Is acute compartment syndrome avoidable?
Complete absence of acute compartment syndrome was observed in a consecutive series of 966 tibial fractures in African patients of diverse ethnic groups, reviewed retrospectively at our institution. Considering the incidences reported in the literature, we should have experienced between 22 and 86 cases of acute compartment syndrome. The purpose of this prospective study was to confirm these findings and at the same time to look for possible explanations for this unexpected observation. During a period of one year and four months, 257 tibial fractures were prospectively analyzed for clinical signs and late sequelae of acute compartment syndrome. In 156 of these patients, presenting 158 fractures of the tibia, the pressure in the anterior compartment was systematically measured. No single case of compartment syndrome was diagnosed in this series, and no late sequelae of acute compartment syndrome were noted. The hypothesis we forward for total absence of acute compartment syndrome is the favourable effect of the continuously high surrounding temperatures on safeguarding the arteriovenous pressure gradient and lowering the vascular resistance. We suggest that further investigation should be carried out to study this hypothesis.


Revealing Microtubule-Dependent Slow-Directed Motility by Single-Particle Tracking.
Microtubules (MTs) are the main component of cytoskeletons, providing long tracks for cargo trafficking across the cytoplasm. In the past years, transport along MTs was frequently reported to be rapid directed motions with speeds of several micrometers per second, but is that all the truth? Using single-particle tracking, we roundly and precisely analyzed the dynamic behaviors of three kinds of cargoes transported along MTs in two types of cells. It was found that during the transport processes, the directed motions of the cargoes were frequently interrupted by nondirected motions which greatly reduced the translocation rate toward the nucleus. What is more, in addition to the widely reported rapid directed motions, a type of directed motions with most speeds below 0.5 μm/s occurred more frequently. On the whole, these slow directed motions took longer than the rapid directed motions and resulted in displacements same as those of the rapid ones. To sum up, while travelling along MTs toward the cell interior, endocytosed cargoes moved alternately in rapid-directed, slow-directed and nondirected modes. In this process, the rapid- and the slow-directed motions contributed almost equally to the cargoes' translocation. This work provides original insights into the transport on MTs, facilitating a more comprehensive understanding of intracellular trafficking.


The neurologist and Harvard criteria for brain death.
The Harvard ad hoc committee to examine the definition of brain death, chaired by anesthesiologist Beecher, published their report in 1968. Throughout the years, the committee has been a target of criticism. However, the workings of the ad hoc committee have not been carefully evaluated, and could provide insight into the role of the neurologists and their interaction with contemporaries. Review of the original files and interviews with three surviving members-Adams, Potter, and Murray-revealed 1) a major role and original contributions of the neurologists Schwab and Adams in defining criteria, and 2) a swift and decisive working committee that formulated a document aimed at simplicity and accuracy, and without special interest.


Generation of Monoclonal Antibodies against Immunoglobulin Proteins of the Domestic Ferret (Mustela putorius furo).
The domestic ferret (Mustela putorius furo) serves as an animal model for the study of several viruses that cause human disease, most notably influenza. Despite the importance of this animal model, characterization of the immune response by flow cytometry (FCM) is severely hampered due to the limited number of commercially available reagents. To begin to address this unmet need and to facilitate more in-depth study of ferret B cells including the identification of antibody-secreting cells, eight unique murine monoclonal antibodies (mAb) with specificity for ferret immunoglobulin (Ig) were generated using conventional B cell hybridoma technology. These mAb were screened for reactivity against ferret peripheral blood mononuclear cells by FCM and demonstrate specificity for CD79β+ B cells. Several of these mAb are specific for the light chain of surface B cell receptor (BCR) and enable segregation of kappa and lambda B cells. Additionally, a mAb that yielded surface staining of nearly all surface BCR positive cells (i.e., pan ferret Ig) was generated. Collectively, these MαF-Ig mAb offer advancement compared to the existing portfolio of polyclonal anti-ferret Ig detection reagents and should be applicable to a wide array of immunologic assays including the identification of antibody-secreting cells by FCM.


Depression and anxiety among left-behind children in China: a systematic review.
This study aimed to systematically review evidence of the prevalence and predictors of depression and anxiety among 'left-behind children' in rural China. The electronic databases PubMed/MEDLINE and Chinese National Knowledge Infrastructure/Wanfang (Chinese) were utilized to search for terms including 'depression' or 'depressive disorder', 'anxiety' or 'mental health', combined with 'left behind', 'children' and 'China'. High rates of psychological depression/anxiety have been reported among left-behind children compared with their age-matched peers. Prevalence rates of depression are reported to range from 12.1 to 51.4% and of anxiety are reported to range from 13.2 to 57.6%. Variability between studies is likely attributable to methodological variations relating to measures used and research setting. Potential predictors measured in studies include age and gender, types of being left, age/years of separation, socio-economic status, etc. These high rates of reported psychological problems among this group of young people suggest the need to develop more effective approaches to prevention and management.


Analytical Methods for the Determination of Lead in the Environment.
A survey of the methods for the determination of lead in environmental samples is given. These are mainly based on sensitive atomic spectrometry, but alternatives, such as electrochemical and separation methods are also possible. Discussed are also sample preparation and speciation for differentiation between different organometallic forms as well as applications of isotope-selective determinations.


Activation of human T lymphocytes by crosslinking of anti-CD3 monoclonal antibodies.
The proliferation of human T lymphocytes induced by anti-CD3 monoclonal antibodies (mAb) is used as a model for antigen-induced activation via the T cell receptor-CD3 complex. Since both systems are accessory cell (AC)-dependent, an understanding of the role of AC in anti-CD3-induced proliferation may provide an understanding of physiological activation via the T cell receptor. Previous work has implicated receptor crosslinking as an important AC function. To determine its necessity in anti-CD3-induced lymphocyte proliferation, we prepared highly purified T lymphocytes and found that these cells did not respond to the anti-CD3 mAb UCHT1, either alone or with interleukin 1 (IL1), interleukin 2 (IL2), or tetradecanoyl phorbol acetate (TPA). However, the response, as measured by appearance of IL2 receptors and proliferation, was restored by crosslinking with immobilized goat anti-mouse antibodies (GAM) and did not require the addition of IL1, IL2, or TPA. Thus, crosslinking of CD3 receptors was a sufficient signal for proliferation of these cells. Cyclosporine A (CsA) inhibited the activation induced by immobilized UCHT1. Since macrophages are the principle targets of CsA-mediated suppression of mitogen-induced proliferation, but macrophages do not participate in the response to immobilized anti-CD3, this may indicate that CsA was inhibiting crosslinking or a signal generated by it.


Foldamer Architectures of Triazine-Based Sequence-Defined Polymers Investigated with Molecular Dynamics Simulations and Enhanced Sampling Methods.
Triazine-based sequence-defined polymers have recently been developed that are biomimetic and robust. In molecular dynamics (MD) simulations, the triazine polymers were shown to form linear nanorod foldamers through hydrogen bonding and π-π interactions. The nanorod foldamers have motifs resembling those of DNA, α-helices, and β-sheets and have potential to be useful building blocks for new macromolecules and materials. To understand the formation of nanorod foldamers, we investigate how linker structures in the middle of the triazine polymers lead to folding using MD simulations. We found that a variety of linkers can participate in folding but that specific linker structures are more favorable than others, depending on the polymer length. Folding of hexamers into well-defined nanorod foldamers was most favorable with pentanediamine and ortho-xylenediamine linkers in the center of the polymers. Foldamers with ortho-xylenediamine linkers in the center were investigated for longer polymers, i.e., octamers and decamers, using two different enhanced sampling methods, since regular MD simulations had failed to show any folding for these longer polymers. In particular, the recently developed concurrent adaptive sampling (CAS) algorithm and replica exchange molecular dynamics (REMD) were used. We found that the two enhanced sampling methods did lead to the observation of foldamers and that REMD revealed new foldamer architectures where cis-trans isomerizations had occurred. Foldamer formation, diversity, and the strengths and limitations of simulation techniques are discussed. These findings provide new insights into the diversity of foldamer architectures for a new type of biomimetic synthetic polymer.


Detection of horizontal gene transfers from phylogenetic comparisons.
Bacterial phylogenies have become one of the most important challenges for microbial ecology. This field started in the mid-1970s with the aim of using the sequence of the small subunit ribosomal RNA (16S) tool to infer bacterial phylogenies. Phylogenetic hypotheses based on other sequences usually give conflicting topologies that reveal different evolutionary histories, which in some cases may be the result of horizontal gene transfer events. Currently, one of the major goals of molecular biology is to understand the role that horizontal gene transfer plays in species adaptation and evolution. In this work, we compared the phylogenetic tree based on 16S with the tree based on dszC, a gene involved in the cleavage of carbon-sulfur bonds. Bacteria of several genera perform this survival task when living in environments lacking free mineral sulfur. The biochemical pathway of the desulphurization process was extensively studied due to its economic importance, since this step is expensive and indispensable in fuel production. Our results clearly show that horizontal gene transfer events could be detected using common phylogenetic methods with gene sequences obtained from public sequence databases.


Towards complete elucidation of structural factors controlling thermal stability of IL/MOF composites: Effects of ligand functionalization on MOFs.
In this work, we incorporated an ionic liquid (IL), 1-n-butyl-3-methylimidazolium methyl sulfate ([BMIM][MeSO4]) into two different metal organic frameworks (MOFs), UiO-66, and its amino-functionalized counterpart, NH2-UiO-66, to investigate the effects of ligand-functionalization on the thermal stability limits of IL/MOF composites. The as-synthesized IL/MOF composites were characterized in detail by combining X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller analysis (BET), X-ray fluorescence (XRF), infrared spectroscopies (FTIR), and their thermal stability limits were determined by thermogravimetric analysis (TGA). Characterization data confirmed the successful incorporation of the IL into each MOF and indicated the presence of direct interactions between them. A comparison of the interactions in [BMIM][MeSO4]-incorporated UiO-66 and NH2-UiO-66 with those in their 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6])-incorporated counterparts showed that the hydrophilic IL, [BMIM][MeSO4], interacts with the 1,4-benzenedicarboxylate (BDC) ligand of the UiO-66, while the hydrophobic IL, [BMIM][PF6], is interacting with the joints where zirconium metal cluster coordinates with BDC ligand. The TGA data demonstrated that the composite with the ligand-functionalized MOF, NH2-UiO-66, exhibited a lower percentage decrease in the maximum tolerable temperature compared to those of IL/UiO-66 composites. Moreover, it is discovered that when the IL is hydrophilic, its hydrogen bonding ability can be utilized to designate an interaction site on MOF's ligand structure which will lead to a lower reduction in thermal stability limits. These results provide insights for the rational design of IL/MOF composites and contribute towards the complete elucidation of structural factors controlling the thermal stability.


Complex Permittivity of Ionic Liquid Mixtures Investigated by Terahertz Time-Domain Spectroscopy.
Ionic liquids are salts found in their liquid state at ambient temperature. The physicochemical properties of ionic liquids can be tailored by selecting constituent cation and anion from numerous available ions. The physicochemical properties can be further tuned by mixing different neat ionic liquids. Reported data of ionic liquid mixtures reveal that frequently investigated properties such as density, viscosity, and thermal stability follow corresponding mixing laws. Complex permittivity in the interval of terahertz frequencies is of great importance to understand the molecular interactions and the solvation dynamics which drive the macroscopic properties of ionic liquids; however, to the best of our knowledge, there are few reports about the mixing behavior of complex permittivity in ionic liquid mixtures. In this contribution, binary mixtures of 1-butyl-3-methylimidazoulium iodide ([C4C1im]I) and 1-butyl-3- methylimidazoulium bis(trifluoromethylsulfonyl)imide ([C4C1im][NTf2]) are investigated in the terahertz spectral range, and the resulting low-energy spectra are analyzed in order to clarify the mixing laws at play. The results show that the complex permittivity of mixtures of [C4C1im]I and ([C4C1im][NTf2] obeys a linear mixing law.


Effect of optic nerve transection upon myelin protein gene expression by oligodendrocytes: evidence for axonal influences on gene expression.
The effect of optic nerve transection on myelin protein gene expression was studied in rats following axotomy at two ages: during active myelination (17 days of age) and after peak expression of the genes (35 days of age). mRNA levels for proteolipid protein, myelin basic protein and myelin-associated glycoprotein were assessed by northern and dot blotting and by in situ hybridization using tissue sections and cultured individual oligodendrocytes. Transection at 17 days caused down-regulation of mRNAs for proteolipid protein, myelin basic protein and myelin-associated glycoprotein by 5 days after axotomy with an increase in GFAP mRNA. A more protracted change followed axotomy at 35 days of age. The abundance of mRNAs for proteolipid protein and myelin basic protein was significantly reduced by 28 days after transection in the affected nerve. Quantification of proteolipid protein mRNA expression in individual oligodendrocytes confirmed the down-regulation. However, in contrast to the effects on the major myelin proteins, the abundance of myelin-associated glycoprotein mRNA increased in the affected nerve for at least the initial month after lesioning at 35 days. The results show that optic nerve transection has significant effects on myelin protein mRNA expression in oligodendrocytes of optic nerve. However, the changes in myelin protein gene activity are relatively small and more protracted than those seen in Schwann cells after peripheral nerve section. Because axotomy also causes marked changes in the glial population of the optic nerve it is not possible unequivocally to ascribe the alteration in gene expression to loss of axons. However, the data may provide evidence that axons do influence myelin protein genes in oligodendrocytes and are necessary for them to develop their full expression.


[Simulation-based robot-assisted surgical training].
Since the first use of robotic surgical system in 2000, the robot-assisted technology has gained wide popularity throughout the world. Robot-assisted surgical training is a complex issue that requires significant efforts from students and teacher. During the last two decades, simulation-based training had received active development due to wide-spread occurrence and popularization of laparoscopic and robot-assisted surgical techniques. We performed a systematic review to identify the currently available simulators for robot-assisted surgery. We searched the Medline and Pubmed, English sources of literature data, using the following key words and phrases: "robotics", "robotic surgery", "computer assisted surgery", "simulation", "computer simulation", "virtual reality", "surgical training", and "surgical education". There were identified 565 publications, which meet the key words and phrases; 19 publications were selected for the final analysis. It was established that simulation-based training is the most promising teaching tool that can be used in the training of the next generation robotic surgeons. Today the use of simulators to train surgeons is validated. Price of devices is an obvious barrier for inclusion in the program for training of robotic surgeons, but the lack of this tool will result in a sharp increase in the duration of specialists training.


A randomized prospective study of the cost-effectiveness of the conventional spike, O-set, and UVXD techniques in continuous ambulatory peritoneal dialysis.
To compare the clinical outcome and cost-effectiveness of three techniques for continuous ambulatory peritoneal dialysis (CAPD): the conventional spike technique (C), the O-set (O), and UVXD (U, ultraviolet irradiation connection box). A randomized and prospective comparison of three CAPD techniques. A tertiary referral and a satellite dialysis center. One hundred patients with end-stage renal failure between 10 and 70 years of age, with good hand-eye coordination and not anticipated to receive a living related transplant within 6 months. Patients were randomized by referral to a table of random numbers to perform one of the three CAPD techniques. Training time, details of peritonitis and exit-site infection (ESI) including the costs of antibiotic treatment, outpatient visits, hospital stays, technique, and patient survival were analyzed after a minimum follow-up period of one year. There were 38, 31, and 31 patients in groups C, O, and U, respectively, and the total observation periods were 838, 802, and 745 patient-months, respectively. The peritonitis rates for C, O, and U were 21.5, 30.8, and 29.8 patient-months/episode, respectively. The corresponding ESI rates were 16.4, 14.9, and 24 patient-months/episode, respectively. When the time from the commencement of CAPD to the first infection was expressed using the Kaplan-Meier life table analysis, 39.5%, 67.7%, and 61.3% of patients in Groups C, O, and U were free from peritonitis at one year (p = 0.088). The corresponding figures for ESI were 52.6%, 48.4%, and 61.3% (p = 0.35). There was no significant difference in technique survival in the three treatment groups. An analysis of the costs related to the use of antibiotics, outpatient visits, and hospital stays necessary for the treatment of peritonitis and ESI and those related to training time, additional equipment, and consumables required for the three CAPD techniques showed that, overall, the cost in O was the lowest, followed by U and C (U.S. $158, $170, and $179 per patient-month, respectively). It was concluded that the O-set is a more cost-effective CAPD technique than UVXD, while both are more cost-effective than the conventional spike technique.


[Relation of iron supply and iron metabolism to infectious diseases and parasitoses and the competence of the immune system].
In many infectious diseases and in several parasitoses the iron content in the blood plasma occasionally decreases. By reduction of the saturation of the transferrins with iron the bactericidal effect of the blood plasma is increased. In these cases the iron absorption into the liver is increased and the iron excretion from the reticulohistiocytic system decreased. The oral intake of easily soluble iron compounds which goes far beyond the need repeatedly an enteral increase of germs of Yersinia enterocolitica and a transition into the blood, respectively, was stated. The parenteral administration of Fe-dextran from time to time leads to an enrichment of this compound in macrophages, the performance of phagocytosis of which is thus restricted. The iron deficiency decreases the functional capacity of the immune system. The functional ability of the T- and B-lymphocytes as well as of the macrophages is reduced. The importance of the transferrins, of haemopexin, of haptoglobin and of lactoferrin for the defense of infections is demonstrated.


Evolution of heavy metal speciation during the aerobic composting process of sewage sludge.
The contents of heavy metals and their bioavailability to the soil-plant system were the major limitation to the application of sewage sludge compost in soil. This study was conducted to determine the evolution of heavy metal speciation in the course of an aerobic composting, and investigate the influence of changes of composting process parameters including pH, temperature and organic matter (OM) content on distribution of heavy metal speciation in composted sludge. The sequential extraction procedure developed by Tessier et al. was used in sludge compost to determine the heavy metal speciation. Results showed that, during composting, (1) the contents of the residue fraction for Pb, Zn and Cd were decreased but those for Ni and Cr were increased; the Cu residue fraction was almost constant; (2) the contents of the total mobile fractions (including fractions 1-4) for Zn and Pb were significantly increased, but the increase of those for Cu and Ni were not so remarkable; (3) there were significant degrees of correlation between heavy metal fractions and changes of some selected parameters (for example, pH, composting temperature, and OM content). Only the content of the total mobile fractions for Cu could be predictable from its total content. For the prediction of the total mobile fractions of Zn, Ni, Cd and Cr, the R(2) value was significantly increased by the inclusion of other variables such as pH, temperature and OM content.


Vascular calcification does not predict anastomotic leak or conduit necrosis following oesophagectomy.
Anastomotic leaks (AL) and gastric conduit necrosis (CN) are serious complications following oesophagectomy. Some studies have suggested that vascular calcification may be associated with an increased AL rate, but this has not been validated in a United Kingdom population. To investigate whether vascular calcification identified on the pre-operative computed tomography (CT) scan is predictive of AL or CN. Routine pre-operative CT scans of 414 patients who underwent oesophagectomy for malignancy with oesophagogastric anastomosis at the Queen Elizabeth Hospital Birmingham between 2006 and 2018 were retrospectively analysed. Calcification of the proximal aorta, distal aorta, coeliac trunk and branches of the coeliac trunk was scored by two reviewers. The relationship between these calcification scores and occurrence of AL and CN was then analysed. The Esophagectomy Complications Consensus Group definition of AL and CN was used. Complication data were available in n = 411 patients, of whom 16.7% developed either AL (15.8%) or CN (3.4%). Rates of AL were significantly higher in female patients, at 23.0%, compared to 13.9% in males (P = 0.047). CN was significantly more common in females, (8.0% vs 2.2%, P = 0.014), patients with diabetes (10.6% vs 2.5%, P = 0.014), a history of smoking (10.3% vs 2.3%, P = 0.008), and a higher American Society of Anaesthesiologists grade (P = 0.024). Out of the 14 conduit necroses, only 4 occurred without a concomitant AL. No statistically significant association was found between calcification of any of the vessels studied and either of these outcomes. Multivariable analyses were then performed to identify whether a combination of the calcification scores could be identified that would be significantly predictive of any of the outcomes. However, the stepwise approach did not select any factors for inclusion in the final models. The analysis was repeated for composite outcomes of those patients with either AL or CN (n = 69, 16.7%) and for those with both AL and CN (n = 10, 2.4%) and again, no significant associations were detected. In the subset of patients that developed these outcomes, no significant associations were detected between calcification and the severity of the complication. Calcification scoring was not significantly associated with Anastomotic Leak or CN in our study, therefore should not be used to identify patients who are high risk for these complications.


Rationale and design of the PROspective ATHletic Heart (Pro@Heart) study: long-term assessment of the determinants of cardiac remodelling and its clinical consequences in endurance athletes.
Exercise-induced cardiac remodelling (EICR) results from the structural, functional and electrical adaptations to exercise. Despite similar sports participation, EICR varies and some athletes develop phenotypic features that overlap with cardiomyopathies. Training load and genotype may explain some of the variation; however, exercise 'dose' has lacked rigorous quantification. Few have investigated the association between EICR and genotype. (1) To identify the impact of training load and genotype on the variance of EICR in elite endurance athletes and (2) determine how EICR and its determinants are associated with physical performance, health benefits and cardiac pathology. The Pro@Heart study is a multicentre prospective cohort trial. Three hundred elite endurance athletes aged 14-23 years will have comprehensive cardiovascular phenotyping using echocardiography, cardiac MRI, 12-lead ECG, exercise-ECG and 24-hour-Holter monitoring. Genotype will be determined using a custom cardiomyopathy gene panel and high-density single-nucleotide polymorphism arrays. Follow-up will include online tracking of training load. Cardiac phenotyping will be repeated at 2, 5, 10 and 20 years. The primary endpoint of the Pro@Heart study is the association of EICR with both training load and genotype. The latter will include rare variants in cardiomyopathy-associated genes and polygenic risk scores for cardiovascular traits. Secondary endpoints are the incidence of atrial and ventricular arrhythmias, physical performance and health benefits and their association with training load and genotype. The Pro@Heart study is the first long-term cohort study to assess the impact of training load and genotype on EICR. NCT05164328; ACTRN12618000716268.


On the evolutionary advantage of coagulation factor V Leiden (FVL).
Carriership of coagulation factor V Leiden (FVL) is by far the most common thrombophilia in Western populations. FVL is caused by a single point mutation in the gene coding for coagulation factor V (FV) causing a lifelong procoagulatory state with an increased risk of venous thromboembolism (VTE) which might be fatal. It is believed that the mutation occurred in one person 21,000 years ago and today 3% to 15% of the Western populations are carriers. A potentially dangerous mutation such as FVL ought to be rare and should have been reduced, if not eradicated, by selection during the course of human evolution. Thus, FVL must confer the carriers with an evolutionary advantage in order to be so prevalent. Lower risk of profuse bleeding and increased fecundity might give carriers an advantage. In this paper we give an updated short background and discuss possible evolutionary advantages and disadvantages.


The serine/threonine phosphatase PP4 is required for pro-B cell development through its promotion of immunoglobulin VDJ recombination.
PP4 phosphatase regulates a number of crucial processes but the role of PP4 in B cells has never been reported. We generated B cell-specific pp4 knockout mice and have identified an essential role for PP4 in B cell development. Deficiency of PP4 in B lineage cells leads to a strong reduction in pre-B cell numbers, an absence in immature B cells, and a complete loss of mature B cells. In PP4-deficient pro-B cells, immunoglobulin (Ig) DJ(H) recombination is impaired and Ig µ heavy chain expression is greatly decreased. In addition, PP4-deficient pro-B cells show an increase of DNA double-strand breaks at Ig loci. Consistent with their reduced numbers, residual PP4-deficient pre-B cells accumulate in the G1 phase, exhibit excessive DNA damage, and undergo increased apoptosis. Overexpression of transgenic Ig in PP4-deficient mice rescues the defect in B cell development such that the animals have normal numbers of IgM(+) B cells. Our study therefore reveals a novel function for PP4 in pro-B cell development through its promotion of V(H)DJ(H) recombination.


The dextrans--clinical data.
The use of dextrans in clinical practice are mainly based on the following effects: 1. Plasma volume effects 2. Flow Promotion 3. Antithrombotic effects. The dextrans are the only plasma volume substitute with the antithrombotic effect but this discussion will only deal with their effects on plasma volume and flow. The effect on plasma volume--the colloid supported intravascular volume--can be calculated as ml of water held in circulation per gram circulating colloid--for dextran 70 around 20 ml/g, for albumin 18 ml/g and for plasma protein 12-13 ml/g. After infusion of a plasma volume substitute the volume effect depends on dose injected, molecular weight distribution, rate of disappearance from the intravascular department mainly via the kidneys. The clinical experience of a reliable plasma volume expansion can be demonstrated in animal experiments comparing different infusion fluids. The effect on erythrocyte aggregation depends on kind of substance and molecular weight distribution. The flow promoting effect is mainly due to restoration of plasma volume but also related to hemodilution and aggregation. The vasoconstriction seen in shock can be counteracted essentially with colloid supported plasma volume expansion. The supposed influence of the dextrans on the kidney function in some clinical cases has been investigated experimentally.


Oral and craniofacial findings in a patient with methylmalonic aciduria and homocystinuria: review and a case report.
Combined methylmalonic aciduria and homocystinuria (MMA-HC) is a rare metabolic disease characterized by an inborn defect in B12 vitamin metabolism. This case report concerns an 11-year-old patient with MMA-HC, which developed during the neonatal period. The patient shows some of the facial features that were already reported in the literature (high forehead, large floppy, low-set ears, flat philtrum and hypotonia of perioral and masticatory muscles) but no dolichocephalic skull nor long face. The patient also shows signs that had not been previously described: epicanthal folds, broad nasal bridge, long and flat philtrum, amimic expression and, particularly, a postural alteration (the head is rotated and bent towards the left shoulder, which is lower than the right one). Such alteration can be attributed to visual impairment and is responsible for breaking muscular and skeletal balance in the frontal plane, thus causing the horizontal planes of both maxillary bones to converge towards the right--as highlighted by the cephalometric analysis of the Teleradio-graph of the skull in Posteroanterior projection according to Ricketts. As for the patient's teeth, eruption times are normal, but there are anomalies of shape (chisel-like central incisors). As far as dental caries is concerned, the patient's DMFT is 4 (D=4, M=0, F=0). This clinical case highlights the need for dental prevention programs suggested by the pediatrician once the pathology is diagnosed.


Lifestyle advice with or without pelvic floor muscle training for pelvic organ prolapse: a randomized controlled trial.
We evaluated the effect of adding pelvic floor muscle training (PFMT) to a structured lifestyle advice program. This was a single-blinded randomized trial of women with symptomatic pelvic organ prolapse (POP) stage ≥ II. Participants were randomized to a structured lifestyle advice program with or without PFMT. Both groups received similar lifestyle advice in six separate group sessions. The combined group performed group PFMT after an individual assessment. Primary outcome was a global improvement scale at six-month follow-up. Secondary outcomes were the global scale and objective POP at three-month follow-up, symptoms and quality of life including sexuality, at three and six-month follow-up. A clinically relevant change of symptoms was defined as ≥ 15 %. We included 109 women. Eighty-nine women (82 %) completed three months follow-up; 85 (78 %) completed six-month follow-up. At both follow-ups, significantly more women in the combined group reported improvement in the global scale. At the three-month follow-up, the combined group only had significant improvement of POP symptoms while only the lifestyle advice group had significant improvement of quality of life. Change in objective POP and sexuality was nonsignificant. The symptom score improved 17 % in the combined group and 14 % in the lifestyle advice group (P = 0.57). Significantly more women in the lifestyle advice group had sought further treatment at the six-month follow-up. Adding PFMT to a structured lifestyle advice program gave superior results in a global scale and for POP symptoms. Overall effect of either intervention barely reached clinical relevance.


Importance, quality, and engagement: School mental health providers' perceptions regarding within-district transition care coordination practices.
Although care coordination (CC; i.e., the organization of care activities between professionals to facilitate appropriate service delivery; McDonald et al., 2007) has yet to be studied extensively within schools, preliminary research suggests coordinating school mental health supports can be beneficial (Francis et al., 2021) and that interprofessional and interagency collaboration is warranted to meet student needs (McClain et al., 2022). We examined the perceptions of school mental health providers (SMHPs) regarding importance, quality, and engagement with within-district transition CC practices within a multitiered system of support framework. Participants were 163 SMHPs who endorsed being involved in designing, providing, or implementing mental health services in a U.S. school district. The three scales used to measure engagement with CC practices were based on the Care Coordination Measures Atlas (McDonald et al., 2014) and were found to have promising preliminary psychometrics. Descriptive statistics indicated SMHPs endorsed CC as very important but perceived school and district personnel to view it as less important, reported their own quality of CC was slightly above that of their school and district, and regularly engaged in broad CC practices. Moreover, bivariate correlations indicated SMHP's personal views of CC importance were not associated with the quality of school and district CC, yet engagement in broad CC activities was associated with transition facilitation practices, and attitudes about CC were associated with engagement in broad CC activities. Implications of findings are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


[Child mortality in francophone Europe: the state of the matter].
The interest of a comparative approach at a supranational level is to identify and to underscore the trends that sometimes overcome regional characteristics. Therefore among the great variety of parameters likely to influence mortality, the factors acting on levels and the factors acting on trends must be strictly distinguished. What is more striking where comparisons are possible, is the conformity of trends and the fact that evolution is not continuous but moves forward in stages. This is the reason why socio-economic explanations must be excluded. A whole part of Western Europe knew an important decline of infants' mortality at the turn of the XIXth and XXth centuries and probably also of the XVIIIth century. It was such a rapid, simultaneous extensive decline that the interference of very general factors must be acknowledged. Then the question is raised of the effect that a modification in the pathological balance can produce on the chances of infants to survive. The hypothesis considered here is a minor incidence of infectious diseases connected to changing bio-meteorological conditions (a drop in the temperature gap between winter and summer) which would have acted as a transforming mass along with cumulatiave effects because of the interactive synergy between ill-nourishment and infections. The evolution in the XIXth century and the contrasted profiles or mortality according to age confirm the hypothesis of a modification in the nosological context unrelated to the economic conditions.


Patients' satisfaction with the non-communicable diseases services provided at UNRWA health centres in Gaza governorates: a cross-sectional study.
Most health-care organisations are increasingly interested in assessing the quality of their services. Patient satisfaction has a central role in the quality assessment in health care because it reflects the appropriateness of services from the clients' perspectives. The aim of this study was to assess the level of satisfaction in patients with non-communicable diseases (mainly diabetes and hypertension) who receive services from UNRWA health centres in Gaza governorates. In this cross-sectional study we chose a random sample of participants who presented to the randomly selected six health centres for treatment of non-communicable diseases. Through an exit interviewing technique, participants were chosen according to the study eligibility criteria and were requested to complete a questionnaire. The total instrument reliability (Cronbach's Alpha) was very high (0·936). To examine construct validity, we used Factor Analysis Principal Component Extraction with Varimax Rotation and Kaiser Normalisation with a cutoff point of 0·4. The reported variance was 42·28%, indicating high validity. Ethical approval from the Palestinian Ministry of Health (the Helsinki committee) was obtained, and verbal consent was obtained from the participants. 327 (82%) of 400 eligible patients completed the questionnaire. The reported overall satisfaction level with services for non-communicable diseases was moderately high (72%). The study extracted six domains that could constitute a framework for patient satisfaction with services at UNRWA clinics for non-communicable diseases. Elicited satisfaction scores about these domains varied and ranged from 57% to 84%. Although high satisfaction levels were found with general impressions, accessibility, communication, and interpersonal relationships, patients had a low level of satisfaction with the technical quality of services, clinic environment, and convenience of the services. People who were unmarried, working, living in the southern governorates of Gaza, educated, and had received educational materials were more satisfied than their counterparts. Patients who were seen by a specific health provider, who received all their medications from UNRWA, and who had not been turned away from a clinic without receiving the service they came for were more satisfied than their counterparts. The level of patient satisfaction did not differ by sex, age, presence of disability, presence of complications associated with non-communicable diseases, control status, kind of non-communicable disease, type of treatment provided, or duration of the non-communicable disease. Increasing the convenience and promoting the technical quality of work are important to improve the experience of patients with non-communicable disease. Furthermore, health managers and health providers could use these study findings to focus on those who are at risk of losing their satisfaction with services. None.


Plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (RNA-seq) and microarray study.
Control of malaria is threatened by emerging parasite resistance to artemisinin and derivative drug (ART) therapies. The molecular detail of how Plasmodium malaria parasites respond to ART and how this could contribute to resistance are not well understood. To address this question, we performed a transcriptomic study of dihydroartemisinin (DHA) response in P. falciparum K1 strain and in P. berghei ANKA strain using microarray and RNA-seq technology. Microarray data from DHA-treated P. falciparum trophozoite stage parasites revealed a response pattern that is overall less trophozoite-like and more like the other stages of asexual development. A meta-analysis of these data with previously published data from other ART treatments revealed a set of common differentially expressed genes. Notably, ribosomal protein genes are down-regulated in response to ART. A similar pattern of trophozoite transcriptomic change was observed from RNA-seq data. RNA-seq data from DHA-treated P. falciparum rings reveal a more muted response, although there is considerable overlap of differentially expressed genes with DHA-treated trophozoites. No genes are differentially expressed in DHA-treated P. falciparum schizonts. The transcriptional response of P. berghei to DHA treatment in vivo in infected mice is similar to the P. falciparum in vitro culture ring and trophozoite responses, in which ribosomal protein genes are notably down-regulated. Ring and trophozoite stage Plasmodium respond to ART by arresting metabolic processes such as protein synthesis and glycolysis. This response can be protective in rings, as shown by the phenomenon of dormancy. In contrast, this response is not as protective in trophozoites owing to their commitment to a highly active and vulnerable metabolic state. The lower metabolic demands of schizonts could explain why they are less sensitive and unresponsive to ART. The ART response pattern is revealed clearly from RNA-seq data, suggesting that this technology is of great utility for studying drug response in Plasmodium.


Desertification of the peritoneum by thin-film evaporation during laparoscopy.
To assess the effects of gas flow during insufflation on peritoneal fluid and peritoneal tissue regarding transient thermal behavior and thin-film evaporation. The effects of laparoscopic gas on peritoneal cell desiccation and peritoneal fluid thin-film evaporation were analyzed. Measurment of tissue and peritoneal fluid and analysis of gas flow dynamics during laparoscopy. High-velocity gas interface conditions during laparoscopic gas insufflation result in peritoneal surface temperature and decreases up to 20 degrees C/second due to rapid thin-film evaporation of the peritoneal fluid. Evaporation of the thin film of peritoneal fluid extends quickly to the peritoneal cell membrane, causing peritoneal cell desiccation, internal cytoplasmic stress, and disruption of the cell membrane, resulting in loss of peritoneal surface continuity and integrity. Changing the gas conditions to 35 degrees C and 95% humidity maintains normal peritoneal fluid thin-film characteristics, cellular integrity, and prevents evaporative losses. Cold, dry gas and the characteristics of the laparoscopic gas delivery apparatus cause local peritoneal damaging alterations by high-velocity gas flow with extremely dry gas, creating extreme arid surface conditions, rapid evaporative and hydrological changes, tissue desiccation, and peritoneal fluid alterations that contribute to the process of desertification and thin-film evaporation. Peritoneal desertification is preventable by preconditioning the gas to 35 degrees C and 95% humidity.


Delayed Umbilical Cord Blood Clamping: First Line of Defense Against Neonatal and Age-Related Disorders.
The aging body is unable to maintain homeostasis in cell genesis and function. Stem cell-based regenerative medicine may reverse aging and treat age-related disorders. This perspective article discusses the therapeutic effects of stem cell transplantation on neonatal diseases, which may have long-lasting benefits affecting even the aging process. In particular, the article highlights the potential of the earliest transfer of stem cells between a mother and fetus via the umbilical cord during child birth and how this process may modify the clinical practice of umbilical cord clamping. While such umbilical cord clamping is routinely performed in an expeditious manner after birth for stem cell banking, the present article advances the concept that a delay in clamping the umbilical cord may actually allow more stem cells to be delivered from the mother to the fetus. The authors' overarching hypothesis is that early umbilical cord clamping results in an artificial loss of stem cells at birth and increases the infant's susceptibility to both neonatal and age-related diseases, while delaying umbilical cord clamping is perhaps the most effective and non-invasive way to transplant stem cells in order to treat these diseases.


Autism spectrum disorder in children born preterm-role of exposure to perinatal inflammation.
Autism Spectrum Disorder (ASD) is the collective term for neurodevelopmental disorders characterized by qualitative impairments in social interaction, communication, and a restricted range of activities and interests. Many countries, including Australia, have reported a dramatic increase in the number of diagnoses over the past three decades, with current prevalence of ASD at 1 in every 110 individuals (~1%). The potential role for an immune-mediated mechanism in ASD has been implicated by several studies, and some evidence suggests a potential link between prenatal infection-driven inflammation and subsequent development of ASD. Furthermore, a modest number of contemporary studies have reported a markedly increased prevalence of ASD in children born preterm, who are at highest risk of exposure to perinatal inflammation. However, the mechanisms that underpin the susceptibility to infection-driven inflammation during pregnancy and risk of preterm birth, and how these intersect with the subsequent development of ASD in the offspring, is not understood. This review aims to summarize and discuss the potential mechanisms and evidence for the role of prenatal infection on the central nervous system, and how it may increase the susceptibility for ASD pathogenesis in children born preterm.


Avulsion fractures involving the cruciate ligaments.
The evaluation of a child with an acute knee injury is difficult. The injury may be an avulsion fracture involving either of the cruciate ligaments; a common cause is a cycling accident. The amount of fragment displacement dictates the management. Minimal displacement can be treated with immobilization in flexion. Larger displacement requires internal fixation, which can be accomplished arthroscopically. Rehabilitation must be early and aggressive.


Naltrexone and brief counseling to reduce heavy drinking in hazardous drinkers.
The present study examined the utility of daily naltrexone for decreasing alcohol drinking in hazardous drinkers. Forty-one participants participated in a 10-week trial and received 30 min of brief counseling on the first and second week of treatment, as well as a daily dose of 50 mg of naltrexone throughout the trial. Overall, naltrexone-treated participants did not show the same degree of improvement on drinking outcomes as placebo-treated participants. The placebo group drank fewer drinks per drinking day and achieved more abstinence days than the naltrexone group. Craving was also lower for the placebo group. The groups were not balanced on gender or family history of alcoholism and this may explain the lack of effect of naltrexone on the drinking outcomes.


Effects of Desialylation on Chemoattractant Induced Chemotaxis.
The amount of sialic acid on the surface of the neutrophil influences its ability to interact with other cells. Neutrophil activation with various stimuli mobilizes intracellular sialidase to the plasma membrane where it cleaves sialic acid from cell surfaces. Since enhanced neutrophil adherence, spreading, deformability and motility each are associated with surface desialylation and critical to neutrophil diapedesis, we studied the role of sialic acid on neutrophil chemotaxis with interleukin-8 (IL-8), leukotriene B4 (LTB4), fMet-Leu-Phe (fMLP) and complement 5a in vitro. Migration of NANase-treated neutrophil across 3 μ pore size polycarbonate membranes was decreased in response to IL-8 and LTB4 but not to fMLP and complement 5a. These findings suggest that sialic acid content of receptors have a key role on chemoattractant-receptor binding and may be a novel strategy for limiting the inflammatory response.


Current and emerging therapies for the management of chronic inflammation in asthma.
The pathophysiology of asthma, current treatment guidelines, and emerging immunomodulating treatments are reviewed. Asthma is a chronic disease of inflammation, which left untreated, may result in irreversible lung damage. Inhaled antigens elicit a T-helper cell type-2 response, leading to the production of immunoglobulin E (IgE) and eosinophil sensitization. Eosinophil infiltration into the airway is thought to play an important role in chronic inflammation and increases several weeks before an acute exacerbation in moderate to severe asthma. The updated guidelines from the National Asthma Education and Prevention Program and the National Institutes of Health focus on the use of daily antiinflammatory treatment in patients with persistent asthma. Inhaled corticosteroid (ICS) therapy remains the cornerstone for controlling mild and moderate asthma, but when used in higher doses for moderate-to-severe asthma it may cause long-term adverse effects, including osteoporosis and glaucoma. Step-up therapy should be the combination of a long-acting beta-agonist (LABA) and an ICS. Leukotriene modifiers may provide additional symptom control in patients with moderate to severe asthma but have not been shown to be as cost-effective as monotherapy. Newer entities focus on direct immune modulation and include monoclonal antibodies targeting various inflammatory-response receptors (IgE, interleukin [IL]-2, IL-4, and IL-5). Phosphodiesterase-4 (PDE-4) inhibitors may be effective for chronic obstructive pulmonary disease, but have not delivered consistent results for controlling asthma. Cytokine-receptor antagonists and leukocyte-suppressing antiinflammatory drugs (LSAIDs) are currently under investigation and have yielded promising preliminary results as alternatives for the treatment of asthma. Current and emerging therapies for the management of chronic inflammation in asthma include ICSs, LABAs, leukotriene modifiers, monoclonal antibodies, PDE-4 inhibitors, cytokine-receptor antagonists, and LSAIDs.


Influence of environmental information in natural scenes and the effects of motion adaptation on a fly motion-sensitive neuron during simulated flight.
Gaining information about the spatial layout of natural scenes is a challenging task that flies need to solve, especially when moving at high velocities. A group of motion sensitive cells in the lobula plate of flies is supposed to represent information about self-motion as well as the environment. Relevant environmental features might be the nearness of structures, influencing retinal velocity during translational self-motion, and the brightness contrast. We recorded the responses of the H1 cell, an individually identifiable lobula plate tangential cell, during stimulation with image sequences, simulating translational motion through natural sceneries with a variety of differing depth structures. A correlation was found between the average nearness of environmental structures within large parts of the cell's receptive field and its response across a variety of scenes, but no correlation was found between the brightness contrast of the stimuli and the cell response. As a consequence of motion adaptation resulting from repeated translation through the environment, the time-dependent response modulations induced by the spatial structure of the environment were increased relatively to the background activity of the cell. These results support the hypothesis that some lobula plate tangential cells do not only serve as sensors of self-motion, but also as a part of a neural system that processes information about the spatial layout of natural scenes.


Loss of co-ordinate expression of progesterone receptors A and B is an early event in breast carcinogenesis.
Progesterone receptor (PR) mediates the effects of progesterone in mammary tissues and plays a crucial role in normal breast development and in breast cancer. PR proteins are expressed as two isoforms, PRA and PRB, that have different capacities to activate target genes, yet it is unknown whether progesterone action in normal and malignant breast is mediated by PRA and/or PRB. This study determines the relative expression of PRA and PRB in normal breast and in benign, premalignant and malignant archival breast lesions by dual immunofluorescent histochemistry. In normal breast and in proliferative disease without atypia (PDWA) PRA and PRB were co-expressed within the same cells in comparable amounts, implicating both isoforms in progesterone action. In atypical lesions, however, there was a significant increase in predominant expression of PRA or PRB, with lesion progression from the normal state to malignancy. PR isoform predominance, especially PRA predominance, was evident in a high proportion of ductal carcinomas in situ (DCIS) and invasive breast lesions. In the normal breast and in PDWA, the relative expression of PRA and PRB in adjacent cells was homogenous. There was a significant increase in cell-to-cell heterogeneity of PR isoform expression in ADH and DCIS lesions and in the majority of breast cancers. Heterogeneous cell-to-cell expression of PR isoforms occurred prior to overall predominant expression of one isoform in premalignant breast lesions, demonstrating that loss of control of relative PRA:PRB expression is an early event in the development of breast cancer. PRA:PRB ratios within a breast lesion are likely to be important as both markers and effectors of tumor growth and development, and progressively aberrant PR isoform expression may play a role in the etiology of breast cancer.


Micro-shear bond strengths of resin-matrix ceramics subjected to different surface conditioning strategies with or without coupling agent application.
This study aimed to assess the influence of various micromechanical surface conditioning (MSC) strategies with or without coupling agent (silane) application on the micro-shear bond strength (µSBS) of resin- matrix ceramics (RMCs). GC Cerasmart (GC), Lava Ultimate (LU), Vita Enamic (VE), Voco Grandio (VG), and Brilliant Crios (BC) were cut into 1.0-mm-thick slices (n = 32 per RMC) and separated into four groups according to the MSC strategy applied: control-no conditioning (C), air-borne particle abrasion with aluminum oxide particles (APA), 2W- and 3W-Er,Cr:YSGG group coding is missing. The specimens in each group were further separated into silane-applied and silane-free subgroups. Each specimen received two resin cement microtubules (n = 8 per subgroup). A shear force was applied to the adhesive interface through a universal test machine and µSBS values were measured. Data were statistically analyzed by using 3-way ANOVA and Tukey HSD test. Failure patterns were scrutinized under stereomicroscope. RMC material type, MSC strategy, and silanization influenced the µSBS values (P<.05). In comparison to the control group, µSBS values increased after all other MSC strategies (P<.05) while the differences among these strategies were insignificant (P>.05). For control and APA, there were insignificant differences between RMCs (P>.05). The silanization decreased µSBS values of RMCs except for VE. Considerable declines were observed in GC and BC (P<.05). MSC strategies can enhance bond strength values at the RMC - cement interface. However, the choice of MSC strategy is dependent on RMC material type and each RMC can require a dedicated way of conditioning.


Change of Tinnitus with Xenon Phototherapy of the Stellate Ganglion.
To develop a treatment for tinnitus called xenon phototherapy of the stellate ganglion (XPSG) and analyze its effect on tinnitus. Patients with chronic tinnitus received XPSG. Symptoms were assessed subjectively with tinnitus handicap inventory (THI) and numerical rating scale (NRS). THI and NRS scores were analyzed in XPSG (n = 43) and sham treatment (non-XPSG) (n = 18) groups. THI and NRS scores improved significantly after 3 months of XPSG. Severe cases with high THI or NRS score showed greater improvement. No significant difference was observed between before and after sham treatment in non-XPSG groups. XPSG significantly improved THI and NRS scores with high patient satisfaction.


Magnification for the dermatologic surgeon.
Ergonomic practice increases the productivity, quality, and longevity of the dermatologic surgeon. When used properly, magnification devices can be ergonomic and beneficial additions to the dermatologic surgeon's practice. Herein, we review the available magnification options for the dermatologic surgeon and evaluate the options based on cost, design, and functional advantages and disadvantages. Magnification for the dermatologic surgeon may be a useful tool for a healthier, more efficient, and higher-quality practice.


Identification of six new alleles at the FUT1 and FUT2 loci in ethnically diverse individuals with Bombay and Para-Bombay phenotypes.
The Bombay and para-Bombay phenotypes arise from mutations of the FUT1 gene that silence the gene or affect the efficiency of the encoded 2-alpha-fucosyltransferase. Samples from seven individuals of different geographic backgrounds whose red blood cells had an apparent Bombay or para-Bombay phenotype were investigated. Among these, novel FUT1 and FUT2 alleles were identified. Standard serologic techniques were used. Genomic DNA was sequenced with primers that amplified the coding sequence of FUT1 and the related secretor gene, FUT2. Routine ABO genotyping analysis was performed. Five new FUT1 alleles were identified that silenced FUT1 or weakened alpha2FucT1 activity. These were 35C>T, 269G>T (Ala11Val, Gly89Val); 421A>G (Trp140Stop); 538C>T, 1089T>G (Gln180Stop, Ala363Ala); 689A>C (Gln230Pro); and 917C>T (Thr305Ile). In addition, both homozygosity and heterozygosity for the previously reported mutation, 826C>T (Gln276Stop), were observed. Four of seven samples were homozygous for the silencing mutation 428A in FUT2. One new FUT2 allele was identified: 278C>T, 357C>T (Ala93Val, Asn119Asn). These results add to the growing database of apparently sporadic and random mutations in the FUT1 gene and confirm previous reports regarding the lack of ethnic bias. In contrast, our data reinforce the apparent maintenance of the common nonsecretor FUT2 alleles in the population.


Proteomic and oxidative stress analysis in human brain samples of Huntington disease.
Huntington disease (HD) is a neurodegenerative disorder caused by expansion of CAG repeats in exon 1 of the huntingtin gene, affecting initially the striatum and progressively the cortex. This work reports a proteomic analysis of human brain postmortem samples obtained from striatum and cortex of patients with HD compared to samples of age- and sex-matched controls. Antioxidant defense proteins that were strongly induced in striatum, but also detectable in cortex, were identified as peroxiredoxins 1, 2, and 6, as well as glutathione peroxidases 1 and 6. The activities of other antioxidant enzymes such as mitochondrial superoxide dismutase and catalase were also increased in HD. Aconitase, a protein involved in energy metabolism, showed decreased activities in striatum of HD patients. Protein carbonyls, used as markers of oxidative stress, were increased in HD, and glial fibrillary acidic protein, aconitase, gamma-enolase, and creatine kinase B were identified as the main targets. Taken together, these results indicate that oxidative stress and damage to specific macromolecules would participate in the disease progression. Also, these data support the rationale for therapeutic strategies that either potentiate antioxidant defenses or avoid oxidative stress generation to delay disease progression.


Facile Synthesis of MXene-Ti3C2/Co Nanosheet Hydrogel Sensor with the Assistance of a Smartphone for On-Site Monitoring of Glucose in Beverages.
A one-step cobaltous chloride (CoCl2) molten salt method was employed to prepare multilayer MXene-Ti3C2/Co materials with further ultrasonic treatment to acquire single-layer MXene-Ti3C2/Co nanosheets (NSs). MXene-Ti3C2/Co NSs were characterized, and their enzyme-like activities were investigated. Under the catalysis of MXene-Ti3C2/Co NSs, 3,3',5,5'-tetramethylbenzidine (TMB) could be oxidized by H2O2, with the color changing from colorless to blue. The affinity of MXene-Ti3C2/Co NSs to H2O2 and TMB was better than that of nanozymes reported in previous studies. The MXene-Ti3C2/Co NSs were used for the colorimetric determination of H2O2/glucose, with limits of detection (LODs) of 0.033 mM and 1.7 μM, respectively. MXene-Ti3C2/Co NSs embedded in sodium alginate (SA) hydrogel were used to construct a sensor platform. The digital pictures combined with a smartphone-installed app (color recognizer) could be used to analyze RGB values for colorimetric detection of glucose in beverages. This point-of-care testing platform has the advantages of cost-effectiveness and good transferability, with the potential to realize quick, intelligent and on-site detection.


Mutations in the gene encoding filamin A as a cause for familial cardiac valvular dystrophy.
Myxomatous dystrophy of the cardiac valves affects approximately 3% of the population and remains one of the most common indications for valvular surgery. Familial inheritance has been demonstrated with autosomal and X-linked transmission, but no specific molecular abnormalities have been documented in isolated nonsyndromic forms. We have investigated the genetic causes of X-linked myxomatous valvular dystrophy (XMVD) previously mapped to chromosome Xq28. A familial and genealogical survey led us to expand the size of a large, previously identified family affected by XMVD and to refine the XMVD locus to a 2.5-Mb region. A standard positional cloning approach identified a P637Q mutation in the filamin A (FLNA) gene in all affected members. Two other missense mutations (G288R and V711D) and a 1944-bp genomic deletion coding for exons 16 to 19 in the FLNA gene were identified in 3 additional, smaller, unrelated families affected by valvular dystrophy, which demonstrates the responsibility of FLNA as a cause of XMVD. Among carriers of FLNA mutation, the penetrance of the disease was complete in men and incomplete in women. Female carriers could be mildly affected, and the severity of the disease was highly variable among mutation carriers. Our data demonstrate that FLNA is the first gene known to cause isolated nonsyndromic MVD. This is the first step to understanding the pathophysiological mechanisms of the disease and to defining pathways that may lead to valvular dystrophy. Screening for FLNA mutations could be important for families affected by XMVD to provide adequate follow-up and genetic counseling.


Modifying the structure and flow behaviour of aqueous montmorillonite suspensions with surfactant.
Colloidal suspensions of plate-like particles undergo a variety of phase transitions. The predicted isotropic/nematic transition is often pre-empted by a sol/gel transition, especially in suspensions of the most commonly used natural swelling clay montmorillonite (MMT). A number of factors, including charge interactions, flexibility and salt concentration, may contribute to this competition. In this study, the effect of surfactant adsorption on suspensions of MMT was studied using rheology, small-angle X-ray scattering, static light scattering and optical microscopy. The addition of a polyetheramine surfactant reduced the moduli of the system and shifted the sol/gel transition to a much higher clay concentration, compared with suspensions of bare clay particles. Yet, scattering data revealed no change in suspension structure on length scales up to around a micrometre. Primary aggregates remain at this length scale and no nematic phase is formed. There is, however, a change in structure at large length scales (of order 20 μm) where light scattering indicates the presence of string-like aggregates that disappear on addition of surfactant. Microscope images of dried suspensions also revealed a string-like structure. The dried strings show strong birefringence and may consist of concentric cylinders, self-assembled from clay sheets.


Changing the child labor laws for agriculture: impact on injury.
The child labor laws are intended to protect young workers from the most dangerous jobs. However, children who work on their parents' farms are exempt from these laws. We evaluated the potential for preventing the occurrence of farm injuries among children by changing the US Federal Child Labor Laws, Hazardous Occupations Orders for Agriculture. A retrospective case series of 1193 farm injuries among children from the United States and Canada was assembled. The Hazardous Occupations Orders were systematically applied to each case. Injury preventability was estimated. A total of 286 (24%) cases of injury involved immediate family members engaged in farm work. Among these children, 33% of those aged younger than 16 years and 36% of those aged 16 or 17 years were performing work prohibited under the Hazardous Occupations Orders. Removing the family farm exemption from the Hazardous Occupations Orders and raising the age restriction for performing hazardous agricultural work from 16 to 18 years would be efficacious in preventing the most serious injuries experienced by young family farm workers. Potential reductions in injury would meet Healthy People 2010 goals for reducing traumatic injury in the agricultural sector.


Exploiting the Therapeutic Potential of Endogenous Immunomodulatory Systems in Multiple Sclerosis-Special Focus on the Peroxisome Proliferator-Activated Receptors (PPARs) and the Kynurenines.
Multiple sclerosis (MS) is a progressive neurodegenerative disease, characterized by autoimmune central nervous system (CNS) demyelination attributable to a disturbed balance between encephalitic T helper 1 (Th1) and T helper 17 (Th17) and immunomodulatory regulatory T cell (Treg) and T helper 2 (Th2) cells, and an alternatively activated macrophage (M2) excess. Endogenous molecular systems regulating these inflammatory processes have recently been investigated to identify molecules that can potentially influence the course of the disease. These include the peroxisome proliferator-activated receptors (PPARs), PPARγ coactivator-1alpha (PGC-1α), and kynurenine pathway metabolites. Although all PPARs ameliorate experimental autoimmune encephalomyelitis (EAE), recent evidence suggests that PPARα, PPARβ/δ agonists have less pronounced immunomodulatory effects and, along with PGC-1α, are not biomarkers of neuroinflammation in contrast to PPARγ. Small clinical trials with PPARγ agonists have been published with positive results. Proposed as immunomodulatory and neuroprotective, the therapeutic use of PGC-1α activation needs to be assessed in EAE/MS. The activation of indolamine 2,3-dioxygenase (IDO), the rate-limiting step of the kynurenine pathway of tryptophan (Trp) metabolism, plays crucial immunomodulatory roles. Indeed, Trp metabolites have therapeutic relevance in EAE and drugs with structural analogy to kynurenines, such as teriflunomide, are already approved for MS. Further studies are required to gain deeper knowledge of such endogenous immunomodulatory pathways with potential therapeutic implications in MS.


Molecular architecture of the glycogen- committed PP1/PTG holoenzyme.
The delicate alternation between glycogen synthesis and degradation is governed by the interplay between key regulatory enzymes altering the activity of glycogen synthase and phosphorylase. Among these, the PP1 phosphatase promotes glycogenesis while inhibiting glycogenolysis. PP1 is, however, a master regulator of a variety of cellular processes, being conveniently directed to each of them by scaffolding subunits. PTG, Protein Targeting to Glycogen, addresses PP1 action to glycogen granules. In Lafora disease, the most aggressive pediatric epilepsy, genetic alterations leading to PTG accumulation cause the deposition of insoluble polyglucosans in neurons. Here, we report the crystallographic structure of the ternary complex PP1/PTG/carbohydrate. We further refine the mechanism of the PTG-mediated PP1 recruitment to glycogen by identifying i) an unusual combination of recruitment sites, ii) their contributions to the overall binding affinity, and iii) the conformational heterogeneity of this complex by in solution SAXS analyses.


Superficial and deep changes of cellular mechanical properties following cytoskeleton disassembly.
The cytoskeleton, composed of actin filaments, intermediate filaments, and microtubules, is a highly dynamic supramolecular network actively involved in many essential biological mechanisms such as cellular structure, transport, movements, differentiation, and signaling. As a first step to characterize the biophysical changes associated with cytoskeleton functions, we have developed finite elements models of the organization of the cell that has allowed us to interpret atomic force microscopy (AFM) data at a higher resolution than that in previous work. Thus, by assuming that living cells behave mechanically as multilayered structures, we have been able to identify superficial and deep effects that could be related to actin and microtubule disassembly, respectively. In Cos-7 cells, actin destabilization with Cytochalasin D induced a decrease of the visco-elasticity close to the membrane surface, while destabilizing microtubules with Nocodazole produced a stiffness decrease only in deeper parts of the cell. In both cases, these effects were reversible. Cell softening was measurable with AFM at concentrations of the destabilizing agents that did not induce detectable effects on the cytoskeleton network when viewing the cells with fluorescent confocal microscopy. All experimental results could be simulated by our models. This technology opens the door to the study of the biophysical properties of signaling domains extending from the cell surface to deeper parts of the cell.


Biological properties of almond proteins produced by aqueous and enzyme-assisted aqueous extraction processes from almond cake.
The almond cake is a protein-rich residue generated by the mechanical expression of the almond oil. The effects of the aqueous (AEP) and enzyme-assisted aqueous extraction processes (EAEP) on the biological properties of the almond cake protein were evaluated. Total phenolic content (TPC), antioxidant capacity, inhibitory effects against crucial enzymes related to metabolic syndrome, antimicrobial potential, and in vitro protein digestibility profile were assessed. EAEP provided the best results for antioxidant capacity by both ORAC (397.2 µmol TE per g) and ABTS (650.5 µmol TE per g) methods and also showed a high (~ 98%) potential for α-glucosidase inhibition. The AEP resulted in protein extracts with the highest lipase inhibition (~ 70%) in a dose-dependent way. Enzymatic kinetic analyses revealed that EAEP generated uncompetitive inhibitors against α-glucosidase, while EAEP, AEP, and HEX-AEP (used as control) generated the same kind of inhibitors against lipase. No protein extract was effective against any of the bacteria strains tested at antimicrobial assays. An in silico theoretical hydrolysis of amandin subunits corroborated with the results found for antioxidant capacity, enzyme inhibitory experiments, and antimicrobial activity. Digestibility results indicated that the digestive proteases used were efficient in hydrolyzing almond proteins, regardless of the extraction applied and that HEX-AEP presented the highest digestibility (85%). In summary, EAEP and AEP skim proteins have the potential to be used as a nutraceutical ingredient. The biological properties observed in these extracts could help mitigate the development of metabolic syndrome where EAEP and AEP skim proteins could be potentially used as a prophylactic therapy for diabetes and obesity, respectively.


[Changes in nonspecific suppressor factors in the serum of gastric cancer patients after surgery and immunochemotherapy].
After curative surgery for gastric cancers judged macroscopically to be at stage 2 or 3, patients were divided into 4 groups by randomization. As the basic treatment, patients were given one-shot Mitomycin and Tegafur as maintenance therapy for 8 months (group A). PSK (group B), OK-432 (group C) or both PSK and OK-432 (group D) were added to the treatment of group A for 8 months. Sera were obtained from these groups of patients at 4 weeks and 3, 6, 9 and 12 months after surgery. In all of these groups, values of IAP increased slightly at 4 weeks but decreased at 3 months and were maintained at such a level by 12 months. On the other hand, suppressive effects of such sera on the blastogenesis of murine spleen cells in response to PHA varied among these group. In groups A and C, the suppressive effect of sera increased after surgery and was detected continuously by 12 months. In groups B and D, in contrast, the suppressive effect disappeared from 3 to 12 months. The rise and fall of such a suppressive effect of sera may reflect the mode of action of PSK.


PARP1 rs1136410 (A/G) polymorphism is associated with early age of onset of gallbladder cancer.
Evaluation of the association of PARP1 rs1136410 (A/G) polymorphism with gallbladder cancer susceptibility and its prognosis in the Indian population of eastern Uttar Pradesh and western Bihar. PARP1 rs1136410 was genotyped by PCR-RFLP and its association with the prognosis of gallbladder cancer patients were analyzed using Kaplan-Meier plot and log-rank tests. Our results demonstrate that minor allele G is more frequent in gallbladder cancer patients than controls. The frequencies of minor allele G and GG genotype are significantly associated with increased risk of gallbladder cancer. Our data suggest that the minor allele G and homozygous genotype GG are significant predisposing factors for the early age of onset of gallbladder cancer. Similarly, women patients having AG and GG genotypes demonstrate an increased risk of gallbladder cancer. The risk group genotypes (AG + GG) are significantly more frequent in patients with thick gallbladder wall, with jaundice and with the presence of lymph node than in patients with normal gallbladder wall thickness, without jaundice and absence of lymph node involvement. Survival analysis data suggest that patients with risk group genotype (AG + GG) presenting jaundice have shorter overall survival. Our study suggests that the minor allele G of PARP1 rs1136410 (A/G) is a predisposing factor for gallbladder carcinogenesis and is significantly associated with early onset of the disease. Interestingly, the minor allele G is significantly more frequent in the patients with jaundice, lymph node metastasis and gallbladder wall thickness.


Genetic divergence among accessions of melon from traditional agriculture of the Brazilian Northeast.
The genetic divergence of 38 melon accessions from traditional agriculture of the Brazilian Northeast and three commercial hybrids were evaluated using fruit descriptors and microsatellite markers. The melon germplasm belongs to the botanic varieties cantalupensis (19), momordica (7), conomon (4), and inodorus (3), and to eight genotypes that were identified only at the species level. The fruit descriptors evaluated were: number of fruits per plant (NPF), fruit mass (FM; kg), fruit longitudinal diameter (LD; cm), fruit transversal diameter (TD; cm), shape index based on the LD/TD ratio, flesh pulp thickness, cavity thickness (CT; cm), firmness fruit pulp (N), and soluble solids (SS; °Brix). The results showed high variability for all descriptors, especially for NPF, LD, and FM. The grouping analysis based on fruit descriptors produced eight groups without taxonomic criteria. The LD (22.52%), NPF (19.70%), CT (16.13%), and SS (9.57%) characteristics were the descriptors that contributed the most to genotype dissimilarity. The 17 simple sequence repeat polymorphic markers amplified 41 alleles with an average of 2.41 alleles and three genotypes per locus. Some markers presented a high frequency for the main allele. The genetic diversity ranged from 0.07 to 0.60, the observed heterozygosity had very low values, and the mean polymorphism information content was 0.32. Molecular genetic similarity analyses clustered the accessions in 13 groups, also not following taxonomic ranks. There was no association between morphoagronomic and molecular groupings. In conclusion, there was great variability among the accessions and among and within botanic groups.


[Stability and catalytic properties of o-diphenol oxidase. 2. Oxidation of monophenols].
o-Diphenoloxidase from potato tubers is shown to be a hysteretic enzyme which is dimerized during monophenol oxidation. A diagram of the enzyme activation is suggested. It is established that the enzyme activity in reactions of monophenols oxidation is determined by the nature of substituents in the substrate molecule; the higher phenol acidity, the worse its enzymic oxidation. The effect of substituents in the phenol molecule on the enzymic reaction rate may be described in terms of the Hammet equation.


Clinical factors predicting blood pressure reduction after catheter-based renal denervation.
Renal denervation (RD) can lead to a significant and sustained decrease in mean values of arterial blood pressure (BP). However, there is still a subset of patients without a significant BP drop after RD (non-responders). To compare characteristics of RD responders to RD non-responders and to identify the clinical predictors of BP reduction. Thirty-one patients with diagnosed resistant hypertension underwent RD. Three years after RD the analysis of BP reduction was performed in regard to the baseline patient characteristics. After 3 years' follow-up a 10% or more reduction of systolic baseline BP was observed in 74% of patients. Ten percent or more reduction of diastolic baseline BP was observed in 71% of patients. Among responders we observed the following risk factors: hypercholesterolemia in 70%, body mass index (BMI) > 30 kg/m2 in 55%, diabetes mellitus in 35%, current smoking in 5%. Comorbidity included coronary artery disease (CAD) in 30%, cardiomyopathy in 10%, chronic obstructive pulmonary disease (COPD) in 10%, renal insufficiency in 10%, and ventricular arrhythmia in 5%. Among non-responders we observed the following risk factors: hypercholesterolemia in 38%, diabetes mellitus type 2 in 38% and BMI > 30 kg/m2 in 86%. Comorbidity included CAD in 50% and cardiomyopathy in 13% of patients. A 10% reduction of systolic baseline BP was observed in 74% of patients 3 years after renal denervation. Clinical factors like COPD, chronic kidney disease 3a, female sex and hypercholesterolemia increase the chances of effective reduction of BP.


A new combined criterion to better predict malignant lesions in patients with pancreatic cystic neoplasms.
Cystic lesions of the pancreas have been increasingly recognized. Some lesions exhibit benign behavior, while others have unequivocal malignant potential. Thus, accurate identification of malignancy in patients diagnosed with pancreatic cystic neoplasms (PCNs) remains a major challenge. The aim of this study was to define a combined criterion to better predict malignant lesions in patients with PCNs. We retrospectively analyzed 165 patients who underwent resection of PCNs from October 2011 to May 2017. The relationship among malignancy and serum carbohydrate antigen 19-9 (CA19-9), preoperative neutrophil-to-lymphocyte ratio (NLR), and the presence of enhanced solid component on imaging was analyzed. NLR before surgery in patients with malignant PCNs (2.81±2.14) was significantly higher than that in patients diagnosed with pancreatic neuroendocrine tumor (1.90±0.69, P=0.013) or healthy volunteers (1.40±0.48; P<0.001). Serum CA19-9 ≥39 U/mL, NLR >1.976 and presence of enhanced solid component were independent predictors of PCN malignancy. A combined criterion meeting any two or more of the three elements including CA19-9 ≥39 U/mL, NLR >1.976, and presence of enhanced solid component on computed tomography imaging is an indicator with a high positive predictive value of 80.5% and a high negative predictive value of 87.9%, and thus, represents a highly accurate test (86.1%). The new combined criterion is an effective predictor of tumor malignancy in patients with PCNs.


Tissue distribution after intravenous dosing of micafungin, an antifungal drug, to rats.
The tissue distribution after an intravenous dose of micafungin (1 mg/kg), a new echinocandin-like lipopeptide antifungal agent, to male rats was investigated. Micafungin in plasma disappeared biexponentially with a terminal half-life of 5.03 h. Micafungin concentrations in liver, kidney, and lung at the first sampling time (5 min) after dosing were 1.15, 1.64, and 2.58-fold higher than the plasma concentration, and the AUC(0- infinity ) were 1.61, 3.42, and 2.89-fold higher than that for plasma. The terminal half-lives for these tissues were 5.14, 4.87, and 5.31 h, respectively, which were comparable to those for plasma. These results suggest that micafungin distributes rapidly and moderately into tissues such as the liver, kidney, and lungs, and that the concentrations in tissues decreased in parallel with the unchanged drug in plasma.


Novel peptide motifs from lysozyme suppress pro-inflammatory cytokines in macrophages by antagonizing toll-like receptor and LPS-scavenging action.
Lysozyme is commonly found in spots where bacterial infections are most likely to enter the body. Earlier we found that lysozyme possesses five antimicrobial peptide motifs in its N-terminal region which can be generated by newborn pepsin. In this study, we explore the role of these peptides in the anti-inflammatory activity of lysozyme. The five peptides, helix1 (H1), helix2 (H2), H1 and H2 connected with a loop (HLH), H2 extended with either 2 β-strands (H2-S12) or 3 β-strands (H2-S13), were synthesized and examined for anti-inflammatory action. The five peptides dose-dependently decreased, to different degrees, expression of pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β, in lipopolysaccharide (LPS)- or interferon-gamma (INF-γ)-stimulated mouse macrophage cells (RAW264.7). The HLH peptide and its individual helices (H1 and H2) were markedly the most potent anti-inflammatory. When macrophage cells were stimulated with live bacteria (E. coli), H1 peptide was the most powerful suppressor of TNF-α and IL-6 expression, providing evidence that the peptide is able to antagonize the pathogen-induced inflammatory response. Receptor binding assay and docking simulation provided evidence that H1 peptide bind specifically to the pocket for endotoxin binding of the toll-like receptor 4 (TLR-4) of macrophage. The results demonstrate, for the first time, the molecular basis of anti-inflammatory action of lysozyme that N-terminal helical peptides are the main contributors. This exciting finding offers new classes of therapeutic peptides with potential in the treatment of infection-induced inflammatory diseases.


Different affective response to opioid withdrawal in adolescent and adult mice.
Drug withdrawal is suggested to play a role in precipitating mood disorders in individuals with familial predisposition. Age-related differences in affective responses to withdrawal might explain the increased risk of mental illnesses when drug use begins during adolescence. Since there is a lack of animal research examining the effects of opioid withdrawal during adolescence, the present study examined whether there are age-related differences in affective responses to opioid withdrawal. Adolescent and adult mice were injected with two different morphine regimens, namely low and high, which differed in the dosage. Three and nine days following discontinuation of morphine administration, immobility time in the forced swim test (FST) and locomotion (total distance traveled) were evaluated. On withdrawal day 3 (WD3), adolescent mice exhibited a decrease in immobility as compared to controls. No significant differences in immobility were observed on withdrawal day 9 (WD9). This effect on FST behaviors was not due to changes in overall motor activity, since no differences in locomotion were observed on either WD3 or WD9 in adolescent mice. In adults, no differences in either FST or locomotor behaviors were observed on WD3. As expected, on WD9, adult mice exhibited an increase in immobility and a decrease in locomotion. This study demonstrates age-dependent differences in both FST scores and locomotor behaviors during opioid withdrawal. FST behaviors are classically used to evaluate mood in rodents, thus this study suggests that opioid withdrawal might affect mood differentially across age.


The Prevalence and Risk Factors for Low Birth Weight among Term Newborns in Adwa General Hospital, Northern Ethiopia.
Background. World health organization estimates that 25 million LBW babies are born annually worldwide and 95% occur in developing countries. Objective. To assess the prevalence and associated factors of low birth weight among term neonates delivered in Adwa Hospital, Northern Ethiopia. Methods. A cross-sectional study was conducted among neonates delivered in Adwa Hospital. All live births delivered from July 1, 2014, to June 30, 2016, were included in this study. The study participants were selected through systematic sampling technique and the data was collected using a structured questionnaire. Data was entered to Epi Data version 3.1 and analyzed using SPSS version 20 software. To identify independent predictors, bivariate and multivariable binary logistic regressions were employed. Adjusted odds ratio and 95% confidence interval were used to determine the strength of association. Results. The prevalence of term low birth weight was 10%. The risk factors were mothers aged less than 20 years, mothers whose pregnancy was desired, mothers with a history of abortion, and mothers with normal hemoglobin, iron with folic acid, and HIV status. Conclusion. The burden of LBW obtained in this study was in the same range as in some other countries.


Characterization of a ligand binding site in the human transient receptor potential ankyrin 1 pore.
The pharmacology and regulation of Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel activity is intricate due to the physiological function as an integrator of multiple chemical, mechanical, and temperature stimuli as well as differences in species pharmacology. In this study, we describe and compare the current inhibition efficacy of human TRPA1 on three different TRPA1 antagonists. We used a homology model of TRPA1 based on Kv1.2 to select pore vestibule residues available for interaction with ligands entering the vestibule. Site-directed mutation constructs were expressed in Xenopus oocytes and their functionality and pharmacology assessed to support and improve our homology model. Based on the functional pharmacology results we propose an antagonist-binding site in the vestibule of the TRPA1 ion channel. We use the results to describe the proposed intravestibular ligand-binding site in TRPA1 in detail. Based on the single site substitutions, we designed a human TRPA1 receptor by substituting several residues in the vestibule and adjacent regions from the rat receptor to address and explain observed species pharmacology differences. In parallel, the lack of effect on HC-030031 inhibition by the vestibule substitutions suggests that this molecule interacts with TRPA1 via a binding site not situated in the vestibule.


ZAP-70 expression in acute lymphoblastic leukemia: association with the E2A/PBX1 rearrangement and the pre-B stage of differentiation and prognostic implications.
We evaluated the expression of 2 members of the Syk family, ZAP-70 and Syk, in acute lymphoblastic leukemia (ALL) samples, using data derived from a series of 33 T-ALL and 95 B-lineage adult ALL patients analyzed by oligonucleotide arrays. Of the B-lineage ALL cases, 37 were BCR/ABL+, 10 were ALL1/AF4+, 5 were E2A/PBX1+, and 43 carried no known molecular abnormality. ZAP-70 was highly expressed in T-ALL. A high ZAP-70 expression was also found in a proportion of B-lineage ALL, the highest levels being associated with the E2A/PBX1+ group and the lowest with ALL1/AF4+ cases (P < .001). A higher ZAP-70 expression was also observed in the pre-B group (P < .001). Remarkably, Syk expression was always preserved, suggesting that ZAP-70 expression is not substitutive of Syk. At the protein level, ZAP-70 was evaluated on 39 newly diagnosed ALL patients (25 adults, 14 children) and was detected in 23 cases (59%). ZAP-70 expression was consistently found in Ig mu+ cases. Evaluation of long-term outcome in cases without molecular abnormalities showed that the higher levels of ZAP-70 were coupled to a higher relapse rate. In ALL, ZAP-70 expression is associated with the E2A/PBX1 rearrangement and pre-B stage and may have a prognostic role and be a candidate molecule for targeted therapies.


Alterations in serum lipid profile patterns in oral cancer: correlation with histological grading and tobacco abuse.
Albeit alterations in serum lipid profile patterns have long been associated with malignancies, still role of these alterations remains controversial. It has been suggested a causative relationship might exist between plasma lipid levels and oral cancer patients. Further, the habit of tobacco consumption is on the rise and most often the oral cancer patients are afflicted with this menace. As a matter of fact, tobacco contains carcinogens capable of damaging the cell membrane components including lipids. Thus, the purpose of the present review is to discuss the basics of lipids and to evaluate alterations in plasma lipid profile in oral cancer patients and its association with histological grading and tobacco abuse. Pertinent literature was searched in PubMed and Medline by using key words such as serum lipid profile, oral cancer, histological grades and tobacco abuse.


Pancreatic hormones, insulin/glucagon molar ratios, and somatostatin as determinants of avian carbohydrate metabolism.
The endocrine pancreas of birds contains cell populations similar, if not identical, to those found in mammalian pancreata, although the topographical distributions of these cell types differ to some extent. Insulin-secreting (B) cells, glucagon-secreting (A) cells, somatostatin-secreting (D) cells, and pancreatic polypeptide-secreting (PP or F) cells are distributed unequally among the four pancreatic lobes, with most of the A cells located in the third and splenic lobes and PP cells residing in both islet tissue and in acinar tissue. Glucagon appears to be a (the?) major pancreatic hormone involved in metabolic glucoregulation in birds. Yet the essentiality of insulin for this regulatory purpose also has been established. As a result, current thought is directed toward the molar ratio of insulin to glucagon (I/G) as a dominant force in homeostasis rather than toward either of the two hormones separately. Molar I/G ratios have been useful in mammals in studying the needs of the organism to produce glucose to meet a metabolic crisis/need and, when compared with that found in normal Aves, a value of 1.8-2.2 has been established. Such a molar ratio is indicative of a catabolic recovery of nutrients in mammals, suggesting that birds normally are in a catabolic mode (like diabetic, starving, or exercising mammals). Somatostatin (SRIF) is known to inhibit the release of all pancreatic hormones but has a greater inhibitory action on glucagon secretion than it does on any of the other peptides. (It has least effect on APP).(ABSTRACT TRUNCATED AT 250 WORDS)


Mattress for treatment couch.
A thin vinyl foam pad is described for use with radiation therapy treatment couches. This pad provides for adequate patient comfort while supplying a sufficiently firm support as to permit good patient immobilization.


Repair of abdominal aortic aneurysms: the benefits of offering both endovascular and open surgical techniques.
Two treatment options are available for abdominal aortic aneurysms (AAAs): open surgical technique with graft replacement and endovascular aortic aneurysm repair (EVAR) as a minimally invasive procedure. The intention of this review is to highlight the advantages of both procedures and to demonstrate that offering both procedures is beneficial for the patient when he or she makes the important decision regarding which treatment to select. A comparative evaluation of both treatment options is offered as well as a short description of the risk of rupture and its consequences. The authors discuss the latest literature as well as their own experiences. An innovative statistical approach-the propensity score-based Cox model-is presented to evaluate the 2 treatment options. The benefits of offering both EVAR and open surgery permit optimal management of AAA for the individual patient and tailor the treatment to his or her organ dysfunctions and impaired physical status. In addition, EVAR offers a treatment option for otherwise incurable high-risk patients.


Enhanced NO-dependent pulmonary vasodilation limits increased vasoconstrictor sensitivity in neonatal chronic hypoxia.
Augmented vasoconstrictor reactivity is thought to play an important role in the development of chronic hypoxia (CH)-induced neonatal pulmonary hypertension. However, whether this response to CH results from pulmonary endothelial dysfunction and reduced nitric oxide (NO)-mediated vasodilation is not well understood. We hypothesized that neonatal CH enhances basal tone and pulmonary vasoconstrictor sensitivity by limiting NO-dependent pulmonary vasodilation. To test this hypothesis, we assessed the effects of the NO synthase (NOS) inhibitor Nω-nitro-l-arginine (l-NNA) on baseline pulmonary vascular resistance (PVR) and vasoconstrictor sensitivity to the thromboxane mimetic U-46619 in saline-perfused lungs (in situ) from 2-wk-old control and CH (12-day exposure, 0.5 atm) Sprague-Dawley rats. Basal tone was defined as that reversed by exogenous NO (spermine NONOate). CH neonates displayed elevated right ventricular systolic pressure (in vivo) and right ventricular hypertrophy, indicative of pulmonary hypertension. Perfused lungs from CH rats demonstrated greater baseline PVR, basal tone, and U-46619-mediated vasoconstriction compared with control rats in the absence of l-NNA. l-NNA markedly increased baseline PVR and reactivity to U-46619 in lungs from CH neonates, further augmenting vasoconstrictor sensitivity compared with control lungs. Exposure to CH also enhanced NO-dependent vasodilation to arginine vasopressin, pulmonary expression of NOS III [endothelial NOS (eNOS)], and eNOS phosphorylation at activation residue Ser1177 However, CH did not alter lung nitrotyrosine levels, a posttranslational modification reflecting [Formula: see text] scavenging of NO. We conclude that, in contrast to our hypothesis, enhanced basal tone and agonist-induced vasoconstriction after neonatal CH is limited by increased NO-dependent pulmonary vasodilation resulting from greater eNOS expression and phosphorylation at activation residue Ser1177NEW & NOTEWORTHY This research is the first to demonstrate enhanced nitric oxide-dependent vasodilation that limits increased vasoconstrictor reactivity in neonatal pulmonary hypertension. These results suggest that augmented vasoconstriction in this setting reflects changes in smooth muscle reactivity rather than a reduction in nitric oxide-dependent pulmonary vasodilation.


Physical activity and coronary heart disease among asymptomatic hypercholesterolemic men (the Lipid Research Clinics Coronary Primary Prevention Trial).
We examined the relation between reported regular strenuous exercise or hard physical labor and the incidence of coronary heart disease (CHD) death and nonfatal myocardial infarction among 1,533 hypercholesterolemic men aged 35-59 years who were in the placebo group of the Lipid Research Clinics Coronary Primary Prevention Trial. The mean follow-up of the cohort was 7.4 years. The men were free of clinical heart disease at entry; men with an abnormal resting electrocardiogram or graded exercise test also were excluded. Regular physical activity was not associated with the incidence of CHD (RR = .94, 95% CI = .68, 1.38) in this study population. Adjustment by the proportional hazards model for age, low-density lipoprotein cholesterol, smoking, family history of CHD, and occupation did not alter this finding. This observation suggests that reported regular physical activity may not be related to the risk of coronary heart disease among asymptomatic, hypercholesterolemic, middle-aged men.


Using Social Media to Increase Accessibility to Online Teaching Resources.
The key learning points of Surgical Grand Rounds (SGR) are often not accessible at times of exam revision for students. We sought to use Twitter as an online teaching repository. A SGR Twitter profile was created. 23 SGR presentations were made accessible on Twitter over a 3 month period. 93 students were invited to complete a questionnaire assessing usage of the repository. 84 (90%) in total responded, of these, 25 (80.6%) felt that the online provision of SGR through twitter was "useful". The majority (71%) felt that the online content was easily accessible. The novel use of social media is a useful adjunctive educational tool in accessing an online repository of SGR presentations.