Effects of chlorpromazine on hypothalamic aminergic neurons and stress responses in moderate cold.
Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4 degrees C or +23 degrees C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG:NA and 5-HIAA:5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.


Can uterine niche be prevented?
Uterine niche is a potential significant consequence of Caesarean section and is diagnosed by ultrasound. The timing of Caesarean section (during pre, early or advanced labour), location of the incision (distance from the internal os), techniques for opening and closing the uterine cavity, and bladder flap have been frequently mentioned in the literature, however, these factors continue to be a source of disagreement with respect to whether they increase the risk of uterine niche or protect against this complication. In this review, we outline and discuss the possible risk factors that may be responsible for this entity. The main factor upon which obstetricians can act is the rate of first Caesarean section, which can and should be reduced. Moreover, a rather high incision at a distance from the internal os, and a sparing use of bladder detachment should be always kept in mind as well.


Improved yield of recombinant human IFN-α2b from mammalian cells using heterologous signal peptide approach.
The Type I Interferon cytokine family member, Interferon-α2b (hIFN-α2b), modulates a number of important biological mechanisms including anti-proliferation, immunoregulation and antiviral responses. Due to its role in the immune system, hIFN-α2b has been used as a therapeutic modulator in hepatitis C as well as some forms of leukaemia. Clinical grade hIFN-α2b is typically produced in bacterial expression systems that involves complex refolding protocols and subsequent loss of yields. In this study, we describe an expression and purification system for hIFN-α2b from mammalian cells. Application of the Trypsin-1 signal peptide-propeptide domain significantly improved the expression and secretion of hIFN-α2b from HEK293 cells. We established a simple purification strategy that yields homogenous, pure hIFN-α2b that is stable and biologically active.


Effects of glucocorticoids on differentiation of zona glomerulosa of fetal adrenal cortex of rats.
The tissue differentiation of the zona glomerulosa of the fetal adrenal cortex of rats was studied by giving experimental treatments to the fetus in vivo. A low-glucocorticoid-condition was given to the fetus by bilateral adrenalectomy of pregnant rats for removing exogenous glucocorticoids from the fetus, and by brain aspiration of the fetuses for removing the fetal pituitary gland (ACTH) and endogenous glucocorticoids. When the fetus was placed under a low-glucocorticoid-condition for the last couple of days of gestation, poor differentiation of the zona glomerulosa occurred specifically in the fetal adrenal cortex. The degree of the poor differentiation seemed to be proportional to the duration of the low-glucocorticoid-condition. Supplemental administration of glucocorticoids could prevent this poor differentiation of the zona glomerulosa. These results indicate that the tissue differentiation of the zona glomerulosa of the fetal adrenal cortex depends much on glucocorticoids.


Postnatal toxic and acquired disorders.
To develop and function optimally, the brain requires a balanced environment of electrolytes, amino acids, neurotransmitters, and metabolic substrates. As a consequence, organ dysfunction has the potential to induce brain disorders and toxic-metabolic encephalopathies, particularly when occurring during early stages of cerebral maturation. Induced toxicity of three different organ systems that are commonly associated with brain complications are discussed. First, thyroid hormone deficiency caused by intrinsic or extrinsic factors (e.g., environmental toxins) may induce severe adverse effects on child neurological development from reversible impairments to permanent mental retardation. Second, inadequate removal of wastes due to chronic renal failure leads to the accumulation of endogenous toxins that are harmful to brain function. In uremic pediatric patients, the brain becomes more vulnerable to exogenous substances such as aluminum, which can induce aluminum encephalopathy. Following surgical procedures, neurological troubles including focal defects and severe epileptic seizures may result from hypertensive encephalopathy combined with toxicity of immunomodulating substances, or from the delayed consequences of cardiovascular defect. Taken together, this illustrates that organ disorders clearly have an impact on child brain function in various ways.


Painful effects of auditory startle, forehead cooling and psychological stress in patients with fibromyalgia or rheumatoid arthritis.
The aim of this study was to determine whether the clinical pain associated with rheumatoid arthritis or fibromyalgia would increase during standard laboratory tasks and, if so, whether these increases were linked with individual differences in psychological distress. Twenty-three patients with fibromyalgia and 16 patients with rheumatoid arthritis rated changes in clinical pain after an acoustic startle stimulus, during painful forehead cooling, and during stressful mental arithmetic. In addition, pain tolerance was assessed during a submaximal effort tourniquet test, and patients provided ratings of distress on a standard Depression, Anxiety and Stress Inventory. Pain at rest was associated with depression scores in patients with rheumatoid arthritis, and was associated with stress scores in the fibromyalgia group. However, pain tolerance was unrelated to individual differences in psychological distress in either group. In patients with fibromyalgia, clinical pain increased after the acoustic startle stimulus and painful forehead cooling, and increased during stressful mental arithmetic. Arthritic pain also increased during forehead cooling and mental arithmetic in association with indices of psychological distress. These findings suggest that processes linked with individual differences in distress aggravate pain in rheumatoid arthritis, whereas some other mechanism (e.g., failure of stress-related pain modulation processes or an aberrant interaction between nociceptive afferent and sympathetic efferent fibers) triggers stress-induced pain in fibromyalgia.


Protein-deficient diet in pregnant females impairs functional activity of enzyme systems in digestive and non-digestive organs in the offspring.
Activity of disaccharidases in various portions of the small intestine markedly increased in 6-month-old offspring of pregnant females feeding a protein-deficient diet. Activities of amino- and dipeptidases decreased in the kidneys, while alkaline phosphatase activity remained practically unchanged. Probably, information about protein restriction in nutrition of pregnant females is stored in the biochemical memory of adult offspring and promotes the development of metabolic disturbances.


A Viral Platform for Chemical Modification and Multivalent Display.
The ability to chemically modify the surfaces of viruses and virus-like particles makes it possible to confer properties that make them potentially useful in biotechnology, nanotechnology and molecular electronics applications. RNA phages (e.g. MS2) have characteristics that make them suitable scaffolds to which a variety of substances could be chemically attached in definite geometric patterns. To provide for specific chemical modification of MS2's outer surface, cysteine residues were substituted for several amino acids present on the surface of the wild-type virus particle. Some substitutions resulted in coat protein folding or stability defects, but one allowed the production of an otherwise normal virus-like particle with an accessible sulfhydryl on its surface.


Modular training for percutaneous nephrolithotripsy: The safe way to go.
Objectives should be describe a modular training scheme (MTS) which aims to provide training in percutaneous nephrolithotripsy (PCNL) and ensure the safety of the patients. Two trainees with no experience in PCNL attended the MTS under the supervision of an experienced mentor. The MTS included five modules, comprising an initial animal laboratory course (using pigs), to acquire basic skills (Module 1), and Modules 2-5 included making the puncture, tract dilatation, single-stone and large-stone management in clinical cases, respectively. Each participant progressed from one module to the next under constant mentoring and evaluation by the mentor. When the trainees completed the MTS they proceeded to perform 60 PCNL procedures independently while the mentor performed 25 for comparison purposes. A global rating scale was used for the objective evaluation of the trainees. Peri-operative variables were recorded and statistically compared as appropriate. Statistical significance was defined as P < 0.05. One pig and 16 patients, and two pigs and 22 patients, were necessary to complete the MTS by each subject. There were no significant differences among the characteristics of the independently performed operations. The duration of surgery and fluoroscopy achieved a plateau similar to those of the mentor after ≈ 30 patients. The decrease in haemoglobin level, stone-free and complication rates in the patients were similar among the two trainees and the mentor. The complication rate of the trainees and the mentor never exceeded 13.3%. The MTS successfully combined animal and stepwise clinical training based on a standardised technique and objective evaluation.


Comparison of infusions of propofol and methohexitone to provide light general anaesthesia during surgery with regional blockade.
General anaesthesia was induced with, and maintained by, an infusion of either propofol or methohexitone, in patients undergoing surgery with the aid of regional blockade. Both agents provided satisfactory and controllable anaesthesia. Complications were few with a similar incidence for the two drugs. Recovery from anaesthesia was significantly faster following propofol.


Vaginal mucus from ewes treated with progestogen sponges affects quality of ram spermatozoa.
The use of intravaginal sponges (IS) to synchronize estrous onset in ewes provokes vaginitis, an increase in the vaginal bacterial load, and growth of bacterial species that are not present during spontaneous estrous behavior. The objective of the study was to compare the functional sperm parameters after incubating it with mucus collected from the vagina of ewes during spontaneous estrus or estrous synchronized with IS. Pooled spermatozoa were co-incubated with: (1) vaginal mucus collected from ewes in spontaneous estrus; (2) vaginal mucus collected from ewes in estrus pretreated with progestogen-impregnated IS; (3) synthetic mucus; and (4) medium without mucus as a control group. Sperm samples were evaluated after incubating it for 30 and 90 minutes. The number of colony-forming units (CFUs/mL), pH, and osmolality were greater in the mucus collected from ewes treated with IS than from those untreated (P = 0.046; P < 0.0001, and P < 0.0001, respectively). The percentage of sperm with progressive motility was lower after incubation with vaginal mucus collected from estrous ewes treated with IS than in the other three treatments both, 30 and 90 minutes after incubation (P = 0.0009 and P < 0.0001, respectively). The sample incubated for 30 minutes with mucus from ewes treated with IS had a lower percentage of sperm with intact plasma membrane than all the other treatments (P < 0.0001). The percentage of sperm with functional membrane was significantly lower in the sample incubated for 30 minutes with vaginal mucus from ewes treated with IS than in the other three treatments (P < 0.0001). After 90 minutes, the percentage was still lower than that in the sample collected from ewes during their spontaneous estrus (P = 0.0005). The lowest percentages of sperm with acrosome damage were observed in sperm incubated with mucus collected from sheep in spontaneous estrus for 30 and 90 minutes (P < 0.0001 and P = 0.008, respectively). The percentage of apoptotic spermatozoa was greater in samples incubated during 30 minutes with vaginal mucus collected from ewes treated with IS than in the other three groups (P = 0.0005). The functionality and the viability of ram sperm is negatively affected by the cervical mucus of ewes pretreated with progestagen-impregnated IS used in estrous synchronization treatments. This may partially explain the decrease in conception rate obtained with treatments with IS.


Evaluation of quality of life of patients with hirsutism among Turkish women: A single-center cross-sectional study.
Patients with hirsutism have an increased number of psychological diseases including depression, anxiety, and social isolation with decreased quality of life. We aimed to investigate changes in the quality of life of patients with hirsutism among Turkish women. A total of 57 patients diagnosed with hirsutism were included in this study. The patients were investigated in terms of Dermatological Life Quality Index (DLQI) score, concomitant clinical findings, and polycystic ovary syndrome. Modified Ferriman-Gallwey (mFG) was used for the diagnosis of hirsutism. The mean DLQI score of the patients was 9.80 ± 6.50, while the median value of the mFG score was 25 (minimum 8, maximum 34). The mean DLQI score of patients who had an mFG score of four only in one region of the face was statistically higher than women with an mFG score less than four (P = .033). No statistically significant correlation was found between DLQI and mFG scores (P = .254). There was no statistically significant difference in terms of DLQI between women with acne, seborrhea, androgenetic alopecia, menstrual irregularity, or acanthosis nigricans versus those without them (P >.05). The mean DLQI score was statistically significantly higher for patients with PCOS than for those without PCOS (P = .004). As shown by mFG score, quality of life is affected in certain areas for women with hirsutism. The mFG score is not correlated with the quality of life score. Certain areas of excessive hair that lead to stigma may be more important in quality of life for these women. The quality of life seems to be significantly more affected in hirsutism patients with PCOS than those without PCOS. Finally, clinical symptoms and signs appear to have no important role in the quality of life of patients with hirsutism.


Alcohol's effects on sexual decision making: an integration of alcohol myopia and individual differences.
We conducted an experiment to test the applicability of integrating individual perceptions of unprotected sex consequences with alcohol's myopic effects as an explanatory framework for risky sexual decision making in young heterosexual men and women. Male and female participants (N = 61) rated their perceptions of unprotected sex consequences, received alcoholic (target breath alcohol concentration = .10%) or nonalcoholic drinks, and completed a risky sexual decision-making task that included a quantitative measure of sexual decision-making cue attention. Intoxicated participants were more attentive to impelling cues and reported greater sexual risk intentions than sober participants. Mediational analyses indicated that attention to cues fully mediated the alcohol-sexual risk intention relationship. Moderational analyses revealed that alcohol's focusing effect acts in conjunction with pre-existing individual perceptions to influence cue salience directly and sexual risk intentions indirectly. Findings demonstrate the importance of examining predispositional tendencies when investigating alcohol myopia as a mediating mechanism underlying the alcohol-risky sex relationship.


Use of aequorin-based indicators for monitoring Ca2+ in acidic organelles.
Over the last years, there is accumulating evidence that acidic organelles can accumulate and release Ca2+ upon cell activation. Hence, reliable recording of Ca2+ dynamics in these compartments is essential for understanding the physiopathological aspects of acidic organelles. Genetically encoded Ca2+ indicators (GECIs) are valuable tools to monitor Ca2+ in specific locations, although their use in acidic compartments is challenging due to the pH sensitivity of most available fluorescent GECIs. By contrast, bioluminescent GECIs have a combination of features (marginal pH sensitivity, low background, no phototoxicity, no photobleaching, high dynamic range and tunable affinity) that render them advantageous to achieve an enhanced signal-to-noise ratio in acidic compartments. This article reviews the use of bioluminescent aequorin-based GECIs targeted to acidic compartments. A need for more measurements in highly acidic compartments is identified.


A chimeric antibody to L1 cell adhesion molecule shows therapeutic effect in an intrahepatic cholangiocarcinoma model.
Intrahepatic cholangiocarcinoma (ICC), a malignant tumor derived from the intrahepatic bile duct epithelium, has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Thus, there is an urgent need to develop new effective therapeutic strategies for this disease. We previously found that L1 cell adhesion molecule (L1CAM) plays an important role in tumor progression of ICC, and we generated a murine mAb, A10-A3 (IgG1), that binds to the Ig1 domain of L1CAM. In the present study, we further characterized A10-A3, constructed a chimeric A10-A3 antibody (cA10-A3) containing the constant regions of human IgG1, and evaluated the therapeutic potential in a human ICC xenograft nude mice model. The affinities (KD) of A10-A3 and cA10-A3 for soluble L1CAM were 1.8 nM and 1.9 nM, respectively, as determined by competition ELISA. A10-A3 inhibited L1CAM homophilic binding and was slowly internalized into the tumor cells, but it did not significantly inhibit proliferation of ICC cells in vitro. cA10-A3 mediated antibody- dependent cell-mediated cytotoxicity in vitro and displayed anti-tumor activity in the ICC animal model. These results suggest that the humanized A10-A3 antibody may have potential as an anticancer agent for the treatment of ICC.


Electrospinning of in situ synthesized silica-based and calcium phosphate bioceramics for applications in bone tissue engineering: A review.
The field of bone tissue engineering (BTE) focuses on the repair of bone defects that are too large to be restored by the natural healing process. To that purpose, synthetic materials mimicking the natural bone extracellular matrix (ECM) are widely studied and many combinations of compositions and architectures are possible. In particular, the electrospinning process can reproduce the fibrillar structure of bone ECM by stretching a viscoelastic solution under an electrical field. With this method, nano/micrometer-sized fibres can be produced, with an adjustable chemical composition. Therefore, by shaping bioactive ceramics such as silica, bioactive glasses and calcium phosphates through electrospinning, promising properties for their use in BTE can be obtained. This review focuses on the in situ synthesis and simultaneous electrospinning of bioceramic-based fibres while the reasons for using each material are correlated with its bioactivity. Theoretical and practical considerations for the synthesis and electrospinning of these materials are developed. Finally, investigations into the in vitro and in vivo bioactivity of different systems using such inorganic fibres are exposed.


Pharmacist-led medication for pain in France: What population are we talking about? Results of the Optymed study.
Self-medication for alleviating pain is very prevalent in most countries. While safe self-medication is supposed to be dependent on both patient's behaviour and pharmacist's counselling, little is known about the context of the delivery of analgesics available without prescription. The primary objective of the study was to define sociodemographic profiles and behaviours of patients seeking non-prescribed analgesics in French community pharmacies. Secondary objectives included the assessment of pharmacist management and identification of risk-associated patients. This is a cross-sectional, national and multicentre study, including adults who asked for a prescription-free medication for acute or chronic physical pain. Information was collected through separate patient and healthcare professional (HCP) questionnaires. The analysis was based on 1215 and 1271 patient and HCP questionnaires, respectively, collected from 164 pharmacies. The patient population consisted in women and men (ratio 6:4), mainly (71%) under 60 years old. Headaches, rheumatologic and musculoskeletal pains were the most frequent reasons for getting analgesics, with a median pain intensity of 6 on a scale graded from 0 (no pain) to 10 (intolerable pain). The main reasons guiding self-medication were time saving, a well-known pain and a well-known product. The mean time allocated to delivery was 4.7minutes. Indications, dose and posology were almost systematically addressed by the pharmacy staff, while contra-indications, drug-drug interaction or safety were mentioned in around two-third of cases. The proportion of patients identified at risks due to an inappropriate context of self-medication was 15.5%. This study shows a great heterogeneity of the population asking for non-prescribed analgesics in French community pharmacies. While pharmacists were able to identify patients at risks, a significant part may have 'slipped through the net'. The results support further studies to better define patient care pathway and optimize pharmacist-led medication.


Lipoma arborescens: comparison of typical and atypical disease presentations.
To determine whether the aetiology differed between typical cases of lipoma arborescens with unilateral knee involvement and atypical cases involving joints other than the knee, polyarticular disease, and disease outside of the knee joint. Cases of lipoma arborescens involving the knee joint were evaluated for the distribution of the disease and severity of degenerative arthritis. Joints other than the knee were evaluated for the presence and severity of degenerative arthritis, and the distribution was classified as either intra-articular, extra-articular, or both. Clinical history was reviewed for patient age at presentation, a history of inflammatory arthritis, diabetes mellitus, and known steroid use. Fisher's exact test was used to determine whether there was a statistically significant difference between typical and atypical presentations of the disease. Lipoma arborescens was identified in 45 joints in 39 patients. Twenty-eight patients were classified as "typical" and 11 patients had "atypical" disease. There was no significant difference in age at presentation, presence of degenerative arthritis, or known inflammatory arthritis when comparing typical and atypical presentations of the disease. Twenty-eight percent of patients in the present study had atypical presentation of lipoma arborescens with multifocal lipoma arborescens or disease in joints other than the knee. There was no significant difference in age at presentation, presence of degenerative arthritis, or known inflammatory arthritis when comparing typical and atypical presentations of the disease. Of the 39 patients, only three had no evidence of degenerative arthritis, which suggests that many cases of lipoma arborescens are secondary to chronic reactive change in association with degenerative arthritis.


Loop-Mediated Isothermal Amplification (LAMP) for Detection of Ureaplasma diversum from Cervico-vaginal Swab of Buffaloes.
The main plan of the current study was to develop a rapid, robust, and field-applicable loop-mediated isothermal amplification (LAMP) assay for the detection of Ureaplasma diversum. A strain-specific 16S rRNA gene of Ureaplasma diversum was used for detection which was cloned, sequenced, and characterized earlier. LAMP results were visualized within 90 min with the naked eye. Cervico-vaginal swabs of 50 buffaloes were randomly collected from Livestock Research Center of NDRI as per the Institute Animal ethics guidelines. Out of 50 cervico-vaginal swab samples collected randomly, 34 were found positive with LAMP while 16 samples were negative. Conventional PCR results showed the same result. Therefore, the accuracy of the developed LAMP was about 100%. The developed LAMP assay can also be used to screen the animals for Ureaplasma diversum infection in cervico-vaginal swab. However, further study is needed to assess sensitivity and accuracy towards their detection and their relationship in disease diagnosis.


Subtle differences in glycosylation of blood group M and N type glycophorin A detected with anti-Tn lectins and confirmed by chemical analysis.
A higher content of Tn and sialyl-Tn receptors in glycophorin A of blood group N than in that of blood group M was suggested by reactions with anti-Tn lectins. Analysis of beta-elimination products of two blood group M and two blood group N preparations by gas liquid chromatography-mass spectrometry showed that GalNAc-ol was detectable in minor amounts in all analyzed samples and its content was higher in the products obtained from desialylated antigens. Moreover, the content of GalNAc-ol detected in blood group N samples was almost twice as high as in respective blood group M samples. Since blood group M and N antigens differ in two amino-acid residues, our results support the existence of sequence-dependent differences in efficiency of substitution of glycophorin GalNAc-Ser/Thr residues with galactose.


Clinical evaluation of TMJ arthroplasties with insertion of articular eminence prosthesis on ninety patients (an eight year study).
This paper represents an analysis, accomplished over an eight-year period, of 90 individuals who have been operated on for various arthritic diseases of their temporomandibular joints (TMJ). In arthritic changes of the joint, several changes may occur: perforation of the disc, flattening of the articular eminence, asymmetrical condylar movement, and chronic synovitis. This may result in increased synovial pressure on nerve fibers within the capsule of the joint, and a variety of referred pain symptoms. Prior to operation, a careful differential diagnosis was made by an otolaryngologist and, frequently, by a neurologist/neurosurgeon and a psychologist. The prosthesis inserted during surgery was a metallic device which fits over the articular eminence in the upper portion of the joint. This prosthesis accomplished primarily three functions: elimination of the crepitus; restoration of the contour of the eminence; separation of the articular surface of the joint.


Spinal osteoporosis in men.
In 94 men with crush fracture, 40 were found to have primary osteoporosis. Cross-sectional measurements of a number of variables related to bone in these 40 patients were compared to the values in various groups of healthy men aged 20-96. In healthy men, metacarpal and femoral cortical area/total area, bone volume, osteoid surfaces, seam and trabecular width, plasma dihydroepiandrosterone and estrone, and radiocalcium absorption fell with age, whereas eroded surfaces, trabecular number, urine hydroxyproline and calcium/creatinine ratios, plasma alkaline phosphatase, estradiol, androstenedione, cortisol and testosterone remained constant with age. As compared with healthy men, men with primary osteoporosis had reduced femoral cortical area/total area (P less than 0.05), and Singh grade (P less than 0.001) and in seven there was a history of forearm or femoral fracture. On iliac crest biopsy, bone volume (P less than 0.001) and trabecular number (P less than 0.01) were decreased. Plasma alkaline phosphatase (P less than 0.02) was increased but urine hydroxyproline and calcium excretion were not significantly raised. Calcium balance was negative due to failure of absorption to match urinary calcium loss and radiocalcium absorption (P less than 0.01) and plasma 1,25-dihydroxyvitamin D (P less than 0.05) were reduced.


Interaction of the chlorinated hydrocarbon insecticide lindane or DDT with lipids--a differential scanning calorimetry study.
The interaction of DDT and lindane with glycosphingolipids and phospholipids was investigated by employing differential scanning calorimetry. The degree of perturbation produced by lindane is stronger than that of DDT and depends also on the lipid.


Characteristics and prognosis of bloodstream infection in patients with COVID-19 admitted in the ICU: an ancillary study of the COVID-ICU study.
Patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) and requiring intensive care unit (ICU) have a high incidence of hospital-acquired infections; however, data regarding hospital acquired bloodstream infections (BSI) are scarce. We aimed to investigate risk factors and outcome of BSI in critically ill coronavirus infectious disease-19 (COVID-19) patients. We performed an ancillary analysis of a multicenter prospective international cohort study (COVID-ICU study) that included 4010 COVID-19 ICU patients. For the present analysis, only those with data regarding primary outcome (death within 90 days from admission) or BSI status were included. Risk factors for BSI were analyzed using Fine and Gray competing risk model. Then, for outcome comparison, 537 BSI-patients were matched with 537 controls using propensity score matching. Among 4010 included patients, 780 (19.5%) acquired a total of 1066 BSI (10.3 BSI per 1000 patients days at risk) of whom 92% were acquired in the ICU. Higher SAPS II, male gender, longer time from hospital to ICU admission and antiviral drug before admission were independently associated with an increased risk of BSI, and interestingly, this risk decreased over time. BSI was independently associated with a shorter time to death in the overall population (adjusted hazard ratio (aHR) 1.28, 95% CI 1.05-1.56) and, in the propensity score matched data set, patients with BSI had a higher mortality rate (39% vs 33% p = 0.036). BSI accounted for 3.6% of the death of the overall population. COVID-19 ICU patients have a high risk of BSI, especially early after ICU admission, risk that increases with severity but not with corticosteroids use. BSI is associated with an increased mortality rate.


Calcium and Phosphorus: All You Need to Know but Were Afraid to Ask.
Inadequate intake of calcium and phosphorus during the perinatal period can result in metabolic bone disease (MBD), characterized by decreased bone mass, altered bone mineralization, and increased risk for fractures. Preterm neonates have higher risk of developing MBD. Treating MBD involves ensuring adequate calcium and phosphorus intake, early fortification, and vitamin D supplementation. Health care providers should closely monitor nutrient intake, postnatal growth, and screening of preterm neonates at risk for MBD. This review summarizes the critical roles of calcium and phosphorus in regulating bone physiology, how they regulate bone formation and resorption, and their influence on overall bone health.


Physiologic effects of surgical masking in children versus adults.
Surgical masks remain a focal part of the CDC guidelines to decrease COVID-19 transmission. Evidence refuting significant effects of masking on ventilation is mostly limited to small studies, with a paucity of studies on children, and none comparing children to adults. A total of 119 subjects were enrolled (71 adults, 49 children) in a prospective interventional study with each subject serving as their own mask-free control. End tidal CO2 (ETCO2), inspired CO2 (ICO2), and respiratory rate were measured by nasal cannula attached to an anesthesia machine D-fend module. Pulse oximetry and heart rate were also followed. After the mask-free period, an ASTM Level 3 disposable surgical mask was donned and 15 min of mask-worn data were collected. A steady state was confirmed for ETCO2 and ICO2 over the masked period, and mean ICO2 levels rose significantly (p < 0.001) after masking in all age groups. The increase in ICO2 for the 2- to 7-year-old group of 4.11 mmHg (3.23-4.99), was significantly higher (p < 0.001) than the final ΔICO2 levels for both the 7- to 14-year-old group, 2.45 mmHg (1.79-3.12), and adults, 1.47 mmHg (1.18-1.76). For the pediatric group there was a negative, significant correlation between age and ΔICO2, r = -0.49, p < 0.001. Masking resulted in a statistically significant (p < 0.01) rise in ETCO2 levels of 1.30 mmHg in adults and 1.36 mmHg in children. The final respective ETCO2 levels, 34.35 (33.55-35.15) and 35.07 (34.13-36.01), remained within normal limits. Pulse oximetry, heart rate, and respiratory rate were not significantly affected. The physiology of mechanical dead space is discussed, including the inverse relationship of subject age vs ICO2. The methodology and results are compared to previously published studies which detracted from the physiologic safety of surgical masking. The wearing of a surgical mask results in a statistically significant rise in ICO2 and a smaller rise in ETCO2. Because ETCO2 and other variables remain well within normal limits, these changes are clinically insignificant.


Interventions to respond to COVID 19 pandemic in Mumbai and way forward.
With the emergence of COVID 19 pandemic, the approach used by Municipal Corporation of Greater Mumbai (MCGM) was based on all guidelines of COVID 19 prepared by Ministry of Health and Family Welfare (MoHFW). However, Mumbai undertook a special innovate model used in the mission Mumbai - Dharavi for COVID 19. Additionally, MCGM undertook a proactive approach of "chasing the virus" with its 4Ts: 1. Tracing 2. Tracking 3. Testing 4. Treating in high-risk slum clusters and it reflects the result of declining the incidence and case fatality due to COVID 19. Establishing public health surge capacities which include active surveillance, contact-tracing and follow-up besides early detection, isolation and management of cases are important steps for fighting the COVID 19 pandemic. Collaborating with all partners and setting up a Task force for establishing clinical management protocols was unmissable.


Biomolecular diffusional association.
The primary method for the computational study of biomolecular diffusional association is Brownian dynamics. Recent work has seen advances in the efficiency of computing association rates and in the accuracy of simulation models. New areas to which Brownian dynamics has been applied include protein polymerisation and protein adsorption to a surface. There has recently been particularly intense study of protein-protein association, and Brownian dynamics, together with other theoretical and experimental approaches, has led to new insights into the determinants of protein-protein binding kinetics.


Responses of Prorocentrum cordatum (Ostenfeld) Dodge, 1975 (Dinoflagellata) to copper nanoparticles and copper ions effect.
In the present study, changes were determined in morphological, structural-functional, and fluorescent parameters of Prorocentrum cordatum with the addition of CuO nanoparticles (NPs) and copper ions (CuSO4). A stimulating effect of low Cu2+ concentrations (30 μg L-1) on algal growth characteristics was observed. Higher Cu2+ concentration of 60-600 μg L-1 and CuO NPs concentration of 100-520 μg L-1 inhibited algal growth. Ionic copper is more toxic to P. cordatum than NPs. After 72 h of algae cultivation in the medium supplemented with CuSO4 and CuO NPs, EC50 values (calculated based on cell abundance) were of 60 and 300 μg L-1 (in terms of copper ions), respectively. Reduction in algal growth rate is due to disruption in cell cycle, changes in nuclear morphology, chromatin dispersion, and DNA damage. The studied pollutants slightly affected the efficiency of P. cordatum photosynthetic apparatus. Addition of the pollutants resulted in an increased production of reactive oxygen species (ROS). At a concentration of Cu2+ of 120 μg L-1 and a concentration of CuO NPs 0-300 μg L-1 of CuO NPs increase in ROS production is short-term with a decrease at later stages of the experiment. This is probably due to the activation of antioxidant mechanisms in cells and an increase in the concentration of carotenoids (peridinin) in cells. The high values of ROS production persisted throughout the experiment at sublethal copper concentrations (400-600 μg L-1 of CuSO4 and 520 μg L-1 of CuO NPs). Sublethal concentrations of pollutants caused restructuring of cell membranes in P. cordatum. Shedding of cell membranes (ecdysis) and formation of immobile stages (temporary or resting cysts) were recorded. The pronounced mechanical impact of NPs on the cell surface was observed such as-deformation and damage of a cell wall, its "wrinkling" and shrinkage, and adsorption of NP aggregates.


Phase I clinical evaluation of oral and intravenous 4-demethoxydaunorubicin.
Thirteen patients were treated with both the oral and intravenous preparations of 4-demethoxydaunorubicin (DMDR). The drug was well tolerated in both forms. Neutropenia was the dose-limiting side-effect. Approximately 30% of the compound was absorbed when given orally. The maximum tolerated dose was 12.5 mg/m2 intravenously or 50 mg/m2 (10 mg/m2 q d X 5) orally, given every 21-28 days.


How Rice Plants Response to Abiotic Stresses.
With the combustion of fossil fuels, unequal and unsustainable energy and land use, and irrational human activities, greenhouse gas emissions remain high, which leads to global warming [...].


Elderly patients discharged home from the emergency department with minor burns.
To describe the risk factors, etiology and referral patterns of elderly patients treated for minor burns in an urban emergency department (ED). A retrospective chart review was conducted of persons aged 65 years and older who were treated for a minor burn and discharged home from the ED. Medical records were reviewed for 77 burn patients that presented over a 6-year period. Burn patients had significant co-morbid medical illness. The etiology of the burns was scalds (58%), contact (27%) and flame (12%). Sixty-eight percent of the burns were cooking related. Heating pads, curling irons or hot pipes accounted for the majority of contact burns. Three percent of burn patients were referred to a home care agency for a home safety evaluation at the time of discharge from the ED. Cooking-related activities accounted for the majority of minor burns in this series. Common consumer items or environmental hazards were responsible for most contact burns. Elderly patients seen in the ED with minor burns were rarely referred to a home care agency.


Successful nonsurgical therapy of mural thrombosis of the left atrium after mitral valve replacement.
Mural thrombosis of the left atrium is a complication of mitral valve replacement. In this report we present a case of mural thrombosis of the left atrium after mitral valve replacement treated successfully without surgical intervention.


Cardiovascular and psychiatric characteristics associated with oxidative stress markers among adolescents with bipolar disorder.
In the field of bipolar disorder (BD) research there is an absence of validated biomarkers and limited understanding of the biology underlying excessive and premature cardiovascular disease (CVD). Oxidative stress is a potential biomarker in both BD and CVD. To examine psychiatric and cardiovascular characteristics associated with peripheral oxidative stress markers among adolescents with BD, who are at high risk for CVD. Participants were 30 adolescents, 13-19years old, with BD and without CVD. Ultrasonography was used to evaluate vascular function and structure. Traditional CVD risk factors were also measured. Psychiatric assessments were conducted via semi-structured interview. Serum levels of oxidative stress (lipid hydroperoxides (LPH) and protein carbonylation (PC)) were assayed. Compared to published data on adults with BD, adolescents had significantly lower levels of LPH and PC (t52(11.34), p<0.0001; t58(29.68), p<0.0001, respectively). Thicker mean and maximum carotid intima media thickness was associated with greater levels of LPH (r=.455, p=.015; r=.620, p<0.0001, respectively). LPH was associated with diastolic blood pressure (r=-.488, p=0.008) and pulse pressure (r=.543, p=0.003). Mood symptoms and medication were not significantly associated with oxidative stress. Adolescents with BD have lower levels of oxidative stress compared to adults with BD, supporting prevailing illness staging theories for BD. Oxidative stress is robustly associated with a proxy measure of atherosclerosis and may explain in part the increased risk of CVD in BD.


Assessment of airborne particles and bioaerosols concentrations in a waste recycling environment in Brazil.
This study aims to assess the concentrations of size-fractioned particle mass (PM1.0, PM2.5, PM4.0, PM10) and number (PNC0.3, PNC0.5, PNC1.0, PNC2.5), bacteria, and fungi in a Materials Recycling Facility (MRF) in Brazil. The measurements were performed inside the waste processing shed (P1) and in the outdoor environment (P2) during working days in winter and spring of 2017, and summer of 2019. A total of 2,400 min of PM, 1,440 min of PNC, and 216 samples of bioaerosols were collected in the morning and afternoon. P1 has the strongest air contamination with mean values of 475.5 ± 563.7 µg m-3 for PM10, 58.6 ± 36.0 cm-3 for PNC0.3, 1,088.8 ± 825.2 colony-forming units per cubic meter (CFU m-3) for bacteria, and 2,738.3 ± 1,381.3 CFU m-3 for fungi. The indoor/outdoor ratios indicated the large influence of indoor sources due to the activities performed inside P1 that promote the generation and resuspension of pollutants. Gram-positive bacteria dominated with 58.6% of indoor samples. Overall, our results show a critical indoor air quality situation in a Brazilian MRF, which may cause several health risks for waste pickers. Finally, we call attention to the lack of occupational exposure limits for bioaerosols in industrial workplaces and mainly in MRFs.


[Expression and clinical significance of fibroblast activation protein in colorectal carcinoma tissue].
To detect the expression of fibroblast activation protein(FAP) in colorectal cancer tissue, and to investigate the association between expression of FAP with pathological parameters. Fifty-five cancer tissues and 50 normal colorectal samples were examined using immunohistochemistry with anti-FAP polyclonal antibody. The distribution of positive cells in different tissues, and associations of positive cell number with tumor staging, lymph node metastasis and tumor invasion were investigated to evaluate the effects of FAP on pathological progress in colorectal cancer. No FAP expression was observed in 50 normal colorectal tissue samples. FAP positive cells were seen in carcinoma associated fibroblasts(CAFs), and in few colorectal cancer cells. The numbers of FAP positive cells in tissue samples of TNM III(-IIII((40.1±15.9) was significantly greater than that of TNMI(-II( (18.3±7.7)(P<0.01). Furthermore, the number of FAP positive cells in tissue samples with lymph node metastasis (44.4±13.3) was also significantly higher than those without lymph node metastasis (18.5±8.1)(P<0.01). Significant positive correlations were found between the number of FAP-positive cells with the tumor TNM staging and lymph node metastasis(r=0.544 and r=0.793, respectively)(P<0.01). The number of FAP-positive cells was 25.2±8.9 in T2, 32.41±19.30 in T3, and 29.2±16.5 in T4. The association between number of positive cells and depth of invasion was not statistically significant(P>0.05). The FAP mainly expresses in CAFs locating in colorectal cancer tissues. The number of FAP positive cells is positively correlated with TNM staging of colorectal cancer and lymph node metastasis.


Nano-gel containing thermo-responsive microspheres with fast response rate owing to hierarchical phase-transition mechanism.
A new strategy is developed in this study to achieve thermo-responsive microspheres with fast response rates by designing a hierarchical phase-transition mechanism. The proposed thermo-responsive microspheres are composed of poly(N-isopropylacrylamide-co-acrylic acid) (PNA) microsphere matrixes and embedded poly(N-isopropylacrylamide) (PNIPAM) nano-gels, which have different volume phase-transition temperatures (VPTTs). The VPTT of PNIPAM nano-gels (VPTT(1)) is lower than that of PNA microsphere matrixes (VPTT(2)). Upon heating-up, the temperature increases across the VPTT(1) first and then the VPTT(2), as a result the PNIPAM nano-gels shrink earlier than the PNA microsphere matrixes. Upon cooling-down, the temperature decreases across the VPTT(2) first and then the VPTT(1), as a result the PNA microsphere matrixes swell earlier than the PNIPAM nano-gels. Consequently, large amounts of voids and channels form around the nano-gels inside the microsphere matrixes when the temperature changes across the range between VPTT(1) and VPTT(2), which are beneficial to the enhancement of water transport rate inside the microsphere matrixes. The experimental results show that, compared with normal homogeneous PNA (N-PNA) microspheres, the nano-gel containing PNA (C-PNA) microspheres exhibit remarkably fast response rate due to the hierarchical phase-transition mechanism attributed to different VPTT values of the embedded nano-gels and the microsphere matrixes.


Reconstructing complex peripatellar defects using the descending genicular artery perforator flap.
Complex peripatellar defects are commonly reconstructed with free flaps or pedicled muscle flaps, whereas pedicled fasciocutaneous perforator flaps are commonly overlooked. The descending genicular artery perforator (DGAP) flap is a versatile flap that offers thin and pliable tissue that provides ideal 'like with like' peripatellar soft tissue defect reconstruction. This paper aims to demonstrate the safe use of a pedicled fasciocutaneous DGAP flap for extensive traumatic peripatellar defect reconstructions and to exhibit the surgical pearls via a case series. A retrospective cohort study of consecutive complex peripatellar reconstructions with DGAP flaps was conducted from January 2011 to December 2018. Patient demographics, medical comorbidities, aetiology/size/and location of the defects were reviewed. Flap, donor site, and overall surgical outcomes were clinically assessed and documented. Descriptive statistics were conducted and analysed by IBM SPSS Statistics 23. Five consecutive cases with complex peripatellar defects (5 × 8 to 8 × 10 cm) were recruited. Two were males, and three were females, with a mean age of 38.4 years. Four were trauma, and one was an oncological case. Descending genicular artery (DGA) perforators and DGA terminal branches were consistent. One patient needed a split-thickness skin graft to reconstruct the secondary defects. All the flaps survived with an average follow-up of 24 months. The DGAP flap provides a reliable alternative to free flap for the large, complex peripatellar defect. With the inclusion of the proximal long saphenous vein and judicious selection of DGA perforators and its terminal branches, the DGAP flap can be harvested and used safely in the high-velocity impacted knee.


Distributional stress regularity: a corpus study.
The regularity of stress patterns in a language depends on distributional stress regularity, which arises from the pattern of stressed and unstressed syllables, and durational stress regularity, which arises from the timing of syllables. Here we focus on distributional regularity, which depends on three factors. Lexical stress patterning refers to normal stress patterns within words; interlexical stress patterning refers to patterns that arise from word combinations; and contextual stress patterning refers to adjustments in normal lexical stress patterns (such as the well-known phenomenon of "stress clash avoidance"). A corpus study was done to assess the effect of these three factors on distributional stress regularity in conversational and formal spoken English, by comparing the degree of stress regularity in stress-annotated corpus data to randomly manipulated versions of the data and to "citation-form" stress patterns drawn from a phonetic dictionary. The results show that both lexical and interlexical patterning contribute significantly to stress regularity in English; contextual stress patterning does not, and in fact significantly reduces regularity in comparison to citation-form stress patterns.


A single subtype of Epstein-Barr virus in members of multiple sclerosis clusters.
Epidemiological studies strongly indicate an infectious involvement in multiple sclerosis (MS). Epstein-Barr virus (EBV), to which all multiple sclerosis patients are seropositive, is also interesting from an epidemiological point of view. We have reported a cluster of MS patients with 8 members from a small Danish community called Fjelsø. To further evaluate the role of EBV in MS we have investigated the distribution of EBV subtypes in cluster members and in control cohorts. Blood mononuclear cells were isolated from cluster members, unrelated MS patients, healthy controls, including healthy schoolmates to the Fjelsø cluster patients and finally from persons with autoimmune diseases in order to investigate the number of 39 bp repeats in the EBNA 6-coding region in the EBV seropositive individuals. We observed a preponderance of the subtype with 3 39 bp repeats in the EBNA 6-coding region both in the MS patients and the healthy controls. In the Fjels cluster all 8 cluster members were harbouring this subtype, which is significantly different from the finding in healthy controls (n = 16), which include 8 schoolmates to the cluster members and 8 randomly selected healthy persons (Fischer's exact test P = 0.0047), and also compared to all non-clustered individuals studied (P = 0.017). Infection with the same subtype of EBV links together the 8 persons from the Fjelsø cluster who later developed MS. This finding adds to the possibility that development of MS is linked to infection with EBV.


Integrating evidence-based teaching into to clinical practice should improve outcomes.
Sources used were Medline, Embase, the Education Resources Information Centre , Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Health Technology Assessment database, Best Evidence, Best Evidence Medical Education and Science Citation Index, along with reference lists of known systematic reviews. Studies were chosen for inclusion if they evaluated the effects of postgraduate evidence-based medicine (EBM) or critical appraisal teaching in comparison with a control group or baseline before teaching, using a measure of participants' learning achievements or patients' health gains as outcomes. Articles were graded as either level 1 (randomised controlled trials (RCT)) or level 2 (non-randomised studies that either had a comparison with a control group), or a before and after comparison without a control group. Learning achievement was assessed separately for knowledge, critical appraisal skills, attitudes and behaviour. Because of obvious heterogeneity in the features of individual studies, their quality and assessment tools used, a meta-analysis could not be carried out. Conclusions were weighted by methodological quality. Twenty-three relevant studies were identified, comprising four RCT, seven non-RCT, and 12 before and after comparison studies. Eighteen studies (including two RCT) evaluated a standalone teaching method and five studies (including two RCT) evaluated a clinically integrated teaching method. Standalone teaching improved knowledge but not skills, attitudes or behaviour. Clinically integrated teaching improved knowledge, skills, attitudes and behaviour. Teaching of EBM should be moved from classrooms to clinical practice to achieve improvements in substantial outcomes.


Extension of Pd-Mediated One-Pot Ketone Synthesis to Macrocyclization: Application to a New Convergent Synthesis of Eribulin.
Recently reported Pd-mediated one-pot ketone synthesis from an unactivated alkyl bromide and a thioester has been extended to a macrocyclic ketone synthesis. In situ generation of alkylzinc halide via single electron transfer (SET), using NbCpCl4 and CrCl3, was the key for the success of macrocyclization. A new convergent synthesis of eribulin has been achieved, using (1) catalytic asymmetric Ni/Cr-mediated coupling to form the C19-C20 bond, (2) base-induced cyclization to form the methylenetetrahydrofuran ring, and (3) Pd-mediated one-pot ketone synthesis to form the macrocyclic ketone.


[Somatoform disorders-chronic pelvic pain in women].
Pelvic pain in women is a clinically common symptom and a frequent finding in general practitioner, urological, gynecological, and pediatric practice. The list of possible differential diagnoses is long and the clarification ranges from a visual diagnosis to technical and surgical examinations to complex interdisciplinary consultations. But when do we talk about chronic lower abdominal pain? What can be the cause of this and how can we approach it diagnostically and therapeutically? What should we pay attention to? The difficulty begins with the definition. If we look at the national and international guidelines and publications, we find different definitions for chronic pelvic pain. There are various causes of chronic pelvic pain. There is often a combination of physical and psychological factors, which is why it is often not possible to identify a single diagnosis behind chronic pelvic pain syndrome. The clarification of these complaints requires a biopsychosocial approach. Multimodal approaches should be considered in assessment and treatment, and experts from other disciplines should be consulted.


Bone loss in spinal cord-injured patients: from physiopathology to therapy.
Review article on bone metabolism and therapeutic approach on bone loss in patients with spinal cord injury (SCI). The first part aims to describe the process of bone demineralization and its effects on bone mass in patients with SCI. The second part describes and discusses the therapeutic approaches to limiting the alteration in bone metabolism related to neurological lesions. Propara Rehabilitation Center, Montpellier, France. During the first 24 months postinjury, demineralization occurs exclusively in the sublesional areas and predominantly in weight-bearing skeletal sites such as the distal femur and proximal tibia, both of which are trabecular-rich sites. Reduced bone mass, in association with a modified bone matrix property and composition, is very likely at the origin of pathological fractures after minor trauma to which these patients are frequently exposed. Since these fractures may be asymptomatic yet may lead to complications, preventing and managing 'neurological osteoporosis' remains a considerable challenge. Two main approaches are considered: the first consists in applying a mechanical stimulus to the bone tissue by standing, orthotically aided walking or functional electrical stimulation (FES). The second uses medications, particularly antiresorptive drugs such as calcitonin or diphosphonates. To develop well-adapted treatments, a more precise understanding of bone loss etiology is needed. The current rehabilitation programs are based on the idea that the bone physiological changes observed in patients with SCI are due to immobility, but results indicate that alterations inherent to neurological damage may play an even greater role in inducing osteoporosis.


Efficacy and safety of nintedanib in Asian patients with systemic sclerosis-associated interstitial lung disease: Subgroup analysis of the SENSCIS trial.
In the SENSCIS trial in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), nintedanib reduced the rate of decline in forced vital capacity (FVC) (mL/year) over 52 weeks by 44% in comparison with placebo, with manageable adverse events in most patients. We analyzed the efficacy and safety of nintedanib in patients of Asian race. Patients with SSc-ILD were randomized to receive nintedanib or placebo. The outcomes over 52 weeks were analyzed in Asian versus non-Asian patients. Of the 288 patients in each treatment group, 62 (21.5%) in the nintedanib group and 81 (28.1%) in the placebo group were Asian; 90.2% of the Asian patients were enrolled in Asian countries. In the placebo group, the rate of FVC decline over 52 weeks was consistent between Asian and non-Asian patients (-99.9 and -90.6 mL/year, respectively). The effect of nintedanib on reducing the rate of FVC decline over 52 weeks was consistent between Asian (difference, 44.3 mL/year [95% CI: -32.8, 121.4]) and non-Asian patients (difference, 39.0 mL/year [95% CI: -5.1, 83.1]) (treatment-by-time-by-subgroup interaction, p = 0.91). Diarrhea was the most frequent adverse event and was reported in similar proportions of Asian and non-Asian patients in the nintedanib group (80.6% and 74.3%, respectively) and placebo group (28.4% and 32.9%, respectively). In patients with SSc-ILD, nintedanib had a consistent benefit on slowing the progression of SSc-ILD in Asian and non-Asian patients, with a similar adverse event profile. ClinicalTrials.gov NCT02597933.


Esophagopericardial fistula in a scleroderma patient with peptic esophagitis.
Esophageal perforation from peptic ulceration is rare. A patient with scleroderma who had an esophagopericardial fistula caused by peptic esophagitis is described. The fistula mimicked an acute myocardial infarction.


Smoking does influence disease behaviour and impacts the need for therapy in Crohn's disease in the biologic era.
Recently, the notion that smoking may adversely affect Crohn's disease (CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti-TNF drugs might offset the adverse effects of tobacco. To reassess the influence of tobacco smoking on disease phenotype and complications on a time-dependent analysis, taking into account the different therapeutic interventions. We designed a retrospective cohort study of 3224 patients with Crohn's disease. The data were collected from the Spanish national inflammatory bowel disease registry (ENEIDA), including information regarding demographics, clinical characteristics, disease complications, therapeutic interventions and smoking status. Patients were classified as nonsmokers, smokers and former smokers, according to their present and past smoking habits. In the univariate analysis, smokers had more strictures (22.6% vs. 19.3%, P < 0.05) and less colonic involvement (7.2% vs. 10.9%, P < 0.05), and were more frequently under treatment with steroids (91.6% vs. 85.8%, P < 0.05), immunosuppressants (73.5% vs. 63.6% P < 0.05) or anti-TNF drugs (31.4% vs. 25.1%, P < 0.05) than nonsmokers. In the time-dependent multivariate analysis, smokers were found to have a significantly decreased survival free of stricturing disease (HR: 1.5, CI 95% 1.18-1.90) or perianal complications (HR: 1.50, CI 95% 1.01-1.46), and had a higher risk for requiring thiopurine therapy (HR: 1.20, CI 95% 1.05-1.30). These results suggest that, despite the widespread use of immunosuppressants and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course, with increased therapeutic requirements when compared with nonsmokers.


Clinical outcome in patients with 19-mm and 21-mm St. Jude aortic prostheses: comparison at long-term follow-up.
Small-sized prostheses for aortic valve replacement may result in residual left ventricular outflow tract obstruction. Aim of the study was to verify whether implantation of 19-mm versus 21-mm St. Jude Medical standard prostheses (St. Jude Medical, Inc, St. Paul, MN) influences long-term clinical outcome. Two hundred twenty-nine patients who underwent aortic valve replacement with 19 mm (group 1, 53 patients) or 21-mm St. Jude Medical standard prostheses (group 2, 176 patients) were included in the study. Mean follow-up of current survivors was 10+/-4 years. Operative mortality was 7.5% in group 1 and 8.5% in group 2. At discharge, an important patient-prosthesis mismatch (effective orifice area index < or = 0.60 cm2/m2) was present in 18% of group 1 versus 5% in group 2 (p = 0.004). Among patients with body surface area less than 1.70 m2, such mismatch was present in 15% of group 1 versus 2% of group 2 (p = 0.008). At last follow-up New York Heart Association (NYHA) functional class (p < 0.001), left ventricular mass reduction (p = 0.02), mean (p = 0.002) and peak transprosthetic gradients (p < 0.001), and effective orifice area index (p = 0.005) were significantly better in group 2. Freedom from sudden death (92%+/-5% vs 99%+/-1%, p = 0.01), valve-related death (84%+/-6% vs 90%+/-5%, p = 0.02), and cardiac events (56%+/-13% vs 86%+/-4%, p = 0.008), were significantly lower in group 1. Effective orifice area index was an independent predictor of late cardiac events. Although long-term results after aortic valve replacement with small-sized St. Jude Medical standard prostheses are satisfactory, 19-mm valve recipients show a high prevalence of important patient-prosthesis mismatch with less evident functional improvement and higher rate of cardiac events, suggesting a very cautious use of this prosthesis.


Anion radical chain cycloaddition of tethered enones: intramolecular cyclobutanation and Diels-Alder cycloaddition.
[reaction: see text] The anion radicals of certain bis(enones), generated by cathodic reduction, are observed to participate in intramolecular cyclobutanation, yielding bicyclo[3.2.0]heptane derivatives through an anion radical chain mechanism. Evidence for stepwise cycloaddition involving distonic anion radical intermediates is presented. In addition to the novel anion radical cyclobutanations, an unprecedented intramolecular anion radical Diels-Alder product is observed. Parallel trends in substrate scope vis-à-vis the Co-catalyzed bis(enone) cyclobutanation are discussed.


The application of LTR retrotransposons as molecular markers in plants.
Retrotransposons are a major agent of genome evolution. Various molecular marker systems have been developed that exploit the ubiquitous nature of these genetic elements and their property of stable integration into dispersed chromosomal loci that are polymorphic within species. The key methods, SSAP, IRAP, REMAP, RBIP, and ISBP, all detect the sites at which the retrotransposon DNA, which is conserved between families of elements, is integrated into the genome. Marker systems exploiting these methods can be easily developed and inexpensively deployed in the absence of extensive genome sequence data. They offer access to the dynamic and polymorphic, nongenic portion of the genome and thereby complement methods, such as gene-derived SNPs, that target primarily the genic fraction.


DCD Hepatitis C Virus-positive Donor Livers Can Achieve Favorable Outcomes With Liver Transplantation and Are Underutilized.
Hepatitis C virus (HCV)-positive donors (antibody-positive [Ab + ] or nucleic acid test positive [NAT + ] donors) have been underutilized. The aim of this study was to evaluate the utilization of livers from HCV-positive with donation after circulatory death (DCD) and to assess outcomes in recipients of these grafts. Data between 2015 and 2019 were obtained from the United Network for Organ Sharing database. The utilization rates and graft survival among 8455 DCD liver and nonliver donors and 2278 adult DCD liver transplantation (LT) recipients were reviewed on the basis of donor HCV Ab/NAT status. The utilization of Ab + /NAT - donors <40 y and Ab + /NAT + donors ≥40 y was low than utilization of HCV-negative donors ( P < 0.001). Multivariate analysis identified HCV status (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.06-2.48 in Ab + /NAT - , and OR, 1.49; 95% CI, 1.09-2.05 in Ab + /NAT + ) as an independent predictor of nonutilization of liver grafts. The rate of significant liver fibrosis was comparable in Ab + /NAT - (3.5%; P = 0.84) but was higher in Ab + /NAT + (8.7%; P = 0.03) than that in Ab - /NAT - donors. Kaplan-Meier survival curves demonstrated comparable 3-y patient survival in recipients of HCV-positive grafts compared with recipients of HCV-negative grafts ( P = 0.63; 85.6% in Ab - /NAT - , 80.4% in Ab + /NAT - , and 88.7% in Ab + /NAT + ). Patient and graft survival rates are similar between HCV-positive and HCV-negative DCD LT. However, HCV-positive donors are particularly underutilized for DCD LT.


Landscape Dynamics and Ecological Risk Assessment of Cold Temperate Forest Moose Habitat in the Great Khingan Mountains, China.
The change in habitat pattern is one of the key factors affecting the survival of the moose population. The study of the habitat landscape pattern is the key to protecting the Chinese cold-temperate forest moose population and monitoring the global distribution of moose. Through the ecological risk assessment of the moose habitat landscape pattern in a cold-temperate forest, we hope to assess the strength of habitat resistance under stress factors. This study provides a theoretical basis for the protection of the moose population in the cold-temperate forest in China and the establishment of the cold-temperate forest national park. In the study, the MaxEnt model, landscape index calculation and ecological risk assessment model construction were used to analyze the field survey and infrared camera monitoring data from April 2014 to January 2023. The habitat suitability layer of the moose population in the Nanwenghe National Nature Reserve of the Great Khingan Mountains was calculated, and the range of the moose habitat was divided based on the logical threshold of the model. The landscape pattern index of the moose habitat was calculated by Fragstats software and a landscape ecological risk assessment model was established to analyze the landscape pattern and ecological risk dynamic changes of the moose habitat in 2015 and 2020. The results showed that under the premise of global warming, the habitat landscape contagion index decreased by 4.53 and the split index increased by 4.86 from 2015 to 2020. In terms of ecological risk: the area of low ecological risk areas increased by 0.88%; the area of medium ecological risk areas decreased by 1.11%; and the area of high ecological risk areas increased by 0.23%. The fragmentation risk of the landscape pattern of the moose habitat tends to increase, the preferred patch type is dispersed, the degree of aggregation is low, and the risk of patch type transformation increases. The middle and high ecological risk areas are mainly concentrated in the river area and its nearby forests, showing a fine and scattered distribution. Under the interference of global warming and human activities, the fragmentation trend of the moose habitat in the study area is increasing, and the habitat quality is declining, which is likely to cause moose population migration. For this reason, the author believes that the whole cold temperate forest is likely to face the risk of increasing the transformation trend of dominant patch types in the cold-temperate coniferous forest region mainly caused by global warming, resulting in an increase in the risk of habitat fragmentation. While the distribution range of moose is reduced, it has a significant impact on the diversity and ecological integrity of the whole cold-temperate forest ecosystem. This study provides theoretical references for further research on the impact of climate warming on global species distribution and related studies. It is also helpful for humans to strengthen their protection awareness of forest and river areas and formulate reasonable protection and sustainable development planning of cold-temperate forests. Finally, it provides theoretical references for effective monitoring and protection of cold-temperate forests and moose population dynamics.


Dopamine vascular actions of N-substituted derivatives of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN).
N-ethyl, N-n-propyl, N-n-butyl, N,N-di-n-propyl and N-n-propyl-N-n-butyl derivatives of 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) were screened for dopamine vascular agonist activity. Effects of intraarterial injections of the drugs on renal and femoral blood flow were measured in pentobarbital-anesthetized dogs before and after phenoxybenzamine (POB), 5--10 mg/kg. All DDTN derivatives were more potent vasoconstrictors than dopamine (DA) before POB. The di-substituted analogs were approximately 1/4 and the mono-substituted derivatives were about 1/16 as active as norepinephrine as vasoconstrictors. After POB the two di-substituted analogs were about 1/4 as active as DA in causing renal vasodilation. The three mono-substituted analogs produced relatively minor and inconsistent effects on renal blood flow, and were more than 100 times less effective than DA as vasodilators. The two di-substituted analogs markedly increased blood pressure with little effect on cardiac contractility in doses up to 32 micrograms/kg; whereas, the threshold dose of DA is 4--8 micrograms/kg. This and our previous results show that structure activity relationships of DA and ADTN, a semi-rigid analog of DA, are similar. However, the rigid analogs tend to be more potent vasoconstrictors than their flexible chain homologs.


Plant sphingolipids: function follows form.
Plant sphingolipids are structurally diverse molecules that are important as membrane components and bioactive molecules. An appreciation of the relationship between structural diversity and functional significance of plant sphingolipids is emerging through characterization of Arabidopsis mutants coupled with advanced analytical methods. It is increasingly apparent that modifications such as hydroxylation and desaturation of the sphingolipid nonpolar long-chain bases and fatty acids influence their metabolic routing to particular complex sphingolipid classes and their functions in signaling pathways and other cellular processes, such as membrane protein targeting. Here, we review recent reports investigating some of the more prevalent sphingolipid structural modifications and their functional importance in plants.


Increased expression of HMGB1 is associated with poor prognosis in human bladder cancer.
High-mobility group box 1 (HMGB1) is a versatile protein with intranuclear and extracellular functions that is involved in numerous biological and pathological processes, such as transcription, DNA repair, and response to infection and inflammation. HMGB1 overexpression has been reported in a variety of human cancers. However, the clinical significance of HMGB1 expression in bladder cancer (BC) remains unclear. This study is aimed to investigate the correlations between HMGB1 expression and prognosis in patients with BC. HMGB1 protein expression in 164 primary BC tissue specimens was analyzed by immunohistochemistry, and its association with clinicopathologic factors and prognosis was also analyzed. HMGB1 protein had high expression in 87 of 164 cases of BC (53%). HMGB1 overexpression was significantly associated with tumor grade (P < 0.001), and stage (P = 0.001). The Kaplan-Meier survival analysis demonstrated that HMGB1 expression was significantly associated with shorter disease-free survival and overall survival (both P < 0.001). Multivariate analysis further demonstrated that HMGB1 was an independent prognostic factor for patients with BC. HMGB1 might be a new molecular marker to predict the prognosis of patients with BC.


'The only place to go and be in the city': women talk about exercise, being outdoors, and the meanings of a large urban park.
This article explores women's physical activities in an urban park in Brooklyn, NY, USA. Physical inactivity is a growing health concern, and research has begun to address the physical environment, a subset of which looks particularly at the role of the environment for women. These qualitative interviews cited physical features, such as hills, a continuous loop, and trails, but safety was a concern due to traffic or wooded areas. The park provided support for bodily needs, such as rest rooms and freedom to wear comfortable clothes. Nature was described as stimulating the senses and restoring mental capacities, and the park was an important nearby outdoor resource. Results are discussed in the context of current research, in relation to women but also more broadly in relation to research on physical activity and the outdoor environment.


Outcomes of leaflet-shaped acellular dermal matrix with a thickness-gradient for abdominal fascial defect repair in muscle-sparing TRAM flap-based breast reconstruction.
Numerous fascial closure techniques have been used to reduce donor site morbidities after transverse rectus abdominis myocutaneous (TRAM) flap harvest. A leaflet-shaped acellular dermal matrix (ADM) with a thickness gradient was designed to cover the defect effectively and to withstand the pressure applied to the lower portion of the defect. The complication and functional recovery rates of the donor site of the custom ADM were compared with those of previous methods of fascial closure (primary closure and polypropylene mesh assisted closure). A retrospective review of patients undergoing immediate or delayed breast reconstruction using muscle-sparing TRAM flaps was performed. Abdominal bulging, hernia, wound dehiscence, infection, seroma, and hematoma rates were compared. The Back Performance Scale measured four months postoperatively was compared to evaluate the donor site's recovery rate. A total of 173 patients were analyzed. The three groups did not differ in hernia, wound dehiscence, infection, and hematoma rates. However, the abdominal bulging rate was lower in the primary closure group, while the seroma rate was higher in the mesh group. Functional recovery was the fastest in the custom ADM group. A thickness-gradient, leaflet-shaped ADM can be effectively used as an onlay graft to cover the abdominal fascial defect, with similar complication rates, while providing a faster recovery of abdominal function.


[Changes in the evoked activity of the spinal cord after subarachnoidal administration of different amounts of colchicine].
Colchicine solution (0.3-0.01%) depressed the motor activity and evoked potentials of the spinal cord within 1-7 days after subarachnoidal injection of 0.05 ml in white rats. Monosynaptic response of the ventral root was more depressed than the spinal cord dorsum potential.


A pathogenesis related protein, AhPR10 from peanut: an insight of its mode of antifungal activity.
A pathogenesis related protein (AhPR10) is identified from a clone of 6-day old Arachis hypogaea L. (peanut) cDNA library. The clone expressed as a approximately 20 kDa protein in E. coli. Nucleotide sequence derived amino acid sequence of the coding region shows its homology with PR10 proteins having Betv1 domain and P loop motif. Recombinant AhPR10 has ribonuclease activity, and antifungal activity against the peanut pathogens Fusarium oxysporum and Rhizoctonia solani. Mutant protein AhPR10-K54N where lys54 is mutated to asn54 loses its ribonuclease and antifungal activities. FITC labeled AhPR10 and AhPR10-K54N are internalized by hyphae of F. oxysporum and R. solani but the later protein does not inhibit the fungal growth. This suggests that the ribonuclease function of AhPR10 is essential for its antifungal activity. Energy and temperature dependent internalization of AhPR10 into sensitive fungal hyphae indicate that internalization of the protein occurs through active uptake.


Impact of prostate catheter displacement in inverse planning--simulated annealing and geometric optimization.
The aim of this study was to compare inverse planning-simulated annealing (IPSA) with geometric optimization (GO) in high-dose-rate (HDR) prostate brachytherapy, to assess variations in dosimetric indices associated to catheter displacement. We retrospectively studied the dosimetric effect of catheter displacement in 20 patients treated with HDR prostate brachytherapy with salvage intention. The catheter loadings, with optimized dwell positions, from the first fraction were transferred to the catheter positions in the second fraction. Median catheter displacement was 8.7 ± 3.3 mm (range, 2.7 ± 1.1 mm-14.7 ± 1.7 mm). D90% median variations for IPSA and GO were -10% with a maximum of -59%, and -29% with a maximum of -63%, respectively. V100% median variation was -11% with a maximum of -37% for IPSA, and -20% with a maximum of -37% for GO. V150/V100 implant median variations were 15% and 9% for IPSA and GO with maximum values of 65% and 47%, respectively (p < 0.05). No significant differences were observed for V200/V100 indices, nor were any significant differences found for organs at risk. Correlation between mean catheter displacement and dosimetric indices was found only in the planning target volume D90% and V100%; linear regression slopes were -2.0% per mm and -2.6% per mm for IPSA vs. -2.4% per mm and -3.5% per mm for GO. IPSA does not present any additional risk compared with GO in HDR prostate brachytherapy when catheter uncertainties are taken into account. Moreover, IPSA optimization preserves planning target volume coverage better than GO, suggesting that it may be superior when catheter displacement is considered.


Thyroid carcinoma and hot nodule.
A 70-year-old woman presented with a nodule in the thyroid gland. 131I scintigraphy of the gland showed a hot nodule. Histology of the resected thyroid revealed a papillary adenocarcinoma. Although a thyroid carcinoma with a hot nodule seen on the radioiodine isotope scan is a very rare occurrence, it is clinically very important because it may indicate a thyroid malignancy.


Conservative management of Cushing's syndrome in pregnancy. A case report.
A woman with clinical and laboratory findings of Cushing's syndrome was managed during pregnancy without the use of surgery or drugs to lower her serum cortisol. A good maternal and infant outcome was achieved with conservative measures, and surgical removal of an adrenal adenoma was delayed until the postpartum period.


Right-sided endocarditis secondary to a peritoneovenous shunt.
A 51-year-old woman with a peritoneovenous shunt for refractory ascites presented with three months of increasing fatigue, exertional dyspnea, night sweats and positive blood cultures. Imaging revealed multiple pulmonary emboli. Transthoracic  chocardiography demonstrated moderate tricuspid regurgitation and a large pedunculated right atrial mass attached to the interatrial septum. The echocardiographic appearance remained unchanged after one month of antibiotic therapy and  nticoagulation. Intraoperatively, the mass was easily excised and the grossly abnormal tricuspid valve replaced. Pathology revealed endocarditis with multiple bacterial colonies, and fibromyxoid changes consistent with postinflammatory valve disease.


Prediction of technically difficult endoscopic submucosal dissection for large superficial colorectal tumors: a novel clinical score model.
Endoscopic submucosal dissection (ESD) is a promising technique for removing superficial GI tumors, but ESD is technically difficult. The aim of this study was to establish a clinical score model for grading technically difficult colorectal ESD. Data on patients, lesions, and outcomes of colorectal ESD at 2 centers were analyzed. The objective parameter of successful ESD within 60 minutes was set as an endpoint to evaluate the difficulty. Independent predictors of difficulty in the derivation cohort were identified by multiple logistic regression analysis and used to develop a clinical score. We validated the score model in the validation cohort. The clinical score comprised tumor size of 30 to 50 mm (1 point) or ≥50 mm (2 points), at least two-thirds circumference of the lesion (2 points), location in the cecum (1 point), flexure (2 points) or dentate line (1 point), and laterally spreading tumor nongranular lesions (1 point). Areas under the receiver operator characteristic curves for the score model were comparable (derivation [.70] vs internal validation [.69] vs external validation [.69]). The probability of successful ESD within 60 minutes in easy (score = 0), intermediate (score = 1), difficult (score = 2-3), and very difficult (score ≥4) categories were 75.0%, 51.3%, 35.6%, and 3.4% in the derivation cohort; 73.3%, 47.9%, 31.8%, and 16.7% in the internal validation cohort; and 79.5%, 66.7%, 43.3%, and 20.0% in the external validation cohort, respectively. This clinical score model accurately predicts the probability of successful ESD within 60 minutes and can be applied to grade the technical difficulty before the procedure.


Age differences in intertemporal choice among children, adolescents, and adults.
When choosing between sooner-smaller and later-larger rewards (i.e., intertemporal choices), adults typically prefer later-larger rewards more often than children. Intertemporal choice preferences have been implicated in various impulsivity-related psychopathologies, making it important to understand the underlying mechanisms not only in terms of how reward magnitude and delay affect choice but also in terms of how these mechanisms develop across age. We administered an intertemporal choice paradigm to 60 children (8-11 years), 79 adolescents (14-16 years), and 60 young adults (18-23 years). The paradigm systematically varied amounts and delays of the available rewards, allowing us to identify mechanisms underlying age-related differences in patience. Compared with young adults, both children and adolescents made fewer later-larger choices. In terms of underlying mechanisms, variation in delays, absolute reward magnitudes, and relative amount differences affected choice in each age group, indicating that children showed sensitivity to the same choice-relevant factors as young adults. Sensitivity to both absolute reward magnitude and relative amount differences showed a further monotonic age-related increase, whereas no change in delay sensitivity occurred. Lastly, adolescents and young adults weakly displayed a present bias (i.e., overvaluing immediate vs. future rewards; nonsignificant and trend, respectively), whereas children showed a nonsignificant but opposite pattern, possibly indicating that specifically dealing with future rewards changed with age. These findings shed light on the underlying mechanisms that contribute to the development of patience. By decomposing overt choices, our results suggest that the age-related increase in patience may be driven specifically by stronger sensitivity to amount differences with age.


Adenosine A2A receptors inhibit the conductance of NMDA receptor channels in rat neostriatal neurons.
Whole-cell patch clamp experiments were carried out in rat striatal brain slices. In a subset of striatal neurons (70-80%), NMDA-induced inward currents were inhibited by the adenosine A2A receptor selective agonist CGS 21680. The non-selective adenosine receptor antagonist 8-(p-sulphophenyl)-theophylline and the A2A receptor selective antagonist 8-(3-chlorostyryl)caffeine abolished the inhibitory action of CGS 21680. Intracellular GDP-beta-S, which is known to prevent G protein-mediated reactions, also eliminated the effect of CGS 21680. Extracellular dibutyryl cAMP, a membrane permeable analogue of cAMP, and intracellular Sp-cAMPS, an activator of cAMP-dependent protein kinases (PKA), both abolished the CGS 21680-induced inhibition. By contrast, Rp-cAMPS and PKI 14-24 amide, two inhibitors of PKA had no effect. Intracellular U-73122 (a phospholipase C inhibitor) and heparin (an inositoltriphosphate antagonist) prevented the effect of CGS 21680. Finally, a more efficient buffering of intracellular Ca2+ by a substitution of EGTA (11 mM) by BAPTA (5.5 mM) acted like U-73122 or heparin. Hence, A2A receptors appear to negatively modulate NMDA receptor channel conductance via the phospholipase C/inositoltriphosphate/Ca2+ pathway rather than the adenylate cyclase/PKA pathway.


[Psychological support for victims of head trauma].
Patients who are victims of a head trauma are affected throughout their whole person. The reconstruction of their identity is complicated by the implication of neuropsychological disorders. The support takes into account the nature and the severity of the modifications generated by such an event with regard to personal, family, social and professional implications. It is integrative and can be modified over time.


A comparative study of immunodepletion and equalization methods for aortic stenosis human plasma.
Calcified aortic valve disease is a slowly progressive disorder that ranges from mild valve thickening with no obstruction of blood flow, known as aortic sclerosis, to severe calcification with impaired leaflet motion or aortic stenosis. Until now, aortic stenosis (AS) was thought to result from aging and "wear and tear" of the aortic valve, but nowadays, it is known that it presents the same risk factors as atherosclerosis and cardiovascular diseases.A proteomic analysis of plasma could permit to identify the changes in protein expression induced by AS in this biological sample. However, the characterization of human plasma proteome is a very complicated task, due to the wide dynamic range of concentration that separates the most abundant proteins and the less common ones (10-12 orders of magnitude). For this reason, plasma analysis requires pre-fractionation methods, and several such techniques are currently used to deplete albumin and other abundant plasma proteins.In this work we describe two different and optimized protocols to decrease the plasma proteome complexity for proteomic analysis. With this, comprehensive and systematic characterization of the plasma proteome in the healthy and diseased aortic stenosis (AS) state will greatly facilitate the development of "useful" biomarkers for early disease detection, clinical diagnosis, and therapy.


Dystrophic-like alterations characterize orbicularis oris and palatopharyngeal muscles in patients affected by cleft lip and palate.
This study analyzed histological and histochemical features of specimens of the orbicularis oris muscle, and palatal and pharyngeal muscles biopsied during surgery from 33 patients affected by cleft lip and palate. Three groups were studied: 20 patients affected by cleft palate with or without cleft lip (at the time of primary palatoplasty), seven by cleft lip with or without cleft palate (primary lip closure), and six by cleft lip with or without cleft palate (secondary cheiloplasty). Muscle sections were stained with hematoxylin-eosin, modified Gomori trichrome, ATPase reaction at pH 9.4, and NADH-TR. Analyzed parameters included organization, muscle fiber size and type, nuclear changes, presence of ragged-red fibers, degree of fibrosis, and presence of inflammatory infiltrate. In all patients who underwent primary palatoplasty and lip closure we noted dystrophic-like alterations of orbicularis oris and palatopharyngeal muscles, such as variability of fiber size, fiber disorganization, and increased fibrosis. The same alterations were found in adult patients submitted to secondary cheiloplasty, notwithstanding surgical repair. Furthermore, in all groups neither neurogenic atrophy nor ragged-red fibers or inflammatory infiltrate were detected. Muscle damage is a constant event in this deformity, and it could play an important role in its etiopathogenesis. Muscular biopsy during cheiloplasty and palatoplasty could offer useful information about muscle condition and possible functional recovery in cleft lip and palate patients.


Deciphering the molecular mechanism of tetrandrine in inhibiting hepatocellular carcinoma and increasing sorafenib sensitivity by combining network pharmacology and experimental evaluation.
The mechanism of tetrandrine (TET) in hepatocellular carcinoma (HCC) progression and sorafenib (Sora) chemosensitivity deserves investigation. Using network pharmacology approaches to elucidate the mechanisms of TET in HCC. CCK-8, colony formation, and flow cytometry assays were used to measure cell phenotypes. BALB/c nude mice were divided into Control, Sora (10 mg/kg), TET (50 mg/kg), and TET + Sora (10 mg/kg Sora plus 50 mg/kg TET) groups to evaluate the antitumor effects of TET for 21 days. Sora and TET were given by intraperitoneal injection or oral gavage. For SMMC7721 (IC50 = 22.5 μM) and PLC8024 (IC50 = 18.4 μM), TET (10, 20 μM) reduced colony number (0.68 ± 0.04- and 0.50 ± 0.04-fold, 0.56 ± 0.04- and 0.42 ± 0.02-fold), induced cell cycle arrest at G0/G1 stage (1.22 ± 0.03- and 1.39 ± 0.07-fold, 1.37 ± 0.06- and 1.55 ± 0.05-fold), promoted apoptosis (2.49 ± 0.26- and 3.63 ± 0.33-fold, 2.74 ± 0.42- and 3.73 ± 0.61-fold), and inactivated PI3K/AKT/mTOR signalling. Sora (10 μM) decreased cell proliferation, enhanced apoptosis, and inhibited PI3K/AKT/mTOR signalling, and these effects were further aggravated in the combination group. Activating PI3K/AKT/mTOR reversed the effects of TET on cell proliferation and Sora sensitivity. In the combination group, tumour volumes and weights were decreased to 202.3 ± 17.4 mm3 and 151.5 ± 25.8 mg compared with Sora (510.6 ± 48.2 mm3 and 396.7 ± 33.5 mg). TET enhances Sora sensitivity by inactivating PI3K/AKT/mTOR, suggesting the potential of TET as a chemosensitizer in HCC.


Effects of cigarette smoke, carbon monoxide and nicotine on the uptake of fibrinogen by the canine arterial wall.
An animal model has been used to investigate the effects of cigarette smoke, carbon monoxide and nicotine on the uptake of 125I-labelled fibrinogen by the arterial wall. The uptake of fibrinogen in the smoking group (5.5 +/- 2.8 counts.cm-2 x 10(-4)) and carbon monoxide group (6.1 +/- 2.7 counts.cm-2 x 10(-4)) was greater than the uptake in the control group (4.5 +/- 1.4 counts.cm-2 x 10(-4)) but this difference was not significant. In the nicotine group, there was a highly significant increase in wall uptake of 125I-fibrinogen (9.1 +/- 2.1 counts.cm-2 x 10(-4)) (P less than or equal to 0.001). These results suggest that nicotine, a major constituent of cigarette smoke, increases the retention of 125I-fibrinogen by the arterial wall and that this might be one mechanism by which cigarette smoking exerts its atherogenic effect.


Linking clinical measurements and kinematic gait patterns of toe-walking using fuzzy decision trees.
Toe-walking is one of the most prevalent gait deviations and has been linked to many diseases. Three major ankle kinematic patterns have been identified in toe-walkers, but the relationships between the causes of toe-walking and these patterns remain unknown. This study aims to identify these relationships. Clearly, such knowledge would increase our understanding of this gait deviation, and could help clinicians plan treatment. The large quantity of data provided by gait analysis often makes interpretation a difficult task. Artificial intelligence techniques were used in this study to facilitate interpretation as well as to decrease subjective interpretation. Of the 716 limbs evaluated, 240 showed signs of toe-walking and met inclusion criteria. The ankle kinematic pattern of the evaluated limbs during gait was assigned to one of three toe-walking pattern groups to build the training data set. Toe-walker clinical measurements (range of movement, muscle spasticity and muscle strength) were coded in fuzzy modalities, and fuzzy decision trees were induced to create intelligible rules allowing toe-walkers to be assigned to one of the three groups. A stratified 10-fold cross validation situated the classification accuracy at 81%. Twelve rules depicting the causes of toe-walking were selected, discussed and characterized using kinematic, kinetic and EMG charts. This study proposes an original approach to linking the possible causes of toe-walking with gait patterns.


Mass spectrometry-based qualitative and quantitative N-glycomics: An update of 2017-2018.
N-glycosylation is one of the most frequently occurring protein post-translational modifications (PTMs) with broad cellular, physiological and pathological relevance. Mass spectrometry-based N-glycomics has become the state-of-the-art instrumental analytical pipeline for sensitive, high-throughput and comprehensive characterization of N-glycans and N-glycomes. Improvement and new development of methods in N-glycan release, enrichment, derivatization, isotopic labeling, separation, ionization, MS, tandem MS and informatics accompany side-by-side wider and deeper application. This review provides a comprehensive update of mass spectrometry-based qualitative and quantitative N-glycomics in the years of 2017-2018.


Nitric oxide in the flocculus works the inhibitory neural circuits after unilateral labyrinthectomy.
We previously reported that nitric oxide (NO) production in the unipolar brush (UB) cells is involved in vestibular compensation [T. Kitahara, N. Takeda, P.C. Emson, T. Kubo, H. Kiyama, Changes in nitric oxide synthase-like immunoreactivities in unipolar brush cells in the rat cerebellar flocculus after unilateral labyrinthectomy, Brain Res. 765 (1997) 1-6]. To further elucidate the role of NO-mediated signaling in flocculus after unilateral labyrinthectomy (UL), we examined UL-induced Fos expression, a marker of neural activity, in vestibular brainstem with continuous floccular infusions of Nomega-nitro-l-arginine methyl ester (l-NAME), an inhibitor of NO synthase (NOS). After UL with floccular l-NAME infusions, Fos expression appeared in bilateral medial vestibular (MVe) and prepositus hypoglossal (PrH) nuclei. After UL with floccular saline infusions, however, Fos expression was observed only in the ipsi-MVe and contra-PrH. Furthermore, it has been revealed that UL with l-NAME infusions caused more severe vestibulo-ocular disturbances than UL with saline infusions at the initial stage [Kitahara et al. Brain Res. 765 (1997) 1-6]. Therefore, it is suggested that UL with floccular l-NAME infusions activates the contra-MVe and ipsi-PrH neurons and causes more severe imbalance between intervestibular nuclear activities at the initial stage. NO-mediated signaling in flocculus could be a possible driving force of the flocculus-mediated inhibition on the contra-MVe and ipsi-PrH at the initial stage of vestibular compensation.


Acute compartment syndromes.
Acute compartment syndrome is both a limb- and life-threatening emergency that requires prompt treatment. To avoid a delay in diagnosis requires vigilance and, if necessary, intracompartmental pressure measurement. This review encompasses both limb and abdominal compartment syndrome, including aetiology, diagnosis, treatment and outcome. A Pubmed and Cochrane database search was performed. Other articles were cross-referenced. Diagnosis of limb compartment syndrome is based on clinical vigilance and repeated examination. Many techniques exist for tissue pressure measurement but they are indicated only in doubtful cases, the unconscious or obtunded patient, and children. However, monitoring of pressure has no harmful effect and may allow early fasciotomy, although the intracompartmental pressure threshold for such an undertaking is still unclear. Abdominal compartment syndrome requires measurement of intra-abdominal pressure because clinical diagnosis is difficult. Treatment is by abdominal decompression and secondary closure. Both types of compartment syndrome require prompt treatment to avoid significant sequelae.


Species of Taeniacanthus Sumpf, 1871 (Crustacea: Copepoda: Taeniacanthidae) parasitic on boxfishes (Tetraodontiformes: Aracanidae and Ostraciidae) from the Indo-West Pacific region, with descriptions of two new species.
Two new copepod species of the genus Taeniacanthus Sumpf, 1871 (Cyclopoida: Taeniacanthidae) are described from boxfishes (Aracanidae and Ostraciidae) caught in the Indo-West Pacific region: T. larsonae n. sp. from Ostracion nasus Bloch in the Arafura Sea and off Australia and Tetrosomus concatenatus (Bloch) off Japan; and T. thackerae n. sp. from O. immaculatus Temminck & Schlegel off Palau, O. rhinorhynchos Bleeker off Australia, Lactoria cornuta (Linnaeus) and Ostracion sp. off Japan, and Kentrocapros aculeatus (Houttuyn) in the East China Sea. T. larsonae n. sp. differs from its congeners by having several rows of spinules on the large pectinate process of the antenna and by differences in the shape of the sclerotised plates on the rostral area and structure of the maxilliped. T. thackerae n. sp. can be distinguished from its congeners by differences in the shape of the sclerotised plates on the rostral area, the structure of the maxilliped and ornamentation pattern of legs 1-4. Supplemental information for the female of Taeniacanthus ostracionis (Richiardi, 1870) and T. moa (Lewis, 1967), as well as the first description of the male of T. moa, are also provided based on new material collected from ostraciid hosts caught in the Arafura Sea and off Australia, Indonesia and Japan. The four taeniacanthid species reported from boxfishes exhibit variable levels of host-specificity and have broad geographical ranges within the Indo-West Pacific region.