Plasma-derived FVIII/VWF complex shows higher protection against inhibitors than isolated FVIII after infusion in haemophilic patients: A translational study.
Presence of von Willebrand factor (VWF) in FVIII concentrates offers protection against neutralizing inhibitors in haemophilia A (HA). Whether this protection is more evident in plasma-derived (pd) FVIII/VWF or recombinant (r) FVIII concentrates remains controversial. We investigated the protection exerted by VWF against FVIII inhibitors in an in vivo mouse model of HA exposed to pdFVIII/VWF or to various rFVIII concentrates. Haemophilia A mice received the different FVIII concentrates after administration of vehicle or an inhibitory IgG purified from a commercial pool of HA plasma with inhibitors and FVIII:C recoveries were measured. Furthermore, using a novel clinically oriented ex vivo approach, Bethesda inhibitory activities (BU) of a commercial pool of HA plasma with inhibitors were assessed using normal plasma, or plasma from severe HA patients, without inhibitors, after treatment with the same concentrates. in vivo studies showed that pdFVIII/VWF offers markedly higher protection against inhibitors when compared with any of the FVIII products without VWF. More importantly, in the ex vivo studies, plasma from patients treated with pdFVIII/VWF showed higher protection against inhibitors (P values ranging .05-.001) in comparison with that observed in plasma from patients who received FVIII products without VWF, regardless of the type of product evaluated. Data indicate that FVIII+VWF complexes assembled in the circulation after rFVIII infusion are not equivalent to the naturally formed complex in pdFVIII/VWF. Therefore, rFVIII infused into HA patients with inhibitors would be less protected by VWF than the FVIII in pdFVIII/VWF concentrates.


Intramural ganglia in the human urethra.
The urethras from five patients with a thoracic or cervical spinal cord lesion and one patient with carcinoma of the bladder were studied immunohistochemically for neuropeptide Y and vasoactive intestinal polypeptide. Autonomic ganglia, containing two to 21 nerve cell bodies, were found in the smooth and striated muscle regions of the intrinsic external urethral sphincter; they were present rarely in the distal urethra and were absent from the prostatic urethra. Neuropeptide Y immunoreactivity was observed in some of the nerve cell bodies (diameter 25 to 50 microns). Vasoactive intestinal polypeptide immunoreactivity was observed in small cells (diameter 15 to 25 microns.) in the urethral smooth muscle and in the walls of blood vessels that resembled small intensely fluorescent cells but may be nerve cell bodies. Both neuropeptide Y- and vasoactive intestinal polypeptide-immunoreactive nerve fibres were found in the smooth muscle and around blood vessels in the urethra of all patients. Both types of peptide-containing nerves were found associated with striated muscle of the intrinsic external urethral sphincter in patients with spinal cord injury, but only vasoactive intestinal polypeptide-immunoreactive nerves were found in the patient with carcinoma of the bladder in this region. The functions of the autonomic ganglia and vasoactive intestinal polypeptide- and neuropeptide Y-immunoreactive nerves in the human urethra remain to be elucidated.


Accumulation, distribution and loss of cadmium in the marine prosobranch Littorina littorea (L.).
In the present investigation cadmium was studied in Littorina littorea exposed to two ambient concentrations and for various exposure times, as well as after a detoxification period of 74 days. The results are expressed as whole body and individual organ burdens of metal. Organ metal analyses, exposure time and external metal concentrations were correlated using tetradic diagrams to represent four different organ burdens. Linear accumulation appeared to occur in the whole soft body at the cadmium concentrations and times studied. There was also a general linear trend in the accumulation of cadmium in the various organs (gills, kidney, digestive gland/gonad complex and remaining tissue), but at certain exposure times the tissue concentration of cadmium differed from what was expected. Different cadmium distribution patterns were observed as a result of the relative intensity of the accumulation and elimination processes. Because of these inconsistent variables it is generally concluded that for bioindication purposes it is preferable to use the cadmium burdens of the whole soft body rather than those of individual organs. For physiological studies of cadmium, however, the pattern of metal distribution in the organs is necessary to describe the metabolic pathways through the organism.


Early-stage lung cancer associated with higher frequency of chest x-ray up to three years prior to diagnosis.
Symptom awareness campaigns have contributed to improved early detection of lung cancer. Previous research suggests that this may have been achieved partly by diagnosing lung cancer in those who were not experiencing symptoms of their cancer. This study aimed to explore the relationship between frequency of chest x-ray in the three years prior to diagnosis and stage at diagnosis. Lung cancer service in a UK teaching hospital. Patients diagnosed with lung cancer between 2010 and 2013 were identified. The number of chest x-rays for each patient in the three years prior to diagnosis was recorded. Statistical analysis of chest x-ray frequency comparing patients with early- and late-stage disease was performed. One-thousand seven-hundred fifty patients were included - 589 (33.7%) with stage I/II and 1,161 (66.3%) with stage III/IV disease. All patients had at least one chest x-ray in the six months prior to diagnosis. Those with early-stage disease had more chest x-rays in this period (1.32 vs 1.15 radiographs per patient, P = 0.009). In the period 36 months to six months prior to lung cancer diagnosis, this disparity was even greater (1.70 vs 0.92, radiographs per patient, P < 0.001). Increased rates of chest x-ray are likely to contribute to earlier detection. Given the known symptom lead time many patients diagnosed through chest x-ray may not have been experiencing symptoms caused by their cancer. The number of chest x-rays performed could reflect patient and/or clinician behaviours in response to symptoms.


Hydrocortisone-induced DNA endoreplication in human trabecular cells in vitro.
Primary monolayer cultures of trabecular cells and organ cultures of trabecular meshwork, obtained from normal eyes of human subjects (age range, 40 to 70 yr) were exposed to hydrocortisone at concentrations ranging from 10(-4) M to 10(-6) M for periods up to 4 weeks. Phase-contrast microscopy of cultured cells showed an increase in the size of the nuclei (up to three times) and in the extent of the cell cytoplasm compared to those in control cultures, and vesicular structures frequently accumulated in the cytoplasm. Microdensitometry of Feulgen-stained cell nuclei indicated that the cells of the trabecular meshwork in vivo have predominantly diploid levels (2C) of DNA. Many nuclei in the trabecular cell cultures were polyploid and contained DNA values of 4C, 8C, and 16C. Cultures which had been exposed to hydrocortisone showed a significant shift toward the higher DNA classes, in contrast to the untreated control cultures; the average increase in the amount of DNA per nucleus was 36%. We discuss the relevance of these findings to the disease glaucoma in man.


Sequential Associations Between Communication Acts of Children With and Without Autism Spectrum Disorder and Maternal Verbal Responses.
In this study, the sequential associations between child communication acts, including spontaneous communication (SC) and elicited communication (EC), and the types of verbal responses of Iranian mothers (follow-in nondirective, follow-in directive, and redirective responses) were compared between children with autism spectrum disorder (ASD) and young typically developing (TD) children. Participants were 29 children with ASD aged 3-6 years and 40 TD children aged 13-18 months, matched on expressive vocabulary. Using time-window sequential analysis, maternal verbal responses within a time interval of 3 sec following child communication were examined during 15 min of video-recorded mother-child free play interaction. Mothers in the two groups had broadly similar patterns of response to child communication acts, but some differences in responding to child EC. Across both groups, sequential associations were stronger for maternal follow-in nondirective responses to child SC than for this type of response to child EC, and were stronger for follow-in directive responses to child EC than for follow-in directive responses to child SC. Child EC and SC acts were less likely to be followed by redirective responses than other maternal responses, again across both groups. Finally, mothers of children with ASD were more likely than mothers of TD children to follow-in to child EC with both nondirective and directive responses. Our findings suggest that mothers of children with ASD synchronize their responses with their child's SC acts to the same extent as mothers of TD children, and are more synchronous in responding to their child's EC acts. LAY SUMMARY: This observational study examined how Iranian mothers verbally responded to their children's communication acts, based on whether the children's communication was spontaneous (unprompted) or elicited (prompted by the mother). Mothers of children with autism spectrum disorder or typical development responded to their children's spontaneous communication acts in similar ways, but showed some differences in responding to children's elicited communication. By prompting their children to communicate, mothers create opportunities to give additional verbal responses to their children, which may help to support children's further language development.


Field control of bovine parasitic otitis.
Nicotine used at approximately 2 ppm in 0.25% toxaphene dip wash was found to be 95% effective in the treatment and control of bovine parasitic otitis after dipping clinically affected cattle twice weekly for twelve weeks. Only three of 64 clinically affected animals failed to recover completely following the above treatment regime. The viable nematodes, Rhabditis bovis, which were easily isolated from dip tanks prior to treatment, could no longer be isolated 48 hours following dip tank treatment with nicotine. The above results are very significant since the control of bovine parasitic otitis would greatly enhance the productivity of cattle.


The novel family of transcendental Leal-functions with applications to science and engineering.
During the phenomena modelling process in the different areas of science and engineering is common to face nonlinear equations without exact solutions; thus, the need of employing numerical methods to obtain such solutions. Therefore, in order to provide new possibilities for the isolation of variables, we propose a novel family of transcendental functions with new algebraic properties including their integration and differentiation rules. Likewise, in order facilitate the numerical evaluation for every new family set of functions, a highly accurate series of approximations is proposed by employing analytical expressions in terms of known transcendental functions and polynomials combinations. By the use of known functions for the proposed approximations, makes possible the use of any programming language for their respective implementation. In this article, three interesting case studies are presented with applications on: coastal engineering, transmission lines span on electrical engineering, and the planar one-dimensional Bratu equation. Finally, based on the results from study cases, it can be concluded that Leal-functions will have relevant impact in all areas of physics and mathematics, by providing new tools to scientists and engineers for the proposal of new mathematical models and numerical/analytical analysis, design and implementation of new theories and technological innovations.


Incomplete recovery of gut microbiota in marine medaka (Oryzias melastigma) during the depuration phase, after exposure to sulfamethazine/nanoplastics.
The persistence of antibiotics and nanoplastics in aquatic environment poses a great threat to aquatic organisms. In our previous study, significant decreases of bacterial richness and changes of bacterial communities in the Oryzias melastigma gut after sulfamethazine (SMZ) and polystyrene nanoplastics (PS) exposure were observed. Here, the O. melastigma dietary exposed to SMZ (0.5 mg/g, LSMZ; 5 mg/g, HSMZ), PS (5 mg/g, PS) or PS + HSMZ were depurated for 21 days to assess the extent of which these effects were reversible. Our results revealed that most diversity indexes of bacterial microbiota in the O. melastigma gut from the treatment groups were insignificantly different from the control, suggesting a large recovery of bacterial richness. Although the sequence abundances of a few genera remained significantly changed, the proportion of dominant genus was recovered. Exposure to SMZ affected the complexity of the bacterial networks, and the cooperation and exchange events of positively associated bacteria were enhanced during this period. After depuration, increases in the complexity of networks and intense competitions among bacteria were observed, which was beneficial for the robustness of networks. However, the gut bacterial microbiota was less stable, and several functional pathways were dysregulated, relative to the control. In addition, higher occurrence of pathogenic bacteria was found in the PS + HSMZ group relative to the signal pollutant group after depuration, indicating a greater hazard for the mixture of PS and SMZ. Taken together, this study contributes to a better understanding of the recovery of bacterial microbiota in fish gut after individual and combined exposure to nanoplastics and antibiotics.


A comparison of systemic and local dexamethasone administration: From perilymph/cochlea concentration to cochlear distribution.
Different types of inner ear diseases can damage different cochlear subsites by different mechanisms. Steroids administered by different methods are commonly used for treating inner ear diseases. There is reason to believe that dexamethasone (Dex) may reach cochlear subsite targets via different pathways after administration by different methods: Intratympanic (IT), postaural (PA), and intraperitoneal (IP). The purpose of this study was to explore the cochlear concentration and distribution of Dex after administration by different methods. High-performance liquid chromatography-mass spectrometry and immunofluorescence technology were employed to measure and compare the Dex concentration in the perilymph and cochlear tissue and the cochlear distribution of Dex. IT administration resulted in higher Dex concentrations in the perilymph and cochlear tissues than those with the other administration methods. Intratympanic and postaural administration could result in higher Dex concentrations in the organ of Corti than systemic administration, but systemic administration could result in higher Dex concentrations in the stria vascularis than the other administration methods. A decreasing basal-apical gradient of Dex uptake was present in the cochlea after IT but not IP or PA administration. These results indicate that different administration methods result in different Dex distributions, which can be attributed to features of the cochlear vascular system and intracochlear diffusion. Our results provide clinicians with an experimental basis for the use of different steroid injection routes to optimize the effects on inner ear diseases with different target organs.


Molecular structure design of planar zwitterionic polymer electrode materials for all-organic symmetric batteries.
All-organic symmetric lithium-ion batteries (LIBs) show promising prospects in sustainable energy storage systems, due to their environmental friendliness, structural diversity and low cost. Nevertheless, it remains a great challenge to explore suitable electrode materials and achieve excellent battery performance for all-organic symmetric LIBs. Herein, a squaraine-anthraquinone polymer (PSQ) electrode material was designed through rational molecular engineering. The well-designed extended π-conjugated system, donor-acceptor structure, abundant redox-active sites and rational manipulation of weak inter-/intramolecular interactions endow the PSQ electrode with outstanding electrochemical performance. The capacity of the PSQ cathode can be optimized to 311.5 mA h g-1 by in situ carbon-template polymerization. Impressively, PSQ-based all-organic symmetric LIBs displayed high reversible capacity (170.8 mA h g-1 at 50 mA g-1), excellent rate performance (64.9% capacity retention at 4000 mA g-1 vs. 50 mA g-1), ultralong cycle life up to 30 000 cycles at 2000 mA g-1 and 97% capacity retention after 2500 cycles at 500 mA g-1, which is one of the best comprehensive battery performances among the all-organic LIBs reported thus far.


[Familial hemophagocytic lymphohistiocytosis (case report)].
This is the report of a female infant ten weeks of age, who was admitted to our hospital with hyperpyrexia, hemolytic anemia and disseminated intravascular coagulation. The further course of the disease was characterized by: continuing hemolysis resulting in severe normochromic, normocytic anemia, unrelenting disseminated intravascular coagulation, increasing hepato-splenomegaly with hyperbilirubinemia and ascites. No causative infectious organism could be identified. The infant died at the age of 14 weeks from respiratory insufficiency. Autopsy revealed massive hepato-splenomegaly, ascites and bilateral pneumonia. Histologic evaluation demonstrated lymphohistiocytic infiltrates of the periportal areas of the liver, the spleen and lymphnodes. Meninges were infiltered by macrophages with ingested erythrocytes. Differential diagnosis includes an infection with leptospira icterohemorrhagica (Weils disease) and erythrophagocytosis observed after various viral infections. Also histiocytosis X or malignant histiocytosis has to be taken into consideration. The most probable diagnosis in our patient is that of familiar hemophagocytic reticulosis although the familiarity in our patient was lacking. Intra vitam diagnosis can only be established by liver biopsy which could not be performed in our patient due to the severe coagulation disturbance.


Multiple endocrine adenomatosis type IIb. Diagnosis and treatment.
A 29-year-old man with a marfanoid habitus, peculiar mucosal neuromas of the lips and tongue, high arched palate, hyperplastic corneal nerves, and hypertension was found at operation to have medullary carcinoma of the thyroid, parathyroid hyperplasia, and pheochromocytoma. These symptoms and findings are characteristic of multiple endocrine adenomatosis (MEA IIb) syndromes.


Heat shock induction of HSP 89 is regulated in cellular aging.
Induction of heat shock proteins (HSPs) was evaluated as a function of age of the IMR-90 human diploid fibroblasts. Heat shock (42 degrees C) markedly increased the synthesis of proteins with apparent molecular weights of 98, 89, 72, 50, 42 and 25 KDa, with HSP 89 and 72 being most prominent. This heat shock induction of HSPs was inversely correlated to the population doubling level (PDL) of the cell cultures used. For example, the synthesis rate of HSP 89 increased from a basal heat shock of young cells (PDL 18); in the old cells (PDL 51), the increase was from 1% to a maximum of 4% at 10-12 hrs after initiation of the heat shock. Western blot analysis showed that HSP 89 constituted approximately 2 and 10% of total cellular proteins in control and heat shocked (42 degrees C, 12-24 hrs) young cells; corresponding values for the old cells were 2 and 4.5%, respectively. Northern blot quantitation of the amount of mRNA hybridizable to cDNA probes of HSP 89 provided evidence that this age-dependent decrease in induction of HSP 89 in IMR-90 cells was attributable to a transcriptional/pre-translational mechanism.


Prospective Study of Vessel Density by Optical Coherence Tomography Angiography After Intravitreal Bevacizumab in Exudative Age-Related Macular Degeneration.
The aim of this study was to evaluate retinal and choriocapillaris (CC) vessel density, using optical coherence tomography angiography (OCTA), in the macular region at baseline and after three once-monthly intravitreal injections of bevacizumab (loading phase) in patients affected by exudative age-related macular degeneration (AMD). A total 38 eyes of 38 patients with exudative AMD (16 women, 22 men; mean age 72.47 ± 7.46 years) were included in this study. We evaluated vessel density in different macular areas (whole image, fovea and parafovea) of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and CC. In addition, central macular thickness (CMT) and choroidal thickness in the foveal region and 500 µm in the nasal and temporal directions were analyzed by enhanced depth image-OCT. There were no significant differences in vessel density in the SCP, DCP and CC after the loading phase compared to baseline (p > 0.05). In contrast, CMT (p = 0.039; 320.63 ± 175.05 vs. 372.47 ± 167.05 µm) and subfoveal choroidal thickness (SFCT) (p < 0.001; 189.21 ± 37.66 µm vs 170.37 ± 37.96 µm) significantly decreased after the loading phase compared to baseline. No significant correlations were found between SFCT and CC vessel density in the fovea, and between CMT and SCP and DCP (p > 0.05) at baseline and after the loading phase. Also, best corrected visual acuity did not correlate with CMT, SCP and DCP at baseline and after treatment (p > 0.05). Macular and choroidal thickness did not correlate with vessel density, but probably correlated to vascular exudation. The anti-VEGF treatment, acting on vascular hyperpermeability, determines the reduction of the retinal and choroidal exudation, resulting in a decrease of their thicknesses. Consequently, these parameters could reflect the effectiveness of the anti-VEGF injections for treating exudative AMD respect to OCTA parameters. ClinicalTrials.gov indentifier, NTC04138420.


The utility of an autologous blood salvage system in emergency thoracotomy for a hemothorax after chest trauma.
In Japan, little is known about using the Cell Saver in treating blunt or penetrating chest trauma. We therefore report the utility of this autologous blood salvage device. Two patients underwent emergency thoracotomies with the Cell Saver to treat massive hemothorax and made full recoveries. The first was a 29-year-old man who suffered a stab injury to his chest; 5000 ml blood was collected from the thorax, of which about 3000 ml was reinfused. The second was a 51-year-old man involved in a car crash; 1600 ml blood was collected from the thorax, of which about 500 ml was reinfused. When no banked blood is available for an emergency thoracotomy, the Cell Saver is an extremely useful machine. This device is also effective in treating progressive hemorrhagic shock and helpful when the rate of blood loss exceeds the supply available from the blood bank.


Adaptation of intestinal morphology in the temperature-acclimated carp, Cyprinus carpio L.
The effects of temperature and photoperiod acclimation upon the morphology of carp intestinal mucosa have been studied using morphometric techniques. Carp intestine showed an absence of anatomical regionalisation. There was a gradual reduction in the dimensions of villi along the tract. The decrease in the dimensions of the villi was greatest in the anterior half. Temperature acclimation had no effect on intestinal-somatic indices. Acclimation to 10 degrees C or 30 degrees C resulted in large differences in the dimensions of villi. Cold acclimation produced significant increases in mean villus height and breadth along the entire intestine. These villus shape changes resulted in a 58% increase in total mucosal surface area and a 102% increase in total volume of villi in cold-acclimated fish relative to warm-acclimated fish. Surface area of the unmodified intestinal tube increased with cold acclimation by 28%. The total number of villi remained unchanged by thermal acclimation. Because normalisation to a nominal surface area does not take account of the possibility of differentially developed mucosal surfaces in differently acclimated animals, experiments comparing transepithelial transport rates of differently-acclimated fish, using unstripped preparations, overestimates the differences in area-specific transport capacity.


Temporal changes in attention to sad and happy faces distinguish currently and remitted depressed individuals from never depressed individuals.
Depression is associated with attentional biases for emotional information that are proposed to reflect stable vulnerability factors for the development and recurrence of depression. A key question for researchers is whether those who have recovered from depression also exhibit attentional biases, and if so, how similar these biases are to those who are currently depressed. To address this question, the present study examined attention to emotional faces in remitted depressed (N=26), currently depressed (N=16), and never depressed (N=33) individuals. Participants viewed sets of four face images (happy, sad, threatening, and neutral) while their eye movements were tracked throughout an 8-s presentation. Like currently depressed participants, remitted depressed participants attended to sad faces significantly more than never depressed participants and attended to happy faces significantly less. Analyzing temporal changes in attention revealed that currently and remitted depressed participants did not reduce their attention to sad faces over the 8-s presentation, unlike never depressed participants. In contrast, remitted depressed participants attended to happy faces similarly to never depressed participants, increasing their attention to happy faces over the 8-s presentation. The implications for cognitive theories of depression and depression vulnerability are discussed.


Impulse-control disorders in alcoholics are related to sensation seeking and not to impulsivity.
Impulse-control disorders (ICD) include intermittent explosive disorder, kleptomania, trichotillomania, pyromania and pathological gambling. Several studies have suggested that the incidence of pathological gambling and impulsive violent behavior is substantially higher in alcohol-dependent patients than in the general population. The association between ICD and alcoholism, as well as personality characteristics such as sensation seeking and impulsivity, has never been systematically studied. The present study compared the levels of impulsivity and sensation seeking in age- and sex-matched groups of alcohol-dependent patients with concomitant ICD (ICD+, n = 30), alcohol-dependent patients without ICD (ICD-; n = 30) and control subjects (n = 30). All the alcohol-dependent patients (ICD+ and ICD-) were hospitalized for alcohol detoxification. Diagnoses of ICD were based on DSM-IV criteria and the Minnesota Impulsive Disorders Interview. All patients completed the Zuckerman Sensation-Seeking Scale (SSS) and the Barratt Impulsiveness Rating Scale (BIS). Mean scores on the SSS general factor, the SSS disinhibition subscale, and the SSS experience-seeking scale were significantly higher in ICD+ patients than in either ICD- patients or control subjects. By contrast, total scores and subscale scores on the BIS showed no significant differences among the three groups. Thus, it appears that measures of sensation seeking, rather than impulsivity, are relevant in distinguishing between alcohol-dependent patients with and without concomitant impulse control disorders.


Characterization of a novel cell line from pleomorphic adenoma of the parotid gland with myoepithelial phenotype and producing interleukin-6 as an autocrine growth factor.
A cell line was obtained from a primary culture of a pleomorphic adenoma of the parotid gland in a 24-year-old woman. The cells of the line (PA 16/23) grew spontaneously in minimal culture conditions and showed stable morphologic characteristics over 30 passages. PA 16/23 cells had immunophenotypic and ultrastructural features similar to those of transformed myoepithelial cells, which are regarded as the precursors of pleomorphic adenomas. Furthermore, these cells have been demonstrated immunocytochemically to contain interleukin-6 (IL-6) on light and electron microscopic examination. IL-6 also has been found by enzyme-linked immunosorbent assay in the culture supernatant and has been proven to be capable of stimulating growth of the PA 16/23 cells.


Training can modify back muscle response to sudden trunk loading.
Sudden, unexpected loading to the trunk has been reported in the literature as a potential cause of low-back disorders. This study's aim was to investigate the effect of "readiness training" on the response to sudden back loading among untrained healthy individuals. The study included 19 participants and 19 matched controls. All were employees at the National Institute of Occupational Health. The participants received ten 45-min training sessions during a 4-week period. The training focused on reactions to a variety of expected and unexpected sudden trunk loadings, including balance and coordination exercises. Before and after the training, all subjects were tested for reaction to sudden trunk loading (SL). This entailed applying a horizontal force of 58 N to the subject's upper back. Elapsed time--measured between SL and stopping--decreased significantly in the training group (from 337 to 311 ms) compared with the control group. The improved stopping time was associated with a changed EMG signal, characterized by an increase in the early parts of the response (up to 225 ms) and a subsequent decrease. EMG onset latency was unaffected by training. This study is apparently one of the first to demonstrate that the response to sudden trunk loading can be improved in healthy subjects without an increase in pre-activation and associated trunk stiffness. In perspective, the results indicate a possibility for a training-induced reduction of the risk of low-back injuries, e.g., in nurses exposed to sudden trunk perturbations during patient handling.


The relationship between the effect of biphenylcarboxylic acid analogs on glyceride synthesis and conformation.
The inhibition of biphenylcarboxylic acid analogs on glyceride synthesis was studied in association with conformation of the chemicals. Chemicals used were benzoic acid substituted with phenyl, benzoyl and phenoxy groups, phenylphenyloxyacetic acid and p-phenylacetic acid. Twist angles were calculated by a molecular orbital method. Following oral administration of p-phenylbenzoic acid to the rats for 7 days, the decrease of the triglyceride synthesized from [14C]oleic acid was observed in the adipose tissue. The in vitro inhibitions on the formation of fatty acyl-CoA thioester were examined from the influence on the hippuric acid formation from [14C]benzoic acid using the rat liver slices. In the homologous series, high inhibition was observed in para and meta substituents. None, or low inhibitions of ortho-substituted chemicals were related to the steric hindrance of the phenyl ring against carboxyl groups. This hinderance was associated with conformation and with the geometrical relationship between substituted phenyl rings and carbon atoms of carboxylic acid. In the in vitro inhibition on overall formation of diglyceride and triglyceride from [14C]glycerol, o-phenylbenzoic acid showing no inhibition on hippuric acid formation did not show inhibition. However, other ortho-substituted chemicals showed higher inhibition in comparison with the inhibition on hippuric acid formation. The inhibition of para- and meta-substituted chemicals were higher than the corresponding values of ortho substituted compounds.


18F-Fludeoxyglucose PET/Computed Tomography for Assessing Tumor Response to Immunotherapy and Detecting Immune-Related Side Effects: A Checklist for the PET Reader.
After a short summary of the biological basis of the immune checkpoint inhibitors used for the treatment of nonhematologic solid tumors, the issues of pseudoprogression, hyperprogression, and immune-related side effects are discussed as well as their implications for patient management. Recommendations are provided for performing 18F-Fludeoxyglucose PET scanning, assessing tumor response, and reporting immune-related side effects, with representative clinical cases.


Raman spectroscopy, thermal and optical properties of TeO2-ZnO-Nb2O5-Nd2O3 glasses.
The glasses with composition 75TeO2-10ZnO-(15-x)Nb2O5-xNd2O3 (0≤x≤9 mol%) were prepared using melt quenching method and their physical properties such as density (ρ), molar volume (VM), average crosslink density (nc¯), oxygen packing density (OPD) and number of bonds per unit volume (nb) were determined. Raman spectroscopic studies showed that the glass network consists of TeO4, TeO3+1, TeO3 and NbO6 units as basic structural units. The glass transition temperature (Tg), crystallization onset (To) and thermal stability (ΔT) were determined from DSC thermograms. The Raman and DSC results were found to be correlated with the physical properties. In the optical absorption spectra six absorption bands were observed with different relative intensities at around 464, 522, 576, 742, 801 and 871 nm which are assigned to the transition of electrons from (ground state) 4I9/2→G11/2; 4I9/2→2K3/2, 2G7/2; 4I9/2→4G5/2, 4G7/2; 4I9/2→4S3/2; 4F7/2→2H9/2, 4F5/2 and 4I9/2→2F3/2 respectively. From optical absorption data the energy band gap (Eopt) and Urbach energy (ΔE) were calculated.


Screening the Schistosoma mansoni transcriptome for genes differentially expressed in the schistosomulum stage in search for vaccine candidates.
Schistosomiasis affects more than 200 million people worldwide; another 600 million are at risk of infection. The schistosomulum stage is believed to be the target of protective immunity in the attenuated cercaria vaccine model. In an attempt to identify genes up-regulated in the schistosomulum stage in relation to cercaria, we explored the Schistosoma mansoni transcriptome by looking at the relative frequency of reads in EST libraries from both stages. The 400 genes potentially up-regulated in schistosomula were analyzed as to their Gene Ontology categorization, and we have focused on those encoding-predicted proteins with no similarity to proteins of other organisms, assuming they could be parasite-specific proteins important for survival in the host. Up-regulation in schistosomulum relative to cercaria was validated with real-time reverse transcription polymerase chain reaction (RT-PCR) for five out of nine selected genes (56%). We tested their protective potential in mice through immunization with DNA vaccines followed by a parasite challenge. Worm burden reductions of 16-17% were observed for one of them, indicating its protective potential. Our results demonstrate the value and caveats of using stage-associated frequency of ESTs as an indication of differential expression coupled to DNA vaccine screening in the identification of novel proteins to be further investigated as potential vaccine candidates.


Preparation of ordered mesoporous carbons with an intergrown p6mm and cubic Fd3m pore structure using a copolymer as a template.
Ordered mesoporous carbons (OMCs) with an intergrown two-dimensional p6mm and three-dimensional Fd3m pore structure have been prepared by the carbonization of reverse copolymer-phenolic resin composites, which were themselves formed by a soft-template method by simply adjusting the ratios of ethanol and hexane. The microstructure of the OMCs was analyzed by small-angle X-ray scattering, nitrogen adsorption isotherms, and transmission electron microscopy. The results showed the structure of the OMCs obtained have the mesophase transition from p6mm to the intergrowth of p6mm/Fd3m and finally to Fd3m as the ratio of ethanol to hexane is changed.


Combined effect of temperature and nutritional regime on the elimination of the lipophilic toxin okadaic acid in the naturally contaminated wedge shell Donax trunculus.
The influence of nutritional regime and water temperature on depuration rates of OA-group toxins in the wedge shell Donax trunculus was examined by exposing naturally contaminated specimens to three nutritional regimes (microalgae, commercial paste of microalgae, and starvation) for 14 days at 16 °C and 20 °C. Total OA was quantified in the whole soft tissues of the individuals collected in days 2, 4, 6, 8, 10, 12 and 14. Mortality, dry weight, condition index, gross biochemical composition and gametogenic stages were surveyed. Low variation of glycogen and carbohydrates during the experiments suggest that wedge shells were under non-dramatic stress conditions. Wedge shells fed with non-toxic diets showed similar depuration rates being 15 and 38% higher than in starvation, at 16 and 20 °C, respectively. Depuration rates under non-toxic diets at 20 °C were 71% higher than at 16 °C. These results highlight the influence of water temperature on the depuration rate of total OA accumulated by D. trunculus, even when the increase is of only 4 °C, as commonly observed in week time scales in the southern Portuguese coastal waters. These results open the possibility of a faster release of OA in harvested wedge shells translocated to depuration systems when under a slight increase of water temperature.


Mutual metabolic suppression between benzene and toluene in man.
The exposure intensity during a shift and the metabolite levels in the shift-end urine were examined in male workers exposed to either benzene (65 subjects; the benzene group), toluene (35 subjects; the toluene group), or a mixture of both (55 subjects; the mixture group). In addition, 35 non-exposed male workers (the control group) were similarly examined for urinary metabolites to define background levels. A linear relationship was established between the intensity of solvent exposure and the corresponding urinary metabolite levels (i.e. phenol, catechol and quinol from benzene, and hippuric acid and o-cresol from toluene) in each case when one of the three exposed groups was combined with the control group for calculation. Comparison of regression lines in combination with regression analysis disclosed that urinary levels of phenol and quinol (but not catechol) were lower in the mixture group than in the benzene group when the intensities of exposure to benzene were comparable, indicating that the biotransformation of benzene to phenolic compounds (excluding catechol) in man is suppressed by co-exposure to toluene. Conversely, metabolism of toluene to hippuric acid was suppressed by benzene co-exposure. Conversion of toluene to o-cresol was also reduced by benzene, but to a lesser extent. The significance of the present findings on the mutual suppression of metabolism between benzene and toluene is discussed in relation to solvent toxicology and biological monitoring of exposure to the solvents.


Sensitivity and specificity of standardised allergen extracts in skin prick test for diagnoses of IgE-mediated respiratory allergies.
Skin prick tests (SPTs) are essential for the diagnosis of IgE-mediated allergy and are influenced by extract quality, biological potency and concentration of allergen. In this open multicentre study 431 patients, aged 18-64 years were enrolled. Patients had a history of IgE-mediated allergy and a sensitisation (previous positive SPT of any manufacturer) against at least one of the investigated allergens: 6-grass pollen, house dust mite, birch and mugwort pollen. In our study, these allergens were tested in five concentrations each. To establish the optimal trade-off between sensitivity and specificity, the area under the receiver operating characteristic (ROC) curve was estimated by comparing the outcome of the SPT with three methods referred to as 'reference methods' (specific IgE, clinical case history and a previous SPT). For all allergens and reference methods, the area under the ROC curves were highly significant (p < 0.001). Specific IgE reference method resulted in the largest area under the curve (AUC) for all allergens (0.80-0.90) followed by previous SPT (0.70-0.87) and case history (0.65-0.74). Sensitivity of SPT increased with increasing concentration and specificity decreased. For all allergens, compared to specific IgE, the highest sensitivity (specificity at least 80%) was observed for the SPT solution of 50,000 Standardised Units (SU)/mL (grass pollen, birch pollen, house dust mite and mugwort). In this study, with a large number of patients, it was demonstrated that clinical case history, previous SPT and specific IgE measurement could all be used as reference methods for the assessment of sensitivity/specificity of SPT solutions. The comparison of SPT with specific IgE resulted in the largest AUC. The highest sensitivity was observed for the SPT solution of 50,000 SU/mL.Trial registration EudraCT: 2006-005304-14.


Electrochemical Reduction of CO2 to CO over Transition Metal/N-Doped Carbon Catalysts: The Active Sites and Reaction Mechanism.
Electrochemical CO2 reduction to value-added chemicals/fuels provides a promising way to mitigate CO2 emission and alleviate energy shortage. CO2 -to-CO conversion involves only two-electron/proton transfer and thus is kinetically fast. Among the various developed CO2 -to-CO reduction electrocatalysts, transition metal/N-doped carbon (M-N-C) catalysts are attractive due to their low cost and high activity. In this work, recent progress on the development of M-N-C catalysts for electrochemical CO2 -to-CO conversion is reviewed in detail. The regulation of the active sites in M-N-C catalysts and their related adjustable electrocatalytic CO2 reduction performance is discussed. A visual performance comparison of M-N-C catalysts for CO2 reduction reaction (CO2 RR) reported over the recent years is given, which suggests that Ni and Fe-N-C catalysts are the most promising candidates for large-scale reduction of CO2 to produce CO. Finally, outlooks and challenges are proposed for future research of CO2 -to-CO conversion.


Spatiotemporal control of root immune responses during microbial colonization.
The entire evolutionary trajectory of plants towards large and complex multi-cellular organisms has been accompanied by incessant interactions with omnipresent unicellular microbes. This led to the evolution of highly complex microbial communities, whose members display the entire spectrum of pathogenic to mutualistic behaviors. Plant roots are dynamic, fractally growing organs and even small Arabidopsis roots harbor millions of individual microbes of diverse taxa. It is evident that microbes at different positions on a root surface could experience fundamentally different environments, which, moreover, rapidly change over time. Differences in spatial scales between microbes and roots compares to humans and the cities they inhabit. Such considerations make it evident that mechanisms of root-microbe interactions can only be understood if analyzed at relevant spatial and temporal scales. This review attempts to provide an overview of the rapid recent progress that has been made in mapping and manipulating plant damage and immune responses at cellular resolution, as well as in visualizing bacterial communities and their transcriptional activities. We further discuss the impact that such approaches will have for a more predictive understanding of root-microbe interactions.


Portion size and meal consumption in domesticated dogs: An experimental study.
Increases in food portion sizes have been identified as a possible contributor to the increased prevalence of obesity in humans. However, little is known about the origin of behavioural tendencies to overeat from larger portion sizes or whether other non-human animals are affected by meal portion size. In the present experimental study, we examined the effect that larger portion sizes have on meal consumption among domesticated dogs (N = 32). Dogs were fed three meals that varied in size on different occasions (150%, 200% and 300% of usual portion size). A repeated measures design was used and food consumption was measured for each meal. Portion size positively affected food consumption, with dogs eating significantly more food as the portion size of meal increased. The effect of portion size on food consumption was also observed when the dogs that finished all available food were excluded from analyses, however not among dogs who did not finish any of the meals. We conclude that the influence larger portions have on food consumption observed in humans is also observed in domesticated dogs. However, it is unclear whether portion size directly biases the amount of food dogs choose to consume, as has been suggested in humans. Further research is now warranted to examine commonalities between human and non-human animal eating behaviour to understand shared behavioural tendencies and their origins.


Therapeutic efficacy of transarterial chemo-embolization with a fine-powder formulation of cisplatin for hepatocellular carcinoma.
To evaluate the efficacy of transarterial chemoembolization (TACE) using a suspension of a fine-powder formulation of cisplatin (DDPH) in lipiodol (LPD) in the treatment of hepatocellular carcinoma (HCC). The subjects were 262 HCC patients treated with TACE using a DDPH-LPD suspension. The DDPH-LPD suspension was prepared by mixing 50 mg of DDPH into 10 mL of LPD. TACE was repeated when treated lesions relapsed and/or new hepatic lesions were detected. These patients received additional TACE using the same agent. TACE was repeated until complete regression of the tumor was obtained. The primary efficacy endpoint of the current study was the objective early response rate. Secondary efficacy endpoints were progression-free survival (PFS) and overall survival. The objective early response rate was 43.6%. Cumulative PFS rates were 56.7% at 6 mo, 23.1% at 12 mo, 13.4% at 18 mo, and 10.5% at 24 mo. The median PFS was 6.6 mo. Cumulative survival rates were 90.6% at 6 mo, 81.9% at 12 mo, 70.5% at 24 mo, and 58.8% at 36 mo. Median survival time was 46.6 mo. All adverse reactions were controllable by temporary suspension of treatment. No serious complications or treatment-related deaths were observed. TACE using a suspension of DDPH in LPD may be a useful treatment for HCC.


Topographic representation of the sensory and motor roots of the vagus nerve in the medulla of goldfish, Carassius auratus.
The coelomic root of the vagus nerve in goldfish is connected with sensory and motor nuclei of the medulla that are distinct from those serving the orobranchial roots of the same nerve. The primary sensory nucleus for coelomic sensation is itself divisible into medial and lateral subnuclei on the basis of afferent input and immunocytochemistry. The lateral subnucleus receives sensory input from the specialized chewing organ in the posterior pharynx and is poor in both substance P-like and tyrosine-hydroxylase-like immunoreactivities. The medial subnucleus receives input from the subdiaphragmatic gastrointestinal tract and is rich in substance P-like and tyrosine-hydroxylase-like immunoreactivities. The primary sensory fibers that innervate the gastrointestinal tract also project directly to the area postrema and to the vicinity of subdiaphragmatic visceral motor neurons. The vagal motor neuronal pool is divisible into three columns: paramedian (cardiac), medial, and lateral. The paramedian group innervates the heart and is situated in a loosely aggregated column at the boundary zone between the ventricular ependyma and the underlying brainstem. The medial vagal motor neurons innervate the subdiaphragmatic viscera, while the lateral column motor neurons innervate the posterior pharynx and muscles of the chewing organ. The motor neurons in this motor column are arranged in a topographic rostrocaudal order within the motor column according to the muscle of innervation. Thus both the general visceral sensory and general visceral motor nuclei of the medulla are organized into functional domains. Furthermore, in the goldfish, the special visceral (gustatory) and general visceral sensory nuclei form a continuous series in the medulla with the external and oral systems represented anteriorly and the pharyngeal and digestive systems represented posteriorly.


New-onset diabetes after transplantation.
New-onset diabetes after transplantation (NODAT) is associated with significant morbidity and mortality. Given the availability of simple diagnostic methods and the known benefits of strict glycemic control, patients should be screened frequently after organ transplantation. The management of NODAT is multifaceted and aimed at both treatment and prevention of complications. Evaluation of patient risk for post-transplant diabetes mellitus and its complications is an important consideration in initial selection and subsequent modification of the immunosuppressive regimen.


Differences in clinical reasoning between female and male medical students.
In undergraduate medical education virtual patients (VPs) are a suitable method to teach clinical reasoning and support the visualization of this thinking process in a safe environment. The aim of our study was to investigate differences in the clinical reasoning process and diagnostic accuracy of female and male medical students. During the summer term 2020, we provided access to 15 VPs for undergraduate students enrolled in a medical school in Bavaria, Germany. All interactions of the 179 learners within the VP system CASUS were recorded, exported, and analyzed. We found significant differences in the clinical reasoning of female and male learners. Female students documented more findings, differential diagnoses, tests, and treatment options and more often created a summary statement about the VP. Their overall performance was higher than those of their male peers, but we did not see any significant differences in diagnostic accuracy. The significant differences between male and female medical students should be considered when planning teaching and research activities. A future study should investigate whether these differences can also be found in physicians.


Three-dimensional geometry analysis of the stomach in type II diabetic GK rats.
The stomach is affected in more than half of all diabetic patients. The present study aims to investigate 3D geometry, 3D tension distribution and the elasticity in the stomach and its non-glandular and glandular regions in five non-diabetic and five Goto-Kakizaki (GK) rats (type 2 diabetic model). The stomachs were distended in vitro using a pressure range from 0 to 8 cm H2O. Gastric compliance curves, the surface principal radii of curvature, the surface tension, and circumferential and longitudinal deformation-pressure curves were calculated based on 3D non-diabetic and the diabetic stomach models. Diabetes lowered the gastric compliance in the non-glandular stomach and the whole stomach (P<0.02). The radii of curvature and tension distribution were non-homogeneous in both the diabetic and the non-diabetic stomach due to the complex geometry. Furthermore, diabetes increased the circumferential stiffness in the non-glandular part (P<0.001). The diabetic stomach exhibited lower material compliance not only in the proximal stomach but also in the entire stomach. The biomechanical properties differed between regions and in different directions in both the non-diabetic and the diabetic stomach. The changes due to diabetes may contribute to the delayed gastric emptying and the symptoms in diabetic patients.


Level of ETB receptor mRNA is down-regulated by endothelins through decreasing the intracellular stability of mRNA molecules.
Using ROS17/2 rat osteosarcoma cells as a model system, we examined the possibility that endothelin (ET)-induced down-regulation of ETB receptor was accompanied by a decrease in levels of ETB receptor mRNA. Northern blot analysis showed that low doses of ET-1 and ET-3 caused a transient decrease in ETB receptor mRNA in the cells. The maximum decrease in the levels of ETB receptor mRNA (80%) occurred after 2-4 h of exposure of the cells to ETs and was followed by a gradual recovery to control levels by 24 h. The effects were dose-dependent (EC50-1 nM), and ET-1 and ET-3 were almost equipotent in eliciting the response. The addition of either ionomycin, a Ca2+ ionophore, or phorbol dibutyrate, a protein kinase C activator, mimicked the effect of ETs. These results suggested that ETs-induced down-regulation of ETB receptor mRNA was mediated by the activation of ETB receptor and that it may have involved ETB receptor coupled second messenger pathways. We also showed that ETB receptor mRNA had a long intracellular life span which suggested that ETs-induced down-regulation of ETB receptor mRNA may have been due to a decrease in the stability of mRNA, rather than inactivation of the transcription of mRNA.


Development of an evidence-informed leisure time physical activity resource for adults with spinal cord injury: the SCI Get Fit Toolkit.
To systematically develop an evidence-informed leisure time physical activity (LTPA) resource for adults with spinal cord injury (SCI). Canada. The Appraisal of Guidelines, Research and Evaluation (AGREE) II protocol was used to develop a toolkit to teach and encourage adults with SCI how to make smart and informed choices about being physically active. A multidisciplinary expert panel appraised the evidence and generated specific recommendations for the content of the toolkit. Pilot testing was conducted to refine the toolkit's presentation. Recommendations emanating from the consultation process were that the toolkit be a brief, evidence-based resource that contains images of adults with tetraplegia and paraplegia, and links to more detailed online information. The content of the toolkit should include the physical activity guidelines (PAGs) for adults with SCI, activities tailored to manual and power chair users, the benefits of LTPA, and strategies to overcome common LTPA barriers for adults with SCI. The inclusion of action plans and safety tips was also recommended. These recommendations have resulted in the development of an evidence-informed LTPA resource to assist adults with SCI in meeting the PAGs. This toolkit will have important implications for consumers, health care professionals and policy makers for encouraging LTPA in the SCI community.


Oral exposure to Microcystis increases activity-augmented antioxidant enzymes in the liver of loach (Misgurnus mizolepis) and has no effect on lipid peroxidation.
Recently, eutrophication has induced severe cyanobacterial blooms in the Naktong River, the second largest river of Korea. In the present study, lipid peroxidation and the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, were evaluated in the liver of loach (Misgurnus mizolepis) that were orally exposed to a low dose of Microcystis through dietary supplementation with bloom scum. Loach received 75 mg of dry cells/kg body weight mass (equal to 10 microg microcystin-RR/kg body mass), for 28 days under controlled conditions. Antioxidant enzymatic activity and lipid peroxidation were measured after termination of exposure. The activities of antioxidant enzyme were significantly increased in the livers of toxin-exposed loach after 28 days of exposure, as compared to control fish. However, lipid peroxidation remained stable in both groups. These results suggest that antioxidant enzymes were able to eliminate oxidative stress induced by low concentrations of microcystins and to prevent increased lipid peroxidation in the liver of loach.


Decision-making impairments under ambiguous and risky situations in patients with prefrontal tumor: A neuropsychological study.
The neural mechanism underlying decision-making, which is an important component of executive function, is complex and not fully understood. Few studies have directly investigated the two types of decision-making functions - under ambiguity and under risk - in patients with brain tumors in different brain regions. Participants were classified into the ventral prefrontal cortex tumor group (VPFC, n = 27), the dorsolateral prefrontal cortex tumor group (DLPFC, n = 29), and matched healthy controls (HCs, n = 32). All participants were given a battery of neuropsychological tests, and they then performed the Iowa Gambling Task (IGT) and the Game of Dice Task (GDT) to assess their decision-making under ambiguity and under risk, respectively. The two patient groups performed significantly worse on attention, memory, information processing, and executive function. Additionally, patients in the DLPFC group performed significantly worse on the memory and information processing tests compared with the VPFC and HC groups. This study found that the decision-making functions of participants in the VPFC and DLPFC tumor groups were impaired to varying degrees. Among them, there was decision-making impairment under ambiguity and under risk in the VPFC group, and there was decision-making impairment under risk in the DLPFC group.


Possible role of laccase from Fusarium incarnatum UC-14 in bioremediation of Bisphenol A using reverse micelles system.
Bisphenol A [2,2 bis (4 hydroxyphenyl) propane] is widely used in the variety of industrial and residential applications such as the synthesis of polymers including polycarbonates, epoxy resins, phenol resins, polyesters and polyacrylates. BPA has been recognized as an Endocrine Disrupting Chemicals (EDC), thus it is necessary to assess its biodegradability or fate in the natural environment. In general, environmental pollutant such as BPA does not dissolve in aqueous media, owing to their high hydrophobicity, and hence non-aqueous catalysis can be employed to enhance biodegradability of phenolic environmental pollutant. Purified laccase hosted in reverse micelles using ternary system of isooctane: AOT [Bis (2-ethylhexyl) sulphosuccinate sodium salt)]:water having hydration ratio (Wo) of 30 with protein concentration of 43.5 μg/ml was found to eliminate 91.43% of 200 ppm of Bisphenol A at 50 °C, pH-6.0 when incubated with laccase/Reverse Micelles system for 75 min. GC-MS analysis of isooctane soluble fractions detected the presence of 4,4'-(2 hydroxy propane 1,2 diyl) diphenol, bis (4-hydroxylphenyl) butenal and 2-(1-(4-hydroxyphenyl) vinyl) pent-2-enal indicated degradation of BPA by two oxidation steps and one ring opening step (C-C bond cleavage). Laccase/RM system exhibited several advantages for the oxidative degradation of hydrophobic phenols mainly because of the solubility of either enzyme or substrate was improved in organic media and the stable activity of laccase in organic media was achieved.


Acute sixth nerve palsy in a young man, beware of the 'red herring'.
Cranial nerve palsies has several etiologies including vascular insufficiency, neoplasm, trauma and inflammation. Isolated sixth nerve palsy is an extremely rare presenting feature of leukemia. We describe an unusual ocular presentation of a bilateral progressive sixth nerve palsy in a young male with a preceding head injury. Acquired sixth nerve palsies in young adults may be due to trauma but in the absence of a definitive history other systemic processes must be outruled. We describe a case of bilateral sixth nerve palsy in a patient with ALL with no obvious CNS involvement. Potential etiological mechanisms are discussed.


The conversion of glyceraldehyde-3-phosphate dehydrogenase to an acylphosphatase by trinitroglycerin and inactivation of this activity by azide and ascorbate.
Trinitroglycerin oxidizes the essential sulfhydryl group, Cys-149, of pig muscle glyceraldehyde-3-phosphate dehydrogenase (D-glyceraldehyde-3-phosphate : NAD+ oxidoreductase(phosphorylating) EC 220.127.116.11) TO A SLUFENIC ACID, NOT TO A DISULFIDE. This conclusion is based on the observation that the inactivation of the dehydrogenase activity of the enzyme by the organic nitrate induces the acylphosphatase activity which is catalyzed by the sulfenic acid form of the enzyme. Inorganic nitrite is released during this process which is stoichiometric with the degree of inactivation of the dehydrogenase. The acylphosphatase activity induced by trinitroglycerin, unlike the dehydrogenase activity, is sensitive to CN-. Treatment of the enzyme oxidized with trinitroglycerin with 14-CN- leads to the incorporation of protein-bound 14-CN-, which is stoichiometric with the degree of inactivation of the dehydrogenase. Treatment of the sulfenic acid form of glyceraldehyde-3-phosphate dehydrogenase at pH 5.3 with a 10-fold molar excess of azide over the concentration of enzyme subunit completely inactivates the acylphosphatase reaction catalyzed by the oxidized enzyme. Concomitantly, the dehydrogenase activity catalyzed by the sulfhydryl form of the enzyme reappears which indicates that excess azide reduces the sulfenic acid which is required for the acylphosphatase. Treatment of the oxidized enzyme with a stoichiometric amount of azide at pH 5.3 stimulates the acylphosphatase activity and does not lead to the reappearance of dehydrogenase activity. When the sulfenic acid form of the enzyme is incubated with 20 mM L-ascorbate at pH 5.3, the acylphosphatase activity is completely inactivated and the dehydrogenase activity catalyzed by the reduced form of the enzyme is recovered. Thus, L-ascorbate also reduces the protein sulfenic acid which is required for the acylphosphatase activity.


Shift-Current Photovoltaics Based on a Non-Centrosymmetric Phase in In-Plane Ferroelectric SnS.
The shift-current photovoltaics of group-IV monochalcogenides has been predicted to be comparable to those of state-of-the-art Si-based solar cells. However, its exploration has been prevented from the centrosymmetric layer stacking in the thermodynamically stable bulk crystal. Herein, the non-centrosymmetric layer stacking of tin sulfide (SnS) is stabilized in the bottom regions of SnS crystals grown on a van der Waals substrate by physical vapor deposition and the shift current of SnS, by combining the polarization angle dependence and circular photogalvanic effect, is demonstrated. Furthermore, 180° ferroelectric domains in SnS are verified through both piezoresponse force microscopy and shift-current mapping techniques. Based on these results, an atomic model of the ferroelectric domain boundary is proposed. The direct observation of shift current and ferroelectric domains reported herein paves a new path for future studies on shift-current photovoltaics.


Sex differences in cardiovascular and all-cause mortality in nonalcoholic fatty liver disease in the US population.
Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver condition. In the United States (US), the prevalence of NAFLD in men is higher than that in women. This study aimed to evaluate sex differences in long-term all-cause and cardiovascular (CV) outcomes in patients with NAFLD. We collected data from participants aged ≥18 years from the National Health and Nutrition Examination Surveys, 2000-2014, which included seven continuous 2-year surveys. A US Fatty Liver Index score of ≥30 was used to define NAFLD. We used a weighted Cox proportional hazards model to compare sex differences in overall and CV mortality. The all-cause and CV mortality rates were obtained from the National Center for Health Statistics. From the selected 2627 participants with NAFLD, 65.4% were males. Men had a significantly higher all-cause mortality than women (12.4% vs. 7.7%; p = 0.005), and the risk of CV death was higher in women with NAFLD aged ≤60 years (adjusted hazard ratio 0.214, 95% confidence interval 0.053-0.869, p = 0.031). Men with a body mass index >30 kg/m2 and diabetes showed a higher risk of all-cause mortality. Sex differences in CV events were not apparent in the patients aged >60 years. Male sex was associated with all-cause mortality in all the age groups. However, CV death is influenced by age, with a higher risk in young and middle-aged women and no apparent difference in older patients.


The Role of Positron Emission Tomography Imaging in Radiotherapy Target Delineation.
Positron emission tomography (PET) is an advanced functional imaging modality in oncology care for the diagnosis, staging, prognostication, and surveillance of numerous malignancies. PET can also offer considerable advantages for target volume delineation as part of radiation treatment planning. In this review, data and clinical practice from 6 general oncology disease sites are assessed to descriptively evaluate the role of PET in target volume delineation. Also highlighted are several specific and practical utilities for PET imaging in radiation treatment planning. Publication of several ongoing prospective trials in the future may further expand the utility of PET for target delineation and patient care.


ER-stress-induced transcriptional regulation increases protein synthesis leading to cell death.
Protein misfolding in the endoplasmic reticulum (ER) leads to cell death through PERK-mediated phosphorylation of eIF2α, although the mechanism is not understood. ChIP-seq and mRNA-seq of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), key transcription factors downstream of p-eIF2α, demonstrated that they interact to directly induce genes encoding protein synthesis and the unfolded protein response, but not apoptosis. Forced expression of ATF4 and CHOP increased protein synthesis and caused ATP depletion, oxidative stress and cell death. The increased protein synthesis and oxidative stress were necessary signals for cell death. We show that eIF2α-phosphorylation-attenuated protein synthesis, and not Atf4 mRNA translation, promotes cell survival. These results show that transcriptional induction through ATF4 and CHOP increases protein synthesis leading to oxidative stress and cell death. The findings suggest that limiting protein synthesis will be therapeutic for diseases caused by protein misfolding in the ER.


Breast cancer risk stratification for mammographic screening: A nation-wide screening cohort of 24,431 women in Singapore.
Breast cancer incidence is increasing in Asia. However, few women in Singapore attend routine mammography screening. We aim to identify women at high risk of breast cancer who will benefit most from regular screening using the Gail model and information from their first screen (recall status and mammographic density). In 24,431 Asian women (50-69 years) who attended screening between 1994 and 1997, 117 developed breast cancer within 5 years of screening. Cox proportional hazard models were used to study the associations between risk classifiers (Gail model 5-year absolute risk, recall status, mammographic density), and breast cancer occurrence. The efficacy of risk stratification was evaluated by considering sensitivity, specificity, and the proportion of cancers identified. Adjusting for information from first screen attenuated the hazard ratios (HR) associated with 5-year absolute risk (continuous, unadjusted HR [95% confidence interval]: 2.3 [1.8-3.1], adjusted HR: 1.9 [1.4-2.6]), but improved the discriminatory ability of the model (unadjusted AUC: 0.615 [0.559-0.670], adjusted AUC: 0.703 [0.653-0.753]). The sensitivity and specificity of the adjusted model were 0.709 and 0.622, respectively. Thirty-eight percent of all breast cancers were detected in 12% of the study population considered high risk (top five percentile of the Gail model 5-year absolute risk [absolute risk ≥1.43%], were recalled, and/or mammographic density ≥50%). The Gail model is able to stratify women based on their individual breast cancer risk in this population. Including information from the first screen can improve prediction in the 5 years after screening. Risk stratification has the potential to pick up more cancers.


[Spine surgery in a combat support hospital].
From July 2007 to October 2014, neurosurgical services have been continuously available in a multinational Role 3 combat support hospital in Mazar-e-Sharif (MeS), Afghanistan. In this paper, we analyze a 7-year operative and outpatient spinal surgery caseload experience. The overall annual and monthly caseloads were determined. Additionally, the surgical cases were differentiated relating to the strength of the indication, the location of the surgical site, and the origin of the patients. The outpatient caseload and spectrum of the years 2012 and 2013 were also analyzed. A total of 341 surgeries were performed and 188 of them were spinal surgeries (55.1 %). The vast majority of surgeries were performed for degenerative diseases (127/188; 67.6 %). The proportion of fractures and penetrating injuries (61/188; 32.4%) increased over the observation period. Eighty percent of the immediate and urgent surgeries (within 12 h; n = 70) were performed for these indications. 19.8 % of the surgeries were done as an emergency, whereas 17.3 % had delayed urgency, and 62.9 % were elective procedures. Of the 1026 outpatient consultations documented, 82 % of them were related to spinal diseases. The overall caseload in addition to the distribution of location, strength of indication, and patient origin for MeS are significantly lower than that reported by other International Security Assistance Force (ISAF) nations in eastern and southern Afghanistan. In addition, the rate of elective surgeries and those carried out in civilian Afghan patients is highest in MeS. In comparison with MeS, none of the other ISAF military hospitals shows such a strong concentration of degenerative spinal conditions in their surgical spectrum. Nevertheless, the changing pattern of spine-related diagnoses and surgical therapies in the current conflict represents a challenge for future educational and material planning in comparable missions.


Unraveling a hotspot for TCR recognition on HLA-A2: evidence against the existence of peptide-independent TCR binding determinants.
T cell receptor (TCR) recognition of peptide takes place in the context of the major histocompatibility complex (MHC) molecule, which accounts for approximately two-thirds of the peptide/MHC buried surface. Using the class I MHC HLA-A2 and a large panel of mutants, we have previously shown that surface mutations that disrupt TCR recognition vary with the identity of the peptide. The single exception is Lys66 on the HLA-A2 alpha1 helix, which when mutated to alanine disrupts recognition for 93% of over 250 different T cell clones or lines, independent of which peptide is bound. Thus, Lys66 could serve as a peptide-independent TCR binding determinant. Here, we have examined the role of Lys66 in TCR recognition of HLA-A2 in detail. The structure of a peptide/HLA-A2 molecule with the K66A mutation indicates that although the mutation induces no major structural changes, it results in the exposure of a negatively charged glutamate (Glu63) underneath Lys66. Concurrent replacement of Glu63 with glutamine restores TCR binding and function for T cells specific for five different peptides presented by HLA-A2. Thus, the positive charge on Lys66 does not serve to guide all TCRs onto the HLA-A2 molecule in a manner required for productive signaling. Furthermore, electrostatic calculations indicate that Lys66 does not contribute to the stability of two TCR-peptide/HLA-A2 complexes. Our findings are consistent with the notion that each TCR arrives at a unique solution of how to bind a peptide/MHC, most strongly influenced by the chemical and structural features of the bound peptide. This would not rule out an intrinsic affinity of TCRs for MHC molecules achieved through multiple weak interactions, but for HLA-A2 the collective mutational data place limits on the role of any single MHC amino acid side-chain in driving TCR binding in a peptide-independent fashion.


Rescue of ATPa3-deficient murine malignant osteopetrosis by hematopoietic stem cell transplantation in utero.
Autosomal recessive osteopetrosis (ARO) is a paradigm for genetic diseases that cause severe, often irreversible, defects before birth. In ARO, osteoclasts cannot remove mineralized cartilage, bone marrow is severely reduced, and bone cannot be remodeled for growth. More than 50% of the patients show defects in the osteoclastic vacuolar-proton-pump subunit, ATP6a3. We treated ATP6a3-deficient mice by in utero heterologous hematopoietic stem cell (HSC) transplant from outbred GFP transgenic mice. Dramatic phenotype rescue by GFP osteoclasts was obtained with engraftment, which was observed in most cases. Engraftment survived for variable periods. Recipients were not immunosuppressed, and graft-versus-host disease was not observed in all pups born after in utero treatment. Thus, differentiation of unmatched HSC transplanted in utero is sufficient to prevent fatal defects in ARO and may prevent complications of ARO unresponsive to conventional bone marrow transplantation. The presence of defective cells is not a barrier to the rescue of the phenotype by donor HSC.


Cellular reaction to an acute demyelinating/remyelinating lesion of the rat brain stem: localisation of GD3 ganglioside immunoreactivity.
We describe a simple and reproducible acute demyelinating lesion of the rat brain stem induced by injection of ethidium bromide into the cisterna magna of young adult rats. Using immunofluorescence with a panel of antibodies to cell-specific antigens we have studied the changes in cell populations that occur at various stages during lesion progression and repair. In particular we localized the expression of ganglioside GD3 immunoreactivity, a marker for oligodendroglial progenitors in developing brain. Both astroglia (GFAP+) and oligodendroglia (CNP+) were destroyed during the early response to the ethidium bromide although axons were spared. Splitting of myelin lamellae occurred as early as 4 days post-injection (DPI), with extensive demyelination of the inferior cerebellar peduncle following by 6 DPI. Large numbers of ED1+ and OX-42+ macrophages were present in the lesion site at this stage. Astrogliosis occurred around the perimeter of the lesions. Two populations of GD3+ cells appeared within and around the lesion sites during the demyelination. One population was identified by the phenotype GD3+ ED1+ and thus probably belonged to the macrophage/microglial lineage. In these cells both antigens appeared cytoplasmic. The second population of GD3+ cells exhibited cell membrane GD3 immunoreactivity but did not express the ED1 antigen. These cells are suggested to be oligodendroglial progenitors generated in response to the demyelination. No such cells were seen in control tissue. GD3+ cells were present within the lesion sites from 6 DPI until 10-12 DPI. Following the clearance of myelin debris from the lesions, remyelination was a relatively rapid event with thin MBP+ myelin sheaths first seen at 11-12 DPI. Remyelination, which was extensive by 25 DPI, was predominantly oligodendroglial in origin (MBP+P0- myelin) with only small pockets of peripheral myelin (MBP+P0+ myelin) observed. The present study, in addition to identifying putative glial progenitors within a demyelinated lesion, also demonstrates the difficulties in unambiguously identifying such cells in the normal and damaged adult CNS.


Thin-layer chromatographic determination of major metamizole metabolites in serum and urine.
Thin-layer chromatographic (TLC) methods were developed for pharmacokinetic studies of major metamizole metabolites in serum and urine. These methods proved practicable, selective, accurate and sensitive with detection limits as follows: 4-methylaminoantipyrine 0.6 micrograms/ml serum and 2.0 micrograms/ml urine; 4-aminoantipyrine 0.16 micrograms/ml serum and 1.0 micrograms/ml urine; 4-acetylaminoantipyrine 0.14 micrograms/ml serum and 0.6 micrograms/ml urine; 4-formylaminoantipyrine 0.12 micrograms/ml serum and 1.0 micrograms/ml urine. Samples of 250 microliter suffice for TLC analysis. Following chromatographic separation, detection is performed in the ultraviolet range at 265 nm. Serum and urine levels were determined following a single oral dose of 1 g of metamizole sodium to eight volunteers. These results were compared with those following an accidental overdose of 49 g.


Advocacy Curricula in Graduate Medical Education: an Updated Systematic Review from 2017 to 2022.
Advocacy is an integral component of a physician's professional responsibilities, yet efforts to teach advocacy skills in a systematic and comprehensive manner have been inconsistent and challenging. There is currently no consensus on the tools and content that should be included in advocacy curricula for graduate medical trainees. To conduct a systematic review of recently published GME advocacy curricula and delineate foundational concepts and topics in advocacy education that are pertinent to trainees across specialties and career paths. We conducted an updated systematic review based off Howell et al. (J Gen Intern Med 34(11):2592-2601, 2019) to identify articles published between September 2017 and March 2022 that described GME advocacy curricula developed in the USA and Canada. Searches of grey literature were used to find citations potentially missed by the search strategy. Articles were independently reviewed by two authors to identify those meeting our inclusion and exclusion criteria; a third author resolved discrepancies. Three reviewers used a web-based interface to extract curricular details from the final selection of articles. Two reviewers conducted a detailed analysis of recurring themes in curricular design and implementation. Of 867 articles reviewed, 26 articles, describing 31 unique curricula, met inclusion and exclusion criteria. The majority (84%) represented Internal Medicine, Family Medicine, Pediatrics, and Psychiatry programs. The most common learning methods included experiential learning, didactics, and project-based work. Most covered community partnerships (58%) and legislative advocacy (58%) as advocacy tools and social determinants of health (58%) as an educational topic. Evaluation results were inconsistently reported. Analysis of recurring themes showed that advocacy curricula benefit from an overarching culture supportive of advocacy education and should ideally be learner-centric, educator-friendly, and action-oriented. Combining core features of advocacy curricula identified in prior publications with our findings, we propose an integrative framework to guide design and implementation of advocacy curricula for GME trainees. Additional research is needed to build expert consensus and ultimately develop model curricula for disseminated use.


Intratympanic dexamethasone injection for refractory tinnitus: prospective placebo-controlled study.
The purpose of this study is to investigate the effectiveness of intratympanic dexamethasone injections (ITDI) for refractory tinnitus. A prospective, placebo-controlled, randomized, double-blind study. Thirty patients with refractory tinnitus who were diagnosed in the Department of Otolaryngology, Ajou University Hospital, Suwon, Republic of Korea, between 2006 and 2007 were enrolled and then were assigned into two groups of ITDI (15 patients) or saline (15 patients) by permuted block randomization. Intratympanic injections were double-blind performed four times within 2 weeks. After 4 weeks, we analyzed the improvement and aggravation rates of tinnitus using the following parameters: questionnaires, tinnitus handicap index (THI), loudness matching test, frequency, and duration of tinnitus. The effectiveness rates of ITDI for refractory tinnitus reported in the tinnitus questionnaires, in the THI, and in the loudness matching test were all 33.3% in the steroid group, and 26.7%, 40.0%, and 26.7% in the saline group, respectively. However, there were no statistically significant differences in both groups. To analyze the therapeutic effect of ITDI on tinnitus under 6 months of its development, the improvement rates reported in the tinnitus questionnaires, in the THI, and in the loudness matching test were all 28.5% in the steroid group, and 40.0%, 40.0%, and 30.0% in the saline group, respectively. There were also no statistically significant differences in both groups. ITDI may not be effective for refractory tinnitus. The indication of ITDI for tinnitus needs to be limited to specific cases.


Fulminant Clostridium Septicum myonecrosis in well controlled diabetes: a case report.
Diabetic myonecrosis with Clostridium Septicum is uncommon but carries a high mortality rate. This commensal organism is part of the gastrointestinal tract flora and can become extremely virulent, often in the setting of immuno-suppression such as neutropenia, occult malignancy (commonly caecal) and poorly controlled diabetes. The case report is unusual in that there are few risk factors other than very mild neutropenia. This highlights the opportunistic character of the organism and recommends that a high index of suspicion and vigilance be carried out in the presence of fevers and sepsis, even in the well-controlled diabetic population.


The Role of Pediatric Gastroenterologists in the Evaluation of Complex Aerodigestive Disorders.
Children with aerodigestive disorders frequently have concerns regarding difficulty breathing, swallowing, and growing. In this review, we explored the role of pediatric gastroenterologists in the evaluation of complex aerodigestive disorders and the overall approach to these often-challenging patients. Pediatric gastroenterologists evaluate children with aerodigestive concerns ranging from dysphagia and gastroesophageal reflux to complex congenital abnormalities such as esophageal atresia. Diagnostic tools, such as multichannel intraluminal impedance-pH monitoring, are used for diagnosing gastroesophageal reflux and assessing the correlation with symptoms. Endoscopic evaluation, and in some complex cases, with therapeutic dilations may also be performed. Gastrointestinal dysmotility evaluation with manometry studies are also being increasingly utilized. Multidisciplinary aerodigestive programs can provide a coordinated approach to children with complex airway, pulmonary and gastrointestinal tract disorders. A pediatric gastroenterologist's expertise and specialized skills not only offer many diagnostic tools for these complicated medical cases but are also important in long term medical management.


A type II collagen mutation also results in oto-spondylo-megaepiphyseal dysplasia.
Oto-spondylo-megaepiphyseal dysplasia (OSMED) is a skeletal dysplasia characterized by severe sensorineural hearing loss, enlarged epiphyses and early onset of osteoarthritis. COL11A2 has been reported as a causative gene for OSMED. We have identified a novel COL2A1 mutation at a splice-acceptor site within intron 10 (c.709-2A>G) in an OSMED patient. This mutation caused the skipping of exon 11, and of exons 11 and 13. These exon-skipping events are presumed to cause an in-frame deletion of the triple helical region of the COL2A1 product. Thus, our findings highlight the genetic heterogeneity of OSMED and extend the phenotypic spectrum of type II collagenopathy, as well as confirming the overlap between type II and type XI collagenopathies.


Autacoid and beta-adrenergic agonist modulation of N-formylmethionyl-leucyl-phenylalanine evoked lysosomal enzyme release from human neutrophils.
Isoprenaline, histamine and PGE1 inhibit N-formylmethionyl-leucyl-phenylalanine evoked lysosomal enzyme release from human neutrophils. Their effects are dose-dependent and potentiated by 3-isobutyl-1-methylxanthine pretreatment of the cells. The order of activity is PGE1 greater than isoprenaline greater than histamine. The maximum of inhibition afforded by each agonist depends on the amount of the secretory stimulus, since it is higher at lower concentrations of the secretagogue. Isoprenaline effects are competitively antagonized by propranolol and are mimicked by fenoterol and salbutamol. These results suggest that human neutrophil functions are modulated by endogenous control mechanisms, that can also be activated by drugs acting on the same receptors as the endogenous mediators.


Review article: current gaps and opportunities in HBV prevention, testing and linkage to care in the United States-a call for action.
The World Health Organization (WHO) has set an elimination goal for hepatitis B virus (HBV) by 2030, so a comprehensive review of current HBV testing and care gaps are needed to help formulate solutions and opportunities for action. To summarise current gaps and barriers, and to propose solutions for HBV prevention, testing and linkage to care in the United States METHODS: Relevant guidelines and studies were reviewed including a systematic review of HCC surveillance adherence. A total of 64.5 million (95% CI, 61.3-67.5) high-risk US adults had no evidence of HBV immunity. Only 18.6% (95% CI, 13.5-29.9) of privately insured patients with HBV infection have been diagnosed. Among those with known HBV infection, linkage to care rate (33.3%-57%) was poor and the adherence to guidelines regarding anti-viral therapy (30.66% [95% CI, 30.28-31.03]) and HCC surveillance (8%-87%, from a systematic review) were poor with even more concerning data for care and treatment retention. The causes are complex and include lack of access to medical care, lack of physician knowledge, lack of patient health literacy and awareness, linguistic and cultural barriers and fear of stigma. A 'scale-up' effort is needed to optimise the care continuum to achieve the WHO 2030 targets. As targeted screening policy has leftover 80% of patients undiagnosed, we advocate for universal screening which can help to remove barriers regarding stigma. More active and system level interventions are also needed to improve linkage to care for patients with HBV infection.


In silico modelling of apoptosis induced by photodynamic therapy.
Photodynamic therapy (PDT) is an emergent technique used for the treatment of several diseases. After PDT, cells die by necrosis, apoptosis or autophagy. Necrosis is produced immediately during photodynamic therapy by high concentration of reactive oxygen species, apoptosis and autophagy are triggered by mild or low doses of light and photosensitizer. In this work we model the cell response to low doses of PDT assuming a bi-dimensional matrix of interacting cells. For each cell of the matrix we simulate in detail, with the help of the Gillespie's algorithm, the two main chemical pathways leading to apoptosis. We unveil the role of both pathways in the cell death rate of the tumor, as well as the relevance of several molecules in the process. Our model suggests values of concentrations for several species of molecules to enhance the effectiveness of PDT.


Penile melanosis.
Five patients with penile melanosis are described. The lesions consisted of macular hyperpigmentation of the penile shaft and/or glans. Histologically only hyperpigmentation of the basal cell layer was observed with no melanocytic hyperplasia. Patients had follow-up for 3 to 13 years; enlargement of some lesions was observed, but the condition remained benign. The main differential diagnostic problem was with acral lentiginous melanoma. Penile melanosis shares clinical and microscopic features with Laugier-Hunziker syndrome of the buccal mucosa and vulvovaginal melanosis. We suggest that the three disorders be grouped as essential melanotic hyperpigmentation of mucosa.


Immunobiology and application of toll-like receptor 4 agonists to augment host resistance to infection.
Infectious diseases remain a threat to critically ill patients, particularly with the rise of antibiotic-resistant bacteria. Septic shock carries a mortality of up to ∼40% with no compelling evidence of promising therapy to reduce morbidity or mortality. Septic shock survivors are also prone to nosocomial infections. Treatment with toll-like receptor 4 (TLR4) agonists have demonstrated significant protection against common nosocomial pathogens in various clinically relevant models of infection and septic shock. TLR4 agonists are derived from a bacteria cell wall or synthesized de novo, and more recently novel small molecule TLR4 agonists have also been developed. TLR4 agonists augment innate immune functions including expansion and recruitment of innate leukocytes to the site of infection. Recent studies demonstrate TLR4-induced leukocyte metabolic reprogramming of cellular metabolism to improve antimicrobial function. Metabolic changes include sustained augmentation of macrophage glycolysis, mitochondrial function, and tricarboxylic acid cycle flux. These findings set the stage for the use of TLR4 agonists as standalone therapeutic agents or antimicrobial adjuncts in patient populations vulnerable to nosocomial infections.


Distraction-lengthening of digital rays using a small external fixator.
We present 19 ray lengthenings in 14 patients done with a small external fixator. In six cases the thumb was lengthened and in the other 13 cases, other digital rays. The most frequent reason for lengthening was an amputation sustained in a work accident. All the lengthenings were done by an osteotomy and subsequent gradual distraction with a small external fixator. The mean lengthening achieved was 20 mm (range, 0-32). An iliac-crest graft was needed in nine cases, corrective osteotomy in five cases and a deepening of the web in the six cases of thumb lengthening. In five cases an additional technique was needed to achieve bony consolidation. We have analysed the functional results and the ability to perform activities of daily living and resume employment. Although most of the patients had multiples injuries, the results have been very favourable, achieving a very high level of patient satisfaction.


Risk factors of postoperative bile leakage after liver resection: A systematic review and meta-analysis.
Postoperative bile leakage (POBL) is one of the most common complications after liver resection. However, current studies on the risk factors for POBL and their impacts on surgical outcomes need to be more consistent. This study aims to conduct a meta-analysis to analyze the risk factors for POBL after hepatectomy. We incorporated all eligible studies from Embase, PubMed, and the Web of Science database (until July 2022) into this study. RevMan and STATA software were used to analyze the extracted data. A total of 39 studies, including 43,824 patients, were included in this meta-analysis. We found that gender, partial hepatectomy, repeat of hepatectomy, extended hepatectomy, abdominal drain, diabetes, Child≥B, solitary tumor, and chemotherapy are the factors of grade B and C POBL. Some recognized risk factors were considered potential risk factors for grade B and C bile leakage because no subgroup analysis was performed, like HCC, cholangiocarcinoma, major resection, posterior sectionectomy, bi-segmentectomy, S4 involved, S8 involved, central hepatectomy, and bile duct resection/reconstruction. Meanwhile, cirrhosis, benign diseases, left hepatectomy, and Segment 1 resection were not significant for grade B and C bile leakage. The influence of lateral sectionectomy, anterior sectionectomy, S1 involved, S3 involved, high-risk procedure, laparoscope, and blood loss>1000 mL on POBL of ISGLS needs further research. Meanwhile, POBL significantly influenced overall survival (OS) after liver resection. We identified several risk factors for POBL after hepatectomy, which could prompt the clinician to decrease POBL rates and make more beneficial decisions for patients who underwent the hepatectomy.


Health care costs of heart failure: results from a randomised study of patient education.
Heart failure is a serious syndrome with a bad prognosis. Hospitalisation is common and readmittance rate is high; factors which influence the cost of care and treatment. Only scarce data on detailed patient materials regarding health care costs are known. To describe in detail the health care costs for heart failure patients. Costs for patients (n=108) who completed a randomised education trial were studied for 6 months after hospital discharge. Costs for hospital stay, out-patient visits, diagnostic tests and procedures, laboratory analyses and drug treatment were calculated. Official unit prices list used to reimburse providers of cross-boundary health services and prices for drugs in the Swedish Drug Compendium were employed. The total cost for a heart failure patient was approximately 20000 SEK (2564 US$, 7.80 SEK=1 US$) for 6 months. There was a 27-fold variation between patients. There was no relation between age or sex and cost. In decreasing order cost for hospitalisation was followed by costs for out-patient visits, diagnostic tests and procedures, laboratory analyses and drugs. Hospitalisation was the largest part of the total cost and there was a large inter-individual variation. Efforts to reduce the economic burden should be focused on hospitalisation. Due to skewed distribution, individual data must be considered in the analysis of the efforts.


Using 3D-reconstruction to analyse typical growth trends of the maxillary sinus in children.
There remains a lack of consistent evidence surrounding the developmental anatomy of the maxillary sinus (MS), despite its clinical significance in radiological interpretation and surgical intervention. Our aim was to analyse the typical growth trends of the MS throughout development, to better understand its morphological transformation from birth until late adolescence. Computed Tomography (CT) scans of individuals aged 0-18 years within the Auckland District Health Board region in New Zealand were examined retrospectively. Sixty-five patients were selected for the study after careful review of criteria. Manual 3D-reconstruction was utilised to replicate the MS from CT images and the mean changes in size, volume and shape with increasing age were analysed. Principal component analysis (PCA) was performed to statistically calculate the mean 3D shapes of the MS in each age group and analyse the independent modes of variation evident in sinus morphology between individuals of each age category. At 0-1 years of age, mean MS size was 1.03 × 1.82 × 1.27 cm (width, length, height) with a mean volume of 0.81 cm3. By 16-18 years, mean size increased to 3.39 × 4.30 × 4.63 cm and mean volume became 21.63 cm3. Growth increased linearly but most rapid expansion occurred in the first 4-5 years of life. No significant differences were observed between males and females or right and left sides. Sinus morphology gradually progressed throughout the course of growth from an ellipsoidal structure at its rudimentary phase to a pyramidal shape when fully matured. PCA revealed that within younger age groups significant variation was observed in MS size, while older age groups had relatively less size variation but increased variability in 3D shape. The results of this study can be used as a reference for typical MS growth in healthy children and as a basis to study how disease or surgical intervention may influence sinus development in children.


Low Counts of B Cells, Natural Killer Cells, Monocytes, Dendritic Cells, Basophils, and Eosinophils are Associated with Postengraftment Infections after Allogeneic Hematopoietic Cell Transplantation.
Hematopoietic cell transplant (HCT) recipients are immunocompromised and thus predisposed to infections. We set out to determine the deficiency of which immune cell subset(s) may predispose to postengraftment infections. We determined day 28, 56, 84, and 180 blood counts of multiple immune cell subsets in 219 allogeneic transplant recipients conditioned with busulfan, fludarabine, and Thymoglobulin. Deficiency of a subset was considered to be associated with infections if the low subset count was significantly associated with subsequent high infection rate per multivariate analysis in both discovery and validation cohorts. Low counts of monocytes (total and inflammatory) and basophils, and low IgA levels were associated with viral infections. Low plasmacytoid dendritic cell (PDC) counts were associated with bacterial infections. Low inflammatory monocyte counts were associated with fungal infections. Low counts of total and naive B cells, total and CD56(high) natural killer (NK) cells, total and inflammatory monocytes, myeloid dendritic cells (MDCs), PDCs, basophils and eosinophils, and low levels of IgA were associated with any infections (due to any pathogen or presumed). In conclusion, deficiencies of B cells, NK cells, monocytes, MDCs, PDCs, basophils, eosinophils, and/or IgA plasma cells appear to predispose to postengraftment infections.