[Treatment aspects of interprosthetic femur fractures-retrospective analysis of 70 patients].
Interprosthetic femur fractures (IFF) are rare injuries, whose surgical treatment is basically with osteosynthesis or revision arthroplasty. Various therapy algorithms have been proposed based on very small study collectives. Factors influencing the outcome are not known. The aim of the retrospective monocentric study is to derive a treatment algorithm based on a large number of cases and to identify factors influencing the outcome. Between 2006 and 2020, 70 IFF were identified. The surgical treatment comprised 38 osteosyntheses, 30 revision arthroplasties and 2 amputations. With classification and time to surgery, 69 perioperative variables were recorded. General and operative complications, as well as mortality, were determined in the follow-up period of 1 year. ASA and Charlson score correlated with 1‑year-mortality. In addition, preoperatively increased CRP levels, reduced hemoglobin and the CHA2DS2-VASc score were identified as factors influencing mortality. Surgery within 24 h showed a trend towards fewer general complications. Transferred patients indicated an increased mortality. Based on classification according to Pires et al. or Füchtmeier et al. no clear treatment decision could be made. Relevant criteria for the surgical treatment were fracture localization, implant stability, bone vitality, anchoring possibility of the revision stem, as well as general condition of the patient. The identified factors influencing the outcome correspond to those of patients with hip fractures. IFF should be treated timely. A treatment path was developed on the basis of the largest patient group to date.


Clinical effectiveness of rehabilitation in ambulatory care for patients with persisting symptoms after COVID-19: a systematic review.
Lingering symptoms after acute COVID-19 present a major challenge to ambulatory care services. Since there are reservations regarding their optimal management, we aimed to collate all available evidence on the effects of rehabilitation treatments applicable in ambulatory care for these patients. On 9 May 2022, we systematically searched articles in COVID-19 collections, Embase, MEDLINE, Cochrane Library, Web of Science, CINAHL, PsycArticles, PEDro, and EuropePMC. References were eligible if they reported on the clinical effectiveness of a rehabilitation therapy applicable in ambulatory care for adult patients with persisting symptoms continuing 4 weeks after the onset of COVID-19. The quality of the studies was evaluated using the CASP cohort study checklist and the Cochrane Risk of Bias Assessment Tool. Summary of Findings tables were constructed and the certainty of evidence was assessed using the GRADE framework. We included 38 studies comprising 2,790 participants. Physical training and breathing exercises may reduce fatigue, dyspnoea, and chest pain and may improve physical capacity and quality of life, but the evidence is very weak (based on 6 RCTs and 12 cohort studies). The evidence underpinning the effect of nutritional supplements on fatigue, dyspnoea, muscle pain, sensory function, psychological well-being, quality of life, and functional capacity is very poor (based on 4 RCTs). Also, the evidence-base is very weak about the effect of olfactory training on sensory function and quality of life (based on 4 RCTs and 3 cohort studies). Multidisciplinary treatment may have beneficial effects on fatigue, dyspnoea, physical capacity, pulmonary function, quality of life, return to daily life activities, and functional capacity, but the evidence is very weak (based on 5 cohort studies). The certainty of evidence is very low due to study limitations, inconsistency, indirectness, and imprecision. Physical training, breathing exercises, olfactory training and multidisciplinary treatment can be effective rehabilitation therapies for patients with persisting symptoms after COVID-19, still with high uncertainty regarding these effects. These findings can guide ambulatory care practitioners to treat these patients and should be incorporated in clinical practice guidelines. High-quality studies are needed to confirm our hypotheses and should report on adverse events.


A review of the use of biological agents for chronic inflammatory demyelinating polyradiculoneuropathy.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a group of idiopathic, acquired, immune-mediated inflammatory demyelinating diseases of the peripheral nervous system. A majority of patients with CIDP respond to "first-line" treatment with IVIG, plasmapheresis and/or corticosteroids. There exists insufficient evidence to ascertain the benefit of treatment with "conventional" immunosuppressive drugs. The inconsistent efficacy, long-term financial burden and health risks of non-specific immune altering therapy have drawn recurrent attention to the possible usefulness of a variety of biological agents that target key aspects in the CIDP immunopathogenic pathways. This review aims to give an updated account of the scientific rationale and potential use of biological therapeutics in patients with CIDP. No specific treatment recommendations are given. The discovery, development and application of biological markers by modern molecular diagnostic techniques may help identify drug-naïve or treatment-resistant CIDP patients most likely to respond to targeted immunotherapy.


Fibroepithelioma-like changes occurring in perianal Paget's disease with rectal mucinous carcinoma: case report and review of 49 cases of extramammary Paget's disease.
Anogenital Paget's disease (PD) may be accompanied by varying degrees of epidermal hyperplasia. The histological changes can be reminiscent of fibroepithelioma of Pinkus. We present a case of perianal PD associated with fibroepitheliomatous epidermal hyperplasia in a 76-year-old-man with an underlying rectal mucinous carcinoma. We also carried out a retrospective analysis of 51 biopsies from 49 cases of extramammary PD to see whether particular epidermal changes occur in association with PD in different anatomic locations. A tumor, 3 cm in diameter, was noted in the patient's perianal skin. Histologically, it was composed of anastomosing thin epithelial strands with follicular differentiation. Paget's cells were distributed in the epithelial strands of this tumor as well as in the surrounding epidermis and anal epithelia. In our series of extramammary PD, epidermis was hyperplastic in two of two perianal cases, 26 of 43 genital skin samples, and one of six axillary PD biopsies. The stroma beneath the hyperplastic epidermis tended to be rich in thin collagen fibers and fibroblasts. Anogenital PD was more frequently associated with epidermal hyperplasia than axillary PD. Fibroepitheliomatous hyperplasia may be induced by the altered stroma associated with PD.


Unusual in vivo rearrangements of the Y chromosome with mitotic instability in vitro.
An unusual structural rearrangement of the Y chromosome resulting in seven different cell lines was found in a male infant with coronal synostosis as the only major clinical symptom. At least three different events must have occurred to explain the patient's karyotype: nondisjunction, chromosome breakage followed by translocation, and tetraploidization followed by somatic recombination. In addition, the structurally abnormal Y chromosome appeared to be unstable in vitro.


The changing prevalence of asthma-like respiratory symptoms in South Australian rural schoolchildren.
To describe the changing prevalence of wheezy breathing and doctor-diagnosed asthma, as obtained by questionnaire data, from the years 1984-92 in a sample of South Australian rural schoolchildren. A cross-sectional study of three populations of schoolchildren from the South Australian rural towns of Burra (mid-north), Gladstone (mid-north) and Kingston (southern, coastal). The cumulative or lifetime prevalences and the 12-month period prevalence (current) of respiratory symptoms were estimated from questionnaire data obtained from parental responses for 1032 schoolchildren aged from 5 to 18 years, and compared with prevalences obtained from a previous study. The overall cumulative prevalence of wheezy breathing in 1992 was 36.2%, an increase from 24.1% in 1984 with a 12-month period prevalence of 25.0%. The 1992 cumulative prevalence of doctor-diagnosed asthma was 23.3%. There was no difference in the prevalence of wheeze between the three rural regions studied. A trend to a higher prevalence of doctor-diagnosed asthma in one of the three regions was thought to be due to medical specialist input. The cumulative prevalence for wheeze among school-age children in South Australian rural communities has increased in the period 1984-92. There were no regional differences in the cumulative prevalence rates. The results confirm previous studies in Victoria and New South Wales.


Human capabilities, mild autism, deafness and the morality of embryo selection.
A preimplantation genetic test to discriminate between severe and mild autism spectrum disorder might be developed in the foreseeable future. Recently, the philosophers Julian Savulescu and Guy Kahane claimed that there are strong reasons for prospective parents to make use of such a test to prevent the birth of children who are disposed to autism or Asperger's disorder. In this paper we will criticize this claim. We will discuss the morality of selection for mild autism in embryo selection in a hypothetical in vitro fertilization (IVF) situation where preimplantation genetic diagnosis is performed and compare this with a similar selection for congenital deafness. To do this we first discuss relevant human differences. We then introduce the principle of human capabilities (PC) and compare this principle with the principle of procreative beneficence (PB) introduced by Savulescu and Kahane. We apply the two principles to selection for mild autism and selection for congenital deafness. We argue that PC allows for the selection for mild autism but rules out selection for congenital deafness. PB will not give clear answers; the ruling of PB depends to a large extent on expected social, cultural and political developments. We will argue that PC is preferable to PB. We will discuss arguments for the value of mild autism for individuals who have this condition and argue that they are able to lead a life with human dignity provided autism-friendly social circumstances are present. Neither PC nor PB yields strong reasons for prospective parents to seek to prevent the birth of children who are disposed to mild autism spectrum disorder.


The physico-chemical properties of chia seed polysaccharide and its microgel dispersion rheology.
The polysaccharide gel layer surrounding hydrated chia seeds was extracted using water and isolated by ethanol precipitation. The freeze-dried sample consisted of ∼95% non-starch polysaccharides (35% w/w neutral soluble fraction and 65% w/w negatively charged insoluble fraction). The soluble polysaccharide fraction has molar mass, root-mean square radius and intrinsic viscosity of ∼5×10(5)g/mol, 39nm and 719mL/g, respectively. The whole polysaccharide (included soluble and insoluble fractions) when dispersed in water showed presence of irregular shape, fibrous microgel particles with an average size (D4,3) of ∼700μm. Rheological measurements indicated a 'weak' viscoelastic gel and strong shear dependent properties even at low concentration (0.05% w/w). The viscosity of the dispersion was fairly resistant to variations in temperatures (20-80°C), pH (4-12), ionic strengths (0.01-0.5M NaCl) and cation types (MgCl2, CaCl2, NaCl and KCl). The swollen microgel particles dispersed in soluble polysaccharide continuous phase provided complex and potentially useful rheological properties in food systems.


Expression profile analysis of the polygalacturonase-inhibiting protein genes in rice and their responses to phytohormones and fungal infection.
Polygalacturonase-inhibiting proteins (PGIPs) are typically leucine-rich repeat (LRR) proteins that can inhibit the activity of fungal polygalacturonases (PGs). In this study, two new Ospgip genes, named Ospgip6 and Ospgip7 with consensus sequence of ten imperfect LRR motif located on rice chromosomes 8 and 9, were identified using BLAST analysis. Both of them appear to be extracellular glycoproteins. To have a global view of the dynamic gene expression pattern, seven Ospgip genes were first analyzed using the Affymetrix rice genome array data from online resource. All of these seven Ospgip genes showed variable expression patterns among tissues/organs. In order to further investigate the potential function of these Ospgip genes, the responses of Ospgip genes to the treatment of various phytohormones (abscisic acid, brassinosteroid, gibberellic acid, 3-indole acetic acid, jasmonic acid, kinetin, naphthalene acetic acid and salicylic acid) as well as fungal infection were analyzed by real-time PCR using time course array. Generally, all the Ospgip genes were slightly up-regulated in the indica rice cultivar Minghui 63 under GA(3), KT and NAA treatments (except Ospgip2, which was down-regulated under KT treatment). In the japonica rice cultivar Zhonghua 11, Ospgip genes were regulated by most treatments with the response time variability. We also analyzed putative cis-elements in the promoter regions of Ospgip genes. This dataset provided a versatile resource to understand the regulatory network of Ospgip genes during the process of phytohormones treatment and fungal infection in the model monocotyledonous plant, rice, and could aid in the transgenic breeding against rice fungal diseases. All the seven Ospgip genes showed variable expression patterns in Minghui 63 and their expressions were regulated by different phytohormone treatments or fungal infection in Minghui 63 and Zhonghua 11.


Effects of tafamidis treatment on transthyretin (TTR) stabilization, efficacy, and safety in Japanese patients with familial amyloid polyneuropathy (TTR-FAP) with Val30Met and non-Val30Met: A phase III, open-label study.
The efficacy and safety of tafamidis in transthyretin (TTR) familial amyloid polyneuropathy (TTR-FAP) were evaluated in this open-label study. Japanese TTR-FAP patients (n=10; mean age 60.1 years) received tafamidis meglumine (20mg daily; median treatment duration 713.5 days). The primary endpoint was TTR stabilization at Week 8. Secondary endpoints included Neuropathy Impairment Score-Lower Limb (NIS-LL), Norfolk QOL-DN total quality of life (TQOL), and modified body mass index (mBMI). TTR stabilization was achieved in all patients at Weeks 8 and 26, 9 out of 10 patients at Week 52, and 8 out of 10 patients at Week 78. The percentage (95% CI) of NIS-LL responders (increase from baseline in NIS-LL<2) was 80.0% (44.4, 97.5), 60.0% (26.2, 87.8), and 40.0% (12.2, 73.8) and mean(SD) NIS-LL change from baseline was 2.1 (5.6), 3.6 (4.4), and 3.3 (4.7), at Weeks 26, 52, and 78, respectively. Mean (SD) changes from baseline in TQOL and mBMI at Weeks 26, 52, and 78 were 11.8 (20.0), 9.1 (12.5), and 10.8 (13.7) for TQOL, and 26.6 (61.9), 64.9 (80.0), and 53.7 (81.4) for mBMI, respectively. Ambulation status was preserved in 4 out of 8 patients at Week 78. Most adverse events (AEs) were mild/moderate, with no discontinuations due to AEs. Tafamidis stabilized TTR, was safe and well-tolerated, and was effective over 1.5 years in slowing neurologic progression and maintaining TQOL and nutrition status in TTR-FAP.


Effects of leptophos on rat brain levels and turnover rates of biogenic amines and their metabolites.
Leptophos is a potent acetylcholinesterase inhibitor which causes delayed central-peripheral neuropathy. Rats were administered multiple doses of leptophos until motor deficits were observed in rotorod performance in the highest dosage group. Doses lower than the median effective dose were then administered to other rats and alterations of brain catecholamine and serotonin levels and turnover rates were determined. Turnover rates of brain norepinephrine and dopamine were elevated in rats administered cumulative doses of 75 mg/kg leptophos over a 15-day period. Levels of the major dopamine metabolite, 3,4-dihydroxyphenylacetic acid, appeared to be slightly elevated at this dose level and levels of dopamine were also higher than controls. These observations suggest that leptophos increases brain adrenergic activity. Rats administered the same dose levels had significantly reduced serotonin turnover rates. This observation was possibly artifactual, because rats administered a cumulative dose of 225 mg/kg leptophos showed no difference from controls.


Hybrid fixation: evaluation of a novel technique in adult osteochondritis dissecans of the knee.
Treatment of osteochondritis dissecans of the adult knee requires bone and cartilage integration of the loose fragment. Screw fixation provides primary stability but does not guarantee bony consolidation. Additional biological fixation using osteochondral grafts-hybrid fixation-could improve fragment integration. The study included seven patients [median age 21 years (15-29)] who underwent surgery for Bedouelle IIB or III osteochondritis dissecans of the medial femoral condyle. The technique involved metal screw fixation of the fragment. Mosaicplasty grafts were then press-fitted through the fragment. Cancellous autograft was utilized in the cases of subchondral bone loss. Patients were followed up clinically and radiologically (Hughston score). Screws were removed arthroscopically at 3 months and the cartilage graded using the International Cartilage Repair Society score. Fragment integration was evaluated by MRI Arthrogram (4 patients). Median follow-up was 27 months (7-35). Median clinical Hughston score was 2 (0-3) preoperatively and 4 (2-4) postoperatively. Median radiological Hughston score was 3 (2-4) and 4 (3-4). During arthroscopic removal of metalwork, osteochondritis fragments were well integrated in all cases. The International Cartilage Repair Society score was I in one patients, II in five, and III in one. Postoperative MRI arthrograms confirmed that cartilage and bone integration was complete. Isolated screw fixation of osteochondritis dissecans in adults provides poor bony integration. Mosaicplasty is an alternative but does not retain normal condylar anatomy. The hybrid fixation technique adds a biological "booster" to osteochondritis fixation, with excellent short-term outcome. Further studies are required to investigate the long-term results.


Surface Techniques in Dorsal Preservation.
Classical dorsal preservation rhinoplasty is typically done with impaction osteotomies (push/let down) and a low septal strip. These approaches are potentially highly destabilizing maneuvers in the architecture of the nasal pyramid. This is one of the reasons why these approaches did not have a popular acceptance in the 1960s and 1970s. More recently, the surgeon interested in preservation rhinoplasty has the possibility to do so with surface techniques with more control and, if needed, is easily converted to the standard structured techniques if the surgeon does not feel safe with the procedure.


Pegylated liposomal doxorubicin (PLD)-containing regimen as a novel treatment of monomorphic epithelial intestinal T-cell lymphoma (MEITL): A case report and review of literature.
Monomorphic intestinal T-cell lymphoma (MEITL) is a rare, aggressive peripheral T-cell lymphoma that arises from intestinal epithelial lymphocytes. Currently, MEITL lacks standard treatment options. Under the current treatment regimen, the median survival time for patients is only 7 months. Chemotherapy followed by hematopoietic stem cell transplantation may improve patient outcomes. New anti-lymphoma drugs, including chidamide and PEG-asparaginase, are being tested against MEITL. To our knowledge, there are currently no data on the pegylated liposomal doxorubicin (PLD) regimen for MEITL therapy.Patient concerns, diagnosis and interventions: We report the case of a 54-year-old patient diagnosed with MEITL who presented with abdominal pain and was treated with a cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide regimen containing PLD. After 15 months of follow-up, the patient is currently alive and disease free. The application of doxorubicin liposomes in chemotherapy regimens may be a new way to treat MEITL. We searched the literature on MEITL and selected 52 case reports. We summarized the clinical characteristics and treatment of 53 patients (including the current patient). It highlights 2 important clinical findings. First, for patients with MEITL treated with the cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide regimen, PLD has fewer adverse reactions and better long-term survival than doxorubicin. Second, an early diagnosis is necessary for prompt treatment. We believe that this manuscript will be valuable to all the researchers who are interested in.


Tai chi/yoga reduces prenatal depression, anxiety and sleep disturbances.
Ninety-two prenatally depressed pregnant women were randomly assigned to a tai chi/yoga or a waitlist control group at an average of 22 weeks gestation. The tai chi/yoga group participated in a 20-min group session per week for 12 weeks. At the end of the treatment period the tai chi/yoga group had lower summary depression (CES-D) scores, as well as lower negative affect and somatic/vegetative symptoms subscale scores on the CES-D, lower anxiety (STAI) scores and lower sleep disturbances scores.


Inward remodeling follows chronic vasoconstriction in isolated resistance arteries.
The hypothesis was tested that chronic vasoconstriction is followed by a structural reduction in lumen diameter, measured at full dilation. An in vitro model of pressurized rat skeletal muscle arterioles was used. During a 3-day experimental period, constriction of active vessels was achieved with fetal calf serum or endothelin-1 (ET-1). Maximal dilation revealed inward remodeling from 179 +/- 6.5 microm lumen diameter on day 0 to 151 +/- 6.3 microm on day 3 at 75 mm Hg in vessels incubated with serum (n = 8). Similarly, ET-1 induced inward remodeling from 182 +/- 5.2 to 164 +/- 3.7 microm (n = 6). When constriction during organoid culture was inhibited with papaverin or verapamil, inward remodeling was fully prevented: 184 +/- 6.3 to 184 +/- 5.8 microm for papaverin (n = 6) and 174 +/- 5.5 to 177 +/- 7.4 microm for verapamil (n = 6). A chronic reduction in diameter without tone was achieved in vessels that were kept at a low pressure (2-5 mm Hg; n = 6). Here, no remodeling was found, thereby ruling out that a chronic reduction in diameter alone is sufficient for inward remodeling. These data show that a persistent active reduction in lumen diameter is followed by inward remodeling of arterioles.


Lipid and lipopolysaccharide composition of Escherichia coli surface-altered mutants selected for resistance to levallorphan, tetracaine, and polymyxin.
Certain mutants of Escherichia coli with an altered permeability barrier have an essentially normal lipopolysaccharide, fatty acid, and phospholipid content, with a slight increase in the membrane protein:lipid ratio. The phospholipid metabolism of the lev and tec strains shows an abnormal response to growth in the selective agents levallorphan and tetracaine, respectively.


Commonalities and differences in ECT-induced gray matter volume change between depression and schizophrenia.
Electroconvulsive therapy (ECT) is one of the most effective treatments for depression and schizophrenia, particularly in urgent or treatment-resistant cases. After ECT, regional gray matter volume (GMV) increases have been repeatedly reported both in depression and schizophrenia. However, the interpretation of these findings remains entangled because GMV changes do not necessarily correlate with treatment effects and may be influenced by the intervention itself. We hypothesized that the comparison of longitudinal magnetic resonance imaging data between the two diagnostic groups will provide clues to distinguish diagnosis-specific and transdiagnostic changes. Twenty-nine Japanese participants, including 18 inpatients with major depressive disorder and 11 with schizophrenia, underwent longitudinal voxel-based morphometry before and after ECT. We investigated GMV changes common to both diagnostic groups and those specific to each group. Moreover, we also evaluated potential associations between GMV changes and clinical improvement for each group. In both diagnostic groups, GMV increased in widespread areas after ECT, sharing common regions including: anterior temporal cortex; medial frontal and anterior cingulate cortex; insula; and caudate nucleus. In addition, we found a schizophrenia-specific GMV increase in a region including the left pregenual anterior cingulate cortex, with volume increase significantly correlating with clinical improvement. Transdiagnostic volume changes may represent the effects of the intervention itself and pathophysiological changes common to both groups. Conversely, diagnosis-specific volume changes are associated with treatment effects and may represent pathophysiology-specific impacts of ECT.


Size and composition of membrane protein clusters predicted by Monte Carlo analysis.
Biological membranes contain a high density of protein molecules, many of which associate into two-dimensional microdomains with important physiological functions. We have used Monte Carlo simulations to examine the self-association of idealized protein species in two dimensions. The proteins have defined bond strengths and bond angles, allowing us to estimate the size and composition of the aggregates they produce at equilibrium. With a single species of protein, the extent of cluster formation and the sizes of individual clusters both increase in non-linear fashion, showing a "phase change" with protein concentration and bond strength. With multiple co-aggregating proteins, we find that the extent of cluster formation also depends on the relative proportions of participating species. For some lattice geometries, a stoichiometric excess of particular species depresses cluster formation and moreover distorts the composition of clusters that do form. Our results suggest that the self-assembly of microdomains might require a critical level of subunits and that for optimal co-aggregation, proteins should be present in the membrane in the correct stoichiometric ratios.


Measurement of anti-influenza neuraminidase antibody using a peroxidase-linked lectin and microtitre plates coated with natural substrates.
Neuraminidase-induced removal of sialic acid from natural substrates (desialylation) unmasks saccharides that are specifically recognized by the lectin peanut agglutinin (PNA). We demonstrate that, when a neuraminidase substrate is coated on to the wells of a microplate, it is possible to quantitate the binding of PNA to the desialylated substrate using a peroxidase-conjugated PNA (Po-PNA). The amount of bound PNA correlated directly with the amount of sialic acid removed from the substrate and therefore with the neuraminidase activity. By reacting with specific epitopes that are located near to the enzyme active site, anti-neuraminidase antibodies are capable of inhibiting the virus-induced desialylation of the substrate. Such antibodies therefore reduce the binding of Po-PNA. The advantage of this assay is that since different natural substrates for neuraminidase (erythrocytes, fetuin or gangliosides) can be used to coat the microplates, the capacity of anti-neuraminidase antibody to inhibit the neuraminidase activity towards different types of sialoglycoconjugates can be evaluated. Anti-hemagglutinin or non-specific anti-neuraminidase antibody have no interfering reactivity.


188Re-loaded lipid nanocapsules as a promising radiopharmaceutical carrier for internal radiotherapy of malignant gliomas.
Lipid nanocapsules (LNC) entrapping lipophilic complexes of (188)Re ((188)Re(S(3)CPh)(2)(S(2)CPh) [(188)Re-SSS]) were investigated as a novel radiopharmaceutical carrier for internal radiation therapy of malignant gliomas. The present study was designed to evaluate the efficacy of intra-cerebral administration of (188)Re-SSS LNC by means of convection-enhanced delivery (CED) on a 9L rat brain tumour model. Female Fischer rats with 9L glioma were treated with a single injection of (188)Re-SSS LNC by CED 6 days after cell implantation. Rats were put into random groups according to the dose infused: 12, 10, 8 and 3 Gy in comparison with blank LNC, perrhenate solution (4 Gy) and non-treated animals. The radionuclide brain retention level was evaluated by measuring (188)Re elimination in faeces and urine over 72 h after the CED injection. The therapeutic effect of (188)Re-SSS LNC was assessed based on animal survival. CED of (188)Re perrhenate solution resulted in rapid drug clearance with a brain T (1/2) of 7h. In contrast, when administered in LNC, (188)Re tissue retention was greatly prolonged, with only 10% of the injected dose being eliminated at 72 h. Rat median survival was significantly improved for the group treated with 8 Gy (188)Re-SSS LNC compared to the control group and blank LNC-treated animals. The increase in the median survival time was about 80% compared to the control group; 33% of the animals were long-term survivors. The dose of 8 Gy proved to be a very effective dose, between toxic (10-12 Gy) and ineffective (3-4 Gy) doses. These findings show that CED of (188)Re-loaded LNC is a safe and potent anti-tumour system for treating malignant gliomas. Our data are the first to show the in vivo efficacy of (188)Re internal radiotherapy for the treatment of brain malignancy.


Immunofluorescence studies of chondroitin sulfate proteoglycan biosynthesis: the use of monoclonal antibodies.
Several monoclonal antibodies which recognize different antigenic determinants of chondroitin sulfate proteoglycan were used to study chondroitin sulfate proteoglycan biosynthesis in chicken chondrocyte cultures. The intracellular sites of synthesis and processing and extracellular deposition in matrix were localized by double immunofluorescence reactions. One rat monoclonal antibody, S103L , which recognizes an antigenic determinant of the core protein of the chicken cartilage chondroitin sulfate proteoglycan monomer, was used to identify both extracellular chondroitin sulfate proteoglycan and intracellular compartments containing chondroitin sulfate proteoglycan precursors. Intracellular staining with S103L was localized to perinuclear regions, and, in some chondrocytes, to a few other cytoplasmic vesicles as well. When chondrocytes were not fed for several days, intracellular chondroitin sulfate proteoglycan precursors were accumulated in larger compartments distributed throughout the cytoplasm. Polyclonal chondroitin sulfate proteoglycan antibodies displayed similar staining characteristics. In contrast, several of the monoclonal antibodies, including the rat monoclonals S11D and P100D , and the mouse monoclonals 1-B-5, 3-B-3 and 9-A-2, did not recognize native chondroitin sulfate proteoglycan, but reacted only with chondroitinase ABC-digested (and/or hyaluronidase-digested) chondroitin sulfate proteoglycan. These antibodies were particularly useful in the demonstration of the extracellular codistribution of chondroitin sulfate proteoglycan with either type II collagen or fibronectin. In other experiments, the monoclonal antibodies to chondroitin sulfate proteoglycan served to demonstrate that the perinuclear subset of intracellular compartments is uniquely involved in the addition of chondroitin sulfate oligosaccharides to the chondroitin sulfate proteoglycan core protein. Lastly, using the mouse monoclonal 5-D-4, which recognizes keratan sulfate determinants, the perinuclear region was identified as the site for keratan sulfate addition. Results suggest heterogeneity of keratan sulfate synthesis at the level of individual chondrocytes, even for cells apparently containing equivalent amounts of intracellular chondroitin sulfate proteoglycan.


An essential carboxyl group at the nucleotide binding site of ferredoxin-NADP+ oxidoreductase.
Woodward's reagent K (N-ethyl-5-phenylisoxazolium-3'-sulfonate) inactivated both soluble and membrane bound-ferredoxin-NADP+ reductase of spinach chloroplasts. Either NADP+ or NADPh afforded complete protection against modification. Ki and the apparent Kd for protection afforded by NADP+ depended on the ionic strength of the medium. Nucleophylic displacement of reagent bound to the soluble enzyme by [14C]glycine ethyl ester showed that 5 to 6 carboxyl groups/flavin were modified when the diaphorase activity was completely inhibited. In differential labeling experiments using NADP+ as protective agent, it was shown that enzyme inactivation was due to blocking of only 1 carboxyl group/mol. Derivatized reductase did not bind pyridine nucleotides. Protection by NADP+ of the membrane-bound reductase was higher, and the apparent Kd for NADP+ lower, in the light than in the dark. Inactivation increased abruptly with the external pH, indicating a progressive exposure of the carboxyl group as the pH was raised. The results presented suggest (a) the existence of a light-driven conformational change and a pH-dependent transition in membrane-bound ferredoxin-NADP+ reductase; (b) the presence of an essential carboxyl residue in the nucleotide binding site of the reductase.


Changes in migraine characteristics over 30 days of Ramadan fasting: A prospective study.
To study Ramadan's effect on migraine from the start to the end of the month and the tolerability of patients with migraine to fasting. Fasting is a well-known trigger for migraine. Whether this effect on migraine is the same throughout the whole month, or whether it varies from the first to the last days of the month, has not been studied yet. A prospective cohort observational study was carried out on persons with migraine who fasted from 24 April to 23 May during Ramadan 2020. Each patient was asked to fill out their headache diary starting from Shaaban (the month before Ramadan) to the end of Ramadan. The Ramadan diary was divided by 10 days each, by which the patient was asked to accurately describe their migraine attacks in terms of frequency, duration, and intensity by using the Visual Analog Scale. Migraine attacks during the first day of fasting were assessed separately. A total of 292 known persons with migraine from Egypt completed the study. Their median age was 33 years; 72/292 (24.7%) were male, and 220/292 (75.3%) were female. About 126/236 (53.4%) of the patients had migraine attacks on Ramadan's first day, most of them during fasting. The frequency of migraine attacks was significantly increased in Ramadan (median 4, interquartile range [IQR] 2-7) compared with Shaaban (median 3, IQR 1-6), p = 0.009. The number of attacks was significantly reduced in both the second (median 1, IQR 0-2.25) and the third 10 days of Ramadan (median 1, IQR 1-3) compared with the first 10 days (median 3, IQR 1-5) (p < 0.001 for each). Ramadan's potential exacerbating effect on the frequency of migraine attacks should be discussed with patients with migraine. This effect appears to be limited to the first 10 days of Ramadan and then subsides with successive days of fasting.


Increased body weight in mice with fragile X messenger ribonucleoprotein 1 (Fmr1) gene mutation is associated with hypothalamic dysfunction.
Mutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene are linked to Fragile X Syndrome, the most common monogenic cause of intellectual disability and autism. People affected with mutations in FMR1 have higher incidence of obesity, but the mechanisms are largely unknown. In the current study, we determined that male Fmr1 knockout mice (KO, Fmr1-/y), but not female Fmr1-/-, exhibit increased weight when compared to wild-type controls, similarly to humans with FMR1 mutations. No differences in food or water intake were found between groups; however, male Fmr1-/y display lower locomotor activity, especially during their active phase. Moreover, Fmr1-/y have olfactory dysfunction determined by buried food test, although they exhibit increased compulsive behavior, determined by marble burying test. Since olfactory brain regions communicate with hypothalamic regions that regulate food intake, including POMC neurons that also regulate locomotion, we examined POMC neuron innervation and numbers in Fmr1-/y mice. POMC neurons express Fmrp, and POMC neurons in Fmr1-/y have higher inhibitory GABAergic synaptic inputs. Consistent with increased inhibitory innervation, POMC neurons in the Fmr1-/y mice exhibit lower activity, based on cFOS expression. Notably, Fmr1-/y mice have fewer POMC neurons than controls, specifically in the rostral arcuate nucleus, which could contribute to decreased locomotion and increased body weight. These results suggest a role for Fmr1 in the regulation of POMC neuron function and the etiology of Fmr1-linked obesity.


In vitro and in vivo evaluation of ribavirin and pleconaril antiviral activity against enterovirus 71 infection.
Enterovirus 71(EV71) causes recurring outbreaks of hand, foot and mouth disease and encephalitis leading to complications or death in young children. More effective antiviral drugs are needed to prevent or reduce EV71-related disease and complications. However, there are no standard models currently in use to evaluate activity against EV71 infection both in vitro and in vivo. In this study, the activity of ribavirin and pleconaril against EV71 infection was evaluated in two models. An in vitro EV71 infection model was developed in RD cells, and an in vivo EV71 infection model was applied. Ribavirin and pleconaril effectively increased the viability of infected cells. Pleconaril reduced the morbidity and mortality of one-day-old infected mice, but ribavirin did not protect the infected mice. In all, the results demonstrated that infected cells and infected mice can be used to evaluate antiviral activity of ribavirin and pleconaril against EV71 infection in vitro and in vivo.


Sex-specific preservation of neuromuscular function and metabolism following systemic transplantation of multipotent adult stem cells in a murine model of progeria.
Onset and rates of sarcopenia, a disease characterized by a loss of muscle mass and function with age, vary greatly between sexes. Currently, no clinical interventions successfully arrest age-related muscle impairments since the decline is frequently multifactorial. Previously, we found that systemic transplantation of our unique adult multipotent muscle-derived stem/progenitor cells (MDSPCs) isolated from young mice-but not old-extends the health-span in DNA damage mouse models of progeria, a disease of accelerated aging. Additionally, induced neovascularization in the muscles and brain-where no transplanted cells were detected-strongly suggests a systemic therapeutic mechanism, possibly activated through circulating secreted factors. Herein, we used ZMPSTE24-deficient mice, a lamin A defect progeria model, to investigate the ability of young MDSPCs to preserve neuromuscular tissue structure and function. We show that progeroid ZMPST24-deficient mice faithfully exhibit sarcopenia and age-related metabolic dysfunction. However, systemic transplantation of young MDSPCs into ZMPSTE24-deficient progeroid mice sustained healthy function and histopathology of muscular tissues throughout their 6-month life span in a sex-specific manner. Indeed, female-but not male-mice systemically transplanted with young MDSPCs demonstrated significant preservation of muscle endurance, muscle fiber size, mitochondrial respirometry, and neuromuscular junction morphometrics. These novel findings strongly suggest that young MDSPCs modulate the systemic environment of aged animals by secreted rejuvenating factors to maintain a healthy homeostasis in a sex-specific manner and that the female muscle microenvironment remains responsive to exogenous regenerative cues in older age. This work highlights the age- and sex-related differences in neuromuscular tissue degeneration and the future prospect of preserving health in older adults with systemic regenerative treatments.


[Secondary operations in lip-jaw-palate clefts].
In spite of all interdisciplinary efforts and functionally oriented operation procedures, there are still unsatisfying results in the treatment of cleft lip and palate (CLP) patients. Secondary corrections involve upper lip, nose, and palate (fissures). In some cases, it is necessary to reposition the complete maxilla. Finally, there are indications for speech improving measures and total septorhinoplasties. Dental treatment can be brought to a positive end by means of implant-borne prosthodontic work. In this paper, some of the anatomical and physiologic conditions and surgical procedures are described, which may serve as a basis for a functionally orientated treatment of sequelae after primary CLP care.


Effects of modern loop diuretics on the inner ear a quantitative evaluation using computer technics.
The effects of some modern high ceiling loop diuretics on the guinea-pig's inner ear are tested. Short-time experiments are run registrating the cochlear microphonic potentials (CMP) before and after i.v. bolus injections of a diuretic. A 100-point matrix program is performed by automatic sampling of the CMPs after stimulating by five frequencies at 20 sound pressure levels each. Data can be plotted in different scales within 10 min after the end of a whole-day experiment. The data are on-line processed by a IBM 1800 computer.


Comparison of carcinosarcoma and adenocarcinoma of the gallbladder: a study based on SEER population for propensity matching and nomogram analysis.
Carcinosarcoma of the gallbladder (CSGB) is an uncommon malignancy, and limited literature is available on its clinicopathological features, prognosis, and treatment options. Using the SEER database, we selected 7634 gallbladder adenocarcinoma patients (diagnosed from 2004 to 2015) and 58 carcinosarcoma of the gallbladder patients (diagnosed from 1988 to 2019) based on predetermined criteria. We compared the overall survival (OS) and cancer-specific survival (CSS) before and after propensity score matching in two groups. Cox univariate and multivariate analyses were performed, and a nomogram was further generated to investigate the impact of clinical and pathological variables on the survival of patients with CSGB. Finally, we evaluated the effect of different treatment modalities on the overall survival of CSGB patients. Notably, CSGB patients had larger tumors and underwent surgery more frequently than gallbladder adenocarcinoma patients, with lower rates of deeper tumor infiltrates, and lymph node infiltrates. Conversely, gallbladder adenocarcinoma patients had a higher proportion of AJCC staging (III-IV). Despite these differences, no significant differences were found in OS and CSS between the two groups before and after propensity score matching. For CSGB patients, AJCC staging, surgery and tumor size were significant prognostic factors, while treatment modalities such as surgery combined with chemotherapy, or combined radiochemotherapy, as well as radical resection, did not significantly prolong patient survival. No significant difference was found in survival rates between CSGB and gallbladder adenocarcinoma patients, while radical surgery and different combined treatment modalities did not provide significant survival benefits.


Tissue microarray-based study of hepatocellular carcinoma validating SPIB as potential clinical prognostic marker.
Currently, the prognostic significance of SPIB protein overexpression in human hepatocellular carcinoma (HCC) is unclear. The aim of the present study was to investigate the level of SPIB expression in human HCC in order to determine possible correlations between SPIB expression and clinicopathological findings. The expression of SPIB proteins was detected using immunohistochemical staining in commercial multiple-tissue microarrays as a means of examining expression profiles in patients. Using online biomarker validation tool SurvExpress, we focused on the correlation between SPIB overexpression and survival as well as relapse-free survival (RFS). Results show that SPIB protein expression levels were significantly higher in colon, liver, and stomach tumors than in non-tumor tissues (p<0.05). SPIB overexpression in patients with HCC was also significantly higher than that of the normal samples (p<0.001). Among patients with liver disease, SPIB protein expression levels differ significantly according to the stage of liver disease, specifically between stages I, II, and III of HCC (p<0.05). SPIB expression was also shown to be significantly correlated with age (p=0.046) and histological grade (p=0.027). Furthermore, the SurvExpress analysis suggested that high SPIB and KI-67 mRNA expression were significantly associated with the poor survival of patients with HCC (p<0.05). Our results indicate that cross-talk in the expression of SPIB and KI-67 may be associated with poor prognosis and may potentially serve as a clinical prognostic indicator of HCC. This is the first time that such an association has been reported.


Increased spontaneous immunoglobulin secretion associated with cyclophosphamide-induced immune suppression.
Spontaneous immunoglobulin (Ig) secretion by cells from multiple sclerosis (MS) patients (in the progressive phase) treated with monthly pulse doses of cyclophosphamide (CY) (1000-1600 mg/M2) was measured using the protein A plaque assay, to evaluate the effect of CY treatment on B-cell function. Surprisingly, an increase, rather than a decrease, in Ig-secreting cells was seen following CY treatment. CY-treated MS patients averaged 1380 +/- 535 spontaneous total (IgM + G + A) Ig plaque-forming cells (PFC) per 1 X 10(6) peripheral blood mononuclear cells (MNC), measured at 15-22 days after monthly CY administration, while healthy adults had 280 +/- 47 Ig PFC/10(6) MNC, and MS patients not treated with CY had 300 +/- 43 Ig PFC/10(6) MNC. The observed increase was due to an increase in IgG and IgA PFC. PFC levels remained elevated for 4 weeks following CY treatment, decreasing to control levels by 7-8 weeks post-CY. A small increase in serum IgG level was noted after greater than 12 months of pulse CY therapy; no increase was seen in CSF IgG levels. A preferential decrease in the number of CD4+ T cells was also seen in the CY-treated MS patients. We propose that the observed increase in the number of spontaneous Ig PFC was due to the CY-induced disruption of the CD4+ T cell-mediated control of in vivo activated B cells.


Identification of the rhizospheric microbe and metabolites that led by the continuous cropping of ramie (Boehmeria nivea L. Gaud).
Continuous cropping lowers the production and quality of ramie (Boehmeria nivea L. Gaud). This study aimed to reveal the metagenomic and metabolomic changes between the healthy- and obstacle-plant after a long period of continuous cropping. After 10 years of continuous cropping, ramie planted in some portions of the land exhibited weak growth and low yield (Obstacle-group), whereas, ramie planted in the other portion of the land grew healthy (Health-group). We collected rhizosphere soil and root samples from which measurements of soil chemical and plant physiochemical properties were taken. All samples were subjected to non-targeted gas chromatograph-mass spectrometer (GS/MS) metabolome analysis. Further, metagenomics was performed to analyze the functional genes in rhizospheric soil organisms. Based on the findings, ramie in Obstacle-group were characterized by shorter plant height, smaller stem diameter, and lower fiber production than that in Health-group. Besides, the Obstacle-group showed a lower relative abundance of Rhizobiaceae, Lysobacter antibioticus, and Bradyrhizobium japonicum, but a higher relative abundance of Azospirillum lipoferum and A. brasilense compared to the Health-group. Metabolomic analysis results implicated cysteinylglycine (Cys-Gly), uracil, malonate, and glycerol as the key differential metabolites between the Health- and Obstacle-group. Notably, this work revealed that bacteria such as Rhizobia potentially synthesize IAA and are likely to reduce the biotic stress of ramie. L. antibioticus also exerts a positive effect on plants in the fight against biotic stress and is mediated by metabolites including orthophosphate, uracil, and Cys-Gly, which may serve as markers for disease risk. These bacterial effects can play a key role in plant resistance to biotic stress via metabolic and methionine metabolism pathways.


A Ground-State Dual-Descriptor Strategy for Screening Efficient Singlet Fission Systems.
Exploration of singlet fission (SF) materials is vital for enhancing the photoelectric conversion efficiency of photovoltaic devices, and the development of an effective screening means is in great demand. In this work, we for the first time propose a promising dual-descriptor strategy to predict the SF energetics (ΔESF) from ground-state electronic properties, the gap (GapHL) and exchange energy (KHL) between the highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO), where GapHL plays a dominant role and KHL acts as a correction. This strategy is statistically verified through exploring the effect of N-doping on the electronic/energetic properties of the N-doped tetracene derivatives and isomers. Several rules of thumb are suggested, and the reliability of this strategy is validated by comparison with experiments. This work proposes a novel strategy for exploring SF chromophores with insights into the SF energetics from ground-state properties and certainly has fundamental interest and generality in exploring efficient SF-capable materials.


Preparation and partial characterization of iron-sulfur, iron-selenium, and iron-tellurium complexes of bovine serum albumin.
An artificial Fe-S* protein was prepared by the reaction of bovine serum albumin with FeSO4 and Na2S or with a synthetic Fe-S*-1,4-butanenedithiol complex. These improved methods enabled us to characterize the derivatives from serum albumin. The Fe-S* albumin complex has about 20 iron ions and 14 labile sulfur atoms per molecule of the protein, whose absorption spectrum closely resembled that of 2Fe-2S* proteins. Its electron paramagnetic resonance spectrum exhibited signals different from those of ferredoxins. The addition of p-chloromercuriphenylsulfonate quenched the optical absorption in the visible region as well as the electron paramagnetic resonance signals. These properties of the albumin-iron complex are similar to those of iron-sulfur dithiothreitol and mercaptoethanol complexes, suggesting that the albumin-iron complex has one or more protein ligands besides sulfur lignads. Presumably, the oxygen atom of the tyrosine residue, or other hydroxyamino acids participates in the complex formation. In this context, the albumin polypeptide appears to be incapable of forming an iron-sulfur cluster identical to those of ferredoxins. Yet, from the albumin-iron derivative, the extrusion of the iron-sulfur core with benzenethiol provided products similar to those from ferredoxins. The iron-selenium and iron-tellurium derivatives of the bovine serum albumin were prepared and partially characterized by optical absorption and electron paramagnetic resonsnace spectroscopies. These results imply that both selenium and tellurium can be incorporated into the protein molecule as the respective labile components.


Cholesterol oxidase: thermochemical studies and the influence of hydroorganic solvents on enzyme activity.
Thermal and binary cosolvent studies of the cholesterol oxidase (cholesterol: oxygen oxidoreductase, EC 184.108.40.206) reaction have been carried out using batch microcalorimetry and ultraviolet spectrophotometry respectively. Heat conduction measurements are shown to provide the basis for a serum cholesterol assay yielding results comparable to conventional automated clinical assay. The enthalpy of the reaction for cholesterol oxidation, measured with different sources of the enzyme in the presence and absence of catalase is -113 +/- 7.2 mJ/mumol. The value is agreement with calculated estimates based on bond energies, enthalpies of formation and trigonal additivity contribution calculations. From this heat of reaction the deltaHf0 of cholestenone (c) is calculated to be -490 kJ . mol-1. No evidence for the reverse reaction could be adduced. Enzyme activation with detergent (Surfal) is attributed to the formation of mixed micelles of cholesterol with detergent molecules. The detergent concentration at which the enzyme is half activated corresponds to the critical micelle concentration of Surfal. The enhanced enzyme activity found when ethanol, acetonitrile and dioxane were examined as binary cosolvents with water is ascribed to a conformational change in the enzyme mediated through the altered structuredness of water. This cosolvent effect is abolished in the presence of 0.18% Surfal due to the formation of inverted mixed micelles of detergent with cholesterol.


Outcomes of emergency treatment in ruptured hepatocellular carcinoma in the ED.
The choice of emergency treatment of ruptured hepatocellular carcinoma (HCC) remains controversial. This study analyzed the prognostic factors for ruptured HCC seen in an ED. Patients were retrospectively classified into survival and mortality groups. Fifty-five patients were enrolled into this study, and the hospital mortality rate was 38.2%. There were no associations of clinical presentation, tumor characteristics, and emergency treatment method with patients' prognoses. Significantly higher mortality rate was noted in patients with poor liver function. The time between admission and emergency chemoembolization was significantly shorter in the mortality group than in the survival group (mean, 255 vs 394 minutes). The 1-month survival rate was 69% in patients who received conservative treatment and 59% in patients who underwent emergency chemoembolization. Routine emergency chemoembolization did not improve outcome and was associated with higher mortality and complication rates, especially in patients with poor liver function. Conservative therapy may be a preferable option for patients with ruptured HCC if they have baseline poor liver function.


Serum PTH at 4 h after total thyroidectomy as a predictor of hypocalcemia: a prospective time frame analysis in search of evidence.
There has not been a universal agreement about the timings and the threshold level of PTH that can accurately predict the risk of hypocalcemia. Our study aimed to investigate the changes in the serum PTH levels at various time intervals and correlate it with the development of subsequent hypocalcemia. All patients had a pre-operative serum PTH done and were again assessed intra-operatively, at 4 h, 24 h, 72 h, and 1 month after the thyroid surgery. Absolute serum PTH value at various time points, absolute change in serum PTH values compared to pre-operative level, and relative change (percentage change) in serum PTH values compared with pre-operative levels were used to predict post-operative Hypocalcemia. 49 patients were included in the study. The sensitivity and negative predictive value was 100% for serum PTH at 4 h. There was a statistically significant difference between the groups that required calcium supplementation versus the group that did not require it. The maximum relative reduction in serum PTH value with respect to the pre-operative level occurred at 4 h in the calcium supplement required group which was 82.5%. Use of combination of 4 h serum PTH and relative change at 4 h yielded the best results. A combination of absolute serum PTH level at 4 h and the relative decline in serum PTH at 4 h has the highest diagnostic accuracy. The use of this combined parameter helps to reliably predict patients who would require supplementation.


Up regulation of ICAM-1 gene expression inhibits tumour growth and liver metastasis in colorectal carcinoma.
We have previously reported that decreased intercellular adhesion molecule-1 (ICAM-1) expression in cancer cells is associated with liver metastasis of colorectal cancer. In this study, we have investigated the effect of ICAM-1 gene transfection into the human colorectal cancer cell line LM-H3 on cell adhesiveness and cytotoxicity of peripheral blood mononuclear cells (PBMC) to cancer cells. Furthermore, we have investigated the effects of this gene transfer on subcutaneous tumour and liver metastases of LM-H3 in nude mice. More PBMC adhered to ICAM-1 transfected LM-H3 cells, LM-H3/ICAM-1, than to non-transfected LM-H3 cells and control LM-H3/Vector. Lysis of LM-H3/ICAM-1 cells by PBMC was significantly increased compared with LM-H3/Vector. Liver metastases with LM-H3/ICAM-1 cells were fewer in number and smaller than metastases with LM-H3/Vector. Intra-tumoural injection of ICAM-1 adenoviral vector significantly inhibited the growth of subcutaneous LM-H3 tumour. In conclusion ICAM-1 gene transfection using adenovirus vector might be an effective therapy for liver metastasis of colorectal carcinoma.


Development of the diencephalic relay structures of the visual thalamofugal system in pigeons.
To compare the developmental pattern of the visual tecto- and thalamofugal pathways in the altricial pigeon, we examined the posthatch differentiation of the retinothalamic system. Choleratoxin was injected into the left and right eye to visualize the retinal innervation pattern of the lateral geniculate nucleus of the thalamus (GLd). The calcium-binding proteins parvalbumin and calbindin and GABA(Abeta) receptors were used as indicators for the functional development of the GLd. Although all retinorecipient thalamic target structures were invaded by retinal fibers directly after hatching, density of the projection increased during the first week. While the adult GLd was characterized by a substantial number of cells displaying calbindin-immunoreactivity and by a sparse innervation by parvalbumin-immunoreactive fibers, after hatching no labelling for calcium-binding proteins could be detected. Calbindin-immunoreactivity appeared not before posthatching day 7, while parvalbumin-immunoreactive fibers were detected only after the third week. In contrast, a dense but diffuse GABA(Abeta) receptor-labelling was present from hatching onwards that decreased during development. The delayed expression of calbindin as well as changes in the density of GABA(Abeta) receptors indicate that maturation of GLd neurons extends long into the posthatch period. It is likely that the GABAergic interneurons mainly develop within this posthatch timeframe. Combined with the delayed development of the parvalbumin-positive innervation, the developmental pattern of GLd neurons suggests that the thalamofugal networks are immature after hatching and therefore still sensitive to modulations of posthatch visual experience.


Emotional Labor of Nurses and Phlebotomists in a New Source Plasma Collection Site During the COVID-19 Pandemic.
As uses of plasma-derived medical products increase globally, so does the demand to collect plasma from donors. There is evidence that positive interactions with center staff motivate plasma donors to return. This paper reports on a focused ethnography investigating experiences of nurses and phlebotomists in one of Canadian Blood Services' first source plasma collection center during the COVID-19 pandemic. Participants found the transition from whole blood collection to source plasma amid a global pandemic challenging, but they adapted by coming together as a team, and then worked to put the donor experience first. Their experience resonates with scholarship on emotional labor. As blood services worldwide attempt to increase source plasma collection, there is a need to understand care work that nurses and phlebotomists perform on the front-line. This study offers insight into how blood services can support staff in plasma operations by recognizing emotional labor.


TD-DFT, DFT, docking, MD simulations, and concentration-dependent SERS investigations of a bioactive trifluoromethyl derivative having human acetylcholinesterase and butyrylcholinesterase in silver colloids.
Various concentrations of (E)-4-methoxy-N'-(2-(trifluoromethyl)benzylidene) benzohydrazide (EMT) adsorbed on colloidal silver nanoparticles were studied using SERS and results were compared to the normal Raman spectrum. DFT calculations were used to validate experimental findings. Theoretically, the structures of the EMT and EMT-Ag6 systems were optimized. The UV-Vis spectral analysis's red shift and lower intensity behavior show that EMT has chemisorbed onto Ag nanoparticles. Charge transfer (CT) from Ag to EMT is highlighted by FMO analysis. The CT interaction in EMT and EMT-Ag6 was further verified by MEP and Mulliken charge analyses. The EMT was adsorbed on Ag nanoparticles with tilted orientation and orientation changes with colloidal concentration, according to SERS spectrum analysis. Docking EMT with 4PQE and 5DYW binding affinities are found to be -9.7 and -8.1 kcal/mol. MD simulations give the competence of 5DYW-EMT and 4PQE-EMT in their intended binding interactions and their ability to establish enduring associations with the protein of interest. DFT was used to optimize the molecular structures of EMT and EMT-Ag6 using B3LYP/6-311++G* (LANL2DZ basis set for Ag). A molecular dynamics simulation study was conducted on the 4PQE-EMT and 5DYW-EMT systems using the Desmond software for 100 ns.


Sentinel node in the era of neoadjuvant therapy and locally advanced breast cancer.
The most important determinant of prognosis for patients with breast cancer is the status of the axillary lymph nodes. Axillary lymph node dissection (ALND) has been performed for over a century to stage the cancer, achieve regional control, and perhaps improve survival. In accordance with tradition, ALND has been performed on all patients with the diagnosis of invasive breast cancer. In the early 1990s, this dogma was challenged because of the significant morbidity associated with ALND (paresthesia, extremity lymphedema) and the fact that greater than 50% of all breast cancers are node negative. A less morbid but highly accurate staging procedure, lymphatic mapping and sentinel lymph node biopsy (SNB) was introduced. Currently, the de facto standard of care in breast cancer is to perform LM and SNB in patients with small tumors and clinically negative axilla. While numerous methodological issues are being raised, the utility of LM and SNB identification continues to expand. In the current review we assess the application of this technique to locally advanced breast cancer (LABC) and neoadjuvant chemotherapy. What role does SNB play in locally advanced disease? Is LM and SNB accurate for patients with advanced disease? What influence do axillary metastases have on further treatment? What is the role of SNB in the planning for neoadjuvant patients? The skillful management of patients with breast cancer lies in the delicate balance between maximizing the efficacy of treatment and minimizing its morbidity and failure.


[Laboratory analysis of infectious keratitis in patients following refractive surgery].
To describe the laboratory findings in patients with infectious keratitis, who underwent refractive surgery, correlating the surgical procedure and the time of infection manifestation, and the results of culture and smears. The previous samples were obtained from patients submitted to radial keratotomy (RK), photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) at the Ophthalmology Department of UNIFESP. The infections were classified as early, when they occurred up to 30 days after the surgery, and late when diagnosed after 30 days. In 93 samples, 39 (42%) came from patients submitted to radial keratotomy, 14 (36%) being early infections and 25 (64%) late; 38 (41%) of LASIK, 21 (55%) being early and 17 (45%) late; 16 (17%) of photorefractive keratectomy, 10 (62.5%) being early and 6 (37.5%) late. Eighty-six samples were submitted to culture and smears for bacteria, 43 cultures (50%) and 43 smears (50%) were positive. Seventy-two samples were submitted to culture and smears for fungi, 2 cultures (3%) and 4 smears (6%) were positive. The agreement between culture and smear results was 80.2%; regarding the type of surgery there was no statistically significant relationship between time of onset of infection and surgery.


The no-reflow phenomenon: State of the art.
Primary percutaneous coronary intervention (PCI) is the best available reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI), with nearly 95% of occluded coronary vessels being reopened in this setting. Despite re-establishing epicardial coronary vessel patency, primary PCI may fail to restore optimal myocardial reperfusion within the myocardial tissue, a failure at the microvascular level known as no-reflow (NR). NR has been reported to occur in up to 60% of STEMI patients with optimal coronary vessel reperfusion. When it does occur, it significantly attenuates the beneficial effect of reperfusion therapy, leading to poor outcomes. The pathophysiology of NR is complex and incompletely understood. Many phenomena are known to contribute to NR, including leukocyte infiltration, vasoconstriction, activation of inflammatory pathways and cellular oedema. Vascular damage and haemorrhage may also play important roles in the establishment of NR. In this review, we describe the pathophysiological mechanisms of NR and the tools available for diagnosing it. We also describe the microvasculature and the endothelial mechanisms involved in NR, which may provide relevant therapeutic targets for reducing NR and improving the prognosis for patients.


Protein kinase C differently regulates quisqualate- and 1S,3R-trans aminocyclopentane dicarboxylate-induced phosphoinositide hydrolysis during in vitro development of hippocampal neurons.
Transient peaks of quisqualate (QA)-, but not 1S,3R-1-amino-3-cyclopentane dicarboxylate (1S,3R-ACPD)- and carbachol-induced inositol phosphate formation occur between 2 and 5 days in vitro (DIV) in hippocampal neurons in culture. In order to elucidate the putative origin of such developmental activity differences, the effect of PKC on metabotropic glutamate receptor (mGluR) and muscarinic receptor responses was investigated at 3 and 10 DIV. (i) Stimulation of PKC by phorbol-12,13-dibutyrate inhibited QA, 1S,3R-ACPD and carbachol responses at 3 DIV. At 10 DIV, only 1S,3R-ACPD response was still inhibited by phorbol esters. (ii) Inhibition of PKC by staurosporine at 3 DIV potentiated 1S,3R-ACPD-induced inositol phosphate formation, but had no effect on QA and carbachol responses. At 10 DIV, all responses were potentiated by staurosporine. These data strongly suggest that PKC differently modulates 1S,3R-ACPD- and QA-induced inositol phosphate accumulations during in vitro development. The specific activity of mGluRs during development, vs that of muscarinic receptor, and the peculiar modes of regulation by PKC of these two mGluR activities further suggest their particular involvement in the maturation of neuronal culture.


Hospital admissions for seizure in Italy: a decennial retrospective analysis with a special focus on the burden in the pediatric age.
The aim of the study was to analyze the incidence of hospitalizations for different types of convulsions in Italy during the years 2001-2010, especially in the pediatric age, with a focus on febrile seizures. National hospital discharge records of admissions for any type of convulsion from 2001 to 2010 were analyzed. The incidence rates were calculated considering the pediatric resident population estimated by the Italian Institute of Statistics in the studied years. 675,189 Hospital discharge records were analyzed, 256,126 of which had at least one specific diagnosis code for convulsion. 77 % of seizures were concentrated in the age group 0-3 years (618/100,000 inhabitants). The admission regimen was mainly ordinary (92 %). 97.6 % of admissions were <7 days and 91 % of hospital discharges were ordinary discharges to home. The percentage distribution of seizures showed a constant trend over the considered period. The code "febrile seizures" represented 71.9 % of all seizures in the pediatric population. 94.5 % was concentrated in children aged 0-5 years. The obtained data could be useful to put into the right perspective issues arising from the reports of febrile seizures following the administration of pediatric vaccines.


The Inventory of Functional Status-Dialysis: development and testing.
Development and psychometric testing of the Inventory of Functional Status-Dialysis (IFS-Dialysis), which was designed to measure functional status in persons who are receiving chronic incenter hemodialysis treatment. Three-phase instrument development design: Phase 1--content validity assessment; Phase 2--examination of internal consistency reliability; Phase 3--examination of construct validity. 175 chronic hemodialysis patients recruited from an urban, free-standing, outpatient dialysis center. Content validity was determined using Popham's average congruency proceudre. Internal consistency reliability was determined using Cronbach's alpha reliability coefficient. Construct validity was examined by bivariate correlations between the IFS-Dialysis and the Karnofsky Performance Scale (KPS), and the Medical Outcomes Study Short Form-36 Health Survey (SF-36) in a subsample of 60 patients. Content validity was established at 90%. The alpha reliability coefficient for the IFS-Dialysis was 0.86. Subscale alpha coefficients ranged from 0.71-0.82. Correlation between the IFS-Dialysis and the KPS was 0.55. Correlations between the IFS-Dialysis and SF-36 subscales ranged from 0.14-0.53. The IFS-Dialysis has acceptable content validity, internal consistency, and initial construct validity. Use of the IFS-Dialysis in clinical practice is appropriate.


Estimating and correcting mie scattering in synchrotron-based microscopic fourier transform infrared spectra by extended multiplicative signal correction.
We present an approach for estimating and correcting Mie scattering occurring in infrared spectra of single cells, at diffraction limited probe size, as in synchrotron based microscopy. The Mie scattering is modeled by extended multiplicative signal correction (EMSC) and subtracted from the vibrational absorption. Because the Mie scattering depends non-linearly on alpha, the product of the radius and the refractive index of the medium/sphere causing it, a new method was developed for estimating the Mie scattering by EMSC for unknown radius and refractive index of the Mie scatterer. The theoretically expected Mie contributions for a range of different alpha values were computed according to the formulae developed by Van de Hulst (1957). The many simulated spectra were then summarized by a six-dimensional subspace model by principal component analysis (PCA). This subspace model was used in EMSC to estimate and correct for Mie scattering, as well as other additive and multiplicative interference effects. The approach was applied to a set of Fourier transform infrared (FT-IR) absorbance spectra measured for individual lung cancer cells in order to remove unwanted interferences and to estimate ranges of important alpha values for each spectrum. The results indicate that several cell components may contribute to the Mie scattering.


Pleomorphic pulmonary hamartoma: an apparently unique variant of pulmonary hamartoma.
Pulmonary hamartomas of limited variety have been described. Most present as asymptomatic coin lesions in adults and consist of mesenchymal tissue, usually cartilage, in combination with irregular spaces lined by epithelium. Another form is found in the neonate and involves large portions or all of a lung. This is associated with a developmental aberration and is best described as a "congenital adenomatoid malformation". An apparently unique noninvasive tumor mass was resected from the lung of a middle aged man where it was associated with anomalous lung segmentation and the bronchial and blood supply to the lung. The tumor appeared to be undifferentiated by light microscopic criteria. Neurilemoma, leiomyoma, chordoid tumor, mixed tumor, and neurogenic sarcoma all entered the differential diagnosis. Ultrastructural examination demonstrated a highly complex and unique organization. Such a lesion, apparently developmental in this case, should be recognized and carefully distinguished from the malignant mesenchymal, neurogenic, and teratomatous lesions with which it may be confused. Electron microscopy may be helpful in this regard.


Self-sustained oscillations and chaos in space charge limited currents.
In kinetic simulations of a flow of charged particles between two parallel plate electrodes, it is found that chaotic responses in space charge limited currents can be induced by a periodically varying applied voltage.


Genotyping of the Echinococcus granulosus in Paraffin-Embedded Human Tissue Samples from Iran.
Cystic Echinococcosis (CE) is a medically important disease that is caused by the metacestodes of Echinococcus granulosus. Human hydatid is considered an endemic disease in specific regions of Iran. The goal of the present study was to determine the genetic diversity of E. granulosus from the paraffin-embedded human tissue samples which were collected from the endemic regions of Iran. Fifty-five formalin-fixed and paraffin-embedded hydatid cysts (FFPE) of humans, which had been removed surgically, were obtained from the South Khorasan and Sistan and Baluchistan provinces. These regions are related to the East and Southeast regions of Iran, respectively. The cox1 and nad1 genes from mitochondria were amplified from the extracted DNA and sequenced. The sequences were edited using the BioEdit software. Furthermore, phylogenetic and genetic diversity analyses were performed. Sequencing of the cox1 and nad1 genes from the 44 CE samples was done successfully. Genetic analysis revealed that 38 (86.3%) and 6 (13.6%) of the isolates were G1- and G6-genotypes, respectively. In general, eight and six haplotypes were identified by cox1 and nad1 genes analysis, respectively. For G1 strains, the haplotype diversity index was higher for the cox1 gene (0.6 ± 0.07) in comparison with the nad1 gene (0.4 ± 0.09). The findings of the present study showed that the sheep strain (G1) and the less important camel strain (G6) play the main roles in the transmission cycle of CE in the East and Southeast regions of Iran. Therefore, these results could be useful for managing the hydatid disease control programs in the studied and other similar areas.


Greater nondominant hand proficiency is not associated with enhanced simulated surgical performance.
To determine whether greater nondominant hand proficiency, or handedness approaching ambidexterity, is associated with better two-handed anterior segment surgical outcomes. Repeated-measures study. Our study included 14 resident physicians from various medical specialties, including ophthalmology, from our academic institution. The Eyesi surgical simulator was used to measure the surgical proficiency of 14 resident physicians at our institution on a dominant hand, nondominant hand, and separate bimanual task. The Edinburgh Handedness Inventory (EHI) was used to provide a measure of handedness for each participant. The measured parameters were dominant hand, nondominant hand, and bimanual task scores as determined by the Eyesi surgical simulator and gradients of handedness as determined by the Edinburgh Handedness Inventory for each participant. Having greater nondominant hand proficiency did not enhance two-handed surgical outcomes (p = 0.23). Surgical proficiency was greater bimanually compared with use of the nondominant hand alone (median score 74.0 vs 61.0; p = 0.0007), and bimanual and dominant hand surgical performances were not statistically significantly different from each other (median score 74.0 vs 70.5; p = 0.17). Our study shows that having greater nondominant hand proficiency is not a necessary trait for simulated anterior segment surgical aptitude. Two-handed surgical outcomes are directly related to dominant hand surgical performance but less so to the nondominant hand.


Deletion of the deISGylating enzyme USP18 enhances tumour cell antigenicity and radiosensitivity.
Interferon (IFN) signalling pathways, a key element of the innate immune response, contribute to resistance to conventional chemotherapy, radiotherapy, and immunotherapy, and are often deregulated in cancer. The deubiquitylating enzyme USP18 is a major negative regulator of the IFN signalling cascade and is the predominant human protease that cleaves ISG15, a ubiquitin-like protein tightly regulated in the context of innate immunity, from its modified substrate proteins in vivo. In this study, using advanced proteomic techniques, we have significantly expanded the USP18-dependent ISGylome and proteome in a chronic myeloid leukaemia (CML)-derived cell line. USP18-dependent effects were explored further in CML and colorectal carcinoma cellular models. Novel ISGylation targets were characterised that modulate the sensing of innate ligands, antigen presentation and secretion of cytokines. Consequently, CML USP18-deficient cells are more antigenic, driving increased activation of cytotoxic T lymphocytes (CTLs) and are more susceptible to irradiation. Our results provide strong evidence for USP18 in regulating antigenicity and radiosensitivity, highlighting its potential as a cancer target.


The efficacy of the disinfection of bronchoscopes contaminated in vitro with Mycobacterium tuberculosis and Mycobacterium avium-intracellulare in sputum: a comparison of Sactimed-I-Sinald and glutaraldehyde.
The efficacy of Sactimed-I-Sinald and glutaraldehyde was tested against clinical isolates of Mycobacterium tuberculosis (MTB) and Mycobacterium avium-intracellulare (MAI). An in-use method demonstrated that over 10 disinfection cycles, using an auto-disinfector and a contact time of 60 min, MTB was eradicated in 10 out of 10 cycles with Sactimed-I-Sinald and five out of 10 cycles for glutaraldehyde. For MAI, Sactimed-I-Sinald showed a 5 log reduction at a 60 min contact time, which was not seen with glutaraldehyde. Although further evaluation is necessary, Sactimed-I-Sinald appears a promising alternative to glutaraldehyde.


Thyroid hormone regulates mRNA expression and currents of ion channels in rat atrium.
Atrial fibrillation is one of the common arrhythmias associated with hyperthyroidism. This study examined the effects of thyroid hormone (T3) on mRNA expression and currents of major ionic channels determining the action potential duration (APD) in the rat atrium using the RNase protection assay and the whole-cell patch-clamp technique, respectively. T3 increased the Kv1.5 mRNA expression and decreased the L-type calcium channel mRNA expression, while the Kv4.2 mRNA expression did not change. APD was shorter in hyperthyroid than in euthyroid myocytes. The ultrarapid delayed rectifier potassium currents were remarkably increased in hyperthyroid than in euthyroid myocytes, whereas the transient outward potassium currents were unchanged. L-type calcium currents were decreased in hyperthyroid than in euthyroid myocytes. T3 shifted the current-voltage relationship for calcium currents negatively. In conclusion, T3 increased the outward currents and decreased the inward currents. The resultant changes of ionic currents shortened APD, providing a substrate for atrial fibrillation.


Indigenous Sudanese sorghum-based food: Secondary metabolites and antioxidant activities of traditional Sudanese nonalcoholic beverage Hulu-mur from two sorghum landraces.
Hulu-mur is a Sudanese traditional nonalcoholic beverage that is made from sorghum flour. This work determined the secondary metabolites and antioxidant activities of traditional Sudanese nonalcoholic beverage Hulu-mur from two local sorghum landraces Abjaro and Hegarii. The changes on the total phenolic content (TPC), total flavonoid content (TFC), carotene content, tannins, and antioxidant activity (DPPH, reducing power, and FRAP) were estimated during the preparation of the Hulu-mur flasks. For both landraces, a significant (p < .05) effect on the phytochemical compound and the antioxidant activity was observed during malting and fermentation of sorghum flour. However, the most increase in the TPC and carotene content was observed, whereas tannin and TFC were decreased in the Hulu-mur flasks compared with the malted and fermented samples. The antioxidant activity DPPH, TRP, and FRAP was significantly (p < .05) higher in Hulu-mur flasks than those of raw and processed flour. The partial least squares regression test stated a positive validation score of the Hulu-mur flasks prepared from the both landraces. In conclusion, Hulu-mur drink from Abjaro and Hegarii landraces contain high antioxidants compound, which could improve the health-promoting metabolites in Sorghum-based food.


Body Posture After Mastectomy: Comparison Between Immediate Breast Reconstruction Versus Mastectomy Alone.
Immediate breast reconstruction has been increasingly incorporated as part of breast cancer treatment, especially for the psychological benefits. Currently, there are many options for breast reconstruction surgery, but the impact of the different techniques on body posture has not been widely studied. One study demonstrated that immediate breast reconstruction with a Beker-25 prosthesis could help to preserve body posture after mastectomy; however, there is no evidence regarding the effect of surgery on the body posture of women after breast reconstruction when using autologous tissue. The purpose of this paper is to compare the body postures of women who underwent immediate breast reconstruction using an abdominal flap with those of women who underwent mastectomy alone. This is a cross-sectional study. Seventy-six women diagnosed with breast cancer underwent mastectomy, between 1 and 5 years after the diagnosis, are the participants of the study. Two groups were defined: women who underwent mastectomy and immediate breast reconstruction (n = 38) and women who underwent mastectomy alone (n = 38). To assess body posture, specific anatomical points for obtaining photographs were located and marked in anterior, posterior and right-side and left-side views. The photographs were analysed using Postural Analysis Software/Software de Análise Postural (PAS/SAPO). In the left lateral view, there was a significant difference in the vertical alignment of the trunk (4.2 vs 3.1; p = 0.05). There were no significant differences between the two groups for the variables in the anterior, posterior or right-side views. Women who underwent mastectomy alone, compared with women who underwent immediate breast reconstruction with abdominal flaps, showed differences in the vertical alignment of the trunk, with greater asymmetry between the acromion and greater trochanter, which can mean trunk rotation. No significant differences were found between the two groups in the alignment of the head, shoulders, scapula, or pelvis. Copyright © 2015 John Wiley & Sons, Ltd.


Regeneration of mastoid air cells using polycaprolactone/β-tricalcium phosphate biocomposites: an experimental study.
The study aimed to regenerate pneumatic air cells in guinea pig bulla using three-dimenisonal (3D) biocomposite scaffolds consisting of polycaprolactone/β-tricalcium phosphate (PCL/β-TCP). Prospective controlled study in experimental animals. PCL/β-TCP composites were implanted into the bulla with mucosa preservation in group A (n = 10). PCL/β-TCP composites coated with collagen were implanted in group B (n = 10). After 12 weeks, the bullae were extracted and evaluated by micro-computed tomography (micro-CT) and were processed for histological analyses. In group A, micro-CT showed a well-maintained honeycomb appearance of micropores without obstruction. Regeneration of the mucosa was noted inside the pores of the 3D scaffold. However, partial obstruction of the micropores with new bone formation was evident in group B. Group A showed more satisfactory mucosal regeneration into the micropores. Our results indicate that the 3D scaffold may be amenable for use during mastoidectomy. Further studies for gas exchange in the regenerated mucosa are necessary.


Update on enterovirus 71 infection.
Human enterovirus type 71 (EV71) has emerged as a major cause of viral encephalitis in children worldwide. The identified EV71 receptors provide useful information for understanding EV71replication and tissue tropism. Host factors interact with the internal ribosome entry site (IRES) of EV71 to regulate viral translation. However, the specific molecular features of the EV71 genome that determine virulence remain unclear. The EV71 capsid protein VP1 region might contribute to virulence and neurotropism. Transgenic mice expressing the EV71 receptor that were infected with the virus exhibited a disease similar to that observed in infected humans. Antiviral drug and vaccine development is urgently required to prevent EV71 epidemics. Delineating viral host interactions and identifying specific mechanisms that might control the neural tropism of EV71 pathogenesis would be substantial advances.


Cross analysis of knowledge and learning methods followed by French residents in cardiology.
No scientific assessment of the theoretical teaching of cardiology in France is available. To analyse the impact of the available teaching modalities on the theoretical knowledge of French residents in cardiology. Electronic questionnaires were returned by 283 residents. In the first part, an inventory of the teaching/learning methods was taken, using 21 questions (Yes/No format). The second part was a knowledge test, comprising 15 multiple-choice questions, exploring the core curriculum. Of the 21 variables tested, four emerged as independent predictors of the score obtained in the knowledge test: access to self-assessment (P=0.0093); access to teaching methods other than lectures (P=0.036); systematic discussion about clinical decisions (P=0.013); and the opportunity to prepare and give lectures (P=0.039). The fifth variable was seniority in residency (P=0.0003). Each item of the knowledge test was analysed independently: the score was higher when teaching the item was driven by reading guidelines and was lower if the item had not been covered by the programme (P<0.001). Finally, 91% of students would find it useful to have a national source for each topic of the curriculum; 76% of them would often connect to an e-learning platform if available. It is necessary to rethink teaching in cardiology by involving students in the training, by using teaching methods other than lectures and by facilitating access to self-assessment. The use of digital tools may be a particularly effective approach.


Midnight salivary cortisol secretion and the use of antidepressants were associated with abdominal obesity in women with type 1 diabetes: a cross sectional study.
Abdominal obesity is a risk factor for cardiovascular disease. The aim was to explore the influence of midnight salivary cortisol (MSC), antidepressants and sex on abdominal obesity in type 1 diabetes (T1D). We controlled for physical inactivity, smoking, depression and alexithymia. Cross sectional study of 190 T1D patients (86 women/104 men, 18-59 years, diabetes duration 1-55 years), consecutively recruited from one specialist diabetes outpatient clinic. Anthropometrics, blood pressure, saliva and blood samples were collected, supplemented with data from electronic medical records. Depression and alexithymia were assessed by self-report instruments. MSC (nmol/l) was categorised into 3 levels: high MSC: (≥ 6.7) (n = 64); intermediate MSC: ≥ 3.7- < 6.7) (n = 64); low MSC (< 3.7) (n = 62). Abdominal obesity was defined as waist circumference (meters) ≥ 0.88 for women and as ≥ 1.02 for men. Multiple logistic regression analyses (Backward: Wald) were performed. The Hosmer and Lemeshow test for goodness-of-fit and Nagelkerke R2 were used to evaluate each multiple logistic regression analysis model. The prevalence of abdominal obesity was three times higher in the women than in the men (24% versus 8%) (p = 0.002). Antidepressants were used by 10% of the women and by 4% of the men (p = 0.09). The prevalence of high MSC was 1.7 times higher in the women (43% versus 26%); the prevalence of both intermediate MSC (28% versus 38%) and low MSC (29% versus 36%) were lower in the women (p = 0.048). Significant associations with abdominal obesity were for all 190 patients: female sex (adjusted odds ratio (AOR) 3.4 (confidence interval (CI) 1.4-8.2)) and the use of antidepressants (AOR 4.3 (CI 1.2-14.8)); for the 86 women: high MSC (AOR 18.4 (CI 1.9-181)) and use of antidepressants (AOR 12.2 (CI 2.0-73.6)); and for the 104 men: alexithymia (AOR 5.2 (CI 1.1-24.9)). Clear sex differences were demonstrated with a distinct higher prevalence of abdominal obesity, as well as a distinct higher prevalence of high midnight salivary cortisol in the women with type 1 diabetes. High midnight salivary cortisol secretion and the use of antidepressants were independent risk factors for abdominal obesity in the women.


Replacement of the trapeziometacarpal joint with a cemented (Caffinière) prosthesis.
Between 1978 and 1985, 31 Caffinière prostheses were implanted in the first carpometacarpal joints of 28 patients for treatment of degenerative osteoarthritis (26 patients) or rheumatoid arthritis (2 patients). At follow-up an average of 48 (13 to 77) months after operation, four hands had reoperation, with the replacement of six components, five cups and one metacarpal component. In addition, there were x-ray signs of component loosening in three other cases. Of the 29 thumbs that could be evaluated with regard to pain, 27 had no pain at all or only slight pain, and two patients had moderate pain. No patient suffered from severely disabling pain. Mobility and strength were satisfactory.


Naming speed as a clinical marker in predicting basic calculation skills in children with specific language impairment.
The present study investigated the role of naming speed in predicting the basic calculation skills (i.e., addition and subtraction) of kindergartners with Specific Language Impairment (SLI), when compared to a group of Normal Language Achieving (NLA) children. Fifty-three kindergartners with SLI and 107 kindergartners with NLA were tested on cognitive, linguistic and basic calculation skills. The results showed that phonological awareness, grammatical ability, general intelligence and working memory accounted for the variation in the basic calculation skills of both groups. However, an additional effect of naming speed on both addition and subtraction was found for the group of children with SLI, suggesting that naming speed may act as a clinical marker in identifying those children who are likely to develop problems in basic calculation skills.


The photodegradation of 17 alpha-ethinylestradiol in water containing iron and dissolved organic matter.
17 alpha-ethinylestradiol (EE2) in natural waters can seriously harm ecosystems and human health. Dissolved organic matter (DOM) and iron minerals are ubiquitous in natural waters, and they can shorten the half-life of EE2 in the natural environment. The interaction between dissolved organics and iron affects pollutants' transformation pathways. The mechanism of EE2's adsorption on hematite, magnetite and pyrite was studied. A photo-Fenton system was constructed in which humic acid (HA) and iron minerals degraded EE2 under simulated natural light conditions. Pyrite showed the best adsorption and degradation in acidic conditions (52%) for 5 h. Hydroxyl radical was found to be the main active substance in the photodegradation. The degradation products of EE2 were identified and possible degradation pathways were inferred. These results can contribute to the understanding of the transformation pathways of persistent organic pollutants in natural waters.


Does Socioeconomic Status Affect Stage at Presentation for Larynx Cancer in Canada's Universal Health Care System?
Diagnosis of laryngeal cancer is dependent on awareness that persistent hoarseness needs to be investigated as well as access to an otolaryngologist. This study aimed to better classify and understand 3 factors that may lead to variability in stage at presentation of laryngeal cancer: (1) socioeconomic status (SES), (2) differences in access to health care by location of residence (rural vs urban or by province), and (3) access to an otolaryngologist (by otolaryngologists per capita). Registry-based multicenter cohort analysis. This was a national study across Canada, a country with a single-payer, universal health care system. All persons 18 years or older who were diagnosed with laryngeal cancer from 2005 to 2013 inclusive were extracted from the Canadian Cancer Registry (CCR). Ordered logistic regression was used to determine the effect of income, age, sex, province of residence, and rural vs urban residence on stage at presentation. A total of 1550 cases were included (1280 males and 265 females). The stage at presentation was earlier in the highest income quintile (quintile 5) compared to the lower income quintiles (quintiles 1-4) (odds ratio [OR], 0.68; P < .05). There was a statistically significant difference in stage at presentation based on rural or urban residence within the highest income quintile (OR, 1.73; P < .005). There is a relationship between SES and stage at presentation for laryngeal cancer even in the Canadian universal health care system.


Comparisons of outcomes of open surgery versus endovascular intervention for thrombotic popliteal artery aneurysm with acute lower limb ischemia: a systematic review.
Thrombotic popliteal artery aneurysm (PAA) with acute lower limb ischemia (ALI) is a serious disease leading to amputation. The choice of emergency procedures is not clearly defined, and the difference in therapeutic efficiency between open surgery and endovascular intervention is still unclear. We conducted a comprehensive search through PubMed, Wiley Online Library and ScienceDirect. According to the predefined inclusion and exclusion criteria, eligible articles were screened out, and all relevant data were extracted for further analysis. Our study was designed and developed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guideline. We critically assessed all included articles by Joanna Briggs Institute (JBI) Critical Appraisal Checklists and the Methodological Index for Non-Randomized Studies (MINORS). A total of 29 articles (1338 patients/1387 limbs) were included in the study. After a 1-year follow-up, the primary patency rate of the open surgery group was significantly lower than that of the endovascular intervention group (72.65 vs. 81.46%, P = 0.004), but without significant difference in the secondary patency rate (86.19 vs. 86.86%, P = 0.825). The limb salvage rate of the open surgery group was also significantly lower (83.07 vs. 98.25%, P < 0.001). After the 2-year follow-up, the primary patency rate of the open surgery group was still significantly lower (48.57 vs. 59.90%, P = 0.021). The outcome of endovascular intervention was better than that of open surgery especially in the 1-year limb salvage rate and primary patency rate at the 1-year and 2-year follow-ups.


Effects of 2-, 4- and 12-hour fasting intervals on preoperative gastric fluid pH and volume, and plasma glucose and lipid homeostasis in children.
We evaluated 105 randomly-selected unpremedicated children aged 1-14 years to determine the effects of a 2-, 4- and 12-h preoperative fasting interval on the preoperative gastric fluid pH and volume, and plasma glucose and lipid homeostasis. Each child undergoing elective surgery ingested a large volume (approximately 10 ml/kg b.w.) of apple juice and then fasted for 2, 4 or 12 h before the estimated induction of anaesthesia. After induction of anaesthesia, gastric fluid was aspirated through a large-bore, multiorifice orogastric tube. Plasma concentrations of glucose, total ketone bodies, non-esterified fatty acid (NEFA), triglycerides, and cortisol were measured at the time of induction to evaluate the fasting interval effects on preoperative plasma glucose and lipid homeostasis. There were no significant differences between the three groups in either gastric fluid volume or pH. In addition, there were no significant differences between the groups with respect to the proportion with a pH < 2.5 and volume > 0.4 ml/kg b.w. Neither plasma concentrations of glucose, triglycerides, nor cortisol at the time of anaesthetic induction differed between the three groups. Both 4 and 12 h nil per os (NPO) caused an increase in lipolysis, which was presumably a compensatory mechanism to maintain normoglycaemia. The plasma NEFA and total ketone bodies concentrations were therefore significantly higher in these two fasting intervals than in 2 h NPO. These data suggest that a 2-h NPO, after a large volume of ingested apple juice, may offer additional benefits by preventing an increase in lipolysis during the fasting interval without either increasing the volume of gastric fluid or decreasing the gastric pH.(ABSTRACT TRUNCATED AT 250 WORDS)


Benefit of rectal washout for anterior resection and left sided resections.
To assess the effectiveness of rectal wash out in preventing local recurrence for patients who undergo anterior resection for recto-sigmoid cancer. A best evidence topic was constructed according to a structured protocol. Medline 1948-2015 and EMBASE 1980 to 2015 using the OVID interface: ( Rectal) AND (Washout) AND (Anterior Resection). In addition, the reference lists of the relevant papers were searched. Eight papers among the 17 relevant articles were identified as representing the best evidence including 3 prospective non-randomized studies, 1 retrospective non randomized study and 4 meta-analyses. On the basis of current evidence, rectal washout does not stop local recurrence of cancer after anterior resection or left sided colonic resection, but it may reduce the rate of local recurrence. A randomised controlled trial to address this issue would formally answer this question.