Hyperbaric Oxygen Therapy for Pain, Opioid Withdrawal, and Related Symptoms: A Pilot Randomized Controlled Trial.
Pain, drug cravings, and opioid withdrawal symptoms can interfere with substance use disorder or opioid tapering treatment goals. This pilot study investigated the feasibility of a protocol designed to test opioid withdrawal symptom relief relative to a sham condition after two consecutive days of hyperbaric oxygen therapy (HBOT) for adults prescribed daily methadone for opioid use disorder. Using a double-blind protocol, eight adults were randomized to receive either a full 90-minute HBOT dose in a pressurized chamber with 100% oxygen at 2.0 atmospheres absolute (ATA) or a sham condition receiving 21% oxygen (equivalent to room air within the chamber) at a minimal pressure of ≤1.3 ATA. Measures included study retention, treatment satisfaction, and pre- and post-intervention effects for opioid withdrawal symptoms, drug cravings, pain intensity and interference, sleep quality, and mood. Study retention and treatment satisfaction was high. All measurements improved more, on average, for participants receiving full-dose HBOT treatment than among participants receiving sham treatments except for clinically observed withdrawal symptoms. The largest positive effects were observed in measurements of pain intensity and drug craving. These pilot results provide evidence to support a fully powered study of HBOT as a potential treatment adjunct for adults receiving methadone for opioid use disorder. Trends towards symptom improvements were detected from pre- to post-HBOT in the full treatment arm versus sham condition. More research into novel non-pharmacologic options to relieve distressing symptoms related to pain and opioid use disorder is essential to improve clinical outcomes.


Sleep Promotes Downward Firing Rate Homeostasis.
Homeostatic plasticity is hypothesized to bidirectionally regulate neuronal activity around a stable set point to compensate for learning-related plasticity, but to date only upward firing rate homeostasis (FRH) has been demonstrated in vivo. We combined chronic electrophysiology in freely behaving animals with an eye-reopening paradigm to enhance firing in primary visual cortex (V1) and found that neurons bidirectionally regulate firing rates around an individual set point. Downward FRH did not require N-methyl-D-aspartate receptor (NMDAR) signaling and was associated with homeostatic scaling down of synaptic strengths. Like upward FRH, downward FRH was gated by arousal state but in the opposite direction: it occurred during sleep, not during wake. In contrast, firing rate depression associated with Hebbian plasticity happened independently of sleep and wake. Thus, sleep and wake states temporally segregate upward and downward FRH, which might prevent interference or provide unopposed homeostatic compensation when it is needed most.


Rational Designed Hybrid Peptides Show up to a 6-Fold Increase in Antimicrobial Activity and Demonstrate Different Ultrastructural Changes as the Parental Peptides Measured by BioSAXS.
Antimicrobial peptides (AMPs) are a promising class of compounds being developed against multi-drug resistant bacteria. Hybridization has been reported to increase antimicrobial activity. Here, two proline-rich peptides (consP1: VRKPPYLPRPRPRPL-CONH2 and Bac5-v291: RWRRPIRRRPIRPPFWR-CONH2) were combined with two arginine-isoleucine-rich peptides (optP1: KIILRIRWR-CONH2 and optP7: KRRVRWIIW-CONH2). Proline-rich antimicrobial peptides (PrAMPs) are known to inhibit the bacterial ribosome, shown also for Bac5-v291, whereas it is hypothesized a "dirty drug" model for the arginine-isoleucine-rich peptides. That hypothesis was underpinned by transmission electron microscopy and biological small-angle X-ray scattering (BioSAXS). The strength of BioSAXS is the power to detect ultrastructural changes in millions of cells in a short time (seconds) in a high-throughput manner. This information can be used to classify antimicrobial compounds into groups according to the ultrastructural changes they inflict on bacteria and how the bacteria react towards that assault. Based on previous studies, this correlates very well with different modes of action. Due to the novelty of this approach direct identification of the target of the antimicrobial compound is not yet fully established, more research is needed. More research is needed to address this limitation. The hybrid peptides showed a stronger antimicrobial activity compared to the proline-rich peptides, except when compared to Bac5-v291 against E. coli. The increase in activity compared to the arginine-isoleucine-rich peptides was up to 6-fold, however, it was not a general increase but was dependent on the combination of peptides and bacteria. BioSAXS experiments revealed that proline-rich peptides and arginine-isoleucine-rich peptides induce very different ultrastructural changes in E. coli, whereas a hybrid peptide (hyP7B5GK) shows changes, different to both parental peptides and the untreated control. These different ultrastructural changes indicated that the mode of action of the parental peptides might be different from each other as well as from the hybrid peptide hyP7B5GK. All peptides showed very low haemolytic activity, some of them showed a 100-fold or larger therapeutic window, demonstrating the potential for further drug development.


Postnatal gene transfer into the central nervous system.
Substantial progress has been made in the development of techniques for the expression of foreign genes in the central nervous system of postnatal animals. Fetal and adult brain cells and other cells, including fibroblasts and muscle cells, have been successfully employed as vehicles for foreign gene expression in the central nervous system. Direct gene transfer strategies, such as those using herpes and adenoviral vectors, are presently under intense and fruitful investigation.


Amelioration of autophagy and inflammatory signaling pathways via α-lipoic acid, burdock and bee pollen versus lipopolysaccharide-induced insulin resistance in murine model.
Lipopolysaccharide (LPS) has previously been implicated in insulin resistance by generating an innate immune response and activating inflammatory cascades. Many studies have discovered a relationship between high levels of serum LPS and the advancement of diabetic microvascular problems, indicating that LPS may play a role in the control of critical signaling pathways connected to insulin resistance. The current study focused on signaling pathways linked to insulin resistance and explored probable mechanisms of LPS-induced insulin resistance in a murine model. It next looked at the effects of burdock, bee pollen, and -lipoic acid on LPS-induced inflammation and autoimmune defects in rats. LPS intoxication was induced via ip injection for one week in a dose of 10 mg/kg followed by α-lipoic acid, Burdock and bee pollen in an oral treatment for one month. Following that, biochemical and molecular studies were performed. The RNA expression of the regulating genes STAT5A and PTEN was measured. In addition, ATF-4 and CHOP as autophagy biomarkers were also subjected to mRNA quantification. The results demonstrated a considerable improvement in the -lipoic acid, Burdock, and bee pollen treated groups via modifying oxidative stress indicators as well as molecular ones. Furthermore, glucose concentration in serum and α-amylase were also improved upon treatment with the superiority of α-lipoic acid for modulating all estimated parameters. In conclusion: the results declared in the current study suggested that α-lipoic acid could regulate insulin resistance signaling pathways induced by LPS intoxication.


Zolpidem and memory: a study using the process-dissociation procedure.
There is a dearth of studies which have employed sophisticated paradigms to investigate the effects of zolpidem on memory. To explore anterograde cognitive deficits induced by acute oral doses of zolpidem by means of the process-dissociation procedure (PDP). The present study followed a placebo-controlled, double-blind, parallel-group design. Young, healthy females were randomly allocated to one of three treatments with 12 subjects each: placebo, 5 mg and 10 mg zolpidem. Two word-stem completion tasks were carried out close to theoretical peak-plasma concentration: a) direct inclusion task with cued recall, in which participants had to try to use words seen at study to complete stems; and b) direct exclusion task, in which words seen at study were to be avoided as completions. The PDP was applied to the results in these tasks to yield indices of explicit/controlled (C) and implicit/automatic (A) memory. Classical psychometric tests were also carried out. Zolpidem 10 mg led to cognitive effects similar to benzodiazepines (except for the atypical lorazepam), including impairment of exclusion, but not inclusion-task performance. Results of the application of the PDP were inconclusive but concurred with the pattern established in previously published work on benzodiazepine effects, i.e. that zolpidem (10 mg) impaired C. Zolpidem leads to cognitive effects similar to most benzodiazepines. Although the application of PDP in drug studies may be counterproductive in view of methodological difficulties that are discussed, the pattern of effects on the stem-completion tasks involved in this paradigm is potentially useful in the investigation of cognitive effects of psychoactive drugs.


A population based study of outcomes after evacuation of primary supratentorial intracerebral hemorrhage.
The role of surgery after primary intracerebral hemorrhage (ICH) is controversial. To explore whether hematoma evacuation after ICH had improved short-term survival or functional outcome we conducted a retrospective observational population-based study. We identified all subjects with primary ICH between 1993 and 2008 among the population of Northern Ostrobothnia, Finland. Hematoma evacuation was carried out by using standard craniotomy or through a burr hole. We compared mortality rates and functional outcomes of patients with hematoma evacuation with those treated conservatively. Of 982 patients with verified ICH during the study period, 127 (13%) underwent hematoma evacuation. Surgically treated patients were significantly younger (mean±SD, 63±11 vs. 70±12 years; p<0.001), had larger hematomas (66±36 vs. 28±40 ml; p<0.001), lower Glasgow Coma Scale scores (median, 11 vs. 14; p<0.001) and more frequently subcortical hematomas (68% vs. 24%; p<0.001) than those treated conservatively. In multivariable analysis, hematoma evacuation independently lowered 3-month mortality (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.43-0.88; p<0.03), particularly among patients aged≤70 years with ≥30 ml supratentorial hematomas (adjusted HR, 0.26; 95% CI, 0.14-0.49; p<0.001). However, poor outcome was not improved by surgery (adjusted odds ratio 0.71; 95% CI 0.29-1.70). Improved 3-month survival was observed in patients who had undergone hematoma evacuation relative to patients not undergoing evacuation particularly in the subgroup of patients aged≤70 years with ≥30 ml supratentorial hematomas. Surgery might improve outcome if cases could be selected more precisely and if performed before deterioration.


[Tracheostomy in children with a clinical analysis of 156 cases].
To analyze the etiology and complications of the tracheotomy in children. A hundred and fifty-six cases of tracheotomized children were retrospectively analyzed. Three of the 156 cases died for protopathy, 132 cases extubated smoothly after the protopathies curing, 21 cases (including the laryngeal papilloma 18 ones) left hospital with endotracheal tubes. The complication's incidence rate was 23.1%, of these 1.9% was severer. The children's tracheotomy is distinct. Tracheotomy in children should hold indication correctly and operated versedly and nursed meticulously in order to reduce complications.


[Nuclear alterations on organ cultures of human malignant melanomas (author's transl)].
Report on ultrastructurally striking nuclear anomalies in organ cultures obtained from amelanotic and pigmented human melanomas. These nuclear anomalies are more impressive than the nuclear invaginations present in tumours cells of several other malignant growths. Numerous nuclear fragments varying in size and held together by nuclear membrane bands may occur. The karyoplasm of these nuclei reveals nothing unusual no degenerative changes can be found.


DNA-binding activity of Jun is increased through its interaction with Fos.
Transcription factor AP-1 mediates induction of a set of genes in response to the phorbol ester tumor promoter TPA. Recently, AP-1 preparations from HeLa cells were shown to contain a product of the c-JUN protooncogene (Jun/AP-1) which forms a tight complex with the Fos protein. In this paper, we examine the role of the Fos protein in the DNA-binding activity of the AP-1 complex. We show that the DNA-binding activity of bacterially expressed trpE-Jun fusion proteins is increased many-fold upon their interaction with Fos (or a Fos-related antigen) expressed from a baculovirus vector. The site of Fos interaction is within the DNA-binding domain of Jun/AP-1, and anti-Fos antibodies interfere with the binding of affinity purified AP-1 to DNA. These results suggest that, by associating with Jun/AP-1, Fos is responsible for the formation of a multimeric protein complex that has greater affinity for the target sequence than does Jun/AP-1 alone.


Vitamin D analogues: Potential use in cancer treatment.
The vitamin D receptor (VDR) is a member of the thyroid-steroid family of nuclear transcription factors. Following binding of the active form of vitamin D, i.e., 1,25(OH)2D3 (also known as calcitriol) and interaction with co-activators and co-repressors, VDR regulates the expression of several different genes. Although relatively little work has been carried out on VDR in human cancers, several epidemiological studies suggest that low circulating levels of vitamin D are associated with both an increased risk of developing specific cancer types and poor outcome in patients with specific diagnosed cancers. These associations apply especially in colorectal and breast cancer. Consistent with these findings, calcitriol as well as several of its synthetic analogues have been shown to inhibit tumor cell growth in vitro and in diverse animal model systems. Indeed, some of these vitamin D analogues with low calcemic inducing activity (e.g., EB1089, inecalcitol, paricalcitol) have progressed to clinical trials in patients with cancer. Preliminary results from these trials suggest that these vitamin D analogues have minimal toxicity, but clear evidence of efficacy remains to be shown. Although evidence of efficacy for mono-treatment with vitamin D analogues is currently lacking, several studies have reported that supplementation with calcitriol or the presence of high endogenous circulating levels of vitamin D enhances response to standard therapies.


Autophagy and cellular immune responses.
Autophagy constitutes a mechanism for the sequestration and lysosomal degradation of various cytoplasmic structures, including damaged organelles and invading microorganisms. Autophagy not only represents an essential cell-intrinsic mechanism to protect against internal and external stress conditions but also shapes cellular immunity. Recent evidence indicates that autophagic responses in antigen-donor cells affect the release of several cytokines and "danger signals." Thus, especially when it precedes cell death, autophagy alerts innate immune effectors to elicit cognate immune responses. Autophagy is also important for the differentiation, survival, and activation of myeloid and lymphoid cells. Accordingly, inherited mutations in autophagy-relevant genes are associated with immune diseases, whereas oncogenesis-associated autophagic defects promote the escape of developing tumors from immunosurveillance. Here, we discuss the regulation of autophagy in the course of cellular immune responses and emphasize its impact on the immunogenicity of antigen-donor cells and on the activity of antigen-presenting cells and T lymphocytes.


Correction: Associations of gamma-glutamyl transferase with cardio-metabolic diseases in people living with HIV infection in South Africa.
[This corrects the article DOI: 10.1371/journal.pone.0246131.].


Computer modeling of two inorganic pyrophosphatases.
The yeast Saccharomyces cerevisiae has two inorganic pyrophosphatases that are structurally related. One, PPA1, is a cytoplasmic enzyme. The other, PPA2, is located in the mitochondria and appears to be energy-linked. The sequence similarity of PPA1 and PPA2 is about 66% and the identity is about 50%. All amino acids known to be important for catalysis are conserved, except one glutamate which is substituted by an aspartate in PPA2. The structures of PPA2 and the cytoplasmic PPase from Schizosaccharomyces pombe were modeled based on the three dimensional structure of PPA1. Two cysteines in PPA2 and one in the S. pombe enzyme are located at the catalytic cleft. Four residues form an unique insertion near the entrance of the catalytic cleft in the mitochondrial enzyme.


Distance bias and surgical outcomes.
A body of research has found that patients who travel a significant distance to obtain medical treatment experience better outcomes, a phenomenon termed "distance bias." This study uses risk-adjusted surgical outcomes data to analyze distance bias in a population of patients treated surgically at a tertiary care institution. We used risk-adjusted surgical outcomes data from the National Surgical Quality Improvement Project at the Mayo Clinic to calculate observed and expected risk of a severe complication. Operations were stratified into quintiles based on the distance traveled by the patient. The average age of patients in our cohort was 56.7 years, and 59.2% were female; patients traveled an average of 226 miles for treatment. Patients living closest to the Mayo Clinic (quintile 1) had lower observed and expected risks of a severe complication relative to patients in quintiles 2-5. Patients from quintile 1 had outcomes which were better than predicted [observed:expected risk ratio of 0.82 (range, 0.63-0.99)]. Patients traveling intermediate distances (quintile 2) had outcomes which were worse than predicted [observed:expected risk ratio of 1.18 (range, 1.00-1.42)]. Operations performed on patients from greater distances (quintiles 3-5) had an observed risk of severe complications which was similar to expected. The phenomenon of distance bias which has previously been documented in medical and oncologic treatment is not demonstrated in this study. An opposite phenomenon may be more pertinent, where patients who are treated locally are less likely to have a severe complication and have outcomes which are better than predicted.


The relationship between adjuvant and mitogenic effects of amphotericin methyl ester.
The antifungal polyene amphotericin B (AmB) and its methyl ester derivative (AME) both show potent murine immunostimulant as well as B-cell activating effects. Under certain experimental conditions, AME is a much more potent polyclonal B-cell activator (PBA) than AmB. Notable features of the murine B-cell stimulation induced by AME include: (i) High concentrations of AME (50-100 microgram/ml) are required and even at this level exhibit little or no spleen cell toxicity. (ii) Several lines of evidence suggest that the B-cell activating properties of AME are not involved in the cellular mechanism of adjuvant activity in vivo. (iii) There is a strong correlation between the magnitude of the in vitro PBA effects and the in vivo adjuvant effects of AME in a survey of different mouse strains. This evidence suggests that there is genetic control of the murine lymphoid cell-stimulatory effects of AME and that a small number of genes determines the responsive phenotype.


The use of grammatical morphemes by normal and language-impaired children.
An examination was made of the grammatical morpheme usage of normal children and language-impaired children matched at two different levels of mean utterance length. The language-impaired children displayed less grammatical morpheme usage than the normal children with equivalent mean utterance length. However, no use of alternative features of semantic importance by the language-impaired children was noted, suggesting that no unique patterns for acquiring language were in operation. Instead, it appears that the language-impaired children may have attached less communicative significance to grammatical morphemes.


[Changes of peripheral airways through mechanical ventilation in acute respiratory failure].
To evaluate the morphologic changes in the peripheral airways associated with positive pressure ventilation, fine fiberoptic bronchoscopy (1.8 mm outer diameter) was performed in 12 patients who had no history of prior pulmonary failure. In 19 examinations, the main morphologic findings were paleness and bronchial dilatation in the peripheral airways where increased secretions, pigmentation and stenosis or collapse were also observed. Patients with bronchial dilatation had longer periods of mechanical ventilation (17 +/- 8 days) compared to those without dilation (10 +/- 5 days). The structural destruction in the peripheral airways observed in patients on prolonged positive pressure mechanical ventilation suggests that barotrauma may be more widespread than previously recognized.


Pharmacokinetic profile of N-acetylcysteine amide and its main metabolite in mice using new analytical method.
N-acetylcysteine amide (NACA) is the amide derivative of N-acetylcysteine (NAC) that is rapidly converted to NAC after systemic administration. It has emerged as a promising thiol antioxidant for multiple indications; however, the pharmacokinetic property is yet unclear due to lack of an accurate quantification method. The present investigation aimed to develop an analytical method for simultaneous quantification of NACA and NAC in plasma. A new reagent (2-(methylsulfonyl)-5-phenyl-1,3,4-oxadiazole, MPOZ) was introduced for thiol stabilization during sample processing and storage. Further, we utilized tris (2-carboxyethyl) phosphine (TCEP) to reduce the oxidized forms of NACA and NAC. After derivatization, NACA-MPOZ and NAC-MPOZ were quantified using liquid chromatography-mass spectrometry (LC-MS). The new method was validated and found to have high specificity, linearity, accuracy, precision, and recovery for the quantification of NACA and NAC in plasma. Furthermore, the formed derivatives of NACA and NAC were stable for 48 h under different conditions. The method was utilized in pharmacokinetic study which showed that the bioavailability of NACA is significantly higher than NAC (67% and 15%, respectively). The pharmacokinetic of NACA obeyed a two-compartment open model. The glutathione (GSH)-replenishing capacity was found to be three to four-fold higher after the administration of NACA compared to that observed after the administration of NAC. In conclusion, the present method is simple, robust and reproducible, and can be utilized in both experimental and clinical studies. NACA might be considered as a prodrug for NAC. Furthermore, this is the first report describing the pharmacokinetics and bioavailability of NACA in mouse.


Diabetes augments and inhaled nitric oxide prevents the adverse hemodynamic effects of transfusing syngeneic stored blood in mice.
Stored red blood cells (RBCs) undergo progressive deleterious functional, biochemical, and structural changes. The mechanisms responsible for the adverse effects of transfusing stored RBCs remain incompletely elucidated. Awake wild-type (WT) mice, WT mice fed a high-fat diet (HFD-fed WT) for 4 to 6 weeks, and diabetic (db/db) mice were transfused with syngeneic leukoreduced RBCs or supernatant with or without oxidation (10% of total blood volume) after storage for not more than 24 hours (FRBCs) or 2 weeks (SRBCs). Inhaled nitric oxide (NO) at 80 parts per million was administered to a group of mice transfused with SRBCs. Blood and tissue samples were collected 2 hours after transfusion to measure iron and cytokine levels. SRBCs had altered RBC morphology and a reduced P(50) . Transfusion of SRBCs into WT or HFD-fed WT mice did not produce systemic hemodynamic changes. In contrast, transfusion of SRBCs or supernatant from SRBCs into db/db mice induced systemic hypertension that was prevented by concurrent inhalation of NO. Infusion of washed SRBCs or oxidized SRBC supernatant into db/db mice did not induce hypertension. Two hours after SRBC transfusion, plasma hemoglobin (Hb), interleukin-6, and serum iron levels were increased. Transfusion of syngeneic SRBCs or the supernatant from SRBCs produces systemic hypertension and vasoconstriction in db/db mice. It is likely that RBC storage, by causing in vitro hemolysis and posttransfusion hemoglobinemia, produces sustained NO scavenging and vasoconstriction in mice with endothelial dysfunction. Vasoconstriction is prevented by oxidizing the supernatant of SRBCs or breathing NO during SRBC transfusion.


Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector.
The goal of this study was to modify mesenchymal stem cells (MSCs) cells with a hypoxia-regulated heme oxygenase-1 (HO-1) plasmid to enhance the survival of MSCs in acute myocardial infarction (MI) heart. Although stem cells are being tested clinically for cardiac repair, graft cells die in the ischemic heart because of the effects of hypoxia/reoxygenation, inflammatory cytokines, and proapoptotic factors. Heme oxygenase-1 is a key component in inhibiting most of these factors. Mesenchymal stem cells from bone marrow were transfected with either HO-1 or LacZ plasmids. Cell apoptosis was assayed in vitro after hypoxia-reoxygen treatment. In vivo, 1 x 10(6) of male MSC(HO-1), MSC(LacZ), MSCs, or medium was injected into mouse hearts 1 h after MI (n = 16/group). Cell survival was assessed in a gender-mismatched transplantation model. Apoptosis, left ventricular remodeling, and cardiac function were tested in a gender-matched model. In the ischemic myocardium, the MSC(HO-1) group had greater expression of HO-1 and a 2-fold reduction in the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end labeling-positive cells compared with the MSC(LacZ) group. At seven days after implantation, the survival MSC(HO-1) was five-fold greater than the MSC(LacZ) group; MSC(HO-1) also attenuated left ventricular remodeling and enhanced the functional recovery of infarcted hearts two weeks after MI. A hypoxia-regulated HO-1 vector modification of MSCs enhances the tolerance of engrafted MSCs to hypoxia-reoxygen injury in vitro and improves their viability in ischemic hearts. This demonstration is the first showing that a physiologically inducible vector expressing of HO-1 genes improves the survival of stem cells in myocardial ischemia.


Estrogenic contributions to sexual differentiation in the female guinea pig: influences of diethylstilbestrol and tamoxifen on neural, behavioral, and ovarian development.
We administered the synthetic estrogen, diethylstilbestrol (DES), or the antiestrogen, tamoxifen, to pregnant guinea pigs and observed the consequences for sexual differentiation of their female offspring. Hormones were administered during the period when treatment of fetuses with testosterone influences the development of sex-related traits (approximately Days 30 to 65 of gestation). Ovarian function, masculine and feminine sexual behavior, and the structure of a sexually dimorphic neural region in the preoptic area were assessed in adulthood in hormone-exposed animals and in oil-treated and untreated controls. Prenatal exposure to DES dipropionate (DESDP) caused masculinization and defeminization. DESDP-treated females mounted more than control females, both without hormonal stimulation and when given testosterone propionate (TP) as adults. The sexually dimorphic neural region was also masculinized in these females. In regard to defeminization, they showed delayed vaginal opening, impaired progesterone (P) production, an absence of corpora lutea, and impaired lordosis and mounting responses to estradiol benzoate (EB) and P. Prenatal treatment with tamoxifen produced a complicated pattern of results. Tamoxifen-exposed females evidenced less masculine-typical behavior, showing diminished mounting without hormonal stimulation and in response to TP. However, they also showed delayed vaginal opening, enhanced P production, and impaired mounting in response to EB and P. Their lordosis behavior and the volume of the sexually dimorphic neural region were unaffected. These results suggest that estrogens play a substantial role in sexual differentiation in the guinea pig. High levels of estrogen promote masculine-typical development, and unusually low levels may impair some aspects of both masculine-typical and feminine-typical development.


Human liver type pyruvate kinase: cDNA cloning and chromosomal assignment.
Pyruvate kinase (PK) has four isozymes (L,R,M1,M2) that are encoded mainly by two different genes. We isolated a cDNA clone from a Japanese adult liver lambda gt10 cDNA library by using a rat liver(L)-type PK cDNA probe. One positively hybridizing clone, hlPK-1, which contained a 1,049-base pair cDNA insert, was subjected to DNA sequence analysis. Comparisons of the sequence data with the rat PK cDNAs indicated that the cDNA encoded information for the carboxyl terminal 105 amino acids of a human L-type PK and a 3' untranslated region of 734 nucleotides. Furthermore, the karyotype analysis of several human-mouse hybrid cells and Southern blot analysis of DNAs of the hybrids with a hlPK-1 indicated that the human L-type PK gene is located on chromosome 1.


Oxalobacter formigenes produces metabolites and lipids undetectable in oxalotrophic Bifidobacterium animalis.
In the search for new potential therapies for pathologies of oxalate, such as kidney stone disease and primary hyperoxaluria, the intestinal microbiome has generated significant interest. Resident oxalate-degrading bacteria inhabit the gastrointestinal tract and reduce absorption of dietary oxalate, thereby potentially lowering the potency of oxalate as a risk factor for kidney stone formation. Although several species of bacteria have been shown to degrade oxalate, select strains of Oxalobacter formigenes (O. formigenes) have thus far demonstrated the unique ability among oxalotrophs to initiate a net intestinal oxalate secretion into the lumen from the bloodstream, allowing them to feed on both dietary and endogenous metabolic oxalate. There is significant interest in this function as a potential therapeutic application for circulating oxalate reduction, although its mechanism of action is still poorly understood. Since this species-exclusive, oxalate-regulating function is reported to be dependent on the use of a currently unidentified secreted bioactive compound, there is much interest in whether O. formigenes produces unique biochemicals that are not expressed by other oxalotrophs which lack the ability to transport oxalate. Hence, this study sought to analyze and compare the metabolomes of O. formigenes and another oxalate degrader, Bifidobacterium animalis subsp. lactis (B. animalis), to determine whether O. formigenes could produce features undetectable in another oxalotroph, thus supporting the theory of a species-exclusive secretagogue compound. A comparative metabolomic analysis of O. formigenes strain HC1 (a human isolate) versus B. animalis, another oxalate-degrading human intestinal microbe, was performed by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). Bacteria were cultured independently in anaerobic conditions, harvested, lysed, and extracted by protein precipitation. Metabolite extracts were chromatographically separated and analyzed by UHPLC-HRMS using reverse phase gradient elution (ACE Excel 2 C18-Pentafluorophenyl column) paired with a Q Exactive™ mass spectrometer. The purpose of this study was to assess whether O. formigenes potentially produces unique biochemicals from other oxalate degraders to better understand its metabolic profile and provide support for the theoretical production of a species-exclusive secretagogue compound responsible for enhancing intestinal oxalate secretion. We report a panel of metabolites and lipids detected in the O. formigenes metabolome which were undetectable in B. animalis, several of which were identified either by mass-to-charge ratio and retention time matching to our method-specific metabolite library or MS/MS fragmentation. Furthermore, re-examination of data from our previous work showed most of these features were also undetected in the metabolomes of Lactobacillus acidophilus and Lactobacillus gasseri, two other intestinal oxalate degraders. Our observation of O. formigenes metabolites and lipids which were undetectable in other oxalotrophs suggests that this bacterium likely holds the ability to produce biochemicals not expressed by at least a selection of other oxalate degraders. These findings provide support for the hypothesized biosynthesis of a species-exclusive secretagogue responsible for the stimulation of net intestinal oxalate secretion.


Exposure with response prevention treatment of anorexia nervosa-bulimic subtype and bulimia nervosa.
Binge exposure with response-prevention of bingeing (ERP-B) was evaluated in 20 female Ss within an inpatient eating disorders unit over 9 sessions as an adjunct to standard milieu therapy. Subjects met DSM-III-R criteria for either bulimia nervosa (BN) (n = 13) or the bulimic subtype of anorexia nervosa (AN-B) (n = 7). The average age of the Ss in each group was 26.5 (+/- 8.8) and 24.1 +/- 6.0) yr, respectively. Results indicate significant within-session and pre-post treatment effects in self-report measures 'urge to binge', 'lack of control', 'feelings of guilt' and 'tension'. Further analysis revealed that the AN-B subgroup had significantly greater reduction in 'depression' and 'urge to vomit' compared to the BN group. This study provides preliminary evidence that ERP-B deserves further investigation with long-term follow-up in both BN and AN-B patients and may be particularly advantageous in the AN-B subpopulation.


Castleman's disease and lymphoma: report of eight cases in HIV-negative patients and literature review.
Castleman's disease (CD) is a rare atypical lymphoproliferative disorder associated with a risk of developing malignant lymphoma. We have recorded 8 HIV-negative patients presenting this association, 6 with non-Hodgkin's lymphoma (NHL) and 2 with Hodgkin's disease (HD). After literature review, we analyzed all reported cases of association CD-NHL (n = 23) and CD-HD (n = 27). NHL is more often associated with multicentric CD, its diagnosis being concurrent with CD diagnosis or occurring within 2 years. B-NHL is predominant (71%), and mantle cell lymphoma represents 40% of these B-NHL cases. NHL displays an aggressive course and is liable for death, especially in multicentric CD. HD occurs in localized CD of plasma cell type, usually in the same areas, is more often of interfollicular subtype, and its clinical course seems better than NHL. The association of CD and lymphoma seems to be more than coincidental, and its pathogenesis is discussed.


Analysis of behaviour patterns and thermal responses to a hot-arid climate in rural China.
Climate can greatly affect building design, life style and thermal perception for all groups of people; however, this phenomenon has not yet been rigorously evaluated in China's hot-arid climate. The aim of this paper is to present the results of a thermal comfort survey by evaluating the influence of the hot-arid climate upon the behavioural patterns and thermal comfort responses of 160 residents in 65 traditional vernacular houses in Turfan, China, in 2011. In this survey, there were 206 sets of effective data, and the features of the traditional residential buildings and the human behaviour patterns in Turfan were described and analysed. The results showed that the diversified courtyards and shade spaces were the most obvious features of traditional houses in Turfan. People here typically spend most of their time in one of two spaces for eating, resting, and entertaining. It was found that the preferred temperature was 26.5°C. The preferred air velocity occurred at 0.62m/s. A suitable air velocity range of 0.15-1.24m/s was suggested in Turfan. Moreover, the neutral temperature of the local people was 30.1°C (tg or to). The upper limits of the 80% acceptable zone by using the direct and indirect acceptability method were 32.7 and 33.8°C, respectively. The neutral temperature and upper limit of the acceptable zone in Turfan were higher than those of the adaptive standards. Attention should be paid to the role of thermal comfort in influencing building design by using simple passive cooling strategies. The above results are believed to be potentially valuable for the design and evaluation of residential buildings located in hot-arid climate.


Toward a Broader Understanding of Cystic Fibrosis Epidemiology and Its Impact on Clinical Manifestations.
The incidence of cystic fibrosis remains constant in North America and Western Europe is 1 in 3500 live births, but survival and quality of life have improved. The cystic fibrosis population has shifted toward the adult age range with a concomitant shift in the spectrum of complications. Survival increased because of aggressive symptomatic therapy, earlier diagnosis by newborn screening, and the introduction of modulators of the cystic fibrosis transmembrane conductance regulator, so that predicted median survival age is now about 50 years. In the United States, members of low socioeconomic status populations or members of racial or ethnic minorities have benefitted less from these advances.


Night-time eating in men and women with binge eating disorder.
This study examined the frequency of night-time eating (NE) and its correlates in men and women with binge eating disorder (BED). Two-hundred and seven consecutively evaluated adults (45 men and 162 women) with BED were assessed with semi-structured interviews and a battery of behavioral and psychological measures. Overall, 28% (N = 58) of the participants reported NE. A significantly higher proportion of men (42%) than women (24%) reported NE. Overall, participants who reported NE had a significantly higher body mass index, but otherwise differed little from those who did not report NE. Men and women without NE differed little on behavioral and psychological measures, whereas women with NE had significantly higher levels of eating-, weight-, and shape-concerns than men with NE.


Biosynthesis of ependymins from goldfish brain.
Ependymins beta and gamma constitute a novel family of secretory proteins in the extracellular fluid of goldfish brain. Here we demonstrate that at least two different transcripts exist in goldfish brain differing mainly in the length of their 3' noncoding regions but encoding very similar precursors for ependymins. Both precursors consist of 216 amino acid residues including two potential N-glycosylation sites. Prepro-ependymin-I is the main but not the only precursor of ependymin beta, whereas prepro-ependymin-II is preferentially processed to ependymin gamma. This is in line with our results showing that both ependymins beta and gamma represent different glycoforms with very similar protein backbones. Additionally, we show that both ependymins share the same C-terminal ends indicating that ependymin gamma is not a proteolysis product of ependymin beta. We also demonstrate that processing at three internal pairs of basic residues does not occur in either ependymin.


Establishment of a facial nerve trunk crush injury model and evaluation of facial nerve self-healing in rats.
To facilitate further investigation into the mechanisms of facial nerve regeneration, a simple and reliable model of facial nerve crush injury is essential. Nevertheless, the establishment of such models lacks standardization and repeatability, while the healing capacity of the nerve is often overlooked, potentially affecting future studies. We made facial nerve trunk crush injury models with different pressing times and detected the changes from the distal nerves to the motoneurons via behavior analysis, electrophysiological test, and histomorphometry analysis. It revealed a particular capacity for self-healing following facial nerve crush damage because there was almost no facial motoneuron apoptosis in the MC group during the observation period, and rats in MC group had total facial paralysis in behavioral tests following surgery and varying degrees of recovery 28 days postoperatively with no treatments. As the pressing time increased, the latency, wave amplitude, nerve fiber damage degree, nerve axon ratio, myelin thickness, electroneurograph (ENoG) value, ultrastructural damage, abnormal morphological changes, and the buccal muscle atrophy of each MC group gradually increased or got worse during the observation period. However, after 28 postoperative days, only the ENoG values of the M10min and M12min groups were beyond 90%, indicating no self-healing. It suggests that a stable model of peripheral facial palsy may be created by applying a 12.5 cm mosquito clamped to the facial nerve trunk for at least 10 min, which laid the foundation for the subsequent research to objectively evaluate facial nerve regeneration.


Diversity of the BoLA-DRB3 gene in cattle breeds from tropical and subtropical regions of Argentina.
Bovine leukocyte antigens (BoLA) have been widely studied because of their primary function in the recognition of pathogens by the immune system. To date, however, the characterization of the BoLA-DRB3 gene in Latin American Zebu and mixed zebuine breeds is scarce. By a sequence-based typing method, here we sequenced exon 2 of BoLA class II DRB3 gene in 264 animals from the five most commonly used breeds in northern Argentina (Creole, Brahman, Braford, Brangus, and Nellore).The Bos taurus, Bos indicus, and mixed breeds analyzed here contained 61 previously reported alleles. Genetic diversity was high at both allelic and nucleotide sequence levels, particularly in the mixed breeds Braford and Brangus. In contrast to previous reports on DRB3 diversity, no evidence of balancing selection was found in our data. Differentiation among breeds was highly significant, as shown by FST (FST = 0.052, P < 0.001) and cluster analyses. In accordance with historical origin of the breeds, UPGMA trees and metric multidimensional scaling (MDS) analyses showed that Creole is distantly related to the other zebuine breeds. Among them, Brahman, Braford, and Brangus exhibited the closest affiliations. Despite the overall differentiation of the breeds, analysis of the peptide binding regions at the aminoacid level revealed that the key aminoacids involved in peptide recognition are greatly conserved suggesting little influence of domestication and breeding in functional MHC variability. In sum, this is the first report of BoLA-DRB3 diversity in pure and mixed Bos indicus cattle breeds from Argentina. Knowledge of BoLA-DRB3 variability in breeds adapted to tropical and subtropical environments contributes not only to the characterization of MHC diversity but also to the design of peptide-based vaccines.


[Evaluation of effects of the intravenous cyclophosphamide treatment of primary glomerulonephritis and the estimation of complications].
Primary glomerulonephritis can be treated by the intravenous use of cyclophosphamide. The aim of our study is to evaluate the effect of the drug in the treatment of mentioned diseases and the follow-up of complications. There are 30 patients included in this study, mean-age of 46.83 years. Renal biopsy was performed in 25 patients. Membranoproliferative glomerulonephritis was diagnosed in 36.67% of patients, mesangioproliferative in 16.67%, rapidly progressive in 13,33%, membranous in 10%, chronic in 10%, primary focal segmental glomerulosclerosis in 3,33% and 10% of patients were unclassified They have been treated with cyclophosphamide in intermittent "pulse" doses: once a month fbr the first 6 months and once in 3 months, for 18 months or longer, after that. The drug was given in the recommended dose of 0.5-lg/m of body-surface area, in the combination with a low-dose corticosteroides. Hematological and renal fimnctional tests were checked before every "pulse" dose. Concerning the development of the renal ailure the fivorable effect occurred in 50% of patients. Proteinuria was found in all patients (80% >3.5 gr/24 h). The favorable effect occurred in 80% patients. At the end, serum proteins were normal in 76.67% patients. 30% of patients normalized the erythrocyte sedimentation level. Remission has not been achieved in 23.33% of patients, 10% of patients developed relapse. 20% of patients died infections were the most common complication and they occurred in 30% of patients. Sepsis, leucopenia, Herpes Zoster infection and hemorrhagic cystitis have not occurred in any patient. Malignant tumor was found in 6.67% of patients.


The use of occupation-based interventions and assessments in hand therapy: A cross-sectional survey.
The purpose of this study was to gather information on how hand therapists incorporate occupation-based interventions in their clinical practice and what outcome measures hand therapists use to measure the occupational performance of their clients STUDY DESIGN: Cross-Sectional Survey Design. The 16-item Survey was distributed to members of the American Society of Hand Therapists on two occasions. Three hundred eleven hand therapists responded to the survey. Hand therapists use a variety of occupation-based interventions (OBI) in clinical practice and most believe they are important. Findings from this study reveal that incorporating an occupation-based assessment along with or in place of an assessment of body functions and structures is not performed routinely. One hundred twenty-six (41%) respondents indicated that they use occupation-based activities 26-50% of the time with their clients. The top three OBI interventions used by hand therapists included dressing tasks, cooking and meal preparation, and in hand manipulation of coins and medication. The lack of understanding of the theoretical models regarding occupation-based interventions may be a barrier toward implementation of occupation-based interventions and assessments as many hand therapists may have trained under a medical model. Most respondents to this survey indicated that they believe OBI should be performed by hand therapists and use them routinely in practice. The most frequently used type of assessment was the DASH (Disabilities of the Shoulder Arm & Hand). The least frequently used assessment was the Short Form 36 and patient specific occupation-based assessment.


The diagnostic performance of contrast-enhanced ultrasound (CEUS) for evaluating hepatocellular carcinoma (HCC) juxtaposed to MRI findings; a retrospective single-center analysis of 292 patients.
HCC is the most frequent primary liver cancer entity. Major risk factors comprise chronic HBC and HCV infections, ALD or NAFLD. Apart from the anamnesis, the clinical examination and serologic analysis, an essential part of the diagnostic HCC work-up is due to imaging findings from sonography, CT or MRI scans. HCC lesions feature a distinct vascularization pattern: hyperenhancement during early arterial and hypoenhancement/wash-out during portal venous or delayed phases. CEUS facilitates dynamic assessment of microperfusion patterns of suspicious liver lesions. The purpose of the present retrospective single-center study was to determine the diagnostic value of CEUS for assessing HCC by comparison with findings from MRI scans. Between 2004-2018 292 patients with suspicious liver lesions underwent CEUS and MRI. All patients underwent native B-mode, Color Doppler and CEUS after given informed consent. The applied contrast agent was a second-generation blood pool agent (SonoVue®, Bracco, Milan, Italy). Every CEUS examination was performed and interpreted by a single experienced radiologist (EFSUMB Level 3). CEUS was performed on all included patients without occurrence of any adverse effects. CEUS showed a sensitivity of 96%, a specificity of 91%, a PPV of 95% and a NPV of 94% for analyzing HCC in comparison with MRI as the diagnostic gold standard. With a distinguished safety profile CEUS shows a high diagnostic accuracy in assessing HCC compared to corresponding results from MRI scans.


Mathematical Model of Synaptic Long-Term Potentiation as a Bistability in a Chain of Biochemical Reactions with a Positive Feedback.
Nitric oxide (NO) is involved in synaptic long-term potentiation (LTP) by multiple signaling pathways. Here, we show that LTP of synaptic transmission can be explained as a feature of signal transduction-bistable behavior in a chain of biochemical reactions with positive feedback, formed by diffusion of NO to the presynaptic site and facilitating the release of glutamate (Glu). The dynamics of Glu, calcium (Ca2+) and NO is described by a system of nonlinear reaction-diffusion equations with modified Michaelis-Menten (MM) kinetics. Numerical investigation reveals that the chain of biochemical reactions analyzed can exhibit a bistable behavior under physiological conditions when production of Glu is described by MM kinetics and decay of NO is modeled by means of two enzymatic pathways with different kinetic properties. Our finding extends understanding of the role of NO in LTP: a short high-intensity stimulus is "memorized" as a long-lasting elevation of NO concentration. The conclusions obtained by analysis of the chain of biochemical reactions describing LTP can be generalized to other chains of interactions or for creating the logical elements for biological computers.


Recipient and allograft survival following donation after circulatory death versus donation after brain death for renal transplantation: A systematic review and meta-analysis.
Current evidence based on retrospective and prospective studies demonstrates that donation after circulatory death (DCD) grafts are more susceptible to delayed graft function (DGF) than donation after brain death (DBD) grafts. The short- and long-term survival outcomes of the two cohorts are unclear. Therefore, we performed a systematic review and meta-analysis to estimate the patient and allograft survival outcomes for DCD and DBD in renal transplant surgery. Systematic literature searches were conducted by searching various databases. Fixed and random effects models were used to assess the accumulation of evidence over time. The five-year patient survival rate was significantly better in the DBD than in the DCD cohort. Non-significant differences were observed in 1-, 3- and 10-year patient survival and in the 1-, 3-, 5-, and 10-year graft survival rates between the two cohorts. The acute rejection rate was lower in the DCD cohort than in the DBD cohort. Extended criteria of donor status, delayed graft function and primary non-function were significantly higher in the DCD cohort than in the DBD cohort. This study demonstrates that the short- and long-term survival graft and patient benefits are similar between DCD and DBD kidney transplants. Therefore, large, controlled DCD kidney programmes are urgently needed worldwide in order to increase the number of kidney transplants.


Changes in myocardial blood supply during experimental hypertension treated with verapamil in rabbits.
Rabbit hearts were studied at different periods of experimental arterial hypertension and its treatment with verapamil. Morphological study revealed a progressive decrease in the number of capillaries per unit mass during the development of myocardial hypertrophy in hypertensive hearts. In hypertensive animals treated with verapamil the density of capillaries in both ventricles did not decrease, but verapamil injected to intact animals sharply decreased this parameter.


Detection of zinc translocation into apical dendrite of CA1 pyramidal neuron after electrical stimulation.
Translocation of the endogenous cation zinc from presynaptic terminals to postsynaptic neurons after brain insult has been implicated as a potential neurotoxic event. Several studies have previously demonstrated that a brief electrical stimulation is sufficient to induce the translocation of zinc from presynaptic vesicles into the cytoplasm (soma) of postsynaptic neurons. In the present work I have extended those findings in three ways: (i) providing evidence that zinc translocation occurs into apical dendrites, (ii) presenting data that there is an apparent translocation into apical dendrites when only a zinc-containing synaptic input is stimulated, and (iii) presenting data that there is no zinc translocation into apical dendrite of ZnT3 KO mice following electrical stimulation. Hippocampal slices were preloaded with the "trappable" zinc fluorescent probe, Newport Green. After washout, a single apical dendrite in the stratum radiatum of hippocampal CA1 area was selected and focused on. Burst stimulation (100Hz, 500microA, 0.2ms, monopolar) was delivered to either the adjacent Schaffer-collateral inputs (zinc-containing) or to the adjacent temporo-ammonic inputs (zinc-free) to the CA1 dendrites. Stimulation of the Schaffer collaterals increased the dendritic fluorescence, which was blocked by TTX, low-Ca medium, or the extracellular zinc chelator, CaEDTA. Stimulation of the temporo-ammonic pathway caused no significant rise in the fluorescence. Genetic depletion of vesicular zinc by ZnT3 KO showed no stimulation-induced apical dendrite zinc rise. The present study provides evidence that synaptically released zinc translocates into postsynaptic neurons through the apical dendrites of CA1 pyramidal neurons during physiological synaptic activity.


Activity-based therapy for individuals with spinal cord injury/disease: perspectives of acute care therapists.
An exploratory descriptive study was conducted. To determine if and how occupational therapists (OTs) and physical therapists (PTs) in acute care hospital settings use activity-based therapy (ABT) and its associated technologies. Acute care hospital settings in Canada. Semi-structured interviews were conducted with physical and occupational therapists, licensed in Canada, who worked in an acute care neurological setting with individuals with spinal cord injury or disease (SCI/D). To analyze the data, interpretive description was used. NVivo 12 was used for data management. Five physical therapists and two occupational therapists were interviewed (n = 7). Two therapists declined after reading a description of the study. Through analysis, the following themes were identified as affecting the delivery of ABT as part of SCI/D rehabilitation in the acute care setting: (1) Impact of patient acuity on ABT participation, (2) ABT approach unique to the acute care setting, and (3) Influence of acute care work environment and therapy practice. Throughout these themes, therapists referred to dosage as a limiting factor affecting ABT delivery. Our research reveals that implementing ABT in an acute care setting is challenging considering the high dosage of movement practice required for ABT. To increase dosage and the use of ABT in acute care, strategies could include early patient education on ABT, strategic use of social supports, and use of portable technology already incorporated in acute care.


A Mixed Method Study of Teachers' Appraisals of Student Wellness Services and Supports During COVID-19.
Understanding teachers' appraisals of student wellness services and supports during COVID-19 is essential to strengthening services and improving student health outcomes. This mixed-method study aimed to examine US PK-12 teachers' appraisals of student wellness services and supports during COVID-19. This study focuses on qualitative data from 291 teachers' open-ended responses to the question: "What do you wish your school leaders knew about this (wellness support) aspect of your work?" and whose responses described wellness services and supports. A qualitative content analysis was conducted by an interdisciplinary research team using open- and axial coding. Three main themes emerged. (1) insufficient access to mental health professionals and programming at schools, (2) concern about the quality of available services, and (3) a need for teacher professional development and support on student wellness. Statistically significant differences in teacher appraisals of insufficient access to mental health professionals and programming were found based on grade level taught and percentage of immigrant students in the school. With amplified student wellness needs, school personnel, including school leaders, must consider ways to allocate additional resources/staffing, assess the quality of services and supports, and design professional development opportunities to support teachers' involvement in supporting student wellness needs.


Nanobiotechnological approaches in antinociceptive therapy: Animal-based evidence for analgesic nanotherapeutics of bioengineered silver and gold nanomaterials.
Pain management is a major challenge in healthcare systems worldwide. Owing to undesirable side effects of current analgesic medications, there is an exceeding need to develop the effective alternative therapeutics. Nowadays, the application of nanomaterials is being highly considered, as their exceptional properties arising from the nanoscale dimensions are undeniable. With the increasing use of metal NPs, more biocompatible and costly methods of synthesis have been developed in which different biological rescores including microorganisms, plants and algae are employed. Nanobiotechnology-based synthesis of nanosized particles is an ecological approach offering safe production of nanoparticles (NPs) by biological resources eliminating the toxicity attributed to the conventional routes. This review provides an assessment of biosynthesized silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) as antinociceptive agents in recent studies. Living animal models (mice and rats) have been used for analyzing the effect of biogenic NPs on decreasing the nociceptive pain utilizing different methods such as acetic acid-induced writhing test, hot plate test, and formalin test. Potent analgesic activity exhibited by green fabricated AgNPs and AuNPs represents the bright future of nanotechnology in the management of pain and other social and medicinal issues followed by this unpleasant sensation. Moreover, there NPs showed a protective effects on liver, kidney, and body weight in animal models that make them attractive for clinical studies. However, further research is required to fully address the harmless antinociceptive effect of NPs for clinical usage.


A systematic review and meta-analysis of randomized clinical trials of fire needle combined with ALA-PDT for the treatment of moderate-to- severe acne.
Moderate-to-severe acne affects people's health and quality of life. As first-line therapeutic medications, isotretinoin and antibiotics are used to treat moderate-to-severe acne, but outcomes can be improved. The combination of fire needle and ALA-PDT may be one option. This study evaluated the safety and effectiveness in the treatment of moderate-to-severe acne by the combination with fire needle and ALA-PDT. By July 2022, search PubMed, the Chinese Biomedical Literature dababase, the Cochrane Library, the Chinese Scientific Journal Database, the China National Knowledge Infrastructure, the Web of Science Datebase, Embase Datebase,VIP Database and WanFang Database. To gather RCTs of the combination of fire needle and ALA-PDT for the treatment of moderate-to-severe acne. A meta-analysis was performed according to the Handbook guidelines of Cochrane. Study selection, data extraction, and risk of bias evaluation were all governed by two reviewers, with the help of a third reviewer if necessary. The meta-analysis was carried out with Review Manager Software 5.4. There were a total of 9 RCTs with 862 participants. Clinical efficacy was recorded in nine trials, GAGS score was published in three studies, adverse events were documented in five studies, and the recurrence rate was reported in two studies. Treatment lasted between four and twelve weeks. Combination therapy outperformed monotherapy in terms of clinical efficacy (OR:3.73; 95% CI:2.51, 5.53; p < 0.00001). Additional subgroup analysis revealed that the combination therapy outperformed ALA-PDT alone in terms of clinical effect (OR: 3.20; 95% CI: 2.05, 4.99; p < 0.00001). Additionally, combination therapy outperformed fire needle alone in terms of clinical efficacy (OR:5.66; 95% CI: 2.66, 12.08; p < 0.00001). Studies have also indicated that combination therapy has a stronger benefit in lowering the GAGS score (MD:-3.35; 95% CI:-4.62, -2.09; p < 0.00001). Additionally, there was no discernible difference in the occurrence of adverse events between the combined treatments and monotherapy (OR:1.43; 95% CI: 0.76, 2.69; p = 0.26), and the combined treatment was able to control the recurrence rate (OR:0.18; 95% CI: 0.07, 0.45; P = 0.0002). The efficacy of fire needle combined with ALA-PDT in the treatment of moderate-to-severe acne appears superior to that of ALA-PDT or fire needle alone. However, the conclusions of this study must be interpreted carefully due to the high risk and ambiguity of bias of the included trials.


Positive postpartum well-being: What works for women.
Women's experiences of pregnancy, birth and motherhood extend beyond healthcare provision and the immediate postpartum. Women's social, cultural and political environments shape the positive or negative effects of their experiences through this transition. However, there is limited research concerning the factors that women identify as being protective or promotive of maternal well-being in the perinatal period and motherhood transition. To explore women's views on the factors within healthcare, social, cultural, organizational, environmental and political domains that do or can work well in creating positive perinatal experiences. A qualitative descriptive study with embedded public and participant involvement (PPI). Participants were 24 women who were maternity care service users giving birth in Ireland. Three themes were developed. The first theme, 'tone of care', related to women's interactions with and attitudes of healthcare professionals in setting the tone for the care they experienced. The second theme, 'postpartum presence and support', concerned the professional postpartum supports and services that women found beneficial in the motherhood transition. The final theme, 'flexibility for new families' addresses social and organizational issues around parents returning to paid employment. Women suggested multiple avenues for promoting positive perinatal experiences for women giving birth in Ireland, which may be implemented at healthcare and policy levels. Women identified that maternal health education focuses on supporting informed decision-making processes as a positive and worry-alleviating resource. Additionally, women valued being met by healthcare professionals who regard women as the decision makers in their care experience. Exchanges in which healthcare professionals validate and encourage women in their mothering role and actively involve their partners as caregivers left lasting positive impressions. Extended and professional postpartum support was a common issue, and phone lines or drop-in clinics were suggested as invaluable and affirming assets where women could access personalized support with healthcare professionals who had the knowledge and skills to genuinely approach women's concerns. Social and organizational considerations involved supporting parents to balance their responsibilities as new or growing families in the return to work. Maternity care service users were involved in the interviews and manuscript preparation.


Off-axis measurements of a plano distance power progressive addition lens.
To test that the Humphrey Lens Analyzer can be used validly to measure off-axis powers of progressive addition lenses of low distance power, we made measurements of a plano distance progressive power lens with both a conventional focimeter and the Humphrey Lens Analyzer. The use of the Humphrey Lens Analyzer in two modes, one in which the lens rotated about a point corresponding to the centre-of-rotation of the eye (mode 1) and one in which the lens rotated about its back surface centre of curvature (mode 2), gave off-axis power measurements which were similar to those of conventional measurements. In addition, the Humphrey Lens Analyzer in mode 1 gave prism measurements which were similar to conventional measurements. The Humphrey Lens Analyzer in mode 2 gave prism measurements which were less than those of conventional measurements, but the prism contours were similar and the differences were < 1 delta within 20 mm of the lens centre.


Life-threatening diarrhea in neuroendocrine tumors: two case reports.
Neuroendocrine tumors are rare, heterogeneous neoplasms that produce a wide variety of clinical symptoms. Diarrhea in neuroendocrine tumors is incredibly common and is usually benign in nature. We report two extreme cases of diarrhea in metastatic neuroendocrine tumors that threatened fatality and provide evidence for steroids as a novel agent in the management of vasoactive intestinal peptide tumors. A 63-year-old Caucasian male with a grade 2 (Ki-67 17%) metastatic small bowel neuroendocrine tumor, and a 43-year-old female with a grade 2 (Ki-67 5%) metastatic pancreatic vasoactive intestinal peptide tumor. Both patients suffered life-threatening diarrhea despite extensive treatment modalities, including new systemic agents. This case explains how a lack of compliance and patient under-reporting of symptoms contributed to their challenging clinical course. Only steroids had a significant sustained effect on the diarrhea of the patient with vasoactive intestinal peptide tumor. This report discusses two rare cases of life-threatening diarrhea in neuroendocrine tumors and stresses the importance of accurate clinical history taking, patient education, and compliance for symptom control. The report suggests steroids as a potential novel pharmaceutical option in the management of vasoactive intestinal peptide tumors; this is of great significance as it may provide a new approach to their management and potentially act as a life-saving agent in other oncology patients.


Diabetic Foot Infection: Preliminary Results of a Fast-Track Program with Early Endovascular Revascularization and Local Surgical Treatment.
To demonstrate that a fast-track program consisting in early endovascular revascularization and local surgical treatment saves tissue in patients with diabetic foot infection (DFI). Between January and December 2014, 48 patients with DFI underwent early endovascular revascularization and local surgical treatment at our Diabetic Foot Center. In all cases, endovascular revascularization and local surgical treatment were performed within 1 week from the diagnosis of infection and during the same hospital stay. One-year outcomes were evaluated in terms of survival, primary patency, primary-assisted patency, secondary patency, absence of target lesion restenosis (TLR), and limb salvage. The patients were predominantly males (34 of 48, 70.8%) with a mean age of 72.4 years (range, 51-91). The target vessel was a tibial artery in 34 cases (70.8%). Surgical treatment consisted of debridement without bone resection in 27 cases (56.2%), toe and/or ray amputation in 15 cases (31.2%), Lisfranc amputation in 2 cases (4.2%), transmetatarsal amputation in 2 cases (4.2%). In the remaining 2 cases, a leg amputation was necessary with an overall 30-day major amputation rate of 4.2%. During the follow-up (mean duration 6.9 months, range 1-12) healing of the lesions was obtained in 30 cases (62.5%). Estimated 12-month survival, primary patency, primary-assisted patency, secondary patency, absence of TLR, and limb salvage rates were 83.5%, 53.4%, 65%, 65%, 60.7%, and 86.6%, respectively. A fast-track program consisting in early endovascular revascularization and local surgical treatment contributes to our experience in limiting amputation levels in patients with DFI. A multidisciplinary approach and adoption of diabetic foot triage are essential to achieve these outcomes.


Pediatric Oronasopharyngeal Stricture- A Rare Surgical Complication of Adeno-Tonsillectomy Abstract.
Introduction: Oronasopharyngeal stricture is a rare sequel of oropharyngeal surgical procedure which can cause swallowing difficulty, dyspnea, sleep related breathing disorders, incompetence at the velopharynx due to soft palatal adherence. Case: Here we present a case of nine-year-old girl who presented to us with complains of nasal obstruction since 3 months and symptoms of sleep disordered breathing. She underwent adenotonsillectomy 5 years ago and coblator assisted palatoplasty and stricture release 4 months ago. On examination adenoid facies was noted, postpalatoplasty and tonsillectomy status with stricture between the anterior and posterior tonsillar pillars. Soft palate was stuck to posterior pharyngeal wall. Computed tomography scan was done which depicted homogenously enhancing soft tissue density causing complete nasopharyngeal airway obstruction. Oronasopharyngeal stricture release was performed under general anesthesia. Infant feeding tube was inserted through the nasal cavity and introduced through the oropharynx into exterior and was tied externally which was removed on postoperative day 5. Child is on regular follow up since 5 months and asymptomatic. Discussion: Oropharyngeal stricture is reported as a rare sequela of adenotonsillectomy. Many surgical techniques have been reported for release of similar oropharyngeal and nasopharyngeal stricture patterns such as triamcinolone injection, manual dilation method, plasma hook method, division and skin grafting, local flaps like pharyngeal or palatal mucosal flaps, and free flap techniques. Conclusion: Utmost care must be taken during the surgical procedure of oropharynx to prevent collateral damage to mucosal surfaces which can result in such devastating complications. The online version contains supplementary material available at 10.1007/s12070-023-03694-5.


Analysis of the heat- and cold-related cardiovascular mortality in an urban mediterranean environment through various thermal indices.
During the last decades the effects of thermal stress on public health have been a great concern worldwide. Thermal stress is determined by air temperature in combination with other meteorological parameters, such as relative humidity and wind speed. The present study is focused on the Mediterranean city of Thessaloniki, Greece and it aims to explore the association between thermal stress and mortality from cardiovascular diseases, using both air temperature and other thermal indices as indicators. For that, an over-dispersed Poisson regression function was used, in combination with distributed lag non-linear models, in order to capture the delayed and nonlinear effects of temperature. Our results revealed a reverse J-shaped exposure-response curve for the total population and females and a U-shaped association for males. In all cases examined, the minimum mortality temperature was identified around the 80th percentile of each distribution. It is noteworthy that despite the fact that the highest risks of cardiovascular mortality were estimated for exposure to extreme temperatures, moderate temperatures were found to cause the highest burden of mortality. On the whole, our estimations demonstrated that the population in Thessaloniki is more susceptible to cold effects and in regard with gender, females seem to be more vulnerable to ambient thermal conditions.


More but not less uncertainty makes adult humans' tool selections more similar to those reported with crows.
In this study, we examined whether adult humans' tool selections in a stick-and-tube problem might resemble previously published results of crows' selections if people had more experience solving the problem or were presented with a more ambiguous problem. In Experiments 1a and 1b, when given multiple opportunities to select a stick from a set of 10 to retrieve a candy located either 8 or 16 cm from the opening of a tube, the participants always selected a stick that was long enough to retrieve the candy; however, they did not generally select either the stick whose length matched the object's distance or the longest stick in the set-two outcomes reported in studies with crows. In Experiment 2, participants who were allowed only a brief period of time to study the problem selected a longer stick than did participants allowed unlimited time to do the same. However, only when the candy's distance was 16 cm did these people reliably select the longest stick in the set. It seems that increasing, but not decreasing, people's uncertainty about a problem can make humans' tool selections more similar to those reported with crows.


Pneumatic retinopexy.
Pneumatic retinopexy, a term introduced by Hilton in 1985, describes a recently revised and modified operation used for primary rhegmatogenous retinal reattachment. A gas bubble is injected into the vitreous cavity and the patient positioned so that the bubble closes the retinal break, permitting resorption of subretinal fluid. A chorioretinal adhesion formed around the break secures the retina in place. The history of pneumatic retinopexy is presented as well as recent studies on the subject. Characteristics of intraocular gases are reviewed. A protocol is described for pneumatic repair of complex retinal detachments. Patient selection and surgical techniques are recommended. Pneumatic retinopexy is compared to other retinal reattachment techniques and controversial issues are discussed.


Electrochemical modeling of microbial fuel cells performance at different operating and structural conditions.
Organic matters are directly converted to electricity by microorganisms in microbial fuel cells (MFC). Modeling the performance of MFC sheds light on the behavior of MFC in various operational conditions (e.g. pH and temperature). In the present research, three voltage losses were considered for modeling of the MFC polarization curve. The current research is composed of two parts. In the first part, the polarization curves of various MFCs with different substrates (synthetic wastewater or industrial wastewaters) were reproduced by our model, and model parameters were obtained using experimental data and genetic algorithm optimization. In this part, the electrical performance of 26 systems (12 systems with synthetic wastewater and 14 systems with industrial wastewaters) were modeled with average relative error (ARE) of 17% and a coefficient of determination of 0.9. In the second part, the influence of temperature, pH and hydraulic retention time on the electrical performance of MFC were studied. In this part, parameters were estimated by conventional (estimation of model parameters in each point), and a novel method (estimation of model parameters as a function of operating parameters). It was shown that using second tuning method, the number of estimated parameters decreased, while the error of the model remained at an acceptable level.


Four types of neuron in layer IVab of cat cortical area 17 accumulate 3H-GABA.
Roughly 10% of the neurons in layer IVab of cat area 17 accumulate exogenous 3H-gamma-aminobutyric acid (GABA) but how many types of neuron comprise this population was unknown. We characterized these neurons by partial reconstruction of their somas from serial electron microscope autoradiograms and distinguished four types. GABA 1 was large (greater than 16.5 micron) and dark with a dense distribution of synaptic terminals, substantial geniculate input to the soma, and a moderate accumulation of GABA. GABA 2 was small (less than 13 micron) and pale, also with a dense distribution of terminals but without evidence of somatic geniculate input, and a moderate accumulation of GABA. GABA 3 was radially fusiform (20 micron X 8 micron) with varicose dendrites, a sparse distribution of synaptic terminals, and a heavy accumulation of GABA. GABA 4 was medium in size (15 micron) with a moderate distribution of synaptic terminals and a heavy accumulation of GABA. Reasons are presented for believing that each of these four categories of GABA-accumulating neuron represents a fundamental cell type.


Surgical management of duodenal obstruction in an adult horse.
A 3-year-old Standardbred stallion was admitted for treatment of acute enterocolitis. The horse improved in response to empiric treatment, but subsequently developed ventral edema, scrotal abscessation, and severe laminitis. Improvement again was seen, but on day 29 of hospitalization, the horse developed rapid heart rate and signs of abdominal pain. Exploratory celiotomy revealed complete obstruction of the descending portion of the duodenum, 20 cm caudal to the duodenal sigmoidal flexure. Three-tier duodenojejunostomy and jejunojejunostomy were performed to bypass the duodenal obstruction.


Super-selective and staged glue embolization for labral AVMs using ultra-thin microcatheters: report of two cases.
Treating arteriovenous malformation (AVM) is challenging because of the high recurrence rate and because incomplete resection or embolization can induce aggressive growth. However, a standard strategy is not fully established. Although transcatheter arterial embolization (TAE) is currently almost always part of the treatment, in many cases, single treatment is not curative and only palliative. Additionally, the success and complication rates associated with TAE alone are unclear, and there has been limited study of staged TAE for facial AVMs. Furthermore, few reports have described the details of the procedure. We report two cases of AVM of the upper lip in patients who were successfully treated by staged super-selective TAE at several-month intervals using ultra-thin microcatheters and n-butyl-2-cyanoacrylate. Staged and super-selective TAE may prevent complications and provide high curability and might be a useful treatment in cases of AVM.


Bone mineral density in premenopausal women with major depression.
To investigate the relationship between the major depression and bone mineral density (BMD) in premenopausal women. We compared BMD, plasma cortisol level, osteocalcin and C-telopeptide levels of 35 premenopausal women with major depression with those of 30 healthy women who were matched for age and body mass index. Major depression was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (fourth edition) criteria. Nineteen patients had mild and 16 patients had moderate severity of major depression as measured by Hamilton rating scale for depression. Women with any risk factor for osteoporosis were excluded from the study. All women underwent BMD measurement by DEXA at lumbar (L2-4) and femoral neck region. After an overnight fasting, plasma cortisol levels were measured at 08:00 h by using competitive immunoassay method. Osteocalcin and C-telopeptide were used for the evaluation of bone turnover. There were no significant differences in BMD, plasma cortisol level, osteocalcin and C-telopeptide levels between the patients and the control groups. There was also no correlation between the plasma cortisol level, the duration and the severity of disease, antidepressant drug use and BMD. Major depression had no significant effect on BMD and bone turnover markers in our patient group of mild to moderate severity of the disorder.


Long-term sequelae of isolated chemical "airbag" keratitis.
To report the long-term sequelae of a case of bilateral chemical keratitis caused by airbag deployment. Case report and review of the literature. A 21-year-old woman presented with bilateral reduced vision, photophobia, and tearing after a car accident. Examination revealed some facial burns and severe chemical injury to the cornea and conjunctiva. Immediate irrigation with physiologic saline solution and subsequent treatment with topical antibiotics, corticosteroids, and vitamin C resulted in full restoration of vision but could not prevent permanent corneal damage. Severe alkali injury of the cornea generally has a good prognosis but can lead to permanent damage and persistent complaints of dry eye.


Congenital orbital teratoma: a case report with preservation of the globe and 18 years of follow-up.
Congenital orbital teratomas are extremely rare, usually benign neoplasms, comprised of cells originating from all three germ cell layers. Clinically the tumor appears solid, most of the times is intraconal and presents as a rapidly growing mass leading to a massive unilateral axial proptosis, chemosis, exposure keratopathy, markedly distended eyelids and often, loss of vision. To prevent these complications, tumor excision usually involves enucleation or even orbital exenteration. We report a case of a 1-day old infant who presented with dramatic proptosis at birth due to a true congenital orbital teratoma. We describe the clinical findings, the preoperative neuroimaging, the surgical management which included complete tumor resection with preservation of the globe to allow for optimal orbital growth, the histopathological evaluation, and the clinical course during 18 years of follow up. Every effort to salvage the globe should be made to achieve the best possible orbito-facial development. Furthermore, the value of prompt surgical management with a less invasive transconjunctival globe sparing procedure can be appreciated in our case.


Functions and regulation of T cell-derived interleukin-10.
Interleukin (IL)-10 is an essential anti-inflammatory cytokine and functions as a negative regulator of immune responses to microbial antigens. IL-10 is particularly important in maintaining the intestinal microbe-immune homeostasis. Loss of IL-10 promotes the development of inflammatory bowel disease (IBD) as a consequence of an excessive immune response to the gut microbiota. IL-10 also functions more generally to prevent excessive inflammation during the course of infection. Although IL-10 can be produced by virtually all cells of the innate and adaptive immune system, T cells constitute a non-redundant source for IL-10 in many cases. The various roles of T cell-derived IL-10 will be discussed in this review. Given that IL-10 is at the center of maintaining the delicate balance between effective immunity and tissue protection, it is not surprising that IL-10 expression is highly dynamic and tightly regulated. We summarize the environmental signals and molecular pathways that regulate IL-10 expression. While numerous studies have provided us with a deep understanding of IL-10 biology, the majority of findings have been made in murine models, prompting us to highlight gaps in our knowledge about T cell-derived IL-10 in the human system.


Octopamine receptors in locust nervous tissue.
The octopamine binding site in the nervous tissue of the migratory locust Locusta migratoria is identified as an octopamine receptor of class 2. The binding of octopamine to the binding site is saturable, reversible, stereospecific and shows a pharmacological profile typical for octopamine receptors. Saturation analysis results in a single class of non-interacting binding sites (KD = 7.9 +/- 0.9 nM; Bmax = 160 fmol/mg). The pharmacological analysis shows that the phenyliminoimidazolidines NC7 and NC5 (Ki = 0.29 and 0.87 nM, respectively) are the most potent agonists, and that mianserin (Ki = 1.20 nM) is the most potent antagonist ever reported for octopamine receptors in direct binding studies.


Presidential address to The Knee Society. Choices and compromises in total knee arthroplasty.
The art and science of total knee arthroplasty (TKA) has come a long way in the last 15 years. TKA has become a highly regarded and frequently recommended procedure. However, some of the uncertainties of the past about selection of design continue today, albeit in modified form. Ten years ago the surgeon was faced with a sometimes bewildering choice of prosthetic devices for which there were various indications. The same remains true today.


Study of the early response of Escherichia coli lpcA and ompF mutants to ciprofloxacin.
In most previous studies the sensitivity of Escherichia coli outer membrane mutants to ciprofloxacin (CF) was studied by MIC method. In the present work, the early response of these mutants to CF was studied using physiological and biochemical methods and electrochemical sensors. The use of sensors made it possible to monitor dissolved oxygen, potassium and extracellular sulfide continuously directly in growing cultures in real time. In the absence of CF, no significant differences were found between the mutants deficient in porin OmpF and lipopolysaccharide (LPS) and the parent. The only exception was 5-6 times higher extracellular glutathione and 1.5-3 times lower intracellular glutathione in the lpcA compared to the parent and the ompF. Ciprofloxacin inhibited growth, respiration, membrane potential and K+ consumption, which was less pronounced in both mutants compared to the parent. Changes in these parameters correlated with each other, but not with survival. A reversible increase in sulfide level was observed at 3 μg ml-1 CF in the parent, at 20 μg ml-1 CF in ompF and was absent in lpcA at all concentrations. The data obtained show that the use of electrochemical sensors can provide a more complete understanding of the early response of bacteria to CF.


Cerebral venous thrombosis associated with infective endocarditis in a young patient.
Cerebral venous thrombosis (CVT) is a rare complication of infective endocarditis. It constitutes a diagnostic and therapeutic emergency. We report a case of cerebral thrombophlebitis due to infective endocarditis in order to discuss the diagnosis and management of this situation. The patient was a 19-year-old man presenting with sudden explosive headaches with meningeal syndrome, right hemiparesis and right hypoesthesia. The cerebral CT angiography showed a left parieto-occipital and intraventricular hematoma without classic aneurysm or mycotic aneurysm or arteriovenous malformation. The injected brain magnetic resonance imaging found a CVT in front of a stopped opacification of the left lateral branch of the superior sagittal sinus. The presence of fever, poor oral status and a heart murmur justified the prescription of transthoracic echodoppler. It showed vegetations on healthy aortic valves. The patient was put on antibiotics and anticoagulants with favorable evolution. The absence of usual risk factors for CVT, the negativity of thrombophilia tests, the inflammatory and prothrombotic state associated with the infection reinforce the causal link of infective endocarditis to CVT formation. The etiology of CVT is variable, can be multiple and requires a comprehensive assessment. Infective endocarditis is one of the rare etiologies of CVT. In this case, anticoagulation and antibiotic drugs are indicated, taking into account the risk of intracerebral bleeding.


Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease.
In coeliac disease (CD), the upper bowel lesion is associated with a marked infiltration of the mucosa with Th1 cells secreting interferon gamma (IFNgamma) and expressing the Th1-associated transcription factor, T-bet. However, the molecular mechanisms which regulate T-bet and promote the Th1 cell response are unknown. To examine whether interleukin 21 (IL21), a cytokine that regulates T cell activation, has a role in CD. Duodenal mucosal samples were taken from CD patients and normal controls. IL21 and T-bet were examined by real-time PCR and western blotting, and IFNgamma was assessed by real-time PCR and ELISA. The effect of blockade of endogenous IL21 on the expression of T-bet was examined in an ex vivo culture of biopsies taken from untreated CD patients. Finally, the role of IL21 in controlling T-bet and IFNgamma was also evaluated in cultures of biopsies taken from treated CD patients and cultured with a peptic-tryptic digest of gliadin (PT) in the presence or absence of a neutralising IL21 antibody. Enhanced IL21 RNA and protein expression was seen in duodenal samples from untreated CD patients. Blockade of IL21 activity in biopsies of untreated CD patients reduced T-bet and IFNgamma secretion. Stimulation of treated CD biopsies with PT enhanced IL21 expression, and neutralisation of IL21 largely prevented PT-driven T-bet and IFNgamma induction. IL21 is overproduced in the mucosa of CD patients, where it helps sustain T-bet expression and IFNgamma production.


Effects of a Sociodrama-based Communication Enhancement Program on Mothers of Children with Neurodevelopmental Disorders: A Pilot Study.
The incidence and prevalence of neurodevelopmental disorders have rapidly increased, indicating an urgent need for assistance through parenting interventions. This study aimed to evaluate the effects of a sociodrama-based communication enhancement program on mothers of children with neurodevelopmental disorders. A non-randomized controlled experimental study design was employed. The experimental and control groups had 16 and 18 participants, respectively. The once-a-week six-session intervention was conducted from September to November 2017, in South Korea. The effects of group, time, and group-by-time interactions among the groups were verified using generalized estimating equations with an autoregressive correlation structure. There was a significant decrease in the parenting burden, alongside a significant improvement in parent-child communication and parenting competence in the experimental group compared to the control group. The sociodrama-based communication enhancement program was found to positively influence the parenting burden, communication, and parenting competence of mothers of children with neurodevelopmental disorders. These findings suggest that sociodrama-based programs may be an effective intervention strategy for parents of children with neurodevelopmental disorders. The sociodrama-based communication enhancement program can be applied to decrease parenting burden and improve parent-child communication and parenting competence. Through continuous parenting interventions, an improvement in expressive language and an increase in the attachment behaviors of children with neurodevelopmental disabilities could be expected.


A case of toe macrodactyly treated by application of a vascularised nail graft.
Macrodactyly is a relatively rare congenital abnormality of the fingers and toes and is difficult to treat. We report a new method for treating toe macrodactyly in which a nail with a vascularised pedicle is raised, the toe is shortened to an appropriate length, and the nail transferred to an aesthetically appropriate proximal site. Although this technique is of a higher level of difficulty than conventional procedures involving pedicled nail flaps, allows aesthetically more favourable nail reconstruction by single-stage operation.


In vitro analysis of the trajectories of adhesive microbubbles approaching endothelial cells.
Adhesion is a key process when ultrasound contrast agents, i.e. microbubbles, approach pathological tissues. A way to accomplish tumour targeting is to tether surface engineered microbubbles to endothelial cells of the up-regulated vascularization of cancer tissues. This can be achieved by coupling the microbubbles surface with the Arginine-Glycine-Aspartate, RGD, sequence. Such molecule interacts with the integrin receptors placed on the endothelial cells. Stability and trajectories of RGD modified lipid shelled MBs have been analysed in vitro using microchannels coated with human umbilical vein endothelial cells, HUVEC. In the microchannels realistic conditions, close to the physiological ones, were reproduced replicating shear rate, roughness comparable to the endothelium and channel size mimicking the postcapillary venules. In these conditions, the analysis of the trajectories close to the walls highlights a substantial difference between the modified MBs and the plain ones. Moreover, MBs adhesion has dynamic features recalling the motion of neutrophils engaged near the substrate such as rolling, translations and transient detachments. These findings are useful for the optimization of in vivo imaging and targeting functions.


Determinism and probability in the development of the cell theory.
A return to Claude Bernard's original use of the concept of 'determinism' displays the fact that natural laws were presumed to rule over all natural processes. In a more restricted sense, the term boiled down to a mere presupposition of constant determinant causes for those processes, leaving aside any particular ontological principle, even stochastic. The history of the cell theory until around 1900 was dominated by a twofold conception of determinant causes. Along a reductionist trend, cells' structures and processes were supposed to be accounted for through their analysis into detailed partial mechanisms. But a more holistic approach tended to subsume those analytic means and the mechanism involved under a program of global functional determinations. When mitotic and meiotic sequences in nuclear replication were being unveiled and that neo-Mendelian genetics was being grafted onto cytology and embryology, a conception of strict determinism at the nuclear level, principally represented by Wilhelm Roux and August Weismann, would seem to rule unilaterally over the mosaic interpretation of the cleavage of blastomeres. But, as shown by E.B. Wilson, in developmental processes there occur contingent outcomes of cell division which observations and experiments reveal. This induces the need to admit 'epigenetic' determinants and relativize the presumed 'preformation' of thedevelopmental phases by making room for an emergent order which the accidental circumstances of gene replication would trigger on.


[2,7-Dieth-oxy-8-(4-fluoro-benzo-yl)naphthalen-1-yl](4-fluoro-phen-yl)methanone.
In the mol-ecule of the title compound, C28H22F2O4, the benzoyl groups are aligned almost anti-parallel and the fluorobenzene rings form a dihedral angle of 14.12 (7)°. The dihedral angles between the 2,7-dieth-oxy-naphthalene ring system and the benzene rings are 70.00 (4) and 67.28 (4)°. In the crystal, mol-ecules are linked by C-H⋯O and C-H⋯F hydrogen bonds, forming layers parallel to the ab plane. The layers are further connected by π-π inter-actions [centroid-centroid distances of 3.6115 (10) Å] into a three-dimensional structure.


Reproductive toxicity of Campomanesia xanthocarpa (Berg.) in female Wistar rats.
There is no evidence in the literature that substantiates the safety of Campomanesia xanthocarpa (Berg.) use during pregnancy. Thirty three female rats were randomly assigned to three groups. One group of animals received the Campomanesia xanthocarpa extract via gavage at a dose of 26.3mg/kg/day from 6 to 15 days of pregnancy (organogenic period, T1) and another group received the same extract throughout the gestational period (from the 1st to the 20th day of pregnancy, T2). Control groups received distilled water. Euthanasia was done on 20th day, when the liver, kidney, spleen ovaries, fetuses and their respective placentas were removed. Implantations, reabsorptions, live and dead fetuses were recorded. Campomanesia xanthocarpa, in these experimental conditions, did not disturb the reproductive function of female rats and did not interrupt the progress of the embryofetal development. Moreover, our results provide further evidence that the Campomanesia xanthocarpa treatment reduces reabsorption sites, increases placenta weight and the number of live fetuses and may therefore have therapeutic applications.


Wnt3a mediated activation of Wnt/β-catenin signaling promotes tumor progression in glioblastoma.
Presence of a distinct population of cells that drives tumor progression supports the hierarchical model of tumor development in Glioblastoma (GBM) and substantiates the cancer stem cell hypothesis. Amongst the various developmental signaling pathways that are aberrantly activated, we here show that activated Wnt/β-catenin signaling pathway plays a critical role in malignant transformation and tumor progression in gliomas. We demonstrate that Wnt ligands - Wnt1 and Wnt3a are expressed in a graded manner in these tumors as well as over-expressed in glioma stem cell-lines. A selective inhibition of Wnt signaling pathway by selective knock-down of its ligands Wnt1 and Wnt3a in glioma-derived stem-like cells led to decreased cell proliferation, cell migration and chemo-resistance. Furthermore, Wnt silencing in glioma cells reduced the capacity to form intra-cranial tumors in vivo. Taken together, our study indicates Wnt/β-catenin signaling pathway as an essential driver of glioma tumorigenesis, recognizing role of Wnt3a as an oncogene and thereby offering novel therapeutic strategies for management of these tumors.


More precise localization of the gene for Hunter syndrome.
A linkage analysis between the Hunter syndrome locus (IDS) and four polymorphic loci of the Xq27-Xq28 region, DXS105, DXS98, DXS304, and DXS52, was performed in large families. A significant lod score was obtained between DXS304 and the Hunter gene (Zmax = 6.57 at theta max = 0.0). The Hunter gene can be localized within 7 cM of this marker. In addition, the translocation breakpoint of the Hunter female case described by J. Mossman et al. (1986, Arch. Dis. Child. 58: 911-915) was localized between DXS98 and DXS304 using somatic cell hybrids. These two results are in agreement and give the following order: DXS105-DXS98-IDS-DXS304-DXS52. Probes for these marker loci can thus be used for carrier detection.