Treatment of osteomyelitis with a biodegradable antibiotic implant.
A biodegradable antibiotic implant was developed and evaluated in a localized osteomyelitic rabbit model. The biodegradable antibiotic implant was made of polylactic acid and poly(DL-lactide):co-glycolide combined with vancomycin. Localized rabbit tibial osteomyelitis was developed with Staphylococcus aureus. Infected rabbits were divided into eight groups, depending on treatment with or without debridement, systemic antibiotics, or biodegradable beads. After 4 weeks of therapy, the radiographs were obtained of the involved bones, which also were cultured for concentrations of Staphylococcus aureus per gram of bone. Treatment with antibiotic containing polylactic acid and poly(DL-lactide):co-glycolide beads, with and without systemic vancomycin, resulted in bone colony forming unit levels of 10(2.93) and 10(2.84) colony forming units per gram bone, respectively. These bacterial concentrations were approximately 100 times lower than those observed for all other treatment groups. A biodegradable antibiotic bead may provide extended bactericidal concentrations of antibiotics for the time needed to completely treat the particular orthopaedic infection and does not require the surgery needed to remove the polymethylmethacrylate beads.


Hepatobiliary effects of 90yttrium microsphere therapy for unresectable hepatocellular carcinoma.
(90)Yttrium (Therasphere) microspheres administered via hepatic artery are a valuable option for treatment of hepatocellular carcinoma. This therapy targets tumor nodules while largely sparing hepatic parenchyma. This retrospective study examines liver explants from 13 adult patients with hepatocellular carcinoma who received intrahepatic Theraspheres and subsequently underwent liver transplantation. Histopathologic and laboratory reviews are performed. Theraspheres preferentially migrated to the lobe(s) supplied by the injected artery branches and frequently localized to tumors. Tumors showed a chronology of changes beginning with confluent necrosis typically accompanied by hemorrhage and later by fibrinoid change. This was followed by fibrosis with regenerative activity at tumor peripheries. Adjacent hepatic parenchyma went through a similar sequence of injury and repair that could lead to markedly fibrotic cirrhotic nodules in the vicinity of treated tumors. No consistent pattern of thrombomodulin loss was seen in endothelial cells of the tumors or adjacent parenchyma, suggesting that direct endothelial cell injury was likely not a major contributor to the necrotic process. However, the pattern of injury and repair is suggestive of a localized and subclinical form of radiation-induced liver disease. The pathologist should be aware of these changes to distinguish them from the diffuse "radiation hepatitis" associated with older forms of radiotherapy.


Urinary arginine vasopressin: pattern of excretion in the neonatal period.
The pattern of arginine vasopressin (AVP) secretion in the immediate neonatal period is unclear. Plasma concentrations of AVP are reflected by its urinary excretion, thus providing a noninvasive method for studying the pattern of AVP release in the neonate. In these studies, we determined the pattern of urinary AVP excretion (microU/mg creatinine) during the first 2-4 days after birth in 78 neonates, 53 of whom had various prenatal and/or neonatal complications. In well term (n = 12) and preterm (n = 13) infants mean urinary AVP excretion decreased gradually during the first 24-36 h after birth. Although term and preterm infants with perinatal asphyxia had highest initial levels of urinary AVP (greater than 200 microU/mg creatinine) and a significant negative correlation with the 1-min Apgar score was obtained, their pattern of excretion was similar to respective controls. After delivery, elevated values for urinary AVP excretion were found among infants with neonatal courses complicated by intracranial hemorrhage, hypoxic encephalopathy, and pneumothorax. Urine osmolality did not correlate linearly with urinary AVP levels, but rather attained a maximum value of approximately 400 mosmol/kg at urinary AVP levels less than 200 microU/mg creatinine and then plateaued. It is concluded that the decrease in urinary AVP excretion observed soon after birth generally reflects diminution of the hypersecretion of AVP during parturition; neonates with evidence of intrapartum asphyxia initially have increased urinary AVP excretion; however, the pattern of excretion is similar to normal infants. During the neonatal period insults such as pneumothorax and intracranial hemorrhage may cause hypersecretion of this hormone.


Activation of the phase II enzymes for neuroprotection by ginger active constituent 6-dehydrogingerdione in PC12 cells.
The cellular endogenous antioxidant system plays pivotal roles in counteracting or retarding the pathogenesis of many neurodegenerative diseases. Molecules with the ability to enhance the antioxidant defense thus are promising candidates for neuroprotective drugs. 6-Dehydrogingerdione (6-DG), one of the major components of dietary ginger, has received increasing attention due to its multiple pharmacological activities. However, how this pleiotropic molecule works on the neuronal system has not been studied. This paper reports that 6-DG efficiently scavenges various free radicals in vitro and displays remarkable cytoprotection against oxidative stress-induced neuronal cell damage in the neuron-like rat pheochromocytoma cell line, PC12 cells. Pretreatment of PC12 cells with 6-DG significantly up-regulates a panel of phase II genes as well as the corresponding gene products, such as glutathione, heme oxygenase, quinone oxidoreductase, and thioredoxin reductase. Mechanistic study indicates that activation of the Keap1-Nrf2-ARE pathway is the molecular basis for the cytoprotection of 6-DG. This is the first revelation of this novel mechanism of 6-DG as an Nrf2 activator against oxidative injury, providing the potential therapeutic use of 6-DG as neuroprotective agent.


Combining gene annotations and gene expression data in model-based clustering: weighted method.
It has been increasingly recognized that incorporating prior knowledge into cluster analysis can result in more reliable and meaningful clusters. In contrast to the standard modelbased clustering with a global mixture model, which does not use any prior information, a stratified mixture model was recently proposed to incorporate gene functions or biological pathways as priors in model-based clustering of gene expression profiles: various gene functional groups form the strata in a stratified mixture model. Albeit useful, the stratified method may be less efficient than the global analysis if the strata are non-informative to clustering. We propose a weighted method that aims to strike a balance between a stratified analysis and a global analysis: it weights between the clustering results of the stratified analysis and that of the global analysis; the weight is determined by data. More generally, the weighted method can take advantage of the hierarchical structure of most existing gene functional annotation systems, such as MIPS and Gene Ontology (GO), and facilitate choosing appropriate gene functional groups as priors. We use simulated data and real data to demonstrate the feasibility and advantages of the proposed method.


Diazo-carboxyl Click Derivatization Enables Sensitive Analysis of Carboxylic Acid Metabolites in Biosamples.
Carboxylic acids are central metabolites in bioenergetics, signal transduction, and post-translation protein regulation. However, the quantitative analysis of carboxylic acids as an indispensable part of metabolomics is prohibitively challenging, particularly in trace amounts of biosamples. Here we report a diazo-carboxyl/hydroxylamine-ketone double click derivatization method for the sensitive analysis of hydrophilic, low-molecular-weight carboxylic acids. In general, our method renders a 5- to 2000-fold higher response in mass spectrometry along with improved chromatographic separation. With this method, we presented the near-single-cell analysis of carboxylic acid metabolites in 10 mouse egg cells before and after fertilization. Malate, fumarate, and β-hydroxybutyrate were found to decrease after fertilization. We also monitored the isotope labeling kinetics of carboxylic acids inside adherent cells cultured in 96-well plates during drug treatment. Finally, we applied this method to plasma or serum samples (5 μL) collected from mice and humans under pathological and physiological conditions. The double click derivatization method paves a way toward single-cell metabolomics and bedside diagnostics.


What Factors Drive Staghorn vs Nonstaghorn Pattern Growth in Patients with Metabolic Stones?
Purpose: There has been an increase in the number of staghorn calculi that form in the absence of infection (metabolic staghorns). It is unknown why some large metabolic calculi form as solitary or multiple separate, nonbranching caliceal stones, whereas others develop as staghorn stones forming a cast of the collecting system. We sought to compare these two groups of metabolic stone formers (SFs) in an attempt to shed light on these disparate stone-forming phenomena. Materials and Methods: From January 2017 to September 2018, 190 patients underwent percutaneous nephrolithotomy for stones >2 cm. We identified 86 (45%) patients with a metabolic stone, defined as ≥80% calcium oxalate monohydrate or dihydrate and/or calcium phosphate. Exclusion criteria included stones composed of cystine, >20% uric acid, or any infectious element (struvite or carbonate apatite). Metabolic staghorn and nonstaghorn SFs were compared with respect to medical comorbidity, 24-hour urine parameters, stone and urine microbiology, stone compositions, and intraoperative findings. Statistical differences were assessed using chi-square analysis, Fisher's exact test, and Student's t-test. Results: In total, 25 (29%) staghorn and 61 (71%) nonstaghorn SFs were included for analysis. The groups were statistically similar in age, sex, body mass index, and medical comorbidity. Staghorn SFs had larger stone burdens (p < 0.0001), but did not require more punctures (p = 0.783). Staghorn SFs were more likely to have hyperoxaluria (p = 0.041) and higher mean 24-urine oxalate levels (p = 0.040). There were no other significant differences in 24-hour urine profiles, rates of metabolic abnormalities, stone compositions, stone or urine cultures, presence of collecting system obstruction, or pelvicaliceal anatomy. Conclusions: Although potentially driven by urinary oxalate, whether a metabolic stone will form into a staghorn configuration or not does not appear significantly influenced by standard determinants of stone development, including metabolic profile, cultures, hydronephrosis, and pelvicaliceal anatomy, among others. Further work is needed to elucidate the physicochemical factors that govern the pathogenesis of this increasingly prevalent entity.


[Prolonged local enzyme therapy of suppurative wounds].
The article analyses the results of treatment of 150 patients with purulent diseases of the soft tissues of various localization, in which after surgical treatment the purulent focus immobilized trypsin (50 patients), trypsin with lysozyme immobilized on gauze (50 patients), and antiseptics (50 patients) were used for topical treatment of the formed wounds. The results of the treatment showed that topical prolonged enzyme therapy of purulent wounds with the use of trypsin immobilized on gauze and that with lysozyme promotes cleansing of the wounds, reduces microbial dissemination, intensifies reparative processes, and reduces the terms of treatment.


A Systematic Review and Meta-Analysis of the Risk of Dementia Associated with Benzodiazepine Use, After Controlling for Protopathic Bias.
Benzodiazepine use is highly prevalent in elderly and late middle-aged populations and may be associated with an increased risk of dementia. Observational studies have suggested that benzodiazepine use may increase the risk of dementia, however there have been significant concerns regarding protopathic bias in these studies, precluding conclusive findings. The aim of our study was to investigate the risk of dementia associated with the use of benzodiazepines in elderly patients, after controlling for protopathic bias. We identified observational studies with more than 50 cases, adequate assessment of benzodiazepine exposure, and reliable dementia diagnosis ascertainment, from the MEDLINE, PubMed, EMBASE, CINAHL, LILACS and CENTRAL electronic databases through to 5 June 2018, with no language limits. The association of any current or former use of short- or long-acting benzodiazepines with incident dementia was analysed. A subgroup analysis was performed by the introduction of lag time to assess the effect of protopathic bias. We also performed analyses considering the effect of higher benzodiazepine cumulative doses and adjustment for psychiatric covariates. Study quality was investigated using the Newcastle-Ottawa Scale. We identified 15 studies reported in 14 articles, involving 159,090 cases. Ever use of benzodiazepines was associated with a significantly increased risk of dementia [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.21-1.59]. Those studies that implemented the longest lag times of ≥ 5 years, and hence most likely to overcome protopathic bias, found a risk estimate that was marginally attenuated, but still significant (OR 1.30, 95% CI 1.14-1.48). Long-acting benzodiazepines were associated with a marginally higher magnitude risk (OR 1.21, 95% CI 0.99-1.49) than short-acting benzodiazepines (OR 1.13, 95% CI 1.02-1.26), although the former failed to reach statistical significance (p = 0.059). Our findings indicate that the association between benzodiazepine use and dementia incidence is not purely an artefact due to protopathic bias. Reduction of inappropriate benzodiazepine prescription is likely to attenuate dementia risk.


Trypanosoma congolense: re-expression of a deleted metacyclic variable antigen type in vivo and in vitro.
The expression of variable antigen types (VATs) was determined among dividing populations of T. congolense growing in vivo in rabbit chancres and in vitro on bovine aorta endothelial cell monolayers. Experiments were performed in which a single metacyclic VAT (M-VAT) was deleted from a cultured metacyclic population by neutralisation with a monoclonal antibody and complement. Subsequent expression of the deleted M-VAT and two unrelated M-VATs was determined by an indirect immunofluorescent antibody test. The deleted M-VAT was re-expressed both in vivo and in vitro and the proportions of unrelated M-VATs were not markedly affected by the neutralisation of this single M-VAT. In addition, an overall similarity was observed between M-VAT expression and re-expression in vivo and in vitro.


Effects of immunological castration (Improvest) on changes in dressing percentage and carcass characteristics of finishing pigs.
The objective was to determine which tissue components contributed to the reduction in carcass yield of immunologically castrated (IC) barrows when compared to physically castrated (PC) barrows. The carcass yield of an IC barrow is less than the carcass yield of a PC barrow. This has historically been attributed to the presence of testicles, but the testes have only accounted for approximately 0.25% of live weight. This experiment included PC barrows, intact males, IC barrows, IC barrows fed ractopamine hydrochloride, and gilts. When the pigs reached 15 wk old, they were weighed, assigned to treatments (intact male or IC barrow), and penned in groups of 4 pigs per pen. Pigs designated for immunological castration were given injections at approximately 16 wk old and approximately 20 wk old. Pigs were eligible for harvest 33 d after the second injection when the average weight of the pen reached 130 kg. Immunologically castrated barrows lost on average 0.7% units more live weight during transport and lairage than PC barrows, intact males, or gilts. Physically castrated barrows had a 1.43% unit advantage over IC barrows in carcass yield. The differences in yield can be attributed to differences in testicles, reproductive tract, intestinal mass, gut fill, and some visceral organs. Testicle weight accounted for a 0.28% unit reduction in carcass yield of IC barrows when compared to PC barrows. Additional reproductive tract weights accounted for differences of 0.10% units. Intestinal mass (empty large intestine, small intestine, and stomach) was 0.2% units heavier in IC barrows when compared to PC barrows. Livers from IC barrows were 200 g heavier (P < 0.05) and kidneys were 40 g heavier than the same organs in PC barrows. These 2 organs combined for a 0.15% unit difference in carcass yield between IC and PC barrows. Gut fill, testicles, reproductive tract, intestinal mass, and the liver and kidney accounted for 0.97 of 1.43% unit differences in carcass yield between IC and PC barrows. Immunologically castrated barrows had less marbling than PC barrows, but there were no other differences in pork quality parameters. Cutability differences were less than reported in previous experiments, but IC barrows still had a 1.0% unit advantage in lean cutting yield and a 0.7% unit advantage in carcass cutting yield when compared to PC barrows.


Manganese toxicokinetics at the blood-brain barrier.
Increased manganese (Mn) use in manufacturing and in gasoline has raised concern about Mn-induced parkinsonism. Previous research indicated carrier-mediated brain entry but did not assess brain efflux. Using in situ rat brain perfusion, we studied influx across the blood-brain barrier (BBB*) of three predominant plasma Mn species available to enter the brain: Mn2+, Mn citrate, and Mn transferrin. Our results suggested transporter-mediated uptake of these species. The uptake rate was greatest for Mn citrate. Our results using the brain efflux index method suggested that diffusion mediates distribution from rat brain to blood. To characterize the carriers mediating brain Mn uptake, we used rat erythrocytes, an immortalized murine BBB cell line (b.End5), primary bovine brain endothelial cells (bBMECs), and Sprague Dawley and Belgrade rats. Studies with bBMECs and b.End5 cells suggested concentrative brain Mn2+ and Mn citrate uptake, respectively, consistent with carrier-mediated uptake. Mn2+ uptake positively correlated with pH, suggesting mediation by an electromotive force. Mn2+ uptake was not inhibited by iron or the absence of divalent metal transporter 1 (DMT-1) expression, suggesting an iron-transporter-independent mechanism. Mn2+ uptake inversely correlated with calcium and was affected by calcium channel modulators, suggesting a role for calcium channels. Rat erythrocyte results suggested monocarboxylate transporter 1 (MCT1) and anion exchange transporters do not mediate Mn citrate brain uptake. Considering carrier-mediated brain influx (but not efflux), repeated excessive Mn exposure should produce brain accumulation. Further work is necessary to identify the specific transporter or transporters mediating Mn distribution across the BBB.


Processing Challenges and Opportunities of Camel Dairy Products.
A review on the challenges and opportunities of processing camel milk into dairy products is provided with an objective of exploring the challenges of processing and assessing the opportunities for developing functional products from camel milk. The gross composition of camel milk is similar to bovine milk. Nonetheless, the relative composition, distribution, and the molecular structure of the milk components are reported to be different. Consequently, manufacturing of camel dairy products such as cheese, yoghurt, or butter using the same technology as for dairy products from bovine milk can result in processing difficulties and products of inferior quality. However, scientific evidence points to the possibility of transforming camel milk into products by optimization of the processing parameters. Additionally, camel milk has traditionally been used for its medicinal values and recent scientific studies confirm that it is a rich source of bioactive, antimicrobial, and antioxidant substances. The current literature concerning product design and functional potential of camel milk is fragmented in terms of time, place, and depth of the research. Therefore, it is essential to understand the fundamental features of camel milk and initiate detailed multidisciplinary research to fully explore and utilize its functional and technological properties.


Management issues for women with epilepsy--focus on pregnancy (an evidence-based review): III. Vitamin K, folic acid, blood levels, and breast-feeding: Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the American Epilepsy Society.
A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast-milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in clinically important amounts. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4 mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of levetiracetam and oxcarbazepine (as MHD) levels may be considered. A paucity of evidence limited the strength of many recommendations.


Ultrasensitive mechanical detection of magnetic moment using a commercial disk drive write head.
Sensitive detection of weak magnetic moments is an essential capability in many areas of nanoscale science and technology, including nanomagnetism, quantum readout of spins and nanoscale magnetic resonance imaging. Here we show that the write head of a commercial hard drive may enable significant advances in nanoscale spin detection. By approaching a sharp diamond tip to within 5 nm from a write pole and measuring the induced diamagnetic moment with a nanomechanical force transducer, we demonstrate a spin sensitivity of 0.032 μB Hz(-1/2), equivalent to 21 proton magnetic moments. The high sensitivity is enabled in part by the pole's strong magnetic gradient of up to 28 × 10(6) T m(-1) and in part by the absence of non-contact friction due to the extremely flat writer surface. In addition, we demonstrate quantitative imaging of the pole field with ∼10 nm spatial resolution. We foresee diverse applications for write heads in experimental condensed matter physics, especially in spintronics, ultrafast spin manipulation and mesoscopic physics.


Early treatment of Parkinson's disease with cabergoline delays the onset of motor complications. Results of a double-blind levodopa controlled trial. The PKDS009 Study Group.
This multicentre randomised double-blind 3- to 5-year trial was designed to assess whether initial therapy with cabergoline alone or in combination with levodopa prevents or delays the occurrence of long term motor complications in patients with early Parkinson's disease. Patients eligible for study inclusion (n = 412) had early idiopathic Parkinson's disease (Hoehn and Yahr stages 1 to 3) and had received no previous treatment with levodopa, selegiline or dopamine agonists. Patients were randomised to receive either cabergoline (0.25 to 4 mg once daily) or levodopa (100 to 600 mg/day) titrated over a maximum period of 24 weeks. Once the optimum or maximum tolerated dose was achieved, it was maintained up to the end-point (development of motor complications confirmed at 2 consecutive 3-month visits) or up to a minimum of 3 years' treatment. Open labelled levodopa was added in both treatment arms when the improvement in motor disability [Unified Parkinson's Disease Rating Scale (UPDRS) factor III] decreased below 30% vs baseline. Both treatments improved motor disability, decreasing UPDRS factor III scores and factor II scores for activities of daily living. The development of motor complications (end-point) was significantly less frequent in patients treated with cabergoline than in levodopa recipients (22% vs 34%; p < 0.02). The relative risk of developing motor complications during treatment with cabergoline was more than 50% lower than with levodopa. Serious adverse events, either drug related or not, were slightly more frequent in cabergoline-treated patients (31%) than in those treated with levodopa (25%). The withdrawal rate in the cabergoline vs levodopa group was 16 vs 13%. In conclusion, the study shows that, in patients with early Parkinson's disease, cabergoline is effective either as monotherapy or combined with levodopa. Moreover, starting treatment with cabergoline significantly delays the development of motor complications.


[Diagnostic and therapy of a severe fetal parvovirus-B19-infection with persistence of viral DNA in the mothers blood but inconspicuous serological tests. Case report].
In the 24th week of gestation we diagnosed a severe hydrops fetalis in a 25 year old VI gravid III para, who had contact to parvovirus B19 in the 14th week of gestation. Because of the severe anaemia of the fetus and the massively increased bilirubinoides in the amniotic fluid we decided at the same day to apply the first of four intrauterine transfusions. The serological patterns of maternal blood with highly positive parvovirus-B19-IgG and negative IgM suggested that an infection had occurred. Parvoviral DNA was found in maternal and fetal blood confirming the diagnosis of an acute intrauterine parvovirus-B19 infection. No viral DNA was detected in fetal ascites. IgM in fetal blood was negative. By means of four transfusions, the pregnancy could be prolonged until the 32 + 5th week of gestation while the ascites was declining. When rupture of membranes occurred, a cesarean section had to be performed due to contractions and presentation of the feet. The newborn's blood count exhibited a thrombocytopenia with normal haemoglobin and haematocrit. Five days after delivery, a blood exchange had to be done because of a hyperbilirubinaemia. After seven weeks, the child could be dismissed from hospital in good general status, with decreasing ascites, normal liver function and normal neurological status. The blood of the newborn was tested to be positive for IgG, while IgM-antibodies and parvovirus-B19-DNA were negative. The diagnosis of a parvovirus-B19 infection of a fetus with severe hydrops and anaemia could be verified by a positive proof for DNA in maternal blood, with negative IgM and highly positive parvovirus-B19-IgG and on the other hand highly positive viral DNA in fetal blood and in the amniotic fluid. 10 weeks after contact to parvovirus B19, i. e. in the 24th week of gestation, positive IgG- and negative IgM-antibodies were found in the mother's blood, whereas fetal complications were noticed. These data demonstrate that following an acute parvovirus-B19-infection of the mother IgM-antibodies can be proofed for 6 - 8 (- 10) weeks. On the other side parvovirus-B19-DNA in the mothers blood is detectable by means of PCR for 8 - 10 weeks and in some cases even more than 15 weeks.


Somatotropic responses to soy protein alone and as part of a meal.
GH is an important regulator of growth and body composition. We previously showed that GH release can be promoted by oral ingestion of soy protein; it is not known, however, whether these somatotropic effects of soy protein are also present when soy protein is ingested as part of a complete meal. We compared the effects of oral ingestion of soy protein alone with the effects of a meal containing the same amount of soy protein on GH secretion in six healthy women (body mass index 19-26 kg/m(2), 19-36 years), in a randomized crossover design. During the whole experiment, serum GH, insulin, and glucose were determined every 20 min. GH responses as determined by area under the curve (AUC) and peak values were lower after ingestion of the meal, in comparison with GH responses after the soy protein consumption alone (P<0.05), and did not differ from the placebo. Glucose and insulin responses, both determined as AUC and peak values, were higher after ingestion of the meal, compared with those after ingestion of the protein drink or the placebo (P<0.05). The somatotropic effect of soy protein is reduced and delayed when soy protein is ingested as part of a complete meal. Dietary carbohydrates, by increasing serum levels of glucose and insulin concentration, as well as dietary fat, may have interfered with the somatotropic effects of soy protein.


Plasmonic Probing of Deoxyribonucleic Acid Hybridization at the Single Base Pair Resolution.
Partial DNA duplex formation greatly impacts the quality of DNA hybridization and has been extensively studied due to its significance in many biological processes. However, traditional DNA sensing methods suffer from time-consuming amplification steps and hinder the acquisition of information about single-molecule behavior. In this work, we developed a plasmonic method to probe the hybridization process at a single base pair resolution and study the relationship between the complementarity of DNA analytes and DNA hybridization behaviors. We measured single-molecule hybridization events with Au NP-modified ssDNA probes in real time and found two hybridization adsorption events: stable and transient adsorption. The ratio of these two hybridization adsorption events was correlated with the length of the complementary sequences, distinguishing DNA analytes from different complementary sequences. By using dual incident angle excitation, we recognized different single-base complementary sequences. These results demonstrated that the plasmonic method can be applied to study partial DNA hybridization behavior and has the potential to be incorporated into the identification of similar DNA sequences, providing a sensitive and quantitative tool for DNA analysis.


Almost like a whale - first evidence of suction feeding in a seabird.
Little auks (Alle alle) are one of the most numerous seabird species in the world and feed primarily on copepods in arctic waters. Their high daily energy requirements leave them vulnerable to current changes in the arctic plankton community, where a smaller, less-profitable copepod species (Calanus finmarchicus) becomes increasingly abundant. Little auks have been estimated to require ∼60,000 copepods per day, necessitating prey capture rates of ∼6 copepods per second underwater. To achieve such performance, it has been suggested that little auks capture their prey by (non-visual) filter feeding. We tested this hypothesis by exposing little auks to varying copepod densities within a shallow experimental pool and filming their prey capture behaviour. At none of the copepod densities tested did birds filter feed. Instead, all birds captured copepods by what we identified as visually guided suction feeding, achieved through an extension of their sub-lingual pouch. Suction feeding is very common in fish and marine mammals, but to the best of our knowledge, this is the first time that it has been specifically identified in a seabird species. While presumably less efficient than filter feeding, this behaviour may allow little auks to foster higher resilience when facing the consequences of arctic climate change.


Multicenter study for defining the breakpoint for rifampin resistance in Neisseria meningitidis by rpoB sequencing.
Identification of clinical isolates of Neisseria meningitidis that are resistant to rifampin is important to avoid prophylaxis failure in contacts of patients, but it is hindered by the absence of a breakpoint for resistance, despite many efforts toward standardization. We examined a large number (n = 392) of clinical meningococcal isolates, spanning 25 years (1984 to 2009), that were collected in 11 European countries, Argentina, and the Central African Republic. The collection comprises all clinical isolates with MICs of > or = 0.25 mg/liter (n = 161) received by the national reference laboratories for meningococci in the participating countries. Representative isolates displaying rifampin MICs of < 0.25 mg/liter were also examined (n = 231). Typing of isolates was performed, and a 660-bp DNA fragment of the rpoB gene was sequenced. Sequences differing by at least one nucleotide were defined as unique rpoB alleles. The geometric mean of the MICs was calculated for isolates displaying the same allele. The clinical isolates displaying rifampin MICs of > 1 mg/liter possessed rpoB alleles with nonsynonymous mutations at four critical amino acid residues, D542, H552, S548, and S557, that were absent in the alleles found in all isolates with MICs of < or = 1 mg/liter. Rifampin-susceptible isolates could be defined as those with MICs of < or = 1 mg/liter. The rpoB allele sequence and isolate data have been incorporated into the PubMLST Neisseria database (http://pubmlst.org/neisseria/). The rifampin-resistant isolates belonged to diverse genetic lineages and were associated with lower levels of bacteremia and inflammatory cytokines in mice. This biological cost may explain the lack of clonal expansion of these isolates.


Education differentials by race and ethnicity in the diagnosis and management of hypercholesterolemia: a national sample of U.S. adults (NHANES 1999-2002).
To examine education differentials in screening, awareness, treatment and control of hypercholesterolemia overall and in 3 race/ethnic groups. We analyzed data for a nationally representative sample of 8,429 men and women ages 20 to 85 years, self-reported as white, black, Mexican American, or other race/ethnicity, who participated in the National Health and Nutrition Examination Survey from 1999-2002. Participants with < high school education were 2.5 times less likely than participants with > or = high school education to have been screened for hypercholesterolemia, after adjusting for age and gender (odds ratio: 0.4, 95 % confidence interval: 0.3-0.5, and similar across race/ethnic group). Multivariable models for awareness, treatment and control showed no significant trends associated with education after adjusting for age, gender, race and comorbidities. Higher education significantly increased the odds of being screened for hypercholesterolemia overall and within each race/ethnic group. Education differentials were strongest for hypercholesterolemia screening, and weak or no longer apparent for subsequent steps of awareness, treatment and control. Focusing public health policy on increasing screening for individuals with low education might greatly improve their chances of preventing or mitigating morbidity related to hypercholesterolemia and subsequent cardiovascular disease.


Effect of 180-week water storage on the flexural properties of E-glass and silica fiber acrylic resin composite.
The aim of this study was to determine the effect of long-term water immersion on the flexural properties of fiber-reinforced composite. Continuous, woven, silanized E-glass fibers and woven silica fibers were used to reinforce heat-cured and autopolymerized denture base polymers. Fibers were oriented at a 45-degree angle to the long axis of the test specimens. Control specimens were unreinforced. Dry test specimens and those stored in water for up to 180 weeks were tested with a 3-point loading apparatus. Ultimate transverse strength and flexural modulus of unreinforced and fiber-reinforced composite test specimens decreased during water storage (P < 0.001, analysis of variance). Post hoc analysis revealed that after the storage of 4 weeks no statistically significant reduction occurred. The results of this study suggest that the ultimate transverse strength of the fiber-reinforced composite made from E-glass fibers is reduced by approximately 27% compared to the dry fiber-reinforced composite. The majority of the reduction occurred during 4 weeks of storage in water and remained approximately at that level for 180 weeks.


Adipocyte Microenvironment in Ovarian Cancer: A Critical Contributor?
Ovarian cancer is one of the most common gynecological malignancies and has low survival rates. One of the main determinants of this unfavorable prognosis is the high rate of peritoneal metastasis at diagnosis, closely related to its morbidity and mortality. The mechanism underlying peritoneal carcinomatosis is not clearly defined, but a clear preference for omental spread has been described. Growing evidence suggests that adipose tissue plays a role in promoting cancer onset and progression. Moreover, obesity can lead to changes in the original functions of adipocytes, resulting in metabolic and inflammatory changes in the adipose tissue microenvironment, potentially increasing the risk of tumor growth. However, the specific roles of adipocytes in ovarian cancer have not yet been fully elucidated. Due to the undeniable link between obesity and cancer, the adipose tissue microenvironment could also present a promising therapeutic target that warrants further research. This review discusses the complex relationship between ovarian cancer and the adipose tissue microenvironment.


We all want to live longer, but not grow old.
Population ageing represents a "triumph" and a "challenge" for society. The increase in life expectancy corresponds to an increase of risk factors and age-associated non communicable diseases, with consequent rise in health care costs and the burden of healthcare sustainability. Aim of this analysis is to describe the prevalence of non communicable diseases, comorbidity and disability in non-institutionalized elderly population, aged 75-79 years, examined within the Osservatorio Epidemiologico Cardiovascolare/Health Examination Survey. Cardiovascular disease is the most frequent occurring in 27% of the examined population, followed by diabetes (24%) and chronic kidney disease (21%); 60% of examined elderly population suffers of one or more chronic diseases, while 40% is in a good health. Ninety-three per cent of the examined population is free of disability; cognitive function disorders, assessed by the Folstein's Mini Mental State Examination, are recorded in 21% men and 29% women. In the context of prevention, there is still much that needs to be done. It is important to initiate or maintain preventive actions concerning also this age-group at both community and individual level, to promote the cultural notion that a good quality of life in advanced age is built day by day starting from one's youth through a healthy diet, regular physical activity and non-smoking habit.


Statins: a treatment option for chronic heart failure?
Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, consistently reduce cardiovascular risk. It has recently emerged that cholesterol reduction is not their only mode of action, with current research largely focused on the pleiotropic effects of statins. These include the improvement of endothelial dysfunction, their anti-inflammatory properties, and the mobilization of bone marrow-derived endothelial progenitor cells. All these effects are potentially beneficial in chronic heart failure (CHF), although prospective trials are needed to confirm this. However, cholesterol reduction by statins per se may prove detrimental in patients with CHF, as cholesterol seems to be able to inactivate endotoxin as a stimulus for proinflammatory cytokine production. It is therefore tempting to speculate that low doses of statins still confer pleiotropic effects without lowering plasma cholesterol levels.


["Problem-based learning--inflammation and transplantation": an integrated, subject-centred course in the clinical section of the medical curriculum at the medical school of the University of Muenster].
Conventional medical curricula present information pertinent to chronic inflammatory diseases, infectious diseases and transplantation, via systematic lectures and courses in medical specialties without any integrated approach. The authors report on a 3-week model course that attempts to provide students with an overview of clinical presentation, diagnostics, and therapy of representative disease entities with particular emphasis on the interdisciplinary approach to these problems in hospital practice. In addition to problem-based learning in small groups, the model course comprises interdisciplinary concept lectures, practical demonstrations of specific diagnostic procedures, and bedside teaching. In the meantime, the course "Problem-Based Learning--Inflammation and Transplantation" has been held twice successfully as a mandatory course in the clinical part of the curriculum at the Muenster Medical School.


Greater Telehealth Use Results in Increased Visit Frequency and Lower Physician Related-Distress in Adolescents and Young Adults With Type 1 Diabetes.
Type one diabetes (T1D) management is challenging for adolescents and young adults (AYAs) due to physiological changes, psychosocial challenges, and increasing independence, resulting in increased diabetes distress and hemoglobin A1c (HbA1c). Alternative care models that engage AYAs and improve diabetes-related health outcomes are needed. A 15-month study evaluated an adaptation of the Colorado Young Adults with T1D (CoYoT1) Care model. CoYoT1 Care includes person-centered care, virtual peer groups, and physician training delivered via telehealth. AYAs (aged 16-25 years) were partially randomized to CoYoT1 or standard care, delivered via telehealth or in-person. As the study was ending, the COVID-19 pandemic forced all AYAs to transition to primarily telehealth appointments. This secondary analysis compares changes in clinic attendance, T1D-related distress, HbA1c, and device use between those who attended more than 50% of diabetes clinic visits via telehealth and those who attended more sessions in-person throughout the course of the study. Out of 68 AYA participants, individuals (n = 39, 57%) who attended most (>50%) study visits by telehealth completed more diabetes care visits (3.3 visits) than those (n = 29, 43%) who primarily attended visits in-person (2.5 visits; P = .007). AYAs who primarily attended visits via telehealth maintained stable physician-related distress, while those who attended more in-person visits reported increases in physician-related distress (P = .03). Greater usage of telehealth improved AYA engagement with their care, resulting in increased clinic attendance and reduced physician-related diabetes distress. A person-centered care model delivered via telehealth effectively meets the needs of AYAs with T1D.


Injury and the orchestral environment: part II. Organisational culture, behavioural norms, and attitudes to injury.
The organisational culture, behavioural norms, and attitudes of a workplace have a profound influence on levels of injury and illness amongst its workers. While this is well established in Work Health and Safety literature, very little research has attempted to understand the influence of organisational culture on injury risk in the orchestral profession. To address this, the current study aimed to investigate the influence of organisational culture on injury outcomes for orchestral musicians. Using a qualitative case study methodology, in-depth semi-structured interviews were undertaken with 10 professional orchestral cellists (2 freelance and 8 fulltime members) from a single Australian orchestra. After initial data analysis, further interviews were undertaken with a set of 5 orchestral management staff as a means of data triangulation. All data were analysed using a themes-based "analysis of narrative" approach. The findings indicate that an orchestral culture exists in which musicians see injury as a sign of weakness, failure, and poor musicianship. Such negative perceptions of injury influence musicians to play through considerable levels of pain and continue performing with injuries. Because of perceived judgment from the orchestral group, musicians were found to conceal injuries from colleagues and management staff. Freelance musicians felt that disclosing injuries may lead to decreased work opportunities, and both full-time and casual musicians felt that "opening up" about injury may subject them to group judgment about their technique or musicianship. The study suggests education measures which may be effective at influencing individual behaviours and attitudes as well as cultural change initiatives which could lead to long-term positive health outcomes in the orchestral workplace.


Effect of renal perfusion pressure on sodium reabsorption from proximal tubules of superficial and deep nephrons.
Previous studies in rats have demonstrated that superficial proximal tubule sodium reabsorption does not change in response to alterations in renal perfusion pressure (RPP). The first objective of the present study was to estimate sodium reabsorption in response to acute changes in RPP utilizing fractional lithium reabsorption (FRLi) as an index of fractional sodium reabsorption (FRNa) by the proximal tubule of the kidney as a whole. FRLi decreased in response to increases in RPP, suggesting that sodium reabsorption by the proximal tubule of some nephron population is decreased. Therefore, the second objective of the present study was to test the hypothesis that superficial and deep proximal tubules respond differently to changes in RPP by comparing proximal tubule sodium reabsorption from both nephron populations. In response to an acute change in RPP from 114 +/- 4 to 138 +/- 5 mmHg, FRNa by the proximal tubule and descending limb of Henle's loop in deep nephrons decreased from 71.3 +/- 2.3 to 55.8 +/- 5.6%, but FRNa by the superficial late proximal tubule was not changed: (44.3 +/- 4.8 to 45.1 +/- 3.9%). The urinary fractional reabsorption of sodium decreased from 96.7 +/- 0.6 to 94.5 +/- 0.5%. In summary, these studies demonstrate that increases in RPP have no effect on sodium reabsorption by the proximal tubule of superficial nephrons. In contrast, sodium delivery to the point of micropuncture in the descending limb of Henle's loop of deep nephrons was increased, suggesting inhibition of sodium reabsorption by proximal tubules of deep nephrons in response to increases in RPP.


Association of OSR-1 With Vascular Dysfunction and Hypertension in Polycystic Kidney Disease.
Autosomal-dominant polycystic kidney disease (ADPKD) is associated with oxidative stress and hypertension development before renal function decline and cardiovascular disease development. Oxidative stress-responsive kinase-1 (OSR-1) participates in the signaling regulating Na+ transport during oxidative stress and also plays a role in the regulation of cell volume and blood pressure. Therefore, we aimed to investigate the potential role of OSR-1 in ADPKD patients. Eighty ADPKD patients, 80 healthy controls, and 80 non-ADPKD patients with hypertension were enrolled in this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood samples were taken after 12-h fasting for the measurement of biochemical parameters and OSR-1 gene expression. Vascular dysfunction was assessed using ischemia-induced forearm flow-mediated vasodilation (FMD). Briefly, of the 80 ADPKD patients, 41(51%) were male, and 53(66%) of them were hypertensive. The mean age of the 80 controls was 35.3 ± 12.6 years, and 37(46%) of them were male. The mean age of the 80 non-ADPKD patients with hypertension was 44.6 ± 11.9 years, and 38(47.5) of them were male. There were significant differences in serum OSR-1 gene expression between the ADPKD patients and the control subjects. Serum OSR-1 gene expression was also significantly increased in hypertensive ADPKD patients in comparison with both normotensive ADPKD counterparts and non-ADPKD hypertensive subjects. Serum OSR-1 gene expression was increased in patients with ADPKD than healthy subjects. Low estimated glomerular filtration rate (eGFR), OSR-1 gene expression, total kidney volume (TKV), and high-density lipoprotein (HDL) were also independently associated with hypertension in ADPKD patients.


[Changes in lipid composition of human plasma and erythrocyte membranes due to sodium hydroxybutyrate and normobaric hyperoxia during bed rest].
Gas chromatography was employed to study effects of sodium hydroxybutyrate (GHBA) and normobaric hyperoxia on the fatty-acid composition of total lipids of blood plasma and erythrocyte membranes in 5 normal male volunteers in the baseline data collection period and during 14-d bed rest. Both in plasma and erythrocyte membranes saturated palmitic acid was found increased and polyunsaturated linoleic acid and arachidonic acid reduced.


3,3'-diindolylmethane induces activating transcription factor 3 (ATF3) via ATF4 in human colorectal cancer cells.
3,3'-Diindolylmethane (DIM) is a major in vivo condensation product of indole-3-carbinol, which is present in cruciferous vegetables. Although these compounds have been widely implicated in antitumorigenic and proapoptotic properties in animal as well as in vitro models of cancer, the underlying cellular mechanisms regulated by DIM are only partially understood. Activating transcription factor 3 (ATF3) is a member of the ATF/c-AMP response element-binding (CREB) subfamily of the basic-region leucine zipper family and has been known to induce apoptosis in human colorectal cancer (CRC) cells. The present study was performed to elucidate the molecular mechanism of ATF3 induction by DIM in human CRC cells. The DIM treatment induced apoptosis and induced ATF3 gene expression at protein and messenger RNA levels. DIM increased ATF3 promoter activity, and the region of -84 to +34 within ATF3 promoter was responsible for promoter activation by DIM. This region contained an ATF binding site. Deletion and point mutation of the ATF binding site (-23 to -16) abolished ATF3 promoter activation by DIM, and overexpression of ATF4 enhanced ATF3 transactivation. Chromatin immunoprecipitation assay confirmed the binding of ATF4 in the ATF3 promoter. Inhibition of ATF4 expression by small interference RNA results in repression of DIM-induced ATF3 expression. The current study demonstrates that DIM stimulates ATF3 expression through ATF4-mediated pathway and subsequently induces apoptosis in human CRC cells.


Prenylated Flavonoids from Morus alba L. Cause Inhibition of G1/S Transition in THP-1 Human Leukemia Cells and Prevent the Lipopolysaccharide-Induced Inflammatory Response.
Morus alba L. (MA) is a natural source of many compounds with different biological effects. It has been described to possess anti-inflammatory, antioxidant, and hepatoprotective activities. The aim of this study was to evaluate cytotoxicity of three flavonoids isolated from MA (kuwanon E, cudraflavone B, and 4'-O-methylkuwanon E) and to determine their effects on proliferation of THP-1 cells, and on cell cycle progression of cancer cells. Anti-inflammatory effects were also determined for all three given flavonoids. Methods used in the study included quantification of cells by hemocytometer and WST-1 assays, flow cytometry, western blotting, ELISA, and zymography. From the three compounds tested, cudraflavone B showed the strongest effects on cell cycle progression and viability of tumor and/or immortalized cells and also on inflammatory response of macrophage-like cells. Kuwanon E and 4'-O-methylkuwanon E exerted more sophisticated rather than direct toxic effect on used cell types. Our data indicate that mechanisms different from stress-related or apoptotic signaling pathways are involved in the action of these compounds. Although further studies are required to precisely define the mechanisms of MA flavonoid action in human cancer and macrophage-like cells, here we demonstrate their effects combining antiproliferative and anti-inflammatory activities, respectively.


Calcium buffering in presynaptic nerve terminals. I. Evidence for involvement of a nonmitochondrial ATP-dependent sequestration mechanism.
A latent ATP-dependent Ca storage system is enriched in preparations of pinched-off presynaptic nerve terminals (synaptosomes), and is exposed when the terminals are disrupted by osmotic shock or saponin treatment. The data indicate that a fraction of the Ca uptake (measured with 45Ca) is associated with the intraterminal mitochondria; it is blocked by ruthenium red, by FCCP, and by azide + dinitrophenol + oligomycin. There is, however, a residual ATP-dependent Ca uptake that is insensitive to the aforementioned poisons; this (nonmitochondrial) Ca uptake is blocked by tetracaine, mersalyl and A-23187. Moreover, A-23187 rapidly releases previously accumulated Ca from these (nonmitochondrial) storage sites, whereas the Ca chelator, EGTA, does not. The proteolytic enzyme, trypsin, spares the mitochondria but inactivates the nonmitochondrial Ca uptake mechanism. Chemical measurements of total Ca indicate that the ATP-dependent Ca uptake at the nonmitochondrial sites involves the net transfer of Ca from medium to tissue fragments. This system can sequester Ca when the ambient-ionized Ca2+ concentration (buffered with EGTA) is less than 0.3 micrometer; brain mitochondria take up little Ca when the ionized Ca2+ level is this low. Preliminary subfractionation studies indicate that the nonmitochondrial Ca storage system does not sediment with synaptic vesicles. We propose that this Ca storage system, which has many properties comparable to those of skeletal muscle sarcoplasmic reticulum, may be associated with intraterminal smooth endoplasmic reticulum. This Ca-sequestering organelle may help to buffer intracellular Ca.


Radiation-induced, immunologically mediated regression of an established tumor as an example of successful therapeutic immunomanipulation. Preferential elimination of suppressor T cells allows sustained production of effector T cells.
The results of this study confirm results published by others by showing that sublethal whole-body irradiation of mice bearing immunogenic tumors can result in complete tumor regression. The results show, in addition, that irradiation-induced tumor regression can be prevented by infusion, after irradiation, of Ly-1+,2-,L3T4+ suppressor T cells from the spleens of donors bearing an established tumor, but not by infusion of normal spleen cells. This evidence, plus the demonstration that irradiation fails to cause regression of tumors growing in immunocompetent mice, is consistent with the hypothesis that irradiation-induced regression is immunologically mediated, and that it depends on the ability of irradiation to preferentially eliminate suppressor T cells. By using passive transfer assays to measure the production of effector T cells and suppressor T cells against time of tumor growth, it was shown that irradiation of tumor-bearing mice on day 5 of tumor growth resulted in a failure to generate suppressor T cells on the one hand, and in a sustained production, effector T cells on the other. In other words, irradiation prevented the concomitant antitumor immune response from being downregulated by suppressor T cells. However, giving radiation on day 1 of tumor growth, in contrast to giving it 3-6 d later, caused immunodepression and enhancement of tumor growth. This is in keeping with published evidence showing that, whereas resting effector T cells are highly radiosensitive, antigen-activated effector T cells are relatively radioresistant. It is suggested that the radioresistance of activated effector T cells, coupled with the radiosensitivity of activated suppressor T cells, is the reason for the selectivity of ionizing radiation for suppressor T cells and why a tumor needs to be palpable to undergo regression in response to radiation therapy.


Effector CD8 T Cell-Dependent Zika Virus Control in the CNS: A Matter of Time and Numbers.
Zika virus (ZIKV), a mosquito-borne flavivirus, came into the spotlight in 2016 when it was found to be associated with an increased rate of microcephalic newborns in Brazil. The virus has further been recognized to cause neurologic complications in children and adults in the form of myelitis, encephalitis, acute disseminated encephalomyelitis (ADEM) and Guillain Barre Syndrome in a fraction of infected individuals. With the ultimate goal of identifying correlates of protection to guide the design of an effective vaccine, the study of the immune response to ZIKV infection has become the focus of research worldwide. Both innate and adaptive immune responses seem to be essential for controlling the infection. Induction of sufficient levels of neutralizing antibodies has been strongly correlated with protection against reinfection in various models, while the role of CD8 T cells as antiviral effectors in the CNS has been controversial. In an attempt to improve our understanding regarding the role of ZIKV-induced CD8 T cells in protective immunity inside the CNS, we have expanded on previous studies in intracranially infected mice. In a recent study, we have demonstrated that, peripheral ZIKV infection in adult C57BL/6 mice induces a robust CD8 T cell response that peaks within a week. In the present study, we used B cell deficient as well as wild-type mice to show that there is a race between CXCR3-dependent recruitment of the effector CD8 T cells and local ZIKV replication, and that CD8 T cells are capable of local viral control if they arrive in the brain early after viral invasion, in appropriate numbers and differentiation state. Our data highlight the benefits of considering this subset when designing vaccines against Zika virus.


Celecoxib Encapsulation in β-Casein Micelles: Structure, Interactions, and Conformation.
β-Casein is a 24 kDa natural protein that has an open conformation and almost no folded or secondary structure, and thus is classified as an intrinsically unstructured protein. At neutral pH, β-casein has an amphiphilic character. Therefore, in contrast to most unstructured proteins that remain monomeric in solution, β-casein self-assembles into well-defined core-shell micelles. We recently developed these micelles as potential carriers for oral administration of poorly water-soluble pharmaceuticals, using celecoxib as a model drug. Herein we present deep and precise insight into the physicochemical characteristics of the protein-drug formulation, both in bulk solution and in dry form, emphasizing drug conformation, packing properties and aggregation state. In addition, the formulation is extensively studied in terms of structure and morphology, protein/drug interactions and physical stability. Particularly, NMR measurements indicated strong drug-protein interactions and noncrystalline drug conformation, which is expected to improve drug solubility and bioavailability. Small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM) were combined for nanostructural characterization, proving that drug-protein interactions lead to well-defined spheroidal micelles that become puffier and denser upon drug loading. Dynamice light scattering (DLS), turbidity measurements, and visual observations complemented the analysis for determining formulation structure, interactions, and stability. Additionally, it was shown that the loaded micelles retain their properties through freeze-drying and rehydration, providing long-term physical and chemical stability. Altogether, the formulation seems greatly promising for oral drug delivery.


Behavioral responses to tactile stimuli in children with cerebral palsy.
Children with cerebral palsy often have difficulty processing tactile information. Assessment of tactile processing in children with cerebral palsy frequently relies on the use of informal clinical observations, checklists, and sensory histories without established psychometric properties. It is proposed that a formal approach to the assessment of behavioral responses to tactile stimuli will provide a better understanding of the tactile processing of children with cerebral palsy. This approach also has potential to assist with the development of intervention strategies and the evaluation of progress. The purposes of this article are to review the literature on the tactile processing difficulties of children with cerebral palsy, examine the suitability of existing assessments of tactile processing for children with cerebral palsy, and provide a rationale for a new assessment tool being developed by the authors.


The foot and ankle structures reveal emergent properties analogous to passive springs during human walking.
An objective understanding of human foot and ankle function can drive innovations of bio-inspired wearable devices. Specifically, knowledge regarding how mechanical force and work are produced within the human foot-ankle structures can help determine what type of materials or components are required to engineer devices. In this study, we characterized the combined functions of the foot and ankle structures during walking by synthesizing the total force, displacement, and work profiles from structures distal to the shank. Eleven healthy adults walked at four scaled speeds. We quantified the ground reaction force and center-of-pressure displacement in the shank's coordinate system during stance phase and the total mechanical work done by these structures. This comprehensive analysis revealed emergent properties of foot-ankle structures that are analogous to passive springs: these structures compressed and recoiled along the longitudinal axis of the shank, and performed near zero or negative net mechanical work across a range of walking speeds. Moreover, the subject-to-subject variability in peak force, total displacement, and work were well explained by three simple factors: body height, mass, and walking speed. We created a regression-based model of stance phase mechanics that can inform the design and customization of wearable devices that may have biomimetic or non-biomimetic structures.


The health impact of nighttime eating: old and new perspectives.
Nighttime eating, particularly before bed, has received considerable attention. Limiting and/or avoiding food before nighttime sleep has been proposed as both a weight loss strategy and approach to improve health and body composition. Indeed, negative outcomes have been demonstrated in response to large mixed meals in populations that consume a majority of their daily food intake during the night. However, data is beginning to mount to suggest that negative outcomes may not be consistent when the food choice is small, nutrient-dense, low energy foods and/or single macronutrients rather than large mixed-meals. From this perspective, it appears that a bedtime supply of nutrients can promote positive physiological changes in healthy populations. In addition, when nighttime feeding is combined with exercise training, any adverse effects appear to be eliminated in obese populations. Lastly, in Type I diabetics and those with glycogen storage disease, eating before bed is essential for survival. Nevertheless, nighttime consumption of small (~150 kcals) single nutrients or mixed-meals does not appear to be harmful and may be beneficial for muscle protein synthesis and cardiometabolic health. Future research is warranted to elucidate potential applications of nighttime feeding alone and in combination with exercise in various populations of health and disease.


Genetic dissection of maize (Zea maysL.) trace element traits using genome-wide association studies.
Maize (Zea mays L.) is an important food and feed crop worldwide and serves as a a vital source of biological trace elements, which are important breeding targets. In this study, 170 maize materials were used to detect QTNs related to the content of Mn, Fe and Mo in maize grains through two GWAS models, namely MLM_Q + K and MLM_PCA + K. The results identified 87 (Mn), 205 (Fe), and 310 (Mo) QTNs using both methods in the three environments. Considering comprehensive factors such as co-location across multiple environments, strict significance threshold, and phenotypic value in multiple environments, 8 QTNs related to Mn, 10 QTNs related to Fe, and 26 QTNs related to Mo were used to identify 44 superior alleles. Consequently, three cross combinations with higher Mn element, two combinations with higher Fe element, six combinations with higher Mo element, and two combinations with multiple element (Mn/Fe/Mo) were predicted to yield offspring with higher numbers of superior alleles, thereby increasing the likelihood of enriching the corresponding elements. Additionally, the candidate genes identified 100 kb downstream and upstream the QTNs featured function and pathways related to maize elemental transport and accumulation. These results are expected to facilitate the screening and development of high-quality maize varieties enriched with trace elements, establish an important theoretical foundation for molecular marker assisted breeding and contribute to a better understanding of the regulatory network governing trace elements in maize.


Development of a cytotoxic T-cell assay in rabbits to evaluate early immune response to human T-lymphotropic virus type 1 infection.
Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell lymphoma/leukemia (ATL) following a prolonged clinical incubation period, despite a robust adaptive immune response against the virus. Early immune responses that allow establishment of the infection are difficult to study without effective animal models. We have developed a cytotoxic T-lymphocyte (CTL) assay to monitor the early events of HTLV-1 infection in rabbits. Rabbit skin fibroblast cell lines were established by transformation with a plasmid expressing simian virus 40 (SV40) large T antigen and used as autochthonous targets (derived from same individual animal) to measure CTL activity against HTLV-1 infection in rabbits. Recombinant vaccinia virus (rVV) constructs expressing either HTLV-1 envelope surface unit (SU) glycoprotein 46 or Tax proteins were used to infect fibroblast targets in a (51)Cr-release CTL assay. Rabbits inoculated with Jurkat T cells or ACH.2 cells (expressing ACH HTLV-1 molecule clone) were monitored at 0, 2, 4, 6, 8, 13, 21, and 34 wk post-infection. ACH.2-inoculated rabbits were monitored serologically and for viral infected cells following ex vivo culture. Proviral load analysis indicated that rabbits with higher proviral loads had significant CTL activity against HTLV-1 SU as early as 2 wk post-infection, while both low- and high-proviral-load groups had minimal Tax-specific CTL activity throughout the study. This first development of a stringent assay to measure HTLV-1 SU and Tax-specific CTL assay in the rabbit model will enhance immunopathogenesis studies of HTLV-1 infection. Our data suggest that during the early weeks following infection, HTLV-1-specific CTL responses are primarily targeted against Env-SU.


Real-world assessment and treatment of locally advanced basal cell carcinoma: Findings from the RegiSONIC disease registry.
Limited information is available regarding real-world treatment patterns and their effectiveness and safety in patients with locally advanced basal cell carcinoma, including patients not typically represented in clinical trials. The purpose of the current study was to describe how clinicians diagnose and treat locally advanced basal cell carcinoma in the United States. This prospective, multicenter, observational registry study included patients with newly diagnosed, Hedgehog pathway inhibitor-naive locally advanced basal cell carcinoma without basal cell carcinoma nevus syndrome (n = 433) treated at 75 US academic and community practices, including dermatology, Mohs surgery, and medical oncology sites. The main outcomes of this study were treatment patterns and associated effectiveness and safety for patients with locally advanced basal cell carcinoma in real-world settings. Determination of locally advanced basal cell carcinoma was mainly based on lesion size (79.6% of patients), histopathology (54.3%), extent of involvement (49.0%), and location (46.2%). Within 90 days of determination of locally advanced disease, 115 patients (26.6%) received vismodegib, 251 (58.0%) received surgery/other (non-vismodegib) treatment, and 67 (15.5%) had not yet received treatment (observation). Vismodegib-treated patients had a higher prevalence of high-risk clinical features predictive for locoregional recurrence than those with non-vismodegib treatment or observation. Clinical response rate was 85.1% with vismodegib and 94.9% with non-vismodegib treatment (primarily surgery). The most common adverse events with vismodegib were ageusia/dysgeusia, muscle spasms, alopecia, and weight loss. Rates of cutaneous squamous cell cancers were comparable between vismodegib and non-vismodegib treatment. This prospective observational study offers insight on real-world practice, treatment selection, and outcomes for a nationally representative sample of US patients with locally advanced basal cell carcinoma. For patients with lesions that were not amenable to surgery, vismodegib treatment was associated with effectiveness and safety that was consistent with that observed in clinical trials.


Fatty acid binding proteins in brain development and disease.
Long chain polyunsaturated fatty acids (PUFAs) are critical structural components of the brain and essential for normal brain development. The cellular transportation and physiological actions of PUFAs are mediated by fatty acid binding proteins (FABPs) which are encoded by the intracellular lipid-binding protein gene family. Three of the ten mammalian FABPs identified to date (FABP3, FABP5, FABP7) are expressed in the brain. These three FABPs, along with their fatty acid ligands, have distinct and dynamic spatio-temporal expression profiles that correlate with specific developmental stages and processes in the brain. Functional studies have revealed a variety of roles for FABPs in brain development including the generation of neuronal and/or glial cells, differentiation, neuronal cell migration and axis patterning. A number of transcription factors have been shown to be involved in the developmental regulation of FABP gene expression in the brain. Furthermore, FABPs appear to be major downstream effectors of signaling pathways such as Reelin-Dab1/Notch which mediate neuron-glia crosstalk during brain development. As PUFAs and FABPs play critical roles in brain development, considerable effort has been placed in elucidating their function in the pathogenesis and progression of brain cancers and neuropsychiatric disorders.


Stress fractures of the femoral neck in adults: an observational study on epidemiology, treatment, and reoperations from the Swedish Fracture Register.
Stress fractures of the femoral neck (sFNFs) are uncommon injuries. Studies on sFNFs are rare. We describe the demographics, classification, treatment, reoperation rates, and mortality in a cohort of sFNF patients from the Swedish Fracture Register (SFR). We included 146 patients ≥ 18 years of age with an sFNF registered in the SFR between 2011 and 2020. The cohort was linked with the Swedish Arthroplasty Register and reviewed using medical records and radiographs. We assessed the presence of disorders of bone remodeling, duration of symptoms, fracture classification, treatment, reoperations, and mortality. The mean age was 58 years (21-96), 75% were women and the median duration of symptoms was 23 days (1-266). 40% of patients had disorders of bone remodeling. 54% were undisplaced (uFNF), 30% displaced (dFNF), and 16% basicervical (bFNF). 14% of patients < 60 years were treated nonoperatively, by internal fixation (IF) in 77% and by arthroplasty in 10%. Patients ≥ 60 years were treated nonoperatively in 10%, IF in 40%, and arthroplasty in 49%. Nonoperative treatment was reserved for uFNFs or bFNFs, resulting in 35% receiving late surgery. The overall secondary or late surgery rate was 19%. Mortality was 2% at 90 days and increased to 3% at 1 year. sFNF has a biphasic age distribution. One-third of patients presented with a displaced FNF and those managed nonoperatively for an undisplaced sFNF were at risk of late surgery. The mortality rates for patients with these injuries was low.


Variable maturation and oviposition by female Schistosoma japonicum in mice: the effects of irradiation of the host prior to infection.
The maturation of female Schistosoma japonicum was found to vary greatly within each of two Philippine strains of this parasite and some females did not contain uterine eggs 7 to 15 weeks after infection while others contained numerous eggs before the fifth week of infection. It was found that female worms containing less than 20 uterine eggs contributed little to the accumulation of eggs in the tissues of infected mice. Such worms also generally appeared to be immature. The variable rate of maturation of worms is likely to have profound effects on the immune reactions of mice as well as on the pathologic response to infection. Systematic delay in oviposition was serendipitously found in worms from mice which had been irradiated for other purposes prior to exposure to S. japonicum, and from the fourth to the sixth week after infection egg production by worms in irradiated mice lagged well behind that in intact mice. Seven to 10 weeks after infection these worms were laying normal numbers of eggs, as judged by egg passage per worm pair in the feces and the accumulation of eggs in the tissues. S. mansoni developed normally in irradiated mice.


International medical law and its impact on the ukrainian health care legislation.
Introduction: The Ukrainian state has an urgent necessity of rapid search for essentially new legal and organizational forms of the healthcare system, reform of the legal regulation of healthcare services provision. In the context of European integration, the advancement of the medical industry reform is closely related to consideration of international standards and norms of health care. The aim: To study the impact of international medical law on the Ukrainian health care legislation. Materials and methods: International and Ukrainian regulations and documents on health care were used in the research. System and structural, functional and legal comparative methods as well as systematization, analysis and synthesis were determinative in the research process. Review: Systematization of international documents on health care was made. The major problems in the Ukrainian health care legislation were determined in terms of their conformity with the international legislative norms. The expediency of the Medical Code adoption was grounded and its structure was defined. Conclusions: Most health care international acts are ratified by Ukraine and their provisions are implemented in the legislation. Simultaneously, there is a row of problems, which hinder the Ukrainian health care development and place obstacles in the way of European integration. To remove these obstacles, it is expedient to create a codified act - the Medical Code, which would systematize the provisions of the current medical laws and regulations and fill in the existing gaps in the legal regulation of health care.


A comparison of atomistic and continuum approaches to the study of bonding dynamics in electrocatalysis: microcantilever stress and in situ EXAFS observations of platinum bond expansion due to oxygen adsorption during the oxygen reduction reaction.
Microcantilever stress measurements are examined to contrast and compare their attributes with those from in situ X-ray absorption spectroscopy to elucidate bonding dynamics during the oxygen reduction reaction (ORR) on a Pt catalyst. The present work explores multiple atomistic catalyst properties that notably include features of the Pt-Pt bonding and changes in bond strains that occur upon exposure to O2 in the electrochemical environment. The alteration of the Pt electronic and physical structures due to O2 exposure occurs over a wide potential range (1.2 to 0.4 V vs normal hydrogen electrode), a range spanning potentials where Pt catalyzes the ORR to those where Pt-oxide forms and all ORR activity ceases. We show that Pt-Pt surface bond strains due to oxygen interactions with Pt-Pt bonds are discernible at macroscopic scales in cantilever-based bending measurements of Pt thin films under O2 and Ar. Complementary extended X-ray absorption fine structure (EXAFS) measurements of nanoscale Pt clusters supported on carbon provide an estimate of the magnitude and direction of the in-operando bond strains. The data show that under O2 the M-M bonds elongate as compared to an N2 atmosphere across a broad range of potentials and ORR rates, an interfacial bond expansion that falls within a range of 0.23 (±0.15)% to 0.40 (±0.20)%. The EXAFS-measured Pt-Pt bond strains correspond to a stress thickness and magnitude that is well matched to the predictions of a mechanics mode applied to experimentally determined data obtained via the cantilever bending method. The data provide new quantitative understandings of bonding dynamics that will need to be considered in theoretical treatments of ORR catalysis and substantiate the subpicometer resolution of electrochemically mediated bond strains detected on the macroscale.


Plasma protein binding of (99m)Tc-labeled hydrazino nicotinamide derivatized polypeptides and peptides.
6-Hydrazinopyridine-3-carboxylic acid (HYNIC) constitutes one of the most attractive reagents to prepare (99m)Tc-labeled polypeptides and peptides of various molecular weights in combination with two tricine molecules as coligands. Indeed, (99m)Tc-HYNIC-conjugated IgG showed biodistribution of radioactivity similar to that of (111)In-DTPA-conjugated IgG. However, recent studies indicated significant plasma protein binding when the (99m)Tc labeling procedure was expanded to low molecular weight peptides. In this study, pharmacokinetics of (99m)Tc-HYNIC-conjugated IgG, Fab and RC160 using tricine were compared with their radioiodinated counterparts to evaluate this (99m)Tc-labeling method. In mice, [(99m)Tc](HYNIC-IgG)(tricine)(2) and [(99m)Tc](HYNIC-Fab)(tricine)(2) showed persistent localization of radioactivity in tissues when compared with their (125)I-labeled counterparts. [(99m)Tc](HYNIC-IgG)(tricine)(2) eliminated from the blood at a rate similar to that of (125)I-labeled IgG, while [(99m)Tc](HYNIC-Fab)(tricine)(2) showed significantly slower clearance of the radioactivity than (125)I-labeled Fab. On size-exclusion HPLC analyses, little changes were observed in radiochromatograms after incubation of [(99m)Tc](HYNIC-IgG)(tricine)(2) in murine plasma. However, [(99m)Tc](HYNIC-Fab)(tricine)(2) and [(99m)Tc](HYNIC-RC160)(tricine)(2) demonstrated significant increases in the radioactivity in higher molecular weight fractions in plasma. Formation of higher molecular weight species was reduced when [(99m)Tc](HYNIC-RC160)(tricine)(2) was stabilized with nicotinic acid (NIC) to generate [(99m)Tc](HYNIC-RC160)(tricine)(NIC). [(99m)Tc](HYNIC-RC160)(tricine)(NIC) also demonstrated significantly faster clearance of the radioactivity from the blood than [(99m)Tc](HYNIC-RC160)(tricine)(2). These findings suggested that one of the tricine coligands in (99m)Tc-HYNIC-labeled (poly)peptides would be replaced with plasma proteins to generate higher molecular weight species that exhibit slow blood clearance. In addition, the molecular sizes of parental peptides played an important role in the progression of the exchange reaction of one of the tricine coligands with plasma proteins.


Proteogenomics in microbiology: taking the right turn at the junction of genomics and proteomics.
High-accuracy and high-throughput proteomic methods have completely changed the way we can identify and characterize proteins. MS-based proteomics can now provide a unique supplement to genomic data and add a new level of information to the interpretation of genomic sequences. Proteomics-driven genome annotation has become especially relevant in microbiology where genomes are sequenced on a daily basis and limitations of an in silico driven annotation process are well recognized. In this review paper, we outline different strategies on how one can design a proteogenomic experiment, for example on genome-sequenced (synonymous proteogenomics) versus unsequenced organisms (ortho-proteogenomics) or with the aid of other "omic" data such as RNA-seq. We touch upon many challenges that are encountered during a typical proteogenomic study, mostly concerning bioinformatics methods and downstream data analysis, but also related to creation and use of sequence databases. A large list of proteogenomic case studies of different microorganisms is provided to illustrate the mapping of MS/MS-derived peptide spectra to genomic DNA sequences. These investigations have led to accurate determination of translational initiation sites, pointed out eventual read-throughs or programmed frameshifts, detected signal peptide processing or other protein maturation events, removed questionable annotation assignments, and provided evidence for predicted hypothetical proteins.


Protein Supplementation May Dampen Positive Effects of Exercise on Glucose Homeostasis: A Pilot Weight Loss Intervention.
The role of protein in glucose homeostasis has demonstrated conflicting results. However, little research exists on its impact following weight loss. This study examined the impact of protein supplementation on glucose homeostasis in older adults >65 years with obesity seeking to lose weight. A 12-week, nonrandomized, parallel group intervention of protein (PG) and nonprotein (NPG) arms for 28 older rural adults (body mass index (BMI) ≥ 30 kg/m2) was conducted at a community aging center. Both groups received twice weekly physical therapist-led group strength training classes. The PG consumed a whey protein supplement three times per week, post-strength training. Primary outcomes included pre/post-fasting glucose, insulin, inflammatory markers, and homeostasis model assessment of insulin resistance (HOMA-IR). Mean age and baseline BMI were 72.9 ± 4.4 years and 37.6 ± 6.9 kg/m2 in the PG and 73.0 ± 6.3 and 36.6 ± 5.5 kg/m2 in the NPG, respectively. Mean weight loss was -3.45 ± 2.86 kg in the PG and -5.79 ± 3.08 kg in the NPG (p < 0.001). There was a smaller decrease in pre- vs. post-fasting glucose levels (PG: -4 mg ± 13.9 vs. NPG: -12.2 ± 25.8 mg/dL; p = 0.10), insulin (-7.92 ± 28.08 vs. -46.7 ± 60.8 pmol/L; p = 0.01), and HOMA-IR (-0.18 ± 0.64 vs. -1.08 ± 1.50; p = 0.02) in the PG compared to the NPG. Protein supplementation during weight loss demonstrated a smaller decrease in insulin resistance compared to the NPG, suggesting protein may potentially mitigate beneficial effects of exercise on glucose homeostasis.


Dissociable lexical and phonological influences on serial recognition and serial recall.
The impact of the lexicality of memory items on memory performance was compared in two paradigms, serial recall and serial recognition. Experiments 1 to 3 tested 7- and 8-year-old children. Memory accuracy was only mildly impaired in lists containing nonwords compared with words in a serial recognition task involving judgments of whether the items in two sequences were in the same order (Experiment 1), although a substantial advantage for word over nonword items from the same stimulus pool was found in serial recall (Experiment 2). A stronger influence of lexicality on serial recall than serial recognition was further demonstrated in Experiments 3A and 3B, and in 4A and 4B using adult participants. These experiments also established comparable degrees of sensitivity to the phonological similarity of the memory sequences in the two paradigms. The phonological similarity effect in serial recall was found to arise from increased phoneme order errors, whereas the lexicality effect was due principally to the greater frequency of phoneme identity errors for nonwords. It is proposed that the lexicality effect originates in the redintegration of item information just prior to recall, and that this process is largely bypassed in serial recognition.


Chronic Chagas Cardiomyopathy in the Brazilian Amazon region: clinical characteristics and regional distinctiveness.
This study aims to provide a comprehensive analysis of clinical and epidemiological data related to Chronic Chagas Cardiomyopathy (CCC) in the Amazon region of Brazil. A review of observational, retrospective, and cross-sectional studies related to Chagas Disease in the Amazon region of Brazil was conducted, and a case series addressing CCC in patients treated at the FMT-HVD outpatient clinic, a reference center for Chagas disease in Brazil, was carried out. Clinical characteristics of 55 patients from the Amazon region with CCC were described. The most common electrocardiographic alteration observed was abnormal ventricular repolarization (AVR), present in 40% of cases. The most common echocardiographic finding was left ventricular systolic dysfunction (49%), followed by akinesia or hypokinesia of the inferior and/or inferolateral walls (38.1%) and the presence of an apical aneurysm (32.7%). Overall, this study demonstrates that CCC in the Amazon region presents clinical characteristics and severity that are similar to those observed in other regions. However, certain peculiarities, such as the frequency of right bundle branch block (RBBB) and anterior and septal involvement during the acute phase, require additional investigation to better comprehend the disease in the region. Overall, the study provides crucial clinical insights for the diagnosis and treatment of CCC in the Amazon region.


Training for mobility with exoskeleton robot in spinal cord injury patients: a pilot study.
Wearable robots are people-oriented robots designed to be worn all day, thus helping in the daily activities. They can assist in walking, running, jumping higher or even lifting objects too heavy in normal conditions. The aim of this report was to investigate the changes in gait pattern through 3D gait analysis of subjects with spinal cord injury (SCI) undergoing an adaptive training with a wearable exoskeletal device (ESD). The change in the quality of life was also investigate together with the possibility to wear these devices all day, to improve the mobility. Prospective quasi-experimental study, pre- and post-design. Outpatient SCI patients. On a voluntary basis, eight SCI patients who had never used any ESD device were recruited. Subjects underwent a three-dimensional gait analysis (3D GA) while wearing the ESD at baseline (inclusion) (T0) and after 20 sessions of training over an expected average of 5/6 weeks (T1). The secondary outcome measures were: Participant Satisfaction Questionnaire, 6-Minute Walking Test (6MWT), Borg Scale (the test was administered in indoor and outdoor conditions) and Timed Up-and-Go test (TUG). Spatiotemporal and kinematic parameters were assessed and their change from the beginning to the end of the training was the secondary outcome. No dropouts were recorded during the training and all subjects were able to terminate the protocol (compliant subjects: N.=8). After the training, all person showed some significant improvements for TUG, 6MWT and 10 MWT (Z=-2.521; P=0.008) and for the spatiotemporal and kinematics parameters. This paper confirms that the adaptive training with ESD is safe and feasible in a heterogeneous sample of persons with SCI, especially in ameliorating the interaction between the patients and the device with an improvement of spatiotemporal and kinematics parameters. Since the training has been proven safe and the hypothesis that the subjects with spinal cord injury improving their performance over time and being able to adapt at the use of device in full autonomy at home during all the activities of the daily living has strengthened.


Sports despite masks: no negative effects of FFP2 face masks on cardiopulmonary exercise capacity in children.
Face masks were recognized as one of the most effective ways to prevent the spread of the COVID-19 virus in adults. These benefits were extended to children and adolescents. However, the fear of negative consequences from wearing a face mask during physical exercise led to cancellations of physical education lessons. This further decreased the amount of physical activity available to children and adolescents during the pandemic. However, there is little published data on the potential adverse effects of wearing the most effective and partially mandatory FFP2/N95 face masks during PE or physical activity (PA) in this age. Even though the pandemic has been declared as passed by the WHO, the rise of a new pandemic and thus the use of face masks for limiting its spread is inevitable, so we need to be better prepared for alternative options to lockdown and limitation of PA in such a scenario. Twenty healthy children aged 8-10 years performed two identical cardiopulmonary exercise tests as an incremental step test on a treadmill within an interval of 2 weeks, one time without wearing a protective mask and one time wearing an FFP2 mask. The cardiopulmonary exercise parameter and especially the end-expiratory gas exchange for oxygen and carbon dioxide (petO2 and petCO2) were documented for each step, at rest and 1 min after reaching physical exhaustion. Twelve boys (mean age 8.5 ± 1.4 years) and 8 girls (mean age 8.8 ± 1.4 years) showed no adverse events until maximal exertion. The mean parameters measured at peak exercise did not differ significantly between both examinations (mean peak VO2 = 42.7 ± 9.5 vs 47.8 ± 12.9 ml/min/kg, p = 0.097, mean O2pulse 7.84 ± 1.9 ml/min vs. 6.89 ± 1.8, p = 0.064, mean VE/VCO2slope 33.4 ± 5.9 vs. 34.0 ± 5.3, p = 0.689). The only significant difference was the respiratory exchange rate (RER, 1.01 ± 0.08 vs 0.95 ± 0.08, p = 0.004). The measured respiratory gases (end-tidal O2 and CO2) decreased and respectively increased significantly in almost every step when wearing an FFP2 mask. However, these levels were well below hypercapnia and above hypoxia. In this study, no significant differences in the cardiorespiratory function at peak exercise could be discerned when wearing an FFP2/N95 face mask. While the end-tidal values for CO2 increased significantly and the end-tidal values for O2 decreased significantly, these values did never reach levels of hypercapnia or hypoxia. Furthermore, the children terminated the exercise at a lower RER and heart rate (HR) suggesting a subconscious awareness of the higher strain. Since the detrimental effects of limiting sports during the pandemic are well documented, stopping PE lessons altogether because of the minor physiological effects of wearing these masks instead of simply stopping pushing children to perform at their best seems premature and should be reconsidered in the future. • Wearing a face mask has an influence on psychological, social, and physiological functions in adults. • Because of the observed effects of wearing face masks in adults, physical activity in children was limited during the pandemic. • Wearing an FFP2/N95 mask during physical activity did not lead to hypercapnia or hypoxia in children in this study. • Even though end-tidal CO2 values were significantly higher and end-tidal O2 values significantly lower when wearing an FFP2/N95 face mask, no pathological values were reached.


Increased risk of death from measles in children with a sibling of opposite sex in Senegal.
To examine whether contracting measles from a sibling of the opposite sex affects mortality. Prospective registration during 15-20 years of all births and deaths, including 243 measles related deaths. Measles infection was not registered; however, as in fatal cases measles was probably contracted from a maternal sibling the risk of dying during measles outbreaks was examined in families with two boys, two girls, or a boy and a girl. 31 small villages in two rural areas of eastern Senegal. 766 children living in families with two children aged under 10 years during outbreaks of measles, 107 (14%) of whom died of measles. Deaths from measles, size of village, age and sex of maternal siblings. The interval between outbreaks in the same village was greater than 10 years. The risk of dying of measles was significantly related to age, increasing with the age difference between siblings and decreasing with the size of village. In a multiple logistic regression analysis adjusting for these background factors, children in families with a boy and a girl had a significantly higher mortality than children in families with two boys or two girls (odds ratio = 1.81, 95% confidence interval 1.17 to 2.82). The increase in risk was the same for boys and girls in families with two children one of whom was a boy and one a girl. Cross sexual transmission may be an important determinant of severity of measles infection.


[Mechanism of modulating effect of histamine on the excitation and contraction of smooth muscles of the ureter].
Experiments were carried out on smooth muscle cells (SMC) of the guinea-pig ureter by the double sucrose gap method with simultaneous recording of electrical and contractile activities. The effect of histamine on SMC was studied in normal Krebs solution and in sodium-free Krebs solution with TEA. In normal Krebs solution, histamine was shown to increase the duration of AP plateau and contraction. In sodium-free Krebs solution with TEA, the APs of ureter SMC also had a plateau that was determined by the increased calcium conduction of the membrane. In these conditions, histamine provoked a decrease in the duration of the AP plateau and contraction. The histamine effect was blocked by phencarol both in normal and sodium-free Krebs solution with TEA. A possible role of sodium, calcium and potassium ions in the modulating action of histamine on excitation of ureter SMC is discussed.


Role of Arg180 of the D2 protein in photosystem II structure and function.
On the basis of sequence comparison with the M subunit of the reaction center of purple bacteria, no residues in photosystem II can be clearly identified that may be predicted to correspond to the His residue that binds one of the accessory bacteriochlorophylls in the purple bacterial reaction center. However, the Arg180 residue of the D2 protein is close to where this residue is predicted to be and could conceivably serve as a chlorophyll ligand. To analyze the function of Arg180, it was changed to nine different amino acids in the cyanobacterium Synechocystis sp. PCC 6803. Except for the Arg180-->Gln (R180Q) mutant, the resulting strains were no longer photoautotrophic. The properties of photosystem II upon mutation of Arg180 were probed in strains from which photosystem I had been deleted genetically. Mutations at the Arg180 residue affected oxygen evolution capacity and the amount of photosystem II that was present in thylakoids. Surprisingly, in the Arg180 mutants, EPR signals that may originate from the oxidized redoxactive Tyr160 of the D2 protein (Y(D)ox) were small and generally did not resemble the usual signal IIs, signifying an effect of the Arg180 mutations on the environment surrounding Tyr160. In addition, in most mutants, the charge recombination kinetics between the primary electron-accepting quinone in photosystem II (Q(A)-) and oxidized species on the donor side were faster upon introducing mutations at Arg180 suggesting an increased steady-state concentration of P680+ in the mutants. However, Arg180 mutations also affected Q(A)- oxidation by the secondary electron-accepting quinone (Q(B)). HPLC analysis showed that, in the Arg180 mutants that were assayed, the pheophytin/chlorophyll ratio of photosystem II had not changed, indicating that the mutations did not lead to a pheophytinization of one of the chlorophyll molecules. Even though the results presented do not provide positive evidence that Arg180 of the D2 protein corresponds in function to the ligand to the central Mg in an accessory bacteriochlorophyll in reaction centers of purple bacteria, it is clear that changes in Arg180 greatly affect Tyr160 and P680. Various scenarios are discussed that are compatible with the data presented, and include an apparently close interaction between Arg180, His189, and Tyr160, and the possibility of the involvement of multiple chlorophylls to together form P680.


Metabolic studies in total parenteral nutrition with lipid in man. Comparison with glucose.
A study was undertaken of patients on a regimen of total parenteral nutrition comparing the nitrogen balance, energy substrates, blood amino acids, immunoreactive insulin, and immunoreactive glucagon levels during the sequential infusion of nonprotein calories as either glucose alone (glucose system) or 83% as Intralipid (Pharmacia Fine Chemicals, Montreal, Canada) and 17% glucose (lipid system). These nonprotein calories were administered with a constant background of amino acids (1 g/kg per day), vitamins, and minerals. Each system was infused for a week at a time and the order of infusion randomized. In some patients whole blood arteriovenous (A-V) levels of amino acids were measured across forearm muscle. During the glucose system there was a significantly higher level of pyruvate, lactate, alanine, and immunoreactive insulin, consistent with glucose being the principal source of energy. In contrast, during the lipid system there was a rise in free fatty acids and ketone bodies with a fall in insulin, suggesting that lipid was now the principal source of energy. Despite these two very diverse metabolic situations the nitrogen balance with both systems was positive to a comparable degree after the establishment of equilibrium. Correspondingly, A-V differences of whole blood amino acid nitrogen showed uptake by muscle to an equivalent degree with both systems. Clinical studies indicated that the lipid system as defined herein could be infused by peripheral vein for up to 43 days with resultant weight gain, elevation of serum proteins, and healing of fistulae. Our studies suggest that for both metabolic and clinical reasons exogenously infused lipid is a suitable source of nonprotein calories.