect to feather parts with high exposure to atmospheric influences. In contrast to this, mercury is distributed homogeneously. These different distribution patterns of lead and cadmium in feather vanes, in contrast to mercury, show that there are quite different incorporation paths. Cadmium and lead are deposited exogenously and indicate atmospheric pollution. Mercury in feathers is caused endogenously by food and physiology. Most of the mercury analysed in bird's feathers is in the ecotoxic methylated form and the contents in feathers depend on bioaccumulation in food chains. Feathers are suitable indicators for monitoring heavy metal pollution and give us information about incorporation paths and ecotoxic effects.


Effect of drug loading on the transformation of vesicular into cubic nanoparticles during heat treatment of aqueous monoolein/poloxamer dispersions.
Colloidal dispersions of the pre-equilibrated cubic phase in the monoolein/poloxamer 407/water system, which are under investigation as potential drug carriers, often contain a considerable fraction of undesired non-cubic particles, particularly when prepared with high concentrations of poloxamer. Recent investigations revealed that the non-cubic particles can be transformed into particles of cubic internal structure by heat treatment. The present study investigates the effect of drug loading on the non-cubic to cubic transformation process during autoclaving of the dispersions. The results indicate that the process can also proceed in dispersions loaded with different concentrations of ubidecarenone, tocopheryl acetate, betamethasone-17-valerate, chloramphenicol or miconazole. At low concentration, none of the drugs had pronounced influence on the autoclaved dispersions whereas with increasing drug concentration different effects were observed. Depending on the type of drug no effects (betamethasone-17-valerate), increasing particle size of the dispersions (chloramphenicol, miconazole) or phase separation upon autoclaving (high load of miconazole) was observed. Except for loading with high amounts of chloramphenicol, which led to the formation of cubic phase particles already without additional heat treatment, the properties of the thermally untreated dispersions were virtually unaffected by drug incorporation.


Validation study of women's reporting and recall of major obstetric complications treated at the Philippine General Hospital.
In settings where most births occur at home, collection of data on complications experienced around the time of delivery is often dependent on self-reported data, collected through individual interviews. This paper describes a study designed to validate interview data on obstetric complications by comparing women's responses with data extracted from their medical records. The major complications of hemorrhage, dystocia, sepsis, and eclampsia were the main focus of the study. The sample was drawn from women hospitalized for delivery in a Manila hospital within the past 4 years. The main goal of the study was to assist in development of a survey instrument to be used in a national sample survey of women in the Philippines. The best sensitivity and specificity, respectively, for combinations of questions on these four conditions were: for hemorrhage, 0.70 and 0.78; for dystocia, 0.69 and 0.97; for sepsis, 0.89 and 0.83; and for eclampsia, 0.44 and 0.96. There were no significant differences in the duration of the recall periods according to diagnosis.


Pediatric interhospital transport: diagnostic discordance and hospital mortality.
Determine the rate of discordance between the reason for transport (determined by referring institution) and the final diagnosis (determined by accepting institution), identify factors associated with diagnostic discordance, and determine whether diagnostic discordance is associated with mortality and morbidity. Cross-sectional analysis of prospectively collected transport data using an existing multicenter database. Interfacility transport of neonatal and pediatric patients referred to five tertiary centers during years 1998-2000. Patients were 4,905 neonatal and pediatric patients undergoing interhospital transport ultimately assigned to a general or intensive level of care based on initial triage information. None. Discordant events were categorized by diagnosis, referring hospital location, and physician type. Discordance between primary reason for transport and discharge diagnosis category occurred in 474 (11.5%) transport events (95% confidence interval 10.5-12.5). Significant predictors of diagnostic discordance included diagnoses of gastrointestinal, metabolic, multi-trauma with head injury, multi-trauma without head injury, renal, and toxicology. Acute care, referring physician, and emergency department subpopulations demonstrated similar discordance rates. One hundred ten (2.7%) patients experienced at least one unplanned event (unintended extubation, intubation requiring more than attempts, loss of intravenous access, malpositioned endotracheal tube, medication error, pneumothorax). Of the 474 patients given discordant diagnoses, 16 (3.4%) experienced at least one unplanned event compared with 94 of 3,645 (2.6%) of patients given concordant diagnoses. Hospital mortality for all transport events was 6% (95% confidence interval 5.3-6.7). Of the total discordant population, 37 of 474 died compared with 207 of 3,645 of those with concordant diagnoses (7.8% vs. 5.7%, p = .065). When adjusted for severity, age, and diagnosis, the increased mortality was not statistically significant. Discordance between primary reason for transport and diagnosis category is common in the pediatric interhospital transport population. Although discordance does not appear to lead to increased mortality, further study is needed to determine the impact of diagnostic discordance on other patient outcomes.


Sustained virologic response from hepatitis C from an emergency department screening & linkage program: A retrospective review.
The role of the Emergency Department (ED) as a vital constituent in Hepatitis C (HCV) screening has become increasingly evident. A key component of the ED's role in HCV screening is the ability to effectively link HCV-RNA positive patients to definitive, HCV-specific care, to include direct-acting antiviral (DAA) medication with resultant sustained virologic response (SVR). We sought to consider the rate of HCV-specific linkage, DAA initiation, and SVR obtained in HCV patients identified from an ED screening program. A retrospective chart review was conducted in February of 2022 of all individuals who participated in an opt-out ED-based HCV screening program between January 2018 and December 2019. Data was disaggregated by race, gender, age/birth cohort, insurance status, and achievement of sustained virologic response (SVR). Bivariate analysis using Pearson's chi-square was utilized to compare outcomes based on insurance status, race, sex, and birth cohort. Of 66,634 individuals screened for HCV during the study period, 885 (1.33%) patients were RNA-positive. Of those individuals, 121 (13.67%) were linked to HCV-specific care. Of those linked, the majority (66.9%) were male, white (66.1%; 33.1% Black), baby boomers or older (53.7%) and publicly insured (57.9%; private insurance 23.1%, self-pay 19%). Among linked patients, 88 (72.7%) started DAA medication. Mirroring linked demographics, majority were male (64.8%), white (64.8%), baby boomers or older (52.3%), and publicly insured (57.6%). White patients initiated on DAA were more likely to obtain SVR (64.9% versus 41.9% Black; p = .04) and uninsured patients were more likely to obtain SVR (82.4% versus 50.7% insured; p = .02). Bivariate consideration of SVR-patients specifically demonstrates that Black patients tended to be older, with significant overrepresentation of Baby boomers (77.5%) as compared to whites (37.5%; p < .0001). Black patients were also more likely to be publicly insured (82.5%) while white patients were more likely to have private insurance (28.8%) or be uninsured (26.3%) than their Black counterparts (12.5% and 5% respectively; p < .05). An ED-based HCV screening program can result in successful HCV-specific linkage and care, to include DAA initiation and ultimately, SVR. Among linked patients, specific cohort considerations may demonstrate differences in age and insurance status which may have implications on DAA application and adherence, and therefore, individual ability to achieve SVR.


Mild dehydration and cycling performance during 5-kilometer hill climbing.
Hydration has been shown to be an important factor in performance; however, the effects of mild dehydration during intense cycling are not clear. To determine the influence of mild dehydration on cycling performance during an outdoor climbing trial in the heat (ambient temperature = 29.0°C ± 2.2°C). Crossover study. Outdoor. Ten well-trained, male endurance cyclists (age = 28 ± 5 years, height = 182 ± 0.4 cm, mass = 73 ± 4 kg, maximal oxygen uptake = 56 ± 9 mL·min(-1)·kg(-1), body fat = 23% ± 2%, maximal power = 354 ± 48 W). Participants completed 1 hour of steady-state cycling with or without drinking to achieve the desired pre-exercise hydration level before 5-km hill-climbing cycling. Participants started the 5-km ride either euhydrated (EUH) or dehydrated by -1% of body mass (DEH). Performance time, core temperature, sweat rate, sweat sensitivity, and rating of perceived exertion (RPE). Participants completed the 5-km ride 5.8% faster in the EUH (16.6 ± 2.3 minutes) than DEH (17.6 ± 2.9 minutes) trial (t1 = 10.221, P = .001). Postexercise body mass was -1.4% ± 0.3% for the EUH trial and -2.2% ± 0.2% for the DEH trial (t1 = 191.384, P < .001). Core temperature after the climb was greater during the DEH (39.2°C ± 0.3°C) than EUH (38.8°C ± 0.2°C) trial (t1 = 8.04, P = .005). Sweat rate was lower during the DEH (0.44 ± 0.16 mg·m(-2)·s(-1)) than EUH (0.51 ± 0.16 mg·m(-2)·s(-1)) trial (t8 = 2.703, P = .03). Sweat sensitivity was lower during the DEH (72.6 ± 32 g·°C(-1)·min(-1)) than EUH (102.6 ± 54.2 g·°C(-1)·min(-1)) trial (t8 = 3.072, P = .02). Lastly, RPE after the exercise performance test was higher for the DEH (19.0 ± 1.0) than EUH (17.0 ± 1.0) participants (t9 = -3.36, P = .008). We found mild dehydration decreased cycling performance during a 5-km outdoor hill course, probably due to greater heat strain and greater perceived intensity.


Studies on the kinetics of glycosidases from chemically-induced rat colonic tumours and normal rat colon.
K-m values of beta-N-acetylglucosaminidase (2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase EC 126.96.36.199), beta-N-acetylgalactosaminidase (EC 220.127.116.11), beta-galactosidase (beta-D-galactoside galactohydrolase EC 22.214.171.124) and alpha-L-fucosidase (alpha-L-fucoside fucohydrolase EC 18.104.22.168) of distal colonic tumours, induced in rats by 1,2-dimethylhydrazine, were found to be significantly different compared with the values for the enzymes of the colonic mucosa of the control and tumour-bearing animals and of the proximal colonic tumours. The inhibition kinetics data also showed a significant difference between the enzymes of the distal colon tumours and of other experimental tissues. The data on the effect of pH on enzyme kinetics (pK values) showed no significant difference in the catalytic groups of the active centres of enzymes from tumours and from the control colonic mucosa. Tumour beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase compared with the enzymes from other experimental tissues were found to be different in their thermal inactivation kinetics. K-m values of 14 days old foetal intestinal beta-N-acetylglucosaminidase and beta-N-acetylgalactosaminidase were significantly different from the values obtained for the adult mucosal enzymes but were similar to those of the distal colonic tumour enzymes.


Detection of surface differences between two closely related cell populations by partitioning isotopically labeled mixed cell populations in two-polymer aqueous phases. II. A correction.
The partition behavior of cells in dextran-poly(ethylene glycol) aqueous phases (i.e., the cells' relative affinity for the top or bottom phase or their adsorption at the interface) is greatly dependent on the polymer concentrations and ionic composition and concentration. Appropriate selection of phase system composition permits detection of differences in either charge-associated or lipid-related surface properties. We have now developed a method that can reveal differences by partitioning that fall within experimental error if one were to compare countercurrent distribution (CCD) curves of two closely related cell populations run separately. One cell population is isotopically labeled in vitro (e.g., with 51Cr-chromate) and is mixed with an excess of the unlabeled cell population with which it is to be compared. The mixture is subjected to CCD and the relative specific radio-activities are determined through the distribution. As control we also examine a mixture of labeled cells and unlabeled cells of the same population. The feasibility of this method was established by use of cell mixtures the relative partition coefficients of which were known. The procedure was then used to test for human erythrocyte subpopulations. 51Cr-chromate-labeled human young or old red blood cells were mixed with unfractionated erythrocytes and subjected to CCD in a phase system reflecting charge-associated properties. It was found that older cells had a high, young cells (probably only reticulocytes) a low partition coefficient. Because of the small differences involved these results were not previously obtained.(ABSTRACT TRUNCATED AT 250 WORDS)


[Segmental dilatation of the ileum associated with an omphalocele and a common mesentery. Discussion around 2 cases : chance or morphogenically "related"? (author's transl)].
Segmental dilatation of the ileum is the subject of this report which concerns two cases. Both cases were associated with omphalocele and intestinal malrotation, an observation already noticed by some authors. Is it still a hazardous coincidence or rather a real opportunity which throws light over the explanation of this malformation?


Avian immunosenescence.
Immunosenescence, the aging of the immune system, is well studied in humans. Mammalian immune systems become less capable of fighting pathogens and individuals become more susceptible to infection and cancer in their elder years. Little is currently published on avian immunosenescence even though avian immune function has been well characterized and birds have been critical models in the study of immunology. The value of birds in the study of aging has been well established. Evidence demonstrates a decline in cell-mediated and (or) humoral immune function with age in four species: the barn swallow, collared flycatcher, ruff and Japanese quail. These studies suggest that birds may experience age-related changes in immune function similar to humans. Therefore, avian aging models should be evaluated for changes in immune function and comparisons made between short- and long-lived birds. Specifically, data on age-related changes in innate immunity are lacking for birds and should be characterized. These data will strengthen the use of avian models for the study of aging.


Identification of sequence polymorphism in the D-Loop region of mitochondrial DNA as a risk factor for hepatocellular carcinoma with distinct etiology.
Hepatocellular carcinoma (HCC) is frequently preceded by hepatitis virus infection or alcohol abuse. Genetic backgrounds may increase susceptibility to HCC from these exposures. Mitochondrial DNA (mtDNA) of peripheral blood, tumor, and/or adjacent non-tumor tissue from 49 hepatitis B virus-related and 11 alcohol-related HCC patients, and from 38 controls without HCC were examined for single nucleotide polymorphisms (SNPs) and mutations in the D-Loop region. Single nucleotide polymorphisms (SNPs) in the D-loop region of mt DNA were examined in HCC patients. Individual SNPs, namely the 16266C/T, 16293A/G, 16299A/G, 16303G/A, 242C/T, 368A/G, and 462C/T minor alleles, were associated with increased risk for alcohol- HCC, and the 523A/del was associated with increased risks of both HCC types. The mitochondrial haplotypes under the M haplogroup with a defining 489C polymorphism were detected in 27 (55.1%) of HBV-HCC and 8 (72.7%) of alcohol- HCC patients, and in 15 (39.5%) of controls. Frequencies of the 489T/152T, 489T/523A, and 489T/525C haplotypes were significantly reduced in HBV-HCC patients compared with controls. In contrast, the haplotypes of 489C with 152T, 249A, 309C, 523Del, or 525Del associated significantly with increase of alcohol-HCC risk. Mutations in the D-Loop region were detected in 5 adjacent non-tumor tissues and increased in cancer stage (21 of 49 HBV-HCC and 4 of 11 alcohol- HCC, p < 0.002). In sum, mitochondrial haplotypes may differentially predispose patients to HBV-HCC and alcohol-HCC. Mutations of the mitochondrial D-Loop sequence may relate to HCC development.


Effects of simulated microgravity on human brain nervous tissue.
During spaceflight, the negative effects of space microgravity on astronauts are becoming more and more prominent, and especially, of which on the nervous system is urgently to be solved. For this purpose tissue blocks and primary cells of nervous tissues obtained from glioma of patients were cultivated after culturing for about 7days, explanted tissues and cells were then randomly divided into two groups, one for static culture (control group, C), and the other for rotary processing for 1day, 3days, 5days, 7days and 14days (experiment group, E). Figures captured by inverted microscope revealed that, with short time rotating for 1day or 3days, morphology changes of tissue blocks were not obvious. When the rotary time was extended to 7days or 14days, it was found that cell somas is significantly larger and the ability of adhesion is declined in comparison with that in control group. Additionally, the arrangement of cells migrated from explanted tissues was disorganized, and the migration distance became shorter. In immunofluorescence analysis, β-tubulin filaments in control group appeared to organize into bundles. While in experiment group, β-tubulin was highly disorganized. In conclusion, simulated microgravity treatment for a week affected the morphology of nervous tissue, and caused highly disorganized distribution of cytoskeleton and the increase of cell apoptosis. These morphological changes might be one of the causes of apoptosis induced by simulated microgravity.


Inhibition of cellular proliferation and induction of apoptosis by curcumin in human malignant astrocytoma cell lines.
Nuclear factor (NF)-kappaB is known to control cellular proliferation and apoptosis. In malignant astrocytoma cells, it was reported that NF-kappaB was activated aberrantly and promoted their proliferation. Thus, inhibition of NF-kappaB activity is considered to be a promising therapeutic strategy for malignant astrocytoma. Recently, curcumin, the major constituent of turmeric, was reported to inhibit NF-kappaB activity. In this study, we investigated inhibitory effects of curcumin on NF-kappaB activity and cellular proliferation, and induction of apoptosis by curcumin in human malignant astrocytoma cell lines. Alteration of NF-kappaB activity in NP-2 human malignant astrocytoma cell line after treatment with curcumin was examined using electrophoretic mobility shift assay. Alterations of DNA synthesis and cellular growth in five human malignant astrocytoma cell lines after treatment with curcumin were examined using [(3)H]thymidine incorporation assay and the trypan blue dye exclusion method, respectively. Induction of apoptosis by curcumin in NP-2 and NP-3 human malignant astrocytoma cell lines was examined by DNA-fragmentation analysis and morphological observation. We found that the NF-kappaB activity in NP-2 was significantly reduced by curcumin. The DNA synthesis and the cellular growth were inhibited by curcumin in dose-dependent manner in all the five malignant astrocytoma cell lines. Nuclear condensation and fragmentation, and DNA fragmentation were observed in both NP-2 and NP-3 after the treatment with curcumin. These results indicate that curcumin inhibits the cellular proliferation and induces apoptosis in human malignant astrocytoma cell lines. These results are considered to be resulted from the inhibition of NF-kappaB activity by curcumin.


Preparation of capsaicin-loaded ultrafine fiber film and its application in the treatment of oral ulcers in rats.
A drug-loaded diaphragm is an easy-to-use and effective drug delivery system that is often used to treat mouth ulcers. In this study, an ultrafine fiber film loaded with capsaicin was successfully prepared using the electrospinning technology. poly-L-lactic acid and gelatin were selected as the matrix materials to form the composite fiber, and trifluoroethanol was used as a co-solvent for poly-L-lactic acid, gelatin and capsaicin to prepare the spinning solution, which was simple to fabricate. The prepared fiber films were characterized based on their microscopic morphology and tested to derive their mechanical properties. Thereafter, the capsaicin release behavior of the film was investigated. In vitro experiments revealed certain anti-inflammatory and antibacterial abilities while animal experiments revealed that the capsaicin-loaded ultrafine fiber film could promote the healing of oral ulcers in rats. Healing of the tongue tissue in rats administered 10% capsaicin-loaded fiber film was found to be better than that in rats administered the commercial dexamethasone patch. Overall, this development strategy may prove to be promising for the development of oral ulcer patch formulations.


Maternal deprivation increases cell death in the infant rat brain.
Prolonged separation from the mother can interfere with normal growth and development and is a significant risk factor for adult psychopathology. In rodents, separation of a pup from its mother increases the behavioral and endocrine responses to stress for the lifetime of the animal. Here we investigated whether maternal deprivation could affect brain development of infant rats via changes in the rate of cell death as measured by labeling the 3' end of DNA fragments using terminal transferase (ApopTag). At postnatal day 12 (P12), the number of cells undergoing cell death approximately doubled in the cerebral cortex, cerebellar cortex and in several white matter tracts following 24 h of maternal deprivation. Deprivation strongly increased the number of ApopTag-labeled cells at P6 but not at P20. Stroking the infant rats only partially reversed the effects of maternal deprivation. Increased cell death in white matter tracts correlated with an induction of nerve growth factor which has been previously associated with oligodendrocyte cell death. Cell birth was either unchanged or decreased in response to deprivation. These results indicate that maternal deprivation can alter normal brain development by increasing cell death of neurons and glia, and provides a potential mechanism by which early environmental stressors may influence subsequent behavior.


A serious ethical dilemma.
The death of a young woman late last year has led to a call for changes in the law which allows Jehovah's Witnesses to refuse blood transfusion.


Cell cycle-linked vacuolar pH dynamics regulate amino acid homeostasis and cell growth.
Amino acid homeostasis is critical for many cellular processes. It is well established that amino acids are compartmentalized using pH gradients generated between organelles and the cytoplasm; however, the dynamics of this partitioning has not been explored. Here we develop a highly sensitive pH reporter and find that the major amino acid storage compartment in Saccharomyces cerevisiae, the lysosome-like vacuole, alkalinizes before cell division and re-acidifies as cells divide. The vacuolar pH dynamics require the uptake of extracellular amino acids and activity of TORC1, the v-ATPase and the cycling of the vacuolar specific lipid phosphatidylinositol 3,5-bisphosphate, which is regulated by the cyclin-dependent kinase Pho85 (CDK5 in mammals). Vacuolar pH regulation enables amino acid sequestration and mobilization from the organelle, which is important for mitochondrial function, ribosome homeostasis and cell size control. Collectively, our data provide a new paradigm for the use of dynamic pH-dependent amino acid compartmentalization during cell growth/division.


Enzymic oxidation of monoclonal antibodies by soluble and immobilized bifunctional enzyme complexes.
Site-specific modification of monoclonal antibodies was achieved by oxidation of the carbohydrate moieties of antibodies which are located remote from the antigen binding sites. Sialic acid and galactose are terminal sugars of these carbohydrate chains. Concomitant treatment of the antibodies with neuraminidase and galactose oxidase generated aldehyde groups in the oligosaccharide moieties of immunoglobulins which reacted selectively with amino or hydrazide groups of the matrix. Subsequent immobilization of neuraminidase and galactose oxidase on Eupergit C-adipic dihydrazide proved to be an efficient and selective system for the enzymic oxidation of the monoclonal antibodies without impairing their immunological activity. Oriented immobilization of enzymically oxidized monoclonal antibodies on hydrazide or amino Eupergit C derivatives thus leads to the formation of antibody matrix conjugates which possess high antigen-binding activities.


Design and surface characterization of micropatterned silica coatings for zirconia dental implants.
The use of zirconia as an alternative biomaterial for titanium implants has been increasing due to its biocompatibility, favorable aesthetic features, less potential for early plaque accumulation and mechanical properties. Despite the developed efforts, strategies to promote an effective osseointegration are still enough. In this sense and combining the silica properties to improve bone formation with the micropatterning guidance characteristics, silica coatings with micropatterns were designed and evaluated regarding their hydrophilicity and integrity through resistance to scratch and friction tests against femoral bone plates (simulating implant insertion). A combined sol-gel and soft-lithography techniques were used to produce silica coatings onto zirconia substrates and different techniques were used to characterize the micropatterned silica coatings. The results revealed that the production of lines and pillars micropatterns increases the surface roughness (Ra values) and improves the surface strength adhesion. Through the scratch test, it was possible to verify that the integrity and topography characteristics of all micropatterned coatings were not significantly affected after the friction test meaning that their function is not compromised after implant insertion. Additionally, the lines micropattern was the one that presented the highest hydrophilicity for distilled water, thus being a promising surface to promote improved osseointegration. The combined use of different surface micropatterns could potentially be used to guide bone apposition and avoiding peri-implantitis.


Plasma N-terminal pro-brain natriuretic peptide: a prognostic marker in patients with chronic obstructive pulmonary disease.
Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with secondary pulmonary hypertension and chronic lung disease with right ventricular overload. The aim of the present study was to investigate the use of plasma NT-proBNP levels as a prognostic marker of severe COPD with chronic respiratory failure and latent pulmonary hypertension. Plasma NT-proBNP levels were measured in 61 patients with stable COPD. Plasma NT-proBNP levels, pulmonary function, PaO(2), and PaCO(2) levels and systolic pulmonary artery pressure were compared according to COPD severity. In addition, we examined correlations between plasma NT-proBNP levels and pulmonary function, PaO(2), PaCO(2), and systolic pulmonary artery pressure. The levels of plasma NT-proBNP significantly increased in patients with stage IV and stage III COPD compared to individuals with stage II COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The area under the receiver-operating characteristic curve of plasma NT-proBNP for severe to very severe COPD (FEV(1) <50%) was 0.707 (95% confidence interval [CI] 0.566-0.847, P=0.008). Plasma NT-proBNP levels significantly correlated with %FEV(1) (r= -0.557; P < 0.001), arterial blood gas parameters such as PaCO(2) (r = 0.476; P < 0.001) and PaO(2) (r = -0.347; P = 0.031), and systolic pulmonary artery pressure (r = 0.435; P = 0.001). Plasma NT-proBNP levels increased significantly with disease severity, progression of chronic respiratory failure, and secondary pulmonary hypertension in patients with stable COPD. These results suggest that plasma NT-proBNP can be a useful prognostic marker to monitor COPD progression and identify cases of secondary pulmonary hypertension in patients with stable COPD.


Discriminating between memories: evidence for children's spontaneous elaborations.
Children are more confused than adults about memories for what they said and what they imagined saying. The present studies examine the extent to which this confusion is related to the person subjects imagine. In Experiment 1, subjects (7, 10, and adult) said words and imagined someone (themselves, a parent, or a friend) saying other words. They were then asked to distinguish words they said from words they imagined. Performance varied with age as well as with the person subjects imagined. Further, performance was better for words subjects imagined than for words they said. Metamemory responses indicated subjects of all ages remembered elaborative processing activated spontaneously during imagination when discriminating between memories. When the nature of subjects encodings was constrained (i.e., subjects said and imagined someone saying words as part of a sentence completion task. Experiment 2), performance declined for all age groups. Experiments 3 and 4 suggest that elaborations reported in response to our metamemory questions occurred during imagination and were not solely prompted by our metamemory questions.


Molecular geometry and polarizability of small cadmium selenide clusters from all-electron ab initio and Density Functional Theory calculations.
We have calculated molecular geometries and electric polarizabilities for small cadmium selenide clusters. Our calculations were performed with conventional ab initio and density functional theory methods and Gaussian-type basis sets especially designed for (CdSe)(n). We find that the dipole polarizability per atom converges rapidly to the bulk value.


Risk profile of hepatocellular carcinoma reveals dichotomy among US veterans.
Hepatocellular carcinoma (HCC) is traditionally associated with chronic liver injury resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) infection or excessive consumption of alcohol. In addition, recent evidence links HCC to diabetes. Since these risk factors are prevalent among US veterans, we analyzedcontribution of various etiologies toHCC incidence in this population. Clinicopathological correlates of 150 male US veterans diagnosed with HCC between 2001 and 2010 were analyzed and compared to frequency-matched (2:1) non-cancer controls in a single center. HCC was associated with cirrhosis (odds ratio [OR], 250.84; 95 % confidence interval [CI], 86.92-723.88; p < 0.0001), chronic hepatitis B (OR, 34.30 95 % CI, 1.97-598.47; p = 0.015), chronic hepatitis C (OR, 6.84; 95 % CI, 3.89-12.04; p < 0.0001), alcohol use (OR, 6.76; 95 % CI, 4.35-10.52; p < 0.0001), and smoking (OR, 1.83; 95 % CI, 1.23-2.89; p = 0.009), but surprisingly not with diabetes. Only in a subgroup of HCC patients with no "traditional" risk factors did diabetes become a strong independent predictor of HCC when compared to HCC patients with at least one such risk factor (OR, 10.69; 95 % CI, 1.88-60.63, p = 0.007). This subgroup was further distinguished by older age, increased prevalence of hypertension, nonsmoking, and a trend to develop noncirrhotic HCC. While HCC in US veterans is overwhelmingly linked to cirrhosis due to "traditional" risk factors, it also occurs with a separate clinical profile characterized by diabetes and no evidence of cirrhosis, suggesting distinct mechanisms of hepatocarcinogenesis and needs for surveillance.


Periocular triamcinolone acetonide injections for control of intraocular inflammation associated with uveitis.
To describe the effectiveness of periocular corticosteroid injections for the control of intraocular inflammation associated with noninfectious uveitis. A total of 81 patients (109 eyes) who received a periocular injection were evaluated for active inflammation, visual acuity, intraocular pressure, degree of intraocular inflammation, and the presence of ocular complications, including macular edema. Of all eyes, 36% (95%CI: 25%, 45%) demonstrated clinical resolution of inflammation at the 1-month visit after first injection, and 48% (95%CI: 37%, 59%) at 3 months. For multiple injections, 50% (95%CI: 28%, 72%) demonstrated resolution of inflammation at 1 month after the last injection, and 41% (95%CI: 20%, 63%) resolution of inflammation at 3 months after the last injection. Of the 49 eyes that initially responded, the estimated median time to recurrence was 7.6 months. Approximately half of the treated eyes had resolution of intraocular inflammation at 3 months after corticosteroid injection.


Correlation between HDL2, HDL3 and serum ferritin levels with fatty liver and NAFLD activity score (NAS) in liver histology of organ donors.
Nonalcoholic fatty liver disease (NAFLD) is one of the most important liver diseases. High-density lipoprotein (HDL) has anti-atherogenic properties and its reduction can be associated with fatty liver. Serum ferritin levels are usually elevated in patients with NAFLD. This study aimed to evaluate the correlation between HDL subtypes and serum ferritin levels with evidence of NAFLD in liver histology of organ donors. One hundred organ donor patients who were eligible for the study were included in the study and ferritin; HDL2 and HDL3 were measured in blood samples. Donated liver tissue biopsy specimens were evaluated for fatty liver and NAFLD activity score (NAS). In addition, AST and ALT were measured in recipients 24 h after transplant. All data abstracted and analyzed statistically. Serum HDL2 levels and HDL2/HDL3 ratio in patients with NAS > 1 were significantly lower (P < 0.05). Serum levels of HDL3 and ferritin were not significantly associated with NAS >1 (P > 0.05). In addition, serum ferritin > 1000 ng/ml in organ donors associated with increased AST and ALT levels 24 h after transplantation in the liver organ recipient. Lower HDL2 values and HDL2/HDL3 ratio were associated with increased NAFLD activity score, but HDL3 and ferritin did not show such a relationship. In addition, higher levels of ferritin in organ donors may be associated with increased AST and ALT 24 h after liver transplantation in the organ recipient.


Signaling pathway impact analysis by incorporating the importance and specificity of genes (SPIA-IS).
rlying biology of differentially expressed genes and proteins. Although various approaches have been proposed to identify cancer-related pathways, most of them only partially consider the influence of those differentially expressed genes, such as the gene numbers, their perturbation in the signaling transduction, and the interaction between genes. Signaling-pathway impact analysis (SPIA) provides a convenient framework which considers both the classical enrichment analysis and the actual perturbation on a given pathway. In this study, we extended previous proposed SPIA by incorporating the importance and specificity of genes (SPIA-IS). We applied this approach to six datasets for colorectal cancer, lung cancer, and pancreatic cancer. Results from these datasets showed that the proposed SPIA-IS could effectively improve the performance of the original SPIA in identifying cancer-related pathways.


Entrustable professional activities (EPAs) for postgraduate competency based intensive care medicine training in the Netherlands: The next step towards excellence in intensive care medicine training.
The Competency Based Training in Intensive Care Education (CoBaTrICE) programme developed common standards of ICM training by describing competencies of an intensivist. Entrustable Professional Activities (EPAs) of Intensive Care Medicine (ICM) (EPAsICM) are presented as a new workplace-based assessment tool in competency-based training of intensivists. EPAs are activities to be entrusted to a trainee once he (or she) has attained competence. EPAs emphasise the role of trust between trainees and supervisors. EPAs bridge the gap between competencies and competence. An expert panel of ICM (vice)programme directors and intensivists in The Netherlands integrated the CoBaTrICE and CanMEDS competencies into EPAsICM. Comment and feedback was sought from other ICM programme directors and educational experts and processed in the final version of EPAsICM before implementation in the Dutch ICM training programme. A list of 15 EPAsICM are considered to reflect the spectrum of clinical practice while incorporating the competencies of CoBaTrICE and CanMEDS. The grading system is designed as a 5-point entrustment scale based on the amount of supervision a trainee needs, aligning with daily judgement of trainees by intensivists. EPAsICM is an assessment tool that formalises entrustment decisions and can be a valuable addition in international ICM training.


Essential Tremor - A Cerebellar Driven Disorder?
Abnormal tremors are the most common of all movement disorders. In this review we focus on the role of the cerebellum in Essential Tremor, a highly debilitating but poorly treated movement disorder. We propose a variety of mechanisms driving abnormal burst firing of deep cerebellar nuclei neurons as a key initiator of tremorgenesis in Essential Tremor. Targetting these mechanisms may generate more effective treatments for Essential Tremor.


Focal contracture following injection of succinylcholine in patients with peripheral nerve injury.
Focal muscle contracture in the limb following sytemic administration of depolarizing neuromuscular blocking agents have been demonstrated experimentally with transection or crush injury of the nerve, but has rarely been observed clinically in patients with partial peripheral nerve injury. Three cases of spastic response in the hand and wrist are described in patients with subclinical chronic, subacute, and acute nerve injury, to document the occurrence of this phenomenon under various circumstances.


Linking form and motion in the primate brain.
Understanding dynamic events entails the integration of information about form and motion that is crucial for fast and successful interactions in complex environments. A striking example of our sensitivity to dynamic information is our ability to recognize animate figures by the way they move and infer motion from still images. Accumulating evidence for form and motion interactions contrasts with the traditional dissociation between shape and motion-related processes in the ventral and dorsal visual pathways. By combining findings from physiology and brain imaging it can be demonstrated that the primate brain converts information about spatiotemporal sequences into meaningful actions through interactions between early and higher visual areas processing form and motion and frontal-parietal circuits involved in the understanding of actions.


Laryngeal and tracheal anomalies in an infant with oral-facial-digital syndrome type VI (Váradi-Papp): report of a transitional type.
The oral-facial-digital syndromes (OFDS) comprise a group of disorders involving malformations of the mouth, face, and digits. There are 13 subtypes of the OFDS, and much overlap exists among OFDS patients. Distinct syndromes such as Joubert and Pallister-Hall display many of the same features. This report describes an infant with abnormalities including a hypoplastic/absent cerebellar vermis and forked third metacarpals, consistent with a diagnosis of OFDS type VI (Váradi-Papp). The girl's abnormalities also included malformations of the larynx and trachea, findings never before described in type VI but described in other OFDS subtypes and similar syndromes. Our patient represents a transitional OFDS type, further supporting evidence of a common molecular pathway among these disorders. This report highlights the importance of the radiologist's role in diagnosis.


[Simultaneous diagnosis of pseudomeningocele, tethered cord syndrome and cerebrospinal fluid fistula: Report of a case].
The clinical case is presented on a patient with an extensive sacral dysraphism, a history of myelomeningocele surgical repair in her childhood, as well as tethered cord syndrome. The patient was also diagnosed with pseudomeningocele and a cerebrospinal fluid cutaneous fístula. A surgical approach was used, with encouraging results being obtained in the clinical outcome of the patient. A review of the literature was performed to support the surgical decision in this case.


Oral microbiota affects the efficacy and prognosis of radiotherapy for colorectal cancer in mouse models.
Radiotherapy is inevitably intertwined with various side effects impairing the quality of life of cancer patients. Here, we report the possibility that alterations of the oral microbiota influence the therapeutic efficacy and prognosis of radiotherapy for primary rectal cancer and colorectal cancer (CRC) liver metastases that pathologically disrupt gastrointestinal integrity and function. 16S rRNA sequencing shows that oral microbiota alterations change the gut bacterial composition within tumors but not in adjacent peritumor tissues in CRC mouse models. Specifically, buccal Fusobacterium nucleatum migrates to the CRC locus and impairs the therapeutic efficacy and prognosis of radiotherapy. Administration of a specific antibiotic, metronidazole, abrogates the adverse effects of oral microbiome fluctuation on radiotherapy for CRC. The oral microbiota were also associated with radiation-induced intestinal injury via intestinal microbes. Our findings demonstrate that the oral microbiome in synergy with its intestinal counterparts impinges on the efficacy and prognosis of radiotherapy for CRC.


Prognostic Role of CDKN2A Deletion and p53 Expression and Association With MIPIb in Mantle Cell Lymphoma.
Mantle cell lymphoma (MCL) is a rare type of lymphoma, which despite improvements in therapies in recent decades, remains an incurable disease. There is currently no reliable marker of chemoresistance available. In this study, we investigated the prognostic role of MIPIb and the association with biological markers including SOX11, p53 expression, Ki-67, and CDKN2A. This retrospective study was focused on 23 patients with newly diagnosed classical MCL, treated at the University Hospital of Bari (Italy) between January 2006 and June 2019. We identified a MIPIb value ≥ 5.4440 as a prognostic parameter that correlates with p53 expression and CDKN2A deletion. We also observed that patients with p53 overexpression had a significantly higher MIPIb (5.52 ± 0.53) which in 80% of patients had a value higher than 5.4440. On the other hand, CDKN2A deletion was found more frequently (75%) associated with MIPIb ≥5.4440. Only the CDKN2A deletion was associated with a higher proliferation index, with 66.7% of samples having Ki67 ≥30%. From the survival analysis we found that patients with p53 overexpression and CDKN2A deletion have a significantly worse prognosis with a median overall survival of 50 (P = .012) and 52 months (P = .018), respectively. p53 expression and CDKN2A deletion represent a reliable pretreatment prognostic factor that identifies patients who do not benefit from currently used immunochemotherapy-based therapies and who are candidates for diversified treatments with the aim of improving prognosis. The MIPIb represents a prognostic index that correlates well with these biological alterations and can be used in clinical practice as their surrogate.


Improvement of deficits by transplantation of lentiviral vector-modified human amniotic mesenchymal cells after cerebral ischemia in rats.
Amniotic membrane is known to have the ability to transdifferentiate into multiple organs and is expected to stimulate a reduced immunologic reaction. Human amniotic membrane-derived mesenchymal stem cells (hAMCs) do not express the major histocompatibility complex (MHC) class I molecule and may be expected to show immunologic tolerance. A good deal of research has explored the clinical therapeutic potential of hAMCs. In the present study, we isolated hAMCs and transfected them with the brain derived neurotrophic factor (BDNF) gene using lentiviral vectors. These cells were then transplanted into the brains of rats subjected to a transient middle cerebral artery occlusion (MCAO). The hAMCs survived for three weeks in the brains of the ischemic rats, and some of the transplanted hAMCs expressed the neuronal marker MAP2 and the neuronal progenitor marker Nestin. Furthermore, caspase-3 activity and iNOS expression were decreased in the vicinity of the graft and injection site. Importantly, intracerebral grafting of EGFP-modified hAMCs and BDNF-transduced hAMCs significantly ameliorated behavioral dysfunction in ischemic rats. BDNF-hAMCs ameliorated the behavioral dysfunction of rats more rapidly and effectively relative to EGFP-hAMC-treated rats. Finally, the grafts also reduced the infarct volume. hAMCs survived in the brain tissue and improved functional recovery. Because of the lack of ethical concerns and the high supply of these cells, hAMCs represent a promising clinical treatment for gene delivery similar to stem cell strategies.


Sizeable acquired subglottic cyst in a baby with Williams-Beuren syndrome: association or coincidence?
We describe a case of an acquired subglottic cyst presented with persistent stridor and voice hoarsening in a baby diagnosed with Williams-Beuren syndrome that was born premature and required intubation during neonatal period. We also comment on whether this is a coincidence or there can be an association between impaired elastogenesis, a feature of patients with the syndrome and the formation of a subglottic cyst.


Endonuclease-like activity of heme proteins.
Heme proteins, metmyoglobin, methemoglobin, and metcytochrome c showed unusual affinity for double-stranded DNA. Calorimetric studies show that binding of methemoglobin to calf thymus DNA (CTDNA) is weakly endothermic, and the binding constant is 4.9+/-0.7x10(5) M(-1). The Soret absorption bands of the heme proteins remained unchanged, in the presence of excess CTDNA, but a new circular dichroic band appeared at 210 nm. Helix melting studies indicated that the protein-DNA mixture denatures at a lower temperature than the individual components. Thermograms obtained by differential scanning calorimetry of the mixture indicated two distinct transitions, which are comparable to the thermograms obtained for individual components, but there was a reduction in the excess heat capacity. Activation of heme proteins by hydrogen peroxide resulted in the formation of high valent Fe(IV) oxo intermediates, and CTDNA reacted rapidly under these conditions. The rate was first-order in DNA concentration, and this reactivity resulted in DNA strand cleavage. Upon activation with hydrogen peroxide, for example, the heme proteins converted the supercoiled pUC18 DNA into nicked circular and linear DNA. No reaction occurred in the absence of the heme protein, or hydrogen peroxide. These data clearly indicate a novel property of several heme proteins, and this is first report of the endonuclease-like activity of the heme proteins.


Tumour necrosis factor-α plus interleukin-10 low producer phenotype predicts acute kidney injury and death in intensive care unit patients.
Genetic polymorphism studies of cytokines may provide an insight into the understanding of acute kidney injury (AKI) and death in intensive care unit (ICU) patients. The aim of this study was to investigate whether the genetic polymorphisms of -308 G < A tumour necrosis factor (TNF)-α, -174 G > C interleukin (IL)-6 and -1082 G > A IL-10 may predispose ICU patients to the development of AKI and/or death. In a prospective nested case-control study, 303 ICU patients and 244 healthy individuals were evaluated. The study group included ICU patients who developed AKI (n = 139) and 164 ICU patients without AKI. The GG genotype of TNF-α (low producer phenotype) was significantly lower in the with AKI than without AKI groups and healthy individuals (55 versus 62 versus 73%, respectively; P = 0·01). When genotypes were stratified into four categories of TNF-α/IL-10 combinations, it was observed that low TNF-α plus low IL-10 producer phenotypes were more prevalent in patients with AKI, renal replacement therapy and death (P < 0·05). In logistic regression analysis, low TNF-α producer plus low IL-10 producer phenotypes remained as independent risk factors for AKI and/or death [odds ratio (OR) = 2·37, 95% confidence interval (CI): 1·16-4·84; P = 0·02] and for renal replacement therapy (RRT) and/or death (OR = 3·82, 95% CI: 1·19-12·23; P = 0·02). In this study, the combination of low TNF-α plus low IL-10 producer phenotypes was an independent risk factor to AKI and/or death and RRT and/or death in critically ill patients. Our results should be validated in a larger prospective study with long-term follow-up to emphasize the combination of these genotypes as potential risk factors to AKI in critically ill patients.


Citridones, new potentiators of antifungal miconazole activity, produced by Penicillium sp. FKI-1938. I. Taxonomy, fermentation, isolation and biological properties.
New phenylfuropyridinones and related compounds, designated citridones A, B, B' and C, were isolated along with known CJ-16,173, from the culture broth of Penicillium sp. FKI-1938 by solvent extraction, silica gel column chromatography and HPLC. Citridones (75 microM) potentiate the miconazole activity against Candida albicans, decreasing the IC50 value of miconazole from 14.5 nM to 3.5 to approximately 6.3 nM.


Effects of high stocking density on the galectin gene expression in noble scallop Chalmys nobilis under bacterial infection.
High stocking densities have been shown to have adverse effects on the physiology of bivalves. The noble scallop Chlamys nobilis is one of the most important cultured shellfish in Southern China. However, the effects of scallop stocking density on its immunity is not well understood. In this context, this study was conducted to assess the effect of high stocking density on the galectin (an important protein in innate immunity) gene expression of C. nobilis during bacterial infection. A full-length galectin (CnGal) gene was cloned. The ORF of the CnGal cDNA encodes a predicted protein containing 549 aa with four CRDs and no signal peptide. Our results reveal that high stocking density in the scallop not only led to high mortality and slow growth, but also changed tissue distribution of the CnGal expression. The individuals from the high stocking density group exhibited more differences among tissues than those from the control group, but the highest expression were both recorded in hemolymph. After the Vibrio parahaeomlyticus challenge, the gene's expression levels were all significantly up-regulated in the hemolymph and gill, but the time up to peak was different between the two tissues. The findings of this study could fill a gap in knowledge about how high stocking density affect scallop immunity at the molecular level.


Diversity of Salmonella spp. and fungi in northern Greek rivers and their correlation to fecal pollution indicators.
The prevalence and diversity of Salmonella spp., filamentous fungi, and yeasts and their correlation with fecal pollution indicators (total coliforms, fecal coliforms, enterococci) and total heterotrophic bacteria counts were investigated in 95 water samples from the northern Greek rivers Aliakmon and Axios. Salmonella spp. were isolated in 27.4% of the samples and a total of 19 serotypes were identified. The frequency of Salmonella isolation was higher in the Axios (36.8%) than in the Aliakmon (21.0%) river. Significantly (P<0.001) more Salmonella spp. were recovered during warm (41.4%) than cold (5.4%) months. Salmonella-positive samples showed significantly higher counts of total heterotrophic bacteria and coliforms. Filamentous fungi were isolated from 98.9% and yeasts from 17.9% of the samples with respective mean counts of 2.36 x 10(3) and 1.28 x 10(2)cfu/100mL. Totals of 23 genera of filamentous fungi and 3 genera of yeasts were identified. The most frequent filamentous fungi were Penicillium and Aspergillus, while Candida was the most prevalent yeast. A significant (P<0.001) positive correlation of the fecal pollution indicators was demonstrated only for filamentous fungi. The results of this study indicate that these rivers may be potential pathways for human and other animal contamination with Salmonella spp., filamentous fungi, and yeasts, which contribute to the pollution of marine waters and the surrounding environment.


Improved Sensitivity of Ultrasound-Based Subharmonic Aided Pressure Estimation Using Monodisperse Microbubbles.
Subharmonic aided pressure estimation (SHAPE) has been shown effective for noninvasively measuring hydrostatic fluid pressures in a variety of clinical applications. The objective of this study was to explore potential improvements in SHAPE sensitivity using monodisperse microbubbles. Populations of monodisperse microbubbles were created using a commercially available microfluidics device (Solstice Pharmaceuticals). Size distributions were assessed using a Coulter Counter and stability of the distribution following fabrication was evaluated over 24 hours. Attenuation of the microbubble populations from 1 to 10 MHz was then quantified using single element transducers to identify each formulation's resonance frequency. Frequency spectra over increasing driving amplitudes were investigated to determine the nonlinear phases of subharmonic signal generation. SHAPE sensitivity was evaluated in a hydrostatic pressure-controlled water bath using a Logiq E10 scanner (GE Healthcare). Monodisperse lipid microbubble suspensions ranging from 2.4 to 5.3 μm in diameter were successfully created and they showed no discernable change in size distribution over 24 hours following activation. Calculated resonance frequencies ranged from 2.1 to 6.3 MHz and showed excellent correlation with microbubble diameter (R2 > 0.99). When investigating microbubble frequency response, subharmonic signal occurrence was shown to begin at 150 kPa peak negative pressure, grow up to 225 kPa, and saturate at approximately 250 kPa. Using the Logiq E10, monodisperse bubbles demonstrated a SHAPE sensitivity of -0.17 dB/mmHg, which was nearly twice the sensitivity of the commercial polydisperse microbubble currently being used in clinical trials. Monodisperse microbubbles have the potential to greatly improve the sensitivity of SHAPE for the noninvasive measurement of hydrostatic pressures.


Right atrial myxoma presenting as post partum ascites and fever of unknown origin.
A case is reported of right atrial myxoma presenting clinically as ascites and fever of unknown origin. An extensive work-up, including laboratory investigations, X-ray imaging, laparoscopy and laparotomy, failed to explain the clinical picture which was manifested post partum. Echocardiography was diagnostic and led to the curative treatment of surgical resection.


Development and validation of the system of quality of life instruments for cancer patients: colorectal cancer (QLICP-CR).
To develop and validate a quality of life (QOL) instrument for patients with colorectal cancer, QLICP-CR. Using the programmed decision method and the theory in instrument development, the QLICP-CR was developed and evaluated based on the data measuring QOL thrice from a sample of 110 inpatients of colorectal cancer. The internal consistency α and the test-retest reliability for the overall scale and domains are above 0.70 and 0.79, respectively; the score differences between pretreatment and posttreatment have statistical significance for three domains and the overall instrument, with higher Standardized Response Mean of 0.61, 0.62, 1.33, and 0.80. The QLICP-CR is of good validity, reliability, and responsiveness.


Curcumin attenuates intracerebral hemorrhage-induced neuronal apoptosis and neuroinflammation by suppressing JAK1/STAT1 pathway.
Intracerebral hemorrhage (ICH) is a kind of fatal stroke with the highest mortality and morbidity in the world. To date, there is no effective treatment strategy for ICH. Curcumin, a major active ingredient of Curcuma longa L., possesses a potential anti-inflammatory activity in many types of disease. In the current study, the mechanism underlying curcumin attenuated ICH-induced neuronal apoptosis and neuroinflammation was explored. Herein, we studied that curcumin decreased brain edema and improved neurological function by using brain edema measurement, assessment of neurological-deficient score, immunofluorescence, and Western blotting analyses after ICH. The results showed that curcumin improved ICH-induced neuronal apoptosis and neuroinflammation. Functionally, the polarization of microglia was assessed by immunofluorescence and Western blotting analyses after ICH in the absence or presence of curcumin. The results suggested that the M1-type microglia were activated after ICH, while the effect was blocked by curcumin treatment, suggesting that curcumin alleviates the neuroinflammation and apoptosis of neurons by suppressing the M1-type polarization of microglia. Mechanically, M1 polarization of microglia was regulated by JAK1/STAT1, and the activation of JAK1/STAT1 was blocked by curcumin. Meanwhile, the protective function of curcumin can be blocked by RO8191, an activator of JAK1. Taken together, our study suggested that curcumin improved the ICH-induced brain injury through alleviating M1 polarization of microglia/macrophage and neuroinflammation via suppressing the JAK1/STAT1 pathway.


In vitro modulation of lymphocyte proliferation by prednisolone and interferon-alpha in patients with HTLV-I-associated myelopathy (HAM).
One of the hallmarks of human T-lymphotropic virus type I (HTLV-I) infection is the proliferation in vitro of peripheral blood lymphocytes (PBLs) in the absence of growth factors. This phenomenon, the autologous proliferative response (APR), involves spontaneous growth of HTLV-I-infected T-cells and proliferation of T-cells in response to the infected cells. We studied the modulating effect of prednisolone (PSL) and interferon-alpha (IFN) on APR of PBLs obtained from five patients with HTLV-I-associated myelopathy (HAM). APR was significantly inhibited by PSL and IFN suggesting that APR is important in the pathogenesis of HAM.


[Physiopathology and treatment of cough: an etiological approach].
Chronic cough is a common symptom in the consultation of any general practitioner. It may be idiopathic or reflect a chronic disease. However, cough can become excessive, occurring in response to stimuli that do not usually cause this symptom. This entity is called Cough hypersensitivity syndrome (CHS). Its treatment involves the use of neuromodulator substances that specifically target this hypersensitivity, while maintaining intact the cough reflex, essential for protecting the airways. This review aims to present the current knowledge about the pathophysiology of chronic cough, the initial diagnostic approach that this symptom requires and cough treatments either available or in development.


A cell-autonomous positive-signaling circuit associated with the PDGF-NO-ID4-regulatory axis in glioblastoma cells.
Most cancer-related signaling pathways sustain their active or inactive status via genetic mutations or various regulatory mechanisms. Previously, we demonstrated that platelet-derived growth factor (PDGF) activates Notch signaling through nitric oxide (NO)-signaling-driven activation of inhibitor of differentiation 4 (ID4) in glioblastoma (GBM) stem cells (GSCs) and endothelial cells in the vascular niche of GBM, leading to maintenance of GSC traits and GBM progression. Here, we determined that the PDGF-NO-ID4-signaling axis is constantly activated through a positive regulatory circuit. ID4 expression significantly increased PDGF subunit B expression in both in vitro cultures and in vivo tumor xenografts and regulated NO synthase 2 (NOS2) expression and NO production by activating PDGF signaling, as well as that of its receptor (PDGFR). Additionally, ectopic expression of PDGFRα, NOS2, or ID4 activated the PDGF-NO-ID4-signaling circuit and enhanced the self-renewal of GBM cell lines. These results suggested that the positive regulatory circuit associated with PDGF-NO-ID4 signaling plays a pivotal role in regulating the self-renewal and tumor-initiating capacity of GSCs and might provide a promising therapeutic target for GBM.


Synergistic effect from anaerobic co-digestion of food waste and Sophora flavescens residues at different co-substrate ratios.
When food waste (FW) undergoes anaerobic digestion, the hydrolysis rate is rapid, and thus causes system instability. Sophora flavescens residues (SFRs) are rich in complex hydrolysed substances, such as lignocellulosic material. When combined FW and SFRs can effectively improve the stability of digestion systems and increase biogas yields. In this work, batch anaerobic experiments were conducted at different co-substrate ratios to investigate the performance of co-digestion and the synergistic effect of FW and SFRs. The co-digestion of the two substrates exerted synergistic effects on biogas production and the highest synergy was 120.8%. After digestion, the ratio of hydrolysed chemical oxygen demand (COD) to the entire COD (RCODH) of the co-digestion group was 1.08 times that of the single FW group, which indicated the co-digestion promoted the hydrolysis of substrates. Moreover, the hydrolysis rate constant (kh) of co-digestion group increased by 4.10 times in comparison with that of the single FW group, which indicated the co-digestion increased the hydrolysis rate. In other words, the synergistic effect mainly occurred in the hydrolysis acidification process.


Diabetes and quality of life: a Ugandan perspective.
Quality of life of diabetic patients is not a new concept in literature. The contentious issue however is whether factors associated in literature with quality of life apply to diabetic patients in Uganda. A sample of 219 outpatients attending Mulago diabetic clinic--a national referral hospital in Uganda--is used to provide an understanding of this issue. Quality of life is assessed in the dimensions of role limitation due to physical health, emotional health, treatment satisfaction, physical endurance, and diet satisfaction based on a five-point Likert scale. The analysis is made by patients' characteristics, medical conditions, lifestyle factors, and type of medication using frequency distributions, summary statistics, and a Poisson regression. In the results, we confirm a consensus regarding the influence of age and education level on the quality of life in the dimensions of role limitation and physical endurance (P < 0.05). A similar conclusion is reached with regards to impact of diabetic foot ulcers in the dimension of physical endurance. Thus, the factors associated with quality of life are not entirely unique to diabetic patients in the country.


Survey of physicochemical characteristics and microbial contamination in selected food locally vended in Morogoro Municipality, Tanzania.
Raw milk, raw fruit juice and raw fish are enriched with essential nutrients for human diet but are prone to microbial contamination along the value chain. This cross sectional study was conducted to assess physicochemical characteristics and microbial quality of raw milk, fruit juice and fish from food vendors in Morogoro Municipality, Tanzania. The physicochemical assessment of food samples was done by smell, colour, presence of debris, turbidity, consistence, pH and clot on alcohol test. Hygiene of food containers, personnel and the vending environment was also assessed. Qualitative and quantitative microbial assessment of food was done using standard laboratory protocols as described by Tanzania Bureau of Standards and International Systems of Standards. Raw milk sold in Morogoro was of poor quality since was adulterated with water, contained sediments and clotted on alcohol test. Up to 63 % of the milk samples were contaminated with Escherichia coli and 60 % had higher total viable count (TVC) than the recommended values. Raw fruit juice was stored in dirty containers and sold under unhygienic environment. Seventy-three percent of juice samples had TVC beyond the recommendations while E. coli contamination rate was 63.3 %. The raw fish samples had started spoiling as depicted through sensory evaluation. E. coli contamination rate was 55 % and that of Campylobacter jejuni was 0.5 %. The mean TVC of raw fish was 8.1 (Log cfu/g) and 96.2 % of the fish samples had TVC beyond the recommended limits of 5.0 Log cfu/g. The physicochemical characteristics of food vended in Morogoro Municipality were of poor quality. The food had high bacterial contaminations. This situation poses health risks to the public and losses to food vendors due to spoilage. Stakeholders in food value chain should be educated on safe production and good hygienic practices. Routine quality and safety assessment of locally vended food, inspection of selling premises and regular health check-up of the personnel involved in food vending industry should be instituted.


The experience of being a trauma nurse: a phenomenological study.
The lived experience of being a trauma nurse was explored using a phenomenological qualitative research approach. Seven registered nurses employed in a trauma unit from one large metropolitan Canadian teaching hospital participated in in-depth conversational interviews. Data analysis revealed four sub theme clusters embedded within the overarching theme of Seeing Through Cloudy Situations: being on guard all the time, being caught up short, facing the challenge and sharing the journey. Even though trauma nurses are able to find meaning and satisfaction in their work, the findings of this research reveal the need for support and the assurance of safe work environments as trauma nurses can live with violence and aggression in their daily nursing practice.


Mechanically Regulated Outside-In Activation of an I-Domain-Containing Integrin.
Integrins are heterodimeric transmembrane proteins that mediate cellular adhesion and bidirectional mechanotransductions through their conformational allostery. The allosteric pathway of an I-domain-containing integrin remains unclear because of its complexity and lack of effective experiments. For a typical I-domain-containing integrin αXβ2, molecular dynamics simulations were employed here to investigate the conformational dynamics in the first two steps of outside-in activation, the bindings of both the external and internal ligands. Results showed that the internal ligand binding is a prerequisite to the allosteric transmission from the α- to β-subunits and the exertion of external force to integrin-ligand complex. The opening state of αI domain with downward movement and lower half unfolding of α7-helix ensures the stable intersubunit conformational transmission through external ligand binding first and internal ligand binding later. Reverse binding order induces a, to our knowledge, novel but unstable swingout of β-subunit Hybrid domain with the retained close states of both αI and βI domains. Prebinding of external ligand greatly facilitates the following internal ligand binding and vice versa. These simulations furthered the understanding in the outside-in activation of I-domain-containing integrins from the viewpoint of internal allosteric pathways.


EGF receptor inhibitor erlotinib as a potential pharmacological prophylaxis for posterior capsule opacification.
Posterior capsule opacification (PCO) is the most frequent complication after cataract surgery, leading to a loss of sight if untreated. Erlotinib might be of therapeutic interest as an effective target agent (selective EGF-tyrosin-kinase-1 inhibitor). In this in-vitro study, erlotinib was evaluated for ocular biocompatibility and its effect on cell proliferation, migration, 3D matrix contraction and spreading of human lens epithelial cells. To exclude toxic concentrations, erlotinib was assessed for its biocompatibility on five different human ocular cell types in vitro by the tetrazolium dye-reduction assay (MTT) and the Live-Dead assay. To determine its effect on human lens epithelial cell (HLE-B3) proliferation, the MTT test was performed after incubation with different concentrations of erlotinib. Chemotactic migration was analyzed with the Boyden chamber assay and chemokinetic migration was assessed by time lapse microscopy. Contraction was measured by a 3D collagen type 1 matrix contraction assay, and cell spreading was determined by measuring the cell diameter on a fibronectin coated surface. The maximum non-toxic concentration of erlotinib was determined to be 100 μM in cell culture. Erlotinib potently inhibits human lens epithelial cell proliferation, with an IC50 of about 10 μM (8.8 μM ± 0.9 μM SD; r (2) =0.94). Chemotactic migration (p=0.004) and chemokinetic migration (p=0.001) were reduced significantly in a concentration-based manner. Erlotinib prevented human lens epithelial cells from matrix contraction (p=0.001) and cell-spreading (p=0.001). Erlotinib might become of clinical relevance for PCO prophylaxis in the future since it displayed good biocompatibility on ocular cells and mitigated human lens epithelial cell proliferation, migration, contraction, and spreading in vitro. Further studies are warranted to evaluate its potential for clinical application.


Concurrent Validation of the Inpatient Rehabilitation Facility Patient Assessment Instrument Version 1.4; Sections GG, B, and C.
To validate Sections GG (Self-Care and Mobility Assessment), B (Hearing, Speech, and Vision), and C (Cognitive Patterns) of the Centers for Medicare and Medicaid Services Inpatient Rehabilitation Facility Patient Assessment Instrument (CMS-IRF PAI) Version 1.4 in comparison with Functional Independence Measure (FIM) motor subscale (FIMm) and cognitive subscale (FIMc). Retrospective cohort. Single inpatient rehabilitation facility. Cohort of 1296 patients admitted for rehabilitation after stroke, between October 1, 2016, and October 1, 2019. Not applicable. Sections GG, B, and C scores were compared with FIMm and FIMc using Spearman's and Bland-Altman Analyses. Sections GG and FIMm were highly correlated on admission (ρ=0.919, P<.001) and discharge (ρ=0.929, P<.001). Ceiling effects at discharge were more pronounced for Section GG (8.6%). Bland-Altman analyses revealed a bias toward higher scores on Section GG vs FIMm on admission (Bias=2.3%, P<.001), and discharge (Bias=6.2%, P<.001). Section GG showed bias toward greater gains in function (Bias=3.9%, P<.001), particularly in walking and stairs (bias=3.71%, P<.001). Comparable self-care items accounted for a smaller percentage of the Section GG gains compared with FIMm (bias=-7.5%, P<.001). The internal validity of a scale consisting of Section B and C (B+C scale) was good, (Cronbach's alpha=0.868) and was highly correlated with FIMc (ρ=0.745), but rated patients at a higher level of cognition (bias=20.0%, P<.001) and had a greater ceiling effect (20.4%) on admission compared with the FIMc (0.6%). The B+C scale and Section GG were correlated with FIMc and FIMm subscales but biased toward higher ratings of ability. Ceiling effects may limit discrimination at higher level of cognition/functional independence. The clinical acceptability of Section GG total scores as an outcome measure and predictor of long-term outcomes requires further study.


Obesity in pregnant women: a 20-year analysis of the German experience.
To investigate the longitudinal development of maternal body weight and analyze the influence of obesity on obstetrics during more than two decades in Germany. Data collected from the Federal state of Schleswig-Holstein (German Perinatal Survey) were analyzed with regard to the dynamics of maternal anthropometric variables (body weight, BMI) between 1995-7 and 2004-17. In total 335,511 mothers substantiated the presented study-collective. The statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY. Maternal BMI advanced significantly over the study period. Among a rise in mean periconceptional body weight (67.6-72.0 kg), the segment of obese women increased disproportionately (in average 9.4-19.2%). Despite the observed trend to late giving birth (mean maternal age 1995: 29.3 vs. 30.7 years in 2017), it was not advanced maternal age but parity that influenced the continuous increase in maternal weight (mean maternal body weight 1995-7: primi- bi-, multiparae 67.4, 68.3 and 69.0 kg vs. 2004-17: primi- bi-, multiparae 70.0, 71.5 and 73.2 kg respectively). Obesity is a major problem on health issues in obstetrics. Advancing maternal BMI, increasing mother's age and derived prenatal risks considerably complicate pregnancy and delivery. It has to be emphasized that its consequences do not end with delivery or childbed, but represent a livelong burden to the mother and their offspring. Hence, multimodal strategies to reduce/control periconceptional body weight are mandatory.


Fibrinolytic risk factor clustering and insulin resistance in healthy male relatives of men with intermittent claudication.
Raised fibrinolytic factors predict cardiovascular risk in healthy subjects. The aim of this study was to measure fibrinolytic factors and insulin resistance in healthy male first-degree relatives of men with intermittent claudication younger than 65 years. The study compared 165 healthy first-degree relatives with 165 age-, sex- and race-matched control subjects free from a personal or family history of premature cardiovascular disease. Primary outcome measures were plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA) and D-dimer levels. Insulin resistance was estimated by Homeostasis Model Assessment. Clinical and biochemical risk factors were measured and subjects genotyped for the PAI-1 4G/5G polymorphism. First-degree relatives had significantly higher mean PAI-1 (10.23 versus 7.85 ng/ml; P = 0.024), tPA (9.98 versus 8.29 ng/ml; P < 0.001) and D-dimer levels (56.6 versus 46.1 ng/ml; P = 0.004). They also had significantly higher insulin resistance (1.85 versus 1.53; P < 0.001) and clustered multiple atherogenic risk factors. On multivariate analysis the association between both tPA and D-dimer levels and relative status was independent of other variables. Raised levels of PAI-1, tPA, D-dimer and estimated insulin resistance were present in the healthy male first-degree relatives of men with intermittent claudication. These data support the hypothesis of fibrinolytic risk factor clustering in this high-risk population.


Evolution of structure in RNA.
Evidence is presented that structures formed by RNA and by RNA in association with protein have evolved from simpler structures by successive unions among them. The progressively more complex molecular structures have conferred selective advantage in evolution by progressively enhancing the specificities of the biochemical reactions. Before each union, the RNAs which joined at the time of union belonged to separate reproducing species. The record of unions in RNA therefore reflects unions among species in the biosphere, tracing the evolution of life from quite simple reproducing molecules up to well developed organisms.


Influence of pressure, flow rate, and pulsatility on release of 6-keto-PGF1 alpha and thromboxane B2 in ex vivo-perfused canine veins.
The influence of pressure, flow, and pulsatility on the release of prostacyclin (measured as 6-keto-PGF1 alpha) and thromboxane (measured as TxB2) was assessed in canine jugular veins perfused ex vivo with Hanks' balanced salt solution for five consecutive 15-minute periods. Control segments were perfused at 7 mm Hg with nonpulsatile flow at a rate of 90 ml/min, whereas experimental segments were perfused with pulsatile flow as well as nonpulsatile flow at pressures of 50 or 100 mm Hg and flow rates of 60 or 130 ml/min. Prostacyclin release from control segments during the first 15-minute period was 49.5 +/- 7.4 pg/mm2/15 min, which declined to 13.9 +/- 2.5 pg/mm2/15 min after 60 minutes (p less than 0.002). Arachidonic acid stimulation during the last 15-minute perfusion period increased the release to 56.1 +/- 9.4 pg/mm2/15 min (p less than 0.002). Thromboxane release from control segments was initially 4.4 +/- 1.2 pg/mm2/15 min, which declined to 0.8 +/- 0.2 pg/mm2/15 min after 60 minutes (p less than 0.002), and subsequently increased with arachidonic acid stimulation to 1.3 +/- 0.1 pg/mm2/15 min (p less than 0.01). In contrast to control perfusion conditions, changes in nonpulsatile flow rates did not affect prostacyclin release, whereas thromboxane release was lower when perfused at 60 ml/min. Pressures of 50 and 100 mm Hg increased the initial release of prostacyclin. Similarly, pulsatile flow enhanced prostacyclin release at both low and high pressures, being more pronounced with the latter.(ABSTRACT TRUNCATED AT 250 WORDS)