Skin Perfusion Pressure Predicts Early Wound Healing After Endovascular Therapy in Chronic Limb Threatening Ischaemia.
Skin perfusion pressure (SPP) has been proposed as a method to predict wound healing in chronic limb threatening ischaemia (CLTI). However, studies regarding the impact of SPP before and after endovascular therapy (EVT) on wound healing are limited. This study sought to evaluate the predictive value of SPP for early wound healing in CLTI treated by EVT. Between January 2018 and June 2020, 236 limbs (172 patients) with CLTI that underwent SPP measurement before and after EVT were included. SPP was measured before and 24 - 48 hours after the procedure. Early wound healing was defined as the achievement of complete epithelisation of all wounds without major amputation within three months of EVT. Early wound healing was achieved in 145 (61.4%) limbs after EVT. Baseline SPP (44.1 ± 21.0 mmHg vs. 33.5 ± 21.7 mmHg; p < .001) and post-procedural SPP (61.8 ± 18.5 mmHg vs. 37.4 ± 19.9 mmHg; p < .001) were significantly higher in the wound healing (+) group than in the wound non-healing (-) group. The area under the receiver operating characteristics curve for early wound healing was 0.82 for post-procedural SPP with a cutoff value of 50 mmHg (sensitivity 74.5%, specificity 78.0%). The early wound healing rate was significantly higher with a post-procedural SPP ≥ 50 mmHg compared with a SPP < 50 mmHg (84.4% vs. 35.0%; p < .001). Post-procedural SPP with a cutoff value of 50 mmHg was capable of predicting early wound healing after EVT in CLTI.


Mactanamide and lariciresinol as radical scavengers and Fe2+ ion chelators - A DFT study.
A DFT based kinetic study of OOH radical scavenging potency of mactanamide (MA) and lariciresinol (LA), two natural polyphenols, indicates their nearly equal potential via the proton coupled electron transfer (PCET) mechanism in lipid media. Contribution of C-H bond breaking to this potency is negligible compared to O-H bond breaking, contrary to recent claims. The predicted potency of both compounds is not sufficient to protect biological molecules from oxidative damage in lipid media. In aqueous media, the scavenging potency of MA and LA phenoxide anions via the single electron transfer (SET) mechanism is much higher and may contribute to the protection of lipids, proteins, and DNA from OOH radical damage. Also, MA and LA have the potential to chelate catalytic Fe2+ ions, thus suppressing the formation of dangerous OH radicals via Fenton-type reactions. The monoanionic species of MA and LA show stronger monodentate chelating ability with Fe2+ ion compared to its neutral form. The dianionic specie LA2- exhibited the highest chelation ability with Fe2+ ion via bidentate 1:2 coordination. However, direct radical scavenging and metal chelation could be rarely operative in vivo because MA and LA presumably achieve very low concentrations in systemic circulation.


Investigation of Microbial Translocation, TLR and VDR Gene Polymorphisms, and Recurrence Risk in Stage III Colorectal Cancer Patients.
Gut microbial dysbiosis and microbial passage into the peripheral blood leads to colorectal cancer (CRC) and disease progression. Toll-like (TLR) and vitamin D (VDR) receptors play important role in the immune modulation and polymorphisms that may increase CRC risk and death rates. The aim of the current study was to demonstrate the prognostic value of microbial DNA fragments in the blood of stage III CRC patients and correlate such microbial detection to TLR/VDR polymorphisms. Peripheral blood was collected from 132 patients for the detection of microbial DNA fragments, and TLR/VDR gene polymorphisms. In the detection of various microbial DNA fragments, TLR and VDR polymorphisms was significantly higher compared to healthy group. Homozygous individuals of either TLR or VDR polymorphisms had significantly higher detection rates of microbial DNA fragments. Mutational and MSI status were significantly correlated with TLR9 and VDR polymorphisms. Significantly shorter disease-free survival was associated with patients with BRAF mutated tumors and ApaI polymorphisms, whereas shorter overall survival was associated with the detection of C. albicans. The detection of B. fragilis, as demonstrated by the multivariate analysis, is an independent poor prognostic factor for shorter disease-free survival. TLR/VDR genetic variants were significantly correlated with the detection of microbial fragments in the blood, and this in turn is significantly associated with tumorigenesis and disease progression.


Lung profiles in the isoimmunized pregnancy.
The management of an isoimmunized pregnancy, although not commonly seen today, represents a challenging obstetric problem. The knowledge of fetal lung maturity status is essential in deciding when to perform an intrauterine transfusion, give steroids, or deliver an infant. The interpretation of the fetal lung profile in these patients has been questioned. Charts were reviewed from 99 isoimmunized patients cared for at Los Angeles County/University of Southern California Medical Center, Women's Hospital, from March, 1981, through December, 1983. There were 77 patients who underwent 260 amniocenteses. The lecithin-sphingomyelin ratio, dipalmitoyl phosphatidylcholine, phosphatidylinositol, and phosphatidylglycerol from the amniotic fluid did not differ from the values expected in normal gestations. There were a total of six patients who underwent intrauterine transfusions and the lung profile data were consistent with anticipated values. We conclude that lung maturation is neither delayed nor accelerated in the isoimmunized pregnancy.


E.s.r. radiation studies of erythrocyte membrane haemoglobin interaction.
The dependence of the yield of free radicals in gamma-irradiated, freeze-dried erythrocyte membranes on their haemoglobin content was studied. A non-monotonous relationship was found--different from that observed in mixtures of freeze-dried membranes and haemoglobin, which suggests the existence of radiation-energy transfer between the membranes and bound haemoglobin.


The vascular system of the superior auricular artery: anatomical study and clinical application.
The retroauricular flap has many advantages for facial reconstruction, but it is difficult to perform reconstruction of the upper part of the auricle and its surroundings. We investigated the relationship between the superior auricular artery and its surrounding structures through anatomic studies with seven fresh cadavers and applied the findings clinically. From February 2008 to December 2009, we performed 12 cases with the superior auricular artery island flap to reconstruct defects in the upper region of the auricle and its surroundings. We found that the superior auricular artery is a reliable pedicle for the retroauricular flap. All wounds of the patients were successfully closed, with the exception of one minor complication. The aesthetic outcomes of the donor and recipient sites were satisfactory. The superior auricular artery island flap has several advantages. Therefore, we suggest that the superior auricular artery island flap can be another choice for reconstructing soft tissue defects at the upper region of the auricle and its surrounding area.


Proteome reference map of Lactobacillus acidophilus NCFM and quantitative proteomics towards understanding the prebiotic action of lactitol.
Lactobacillus acidophilus NCFM is a probiotic bacterium adapted to survive in the gastrointestinal tract and with potential health benefits to the host. Lactitol is a synthetic sugar alcohol used as a sugar replacement in low calorie foods and selectively stimulating growth of L. acidophilus NCFM. In the present study the whole-cell extract proteome of L. acidophilus NCFM grown on glucose until late exponential phase was resolved by 2-DE (pH 3-7). A total of 275 unique proteins assigned to various physiological processes were identified from 650 spots. Differential 2-DE (DIGE) (pH 4-7) of L. acidophilus NCFM grown on glucose and lactitol, revealed 68 spots with modified relative intensity. Thirty-two unique proteins were identified in 41 of these spots changing 1.6-12.7-fold in relative abundance by adaptation of L. acidophilus NCFM to growth on lactitol. These proteins included β-galactosidase small subunit, galactokinase, galactose-1-phosphate uridylyltransferase and UDP-glucose-4-epimerase, which all are potentially involved in lactitol metabolism. This first comprehensive proteome analysis of L. acidophilus NCFM provides insights into protein abundance changes elicited by the prebiotic lactitol.


Insulin binds to and promotes the phosphorylation of a Mr 210 000 component of its receptor in detergent extracts of rat liver microsomes.
Insulin in the presence of Mn2+ and [gamma 32P]ATP promoted the phosphorylation of two proteins of Mr 95 000 and Mr 210 000 in detergent extracts of rat liver microsomes. The Mr 210 000 protein was identified as a component od the insulin receptor by immunoprecipitation. It also bound [125I]insulin specifically, was phosphorylated largely on a tyrosine residue and could not be cleaved to smaller subunits under extreme reducing conditions. The Mr 210 000 protein appears to be a component of a sub-population of liver membrane insulin receptors in which insulin-binding and insulin-stimulated tyrosine kinase phosphorylation site(s) reside in a single polypeptide chain.


Enhancement of placenta growth factor expression by oncostatin M in human rheumatoid arthritis synovial fibroblasts.
Oncostatin M (OSM) belongs to IL-6 subfamily and is mostly produced by T lymphocytes. High levels of OSM are detected in the pannus of rheumatoid arthritis (RA) patients and it may arouse the inflammation responses in joints and eventually leads to bone erosion. Placenta growth factor (PLGF) is an angiogenic factor and highly homologous with vascular endothelial growth factor (VEGF). It has been recently reported that PLGF is highly expressed in synovial tissue and enhances the production of proinflammatory cytokines including TNF-α and IL-6. Here, we demonstrated that OSM increased mRNA and protein levels of PLGF in a time- and concentration-dependent manner in RA synovial fibroblasts. Inhibitors of JAK3 and PI3K antagonized OSM-induced production of PLGF. OSM enhanced the phosphorylation of Tyr705-STAT3, Ser727-STAT3, Ser473-Akt, and increased the nuclear translocation of phosphorylated STAT3 time-dependently. Transfection of dominant negative Akt or application of PI3K inhibitorLY294002 significantly inhibited p-Tyr705-STAT3, p-Ser727-STAT3, and PLGF expression, indicating that Akt is involved in JAK3/STAT3/PLGF signaling cascade. To further examine whether STAT3 binds to the promoter region of PLGF, Chip assay was used and it was found that OSM could bind with PLGF promoter, which was inhibited by JAK3 and PI3K inhibitors. Accumulation of PLGF in the pannus may contribute to the inflammation, angiogenesis and joints destruction in RA patients. These findings demonstrated the important role of OSM in the pathology network of RA and provided novel therapeutic drug targets for RA treatment.


A computational framework for studying energetics and resource management in sea turtle migration and autonomous systems.
Sea turtles complete migrations across vast distances, covering entire ocean basins. To track these migrations, satellite tracking tags are attached to their shells. The impact of these tags must be considered to ensure that turtles' natural behavior is not artificially and adversely impacted through tag-related drag, and that the data collected by a small sample of sea turtles accurately represents the larger population. Additionally, it can be difficult to study animal energetics in the field over large migration distances. In this work, we modify a computational behavior model to study how satellite tracking tags affect turtle migration behavior. Our agent based model contains synthetic magnetic field environments that are used for navigation cues, an ocean current, resource distributions that represent locations of food, and an agent that attempts to migrate to several different goals. The agent loses energy as it progresses, and searches for the resource distributions to replenish itself. Our novel simulation framework demonstrates the relationship between an agent's available energy capacity, its energy consumption based on mechanical power expended, and its ability to navigate to all migratory goal points. This study can be utilized to (1) probe the impacts of an animal's energy capacity and foraging behavior on its resulting navigation and ecology, (2) guide future satellite tag designs, and (3) develop usage recommendations for a suitable tracking tag based on the type of experiment being conducted. Our model can be expanded beyond sea turtles to study other marine species (e.g., sharks, whales). Additionally, this model could be expanded to other domains within the marine environment. For example, it could be modified to examine design trade-offs in remotely operated vehicles (ROVs), which share many of the same operational constraints as sea turtles and other migratory species.


Influence of luteinizing hormone-releasing hormone agonists on human mammary carcinoma cell lines and their xenografts.
The specific binding of luteinizing hormone-releasing hormone (LH-RH) agonist in estradiol-dependent MCF-7 and estradiol-independent MDA-MB-231 human breast cancer cells has been studied using [3H]Ovurelin [(D-3H-Phe6),des-Gly10-LH-RH- ethylamide]. The results of Scatchard analyses suggest the presence of a single class of receptor sites, both in cell suspensions and membrane fractions. Evaluation of these peptide receptors appears to reflect additional characteristics of biological behaviour of these human breast cancer cells. The synthetic LH-RH agonist Ovurelin [(D-Phe6),des-Gly10-LH-RH-ethylamide] can directly interfere (25-30%) with the proliferation of MDA-MB-231 human breast cancer cells in culture. The inhibitory effect of Ovurelin in vitro was negligible in the MCF-7 cell line. In the in vivo experiments the treated immunosuppressed mice bearing either MCF-7 or MDA-MB-231 xenografts responded to the high-dose LH-RH analogue Zoladex depot and Decapeptyl depot therapy. Since the MDA-MB-231 tumour was found to be ER-negative it seems possible that the regression of this xenograft results from the direct antitumor action of the LH-RH agonist.


Phenytoin reduces early acetylcholine release after depolarization.
Phenytoin 10 microM inhibits the K-evoked release of acetylcholine (ACh) from synaptosomes, a process which is biphasic. Phenytoin acts only on the early phase of release. Replacement of external Na with Li does not modify phenytoin's effect. Phenytoin augments the spontaneous release of ACh from resting synaptosomes but this effect is eliminated in Li media. It is likely that phenytoin reduces K-evoked Ca uptake and the Na/Ca exchange by separate mechanisms.


Adenosine antagonists potentiate D2 dopamine-dependent activation of Fos in the striatopallidal pathway.
Adenosine antagonists potentiate dopamine-mediated behaviours. A2a adenosine and D2 dopamine receptors are abundantly co-expressed within the striatopallidal subset of striatal neurons, suggesting that this is the site of interaction between A2a and D2 receptors. We show that the D2-dependent induction of the immediate early gene c-Fos occurs in striatopallidal neurons 3 h following injection of reserpine (10 mg/kg). We used this paradigm to test whether adenosine antagonists modulate D2-dependent activation of striatopallidal neurons. The non-selective A1-A2 adenosine antagonists theophylline (25 mg/kg) or 3,7-dimethyl-1-propargylxanthine (25 mg/kg) potentiated the effect of a submaximal dose of the D2 dopamine agonist quinpirole (0.05 mg/kg) to prevent the induction of striatal c-Fos following reserpine. Co-administration of the A2a receptor antagonist 8-(3-chlorostyryl) caffeine (5 mg/kg) with quinpirole (0.05 mg/kg) also attenuated striatal c-Fos induction following reserpine to a greater extent than 0.05 mg/kg quinpirole alone. When administered prior to reserpine, theophylline (25 mg/kg) or 3,7-dimethyl-1-propargylxanthine (25 mg/kg) partially attenuate the induction of striatal c-fos. These results demonstrate that systemic administration of adenosine antagonists enhance D2 dopamine receptor-dependent regulation of c-Fos in the striatopallidal pathway. These results support a functional interaction between A2a adenosine and D2 dopamine receptors in striatopallidal neurons.


Noroviruses in children seen in a hospital for acute gastroenteritis in Finland.
Noroviruses (NoVs) are second only to rotaviruses (RVs) as causative agents of acute gastroenteritis (AGE) in children. The proportional role of NoVs is likely to increase after control of RV by vaccination. We investigated NoVs in children seen in Tampere University Hospital either treated as outpatients or hospitalized because of AGE before universal RV vaccination was implemented in Finland. This prospective study was conducted from September 2006 to August 2008. A total of 1,128 children <15 years of age with symptoms of AGE were enrolled either in the hospital clinic or in a ward, and stool samples for NoV studies were obtained from 759 children. NoVs were found in 196 (26%) cases. In the first year, NoVs were found in 116 (34%) out of 341, and in the second year, in 80 (19%) out of 418 cases. RVs were found respectively in 128 (38%) and 260 (62%) cases in these two seasons. Both RV and NoV were present in 24 cases. NoV genotype GII.4 predominated with a 96% share of the NoV cases in the first season and an 80% share in the second season. Other NoV genotypes seen infrequently were GII.7, GIIb, GI.6, GII.1, GII.2, and GIIc. The median clinical severity of NoV AGE was 14 compared to 16 for RV AGE on a 20-point scale. NoVs were nearly as common as RVs as causative agents of severe AGE in children seen in hospital. After implementing universal RV vaccination, the importance of NoVs will still increase further.


Immune response after immunization with an experimental Toxoplasma gondii ISCOM vaccine.
Mice were immunized with ISCOM preparations of tachyzoites from two different strains of Toxoplasma gondii. The antibody response and the cellular response, as measured in vitro, were comparable with those found in chronically infected mice. When challenged with virulent T. gondii tachyzoites, all the immunized mice died, whereas all the chronically infected mice survived. However, the immunized mice generally survived longer than non-immunized animals.


On the role of cyclic AMP and cyclic GMP in steroid production by bovine cortical cells.
The time course of corticotropin-induced steroidogenesis and changes in intracellular cyclic AMP and cyclic GMP levels were investigated in isolated bovine adrenocortical cells prepared by trypsin digestion. Corticotropin produced a peak rise in cyclic AMP during the first 5 min of stimulation and enhanced steroid production after 15 min. Corticotropin also caused a decrease in cortical cyclic GMP at 5 min; this decrease in cyclic GMP reverted to a 2-3 fold increase at 15-30 min which gradually subsided by 60 min. A steroidogenic concentration of prostaglandin E2 also produced an elevation in the levels of both nucleotides, but the rise in cyclic GMP preceded the rise in cyclic AMP. These results suggest that the relative amounts of cyclic AMP and cyclic GMP, rather than the absolute levels of cyclic AMP, may be a key factor in the regulation of steroidogenesis.


Elevated amounts of protein in C6 glial cells during the growth-inhibitory response elicited by dexamethasone.
Dexamethasone suppresses C6 glial cell proliferation in vitro. This growth-inhibitory response is accompanied by elevated amounts of acid-insoluble protein in the steroid-treated cells relative to controls. These results provide additional evidence that the glucocorticoid acts to arrest C6 cell proliferation in G2.


Automatic Measurement of Postural Abnormalities With a Pose Estimation Algorithm in Parkinson's Disease.
This study aims to develop an automated and objective tool to evaluate postural abnormalities in Parkinson's disease (PD) patients. We applied a deep learning-based pose-estimation algorithm to lateral photos of prospectively enrolled PD patients (n = 28). We automatically measured the anterior flexion angle (AFA) and dropped head angle (DHA), which were validated with conventional manual labeling methods. The automatically measured DHA and AFA were in excellent agreement with manual labeling methods (intraclass correlation coefficient > 0.95) with mean bias equal to or less than 3 degrees. The deep learning-based pose-estimation algorithm objectively measured postural abnormalities in PD patients.


Opportunistic cerebral vasculopathy and stroke in patients with the acquired immunodeficiency syndrome.
To describe an unusual cause of stroke in patients with the acquired immunodeficiency syndrome. An observational case series of hospitalized patients with subsequent autopsy. Clinical, radiological, and pathological examinations were performed. In three of 14 patients with stroke, the infarctions were secondary to an opportunistic vasculopathy caused by Candida albicans, cytomegalovirus, or lymphoma. Opportunistic conditions may lead to vascular abnormalities and subsequent stroke in patients with the acquired immunodeficiency syndrome.


Intensification of the base deficit induced by vagotomy after atropine treatment in dogs.
The effects of atropine treatment on the heart rate, the arterial blood pressure, the respiratory rate, the acid-base profile and the oxygenation of arterial blood were investigated in chloralose anaesthetized dogs. As the I.V. atropine sulphate (1mg/kg) in saline (9% w/v) did not induce base deficit or alter the acid-base profile, the section of vagal parasympathetic (motor) fibres in normal (untreated) ones could not be held responsible for the observed base deficit after their vagotomy. Such observed base deficit was most likely engendered reflexively due to the section of vagal sensory fibres; as only general activation, not the withdrawal (section) of vagal sympathetic fibres might induce such an effect. Moreover, the bilateral vagotomy in these atropinized dogs induced a larger base deficit, which mostly contributed to the increase of H+ion concentration therein. This comparative enhancement of base deficit suggests that the opening of the negative feed back loop of the (aortic chemoreceptor) sensory fibres points to the blocking effect of atropine on the cholinergic link in the central (medulla) chemosensitive mechanism. The base excess observed after vagotomy in propranolol treated animals suggested that the base deficit vagal sensory fibres was mediated through reflexive activation of sympatho-adrenal axis.


Heat-shock proteins in host-pathogen interactions: implications for cystic fibrosis.
The expression of heat-shock proteins by both pathogen and host cells during the phagocytosis of Staphylococcus aureus and Pseudomonas aeruginosa, two bacterial species that colonize the airways of patients with cystic fibrosis, probably contributes to pulmonary inflammation in cystic fibrosis. Here, we discuss the likely signals for heat-shock-protein induction within host and bacterial cells.


Effect of transepithelial concentration gradients on the passive fluxes of sodium across toad bladder.
Bidirectional sodium fluxes across toad bladder were measured after eliminating active transport with ouabain. Mucosal sodium concentration, Cm, was progressively reduced (from 114 to 3 mM) while serosal sodium remained constant. Potential difference was maintained at zero by current passage. The ratio, Q, of the bulk permeability coefficient for sodium, P, to the tracer sodium permeability coefficient, P, was found to remain constant as Cm decreased. Equations were derived on this basis for bidirectional fluxes and for P and P as functions of Cm, which corresponded closely to the observed data. The explanation for the observed value of Q and its constancy under these conditions is uncertain.


Prediction of TTF-1 expression in non-small-cell lung cancer using machine learning-based radiomics.
To explore the feasibility and performance of machine learning-based radiomics models in predicting thyroid transcription factor-1 (TTF-1) expression in non-small cell lung cancer (NSCLC). A total of 227 NSCLC patients were included in this retrospective study and divided into the training set and test set with a ratio of 8:2 randomly. Lung tumors on CT images were semi-automatic segmented utilizing 3D Slicer. Radiomic features quantifying tumor intensity, shape, texture, and transformed wavelet were extracted using a Python toolkit. Variance threshold (VT), principal component analysis (PCA), and least absolute shrinkage selection operator (LASSO) were used to reduce features; logistic regression (LR), random forest (RF), and support vector machine (SVM) were used to develop classifier, respectively. The performance of the models was evaluated by areas under the curves (AUC) of receiver operating characteristic (ROC) curves. Different models were compared by the Delong test to determine the optimal algorithms. Total 1968 radiomic features were extracted from the lung tumors images, and then 13, 15, and 13 stable features were selected by VT, PCA, and LASSO, respectively. Each classifier could discriminate against the TTF-1-positive groups with average AUC ranging from 0.601 to 0.784 in the training set. Among the models, three models constructed by the LASSO method showed satisfactory performance in the test set with AUC ranging from 0.715 to 0.787. The Delong test showed no significant difference between the LASSO models (P > 0.05). Machine learning-based radiomics model could predict the expression of TTF-1 in NSCLC patients.


CD16 polymorphisms and NK activation induced by monoclonal antibody-coated target cells.
CD16 and natural killer (NK) cells appear to play a central role in mediating the anti-tumor effects of monoclonal antibody (mAb) therapy, yet little is known about changes in NK cells that result from interaction of the NK cells with mAb-coated tumor cells under physiologic conditions. We developed a system using peripheral blood mononuclear cells (PBMCs) and either transformed B cells or breast cancer cells to assess how mAbs impact on NK cell phenotype. Rituximab, apolizumab and trastuzumab induced modulation of CD16 and upregulation of CD54 on NK cells when the appropriate target cells were present. Higher concentrations of mAb were needed to induce these changes on NK cells from subjects with the lower affinity CD16 polymorphism. Phenotypic changes were greater in NK cells from subjects with the higher affinity polymorphism even when saturating concentrations of mAb were used, demonstrating increased concentration of mAb can overcome some, but not all, of the influence CD16 polymorphisms have on NK activation. These studies provide a straightforward and easily reproducible technique to measure the ability of mAb-coated tumor cells to activate NK cells in vitro which should be particularly useful as mAbs with varying affinity for both target antigen and Fc receptor (FcR) are developed.


Preparation, hydrolysis, and oral absorption of lactonyl esters of penicillins.
Lactonyl esters of ampicillin and other penicillins have been synthesized as prodrugs designed to improve the oral absorption of the parent penicillins. In general, the esters hydrolyzed rapidly in the presence of tissues including blood and certain of the esters were better absorbed than the parent penicillin. The phthalidyl ester of ampicillin [talampicillin (British Pharmacopoeia approved name), BRL 8988] was selected for extended studies. The compound was found to be well absorbed in various animal species and gave ampicillin serum concentrations in fasting human volunteers 2.5-3 times those obtained for ampicillin itself.


[Hormonal treatment in breast cancer].
The discovery of breast cancer carcinoma sensitivity to estradiol (E) suppression is the starting point of hormonal treatment. Hormonal receptors (ER and PR) are the pathway of the action of estradiol on breast tumor cells. The detection of at least one of these two receptors is needed to classify a tumor as hormone sensitive. The hormonal treatment of breast cancer attempts to suppress the stimulating action of E on tumor cells. This can be done by decreasing E synthesis--ovarian suppression (OS) or aromatase inhibitors (AIs)--or by compelling with E on receptors--tamoxifen (TAM). In advanced breast cancer, hormonal treatment gives good response with few side effects. In young patient, the treatment is based on TAM. It could be associated with OS. In post-menopausal women, AIs are more potent than TAM. They are used in the first line treatment and TAM as a second line. Fulvestrant is not superior TAM or AIs. In the adjuvant setting, hormonal treatment gives a significant reduction of recurrence and death. In young patient, the treatment is based on TAM. It could be associated with OS. In post-menopausal patients, adjuvant treatment must include an AIs for at least one part of the treatment. A survey of bone density is necessary.


[Trichome].
A 4 year-old boy presented an acute pruriginous dermatitis of the hands, forearms and abdomen. A skin surface biopsy revealed numerous trichomes, small prickles present on plants. These trichomes were those of prickly pears and stuck deeply in the skin, inducing an inflammatory reaction known as Sabra dermatitis. A number of plant dermatitides are due to the presence of trichomes such as those due to linden, primula, wild rose or nettle.


Synthesis and analysis of potential α1,3-fucosyltransferase inhibitors.
Fucosyltransferases catalyze the transfer of l-fucose from an activated GDP-β-l-fucose to various acceptor molecules such as N-acetyllactosamine. Frequently fucosylation is the final step within the glycosylation machinery, and the resulting glycans are involved in various cellular processes such as cell-cell recognition, adhesion and inflammation or tumor metastasis. The selective blocking of these interactions would thus be a potential promising therapeutic strategy. The syntheses and analyses of various potential α1,3-fucosyltransferase inhibitors derived from GDP-β-l-fucose containing a triazole linker unit is summarized and the observed inhibitory effect was compared with that of small molecules such as GDP or fucose. To examine their specificity and selectivity, all inhibitors were tested with human α1,3-fucosyltransferase IX and Helicobacter pylori α1,3-fucosyltransferase, which is to date the only α1,3-fucosyltransferase with a known high resolution structure. Specific inhibitors which inhibit either H. pylori α1,3-fucosyltransferase or human fucosyltransferase IX with Ki values in the micromolar range were identified. In that regard, acetylated GDP-galactose derivative Ac-3 turned out to inhibit H. pylori α1,3-fucosyltransferase but not human fucosyltransferase IX, whereas GDP-6-amino-β-l-fucose 17 showed an appreciably better inhibitory effect on fucosyltransferase IX activity than on that of H. pylori fucosyltransferase.


The predictive value of molecular markers (p53, EGFR, ATM, CHK2) in multimodally treated squamous cell carcinoma of the oesophagus.
Pretherapeutic identification of oesophageal squamous cell carcinomas that will respond to neoadjuvant chemoradiotherapy is an important attempt for improvement of patient's prognosis. In the current study, pretherapeutic biopsies from 94 oesophageal squamous cell carcinomas (cT3, cN0/+, cM0) in patients who underwent neoadjuvant chemoradiotherapy (RCTx: 45 Gy plus cisplatin and 5-fluorouracil) and subsequent oesophagectomy in the setting of a single-centre prospective treatment trial were investigated by means of immunohistochemistry. Expression of proteins involved in DNA repair and/or cell-cycle regulation, that is p53, p53 (phosphorylated at Ser15), EGFR, ATM protein kinase (phosphorylated at Ser1981) and checkpoint kinase 2 (CHK2) (phosphorylated at Thr68) was correlated with the response to RCTx and with overall survival. Tumours that were positive for CHK2 expression more frequently showed clinically determined regression after RCTx (69.4%) than tumours that were negative for CHK2 expression (32.1%; P=0.0011), whereas other parameters did not correlate with tumour regression. Expression of ATM correlated with expression of CHK2 (P=0.0061) and p53-phospho (P=0.0064). Expression of p53 correlated with expression of p53-phospho (P<0.0001). In contrast to clinical and histopathological response evaluation, none of the molecular parameters under investigation correlated with overall survival. In conclusion, expression analysis of p53, EGFR CHK2 and ATM has no predictive value in multimodally treated oesophageal squamous cell carcinoma.


The structural basis of African swine fever virus pA104R binding to DNA and its inhibition by stilbene derivatives.
African swine fever virus (ASFV) is a highly contagious nucleocytoplasmic large DNA virus (NCLDV) that causes nearly 100% mortality in swine. The development of effective vaccines and drugs against this virus is urgently needed. pA104R, an ASFV-derived histone-like protein, shares sequence and functional similarity with bacterial HU/IHF family members and is essential for viral replication. Herein, we solved the crystal structures of pA104R in its apo state as well as in complex with DNA. Apo-pA104R forms a homodimer and folds into an architecture conserved in bacterial heat-unstable nucleoid proteins/integration host factors (HUs/IHFs). The pA104R-DNA complex structure, however, uncovers that pA104R has a DNA binding pattern distinct from its bacterial homologs, that is, the β-ribbon arms of pA104R stabilize DNA binding by contacting the major groove instead of the minor groove. Mutations of the basic residues at the base region of the β-strand DNA binding region (BDR), rather than those in the β-ribbon arms, completely abolished DNA binding, highlighting the major role of the BDR base in DNA binding. An overall DNA bending angle of 93.8° is observed in crystal packing of the pA104R-DNA complex structure, which is close to the DNA bending angle in the HU-DNA complex. Stilbene derivatives SD1 and SD4 were shown to disrupt the binding between pA104R and DNA and inhibit the replication of ASFV in primary porcine alveolar macrophages. Collectively, these results reveal the structural basis of pA104R binding to DNA highlighting the importance of the pA104R-DNA interaction in the ASFV replication cycle and provide inhibitor leads for ASFV chemotherapy.


Biochemical pathways involved in the translation of physical stimulus into biological message.
Studies from our laboratory revealed that direct application of physical strain (PS) to cultured bone cells stimulated synthesis of prostaglandin E2 (PGE2) in a specific population of cells. We found that PGE2 induced the cellular production of cAMP in several bone cell types, whereas the induction of DNA synthesis was limited to osteoblastlike cells. Indirect evidence indicated that PS induced the osteoblastlike cells to synthesize PGE2. Other cell types, for example, chondrocytes, when activated by PS, can be induced to produce cAMP and induce DNA synthesis not mediated by PGE2. We have also found that electric stimulation of different populations of bone cells is specifically induced by a certain intensity of the electric field. It seems that electric stimulus circumvents the PGE2 effect and triggers the adenyl cyclase system in the cell directly. The electric field also induces DNA synthesis not via PGE2 production.


(2E)-3-[4-(1H-Benzimidazol-2-ylmeth-oxy)phen-yl]-1-(4-meth-oxy-phen-yl)prop-2-en-1-one.
In the title compound, C(24)H(20)N(2)O(3), the mean plane of the benzimidazole unit makes dihedral angles of 79.88 (11) and 85.44 (12)° with the benzene and 4-meth-oxy-benzene rings, respectively. The benzene and 4-meth-oxy-benzene rings maske a dihedral angle of 16.10 (14)°. A pair of inter-molecular N-H⋯O hydrogen bonds connects adjacent mol-ecules into an inversion dimer, generating an R(2) (2)(26) ring motif. The crystal structure is further stabilized by C-H⋯π inter-actions.


A probabilistic framework for cellular lineage reconstruction using integrated single-cell 5-hydroxymethylcytosine and genomic DNA sequencing.
Lineage reconstruction is central to understanding tissue development and maintenance. To overcome the limitations of current techniques that typically reconstruct clonal trees using genetically encoded reporters, we report scPECLR, a probabilistic algorithm to endogenously infer lineage trees at a single-cell-division resolution by using 5-hydroxymethylcytosine (5hmC). When applied to 8-cell pre-implantation mouse embryos, scPECLR predicts the full lineage tree with greater than 95% accuracy. In addition, we developed scH&G-seq to sequence both 5hmC and genomic DNA from the same cell. Given that genomic DNA sequencing yields information on both copy number variations and single-nucleotide polymorphisms, when combined with scPECLR it enables more accurate lineage reconstruction of larger trees. Finally, we show that scPECLR can also be used to map chromosome strand segregation patterns during cell division, thereby providing a strategy to test the "immortal strand" hypothesis. Thus, scPECLR provides a generalized method to endogenously reconstruct lineage trees at an individual-cell-division resolution.


Inferring the true number of SARS-CoV-2 infections in Japan.
In Japan, as of December 31, 2021, more than 1.73 million laboratory-confirmed cases have been reported. However, the actual number of infections is likely to be under-ascertained due to the epidemiological characteristics such as mild and subclinical infections and limited testing availability in the early days of the pandemic. In this study, we infer the true number of infections in Japan between January 16, 2020, and December 31, 2021, using a statistical modelling framework that combines data on reported cases and fatalities. We used reported COVID-19 deaths and age-specific infection fatality ratios (IFR) to impute the true number of infections. Estimates of IFR were informed from published studies and were adjusted to reflect the effects of pharmaceutical interventions, mass vaccination, and evolving variants. To account for the uncertainty in IFR, we sampled values from relevant distributions. We estimated that as of December 31, 2021, 3.07 million (CrI: 2.05-4.24 million) people had been infected in Japan, which is 1.77 times higher than the 1.73 million reported cases. Our meta-analysis confirmed that these findings were consistent with the intermittent seroprevalence studies conducted in Japan. We have estimated that a substantial number of COVID-19 infections in Japan were unreported, particularly in adults. Our approach provides a more realistic assessment of the true underlying burden of COVID-19. The results of this study can be used as fundamental components to strengthen population health control and surveillance measures.


Characterization of anaerobic oxidation of methane and microbial community in landfills with aeration.
Landfills are the third largest source of anthropogenic CH4 emissions. Anaerobic oxidation of methane (AOM) activity and communities of methane-oxidizing bacteria were investigated in three informal landfills in this study, namely, BJ, CH and SZ landfills, among which BJ and CH represent traditional anaerobic landfills, while the SZ landfill was subjected to aeration to accelerate waste stabilization. The AOM rates of the investigated landfilled wastes ranged from 3.66 to 23.91 nmol g-1 h-1. Among the three landfills, the AOM rate was highest in the SZ-1-Top sample, which was closest to the aeration pipe. Among the possible electron acceptors for AOM, including NO3-, NO2-, SO42- and Fe3+, the NO2--N content was the only variable that was positively correlated with the AOM rate. Compared with α-Proteobacteria methanotrophs, γ-Proteobacteria methanotrophs were more abundant in the landfilled waste, especially Methylobacter, which was detected in nearly all samples. Members of the family Methylomirabilaceae, including Candidatus Methylomirabilis, were also detected in the SZ-1 and SZ-2-Bot samples. The relative abundance of the main methanotrophs in the families Methylomonadaceae, Methylococcaceae, Rokubacteriales and Methylomirabilaceae, the genus Methylocystis and the phylum NC10 were all positive correlations with the contents of NO2--N in the landfilled waste samples. Additionally, significantly positive correlations were observed between the AOM rates and the relative abundance of the main methanotrophs except for the family Methylococcaceae. This indicated that aeration could enhance the conversion of nitrogen compounds in the landfilled waste, in which the high contents of NO2--N could stimulate the growth of methanotrophs and increase AOM rate. These findings are helpful for understanding the mechanisms of CH4 oxidation in landfills and for taking effective measures to mitigate CH4 emissions from landfills.


Nexus between Human Development Index (HDI) and CO2 emissions in a developing country: decoupling study evidence from Bangladesh.
Even if developing nations are entitled to take part in the attempts of decreasing carbon emissions to elude alarming environment change, the consequences of carbon lessening goals in Human Development Index of developing nations continue an issue of dispute. Based on the decoupling relationship and index decomposition, the aim of the study is for determining the nexus between the Human Development Index and CO2 emissions from the year 1990 to 2018 in Bangladesh. The outcomes exposed that Bangladesh accomplished weak and strong decoupling all through the analysis time. From the index decomposition of different factors point of view, it is revealed that variation in economic activity factor produces a significant amount of CO2 emissions which is 0.0623 tonnes, and in terms of percentage, it stands for 105%. While energy intensity and economic structure factors act an indiscernible part in the rise of CO2 emissions and in terms of percentage, it stands for 10.77% and 2.77%, respectively. Contrary, CO2 emissions' coefficient and energy structure factors are liable for decrease carbon emissions to some extent, and in terms of percentage, it replicates 7.27% and 11.97%, respectively. Based on the outcomes, the paper offers regulations for the energy policymaker of Bangladesh on carbon emissions' alleviation policies and an important decision-making indication to speed up low-carbon growth.


Corrigendum: Twenty-Year Clinical Progression of Dysferlinopathy in Patients from Dagestan.
[This corrects the article on p. 77 in vol. 8, PMID: 28337173.].


Nitric oxide signalling in plant interactions with pathogenic fungi and oomycetes.
Nitric oxide (NO) and reactive nitrogen species have emerged as crucial signalling and regulatory molecules across all organisms. In plants, fungi, and fungi-like oomycetes, NO is involved in the regulation of multiple processes during their growth, development, reproduction, responses to the external environment, and biotic interactions. It has become evident that NO is produced and used as a signalling and defence cue by both partners in multiple forms of plant interactions with their microbial counterparts, ranging from symbiotic to pathogenic modes. This review summarizes current knowledge on the role of NO in plant-pathogen interactions, focused on biotrophic, necrotrophic, and hemibiotrophic fungi and oomycetes. Actual advances and gaps in the identification of NO sources and fate in plant and pathogen cells are discussed. We review the decisive role of time- and site-specific NO production in germination, oriented growth, and active penetration by filamentous pathogens of the host tissues, as well in pathogen recognition, and defence activation in plants. Distinct functions of NO in diverse interactions of host plants with fungal and oomycete pathogens of different lifestyles are highlighted, where NO in interplay with reactive oxygen species governs successful plant colonization, cell death, and establishment of resistance.


Targeting of microvillus protein Eps8 by the NleH effector kinases from enteropathogenic E. coli.
Attaching and effacing (AE) lesion formation on enterocytes by enteropathogenic Escherichia coli (EPEC) requires the EPEC type III secretion system (T3SS). Two T3SS effectors injected into the host cell during infection are the atypical kinases, NleH1 and NleH2. However, the host targets of NleH1 and NleH2 kinase activity during infection have not been reported. Here phosphoproteomics identified Ser775 in the microvillus protein Eps8 as a bona fide target of NleH1 and NleH2 phosphorylation. Both kinases interacted with Eps8 through previously unrecognized, noncanonical "proline-rich" motifs, PxxDY, that bound the Src Homology 3 (SH3) domain of Eps8. Structural analysis of the Eps8 SH3 domain bound to a peptide containing one of the proline-rich motifs from NleH showed that the N-terminal part of the peptide adopts a type II polyproline helix, and its C-terminal "DY" segment makes multiple contacts with the SH3 domain. Ser775 phosphorylation by NleH1 or NleH2 hindered Eps8 bundling activity and drove dispersal of Eps8 from the AE lesion during EPEC infection. This finding suggested that NleH1 and NleH2 altered the cellular localization of Eps8 and the cytoskeletal composition of AE lesions during EPEC infection.


Transfusion practice in massively bleeding patients: time for a change?
We identified some fatal cases where massively bleeding patients received inadequate transfusion therapy. The aim of this study was to review and evaluate the transfusion practice in acutely multitransfused patients. Patients receiving > 10 units of red blood cells (RBC) within 24 h of admission and 30 blood components within 7 days of admission were reviewed. Thirty-nine patients were identified, 13 of whom were inadequately transfused (IT) and had a higher mortality (12/13) than adequately transfused (AT) patients 13/26 (P = 0.013). Ten of 13 IT patients developed a microvascular bleed compared to four of 26 in the AT group (P = 0.001) and had a lower platelet count upon arrival at the intensive care unit (40 x 10(9)/l vs. 80 x 10(9)/l, P = 0.024). An early balanced transfusion therapy is vital in massively bleeding patients, and a pro-active approach from the blood bank is warranted. We have introduced an acute transfusion package (ATP) consisting of 5 RBC, 5 FFP and 2 PC units, indicated in massively bleeding patients, securing a balanced transfusion therapy.


Mechanism of tetraborate and silicate ions on the growth kinetics of microarc oxidation coating on a Ti6Al4V alloy.
The growth kinetics mechanism of microarc oxidation (MAO) coatings on Ti6Al4V alloy was studied by designing a binary mixed electrolyte with various SiO3 2- and B4O7 2- ion ratios via scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and potentiodynamic polarization. When the ratio of B4O7 2- in the electrolyte is 100%, B4O7 2- dissolves molten TiO2 at a high temperature, exposing nano-scale filamentary channels in the barrier layer of MAO coating, resulting in the repeated nucleation of microarc in the same area. When the ratio of SiO3 2- in the binary mixed electrolyte reaches 10%, the amorphous SiO2 formed by SiO3 2- at high temperatures from discharge blocks discharge channels and induces microarc nucleation in other regions, thus inhabiting the discharge cascade phenomenon. When the ratio of SiO3 2- in the binary mixed electrolyte increases from 15% to 50%, the amounts of molten oxides cover some of the pores formed by the primary microarc discharge, so part of the secondary discharge preferentially generates in the uncovered pores. Finally, the discharge cascade phenomenon occurs. Moreover, the thickness of the MAO coating obtained in the binary mixed electrolyte containing B4O7 2- and SiO3 2- shows a power function with time.


Selexipag for the treatment of children with pulmonary arterial hypertension: First multicenter experience in drug safety and efficacy.
The European Pediatric Pulmonary Vascular Disease Network (EPPVDN) investigated the safety and efficacy of add-on selexipag, an oral prostacyclin receptor agonist approved for pulmonary arterial hypertension (PAH) in adults, in the largest, exploratory pediatric cohort to date. This is a prospective observational study of 15 consecutive children with PAH, treated with oral add-on selexipag at 3 centers. Most patients underwent cardiac catheterizations at baseline and median of 8 months follow-up. All patients had clinical, echocardiographic, and N-terminal pro b-type natriuretic peptide studies, including the EPPVDN pediatric pulmonary hypertension (PH) risk score. There was no death during the use of selexipag. Two of 15 patients ultimately underwent lung transplantation. One patient with heritable PAH died on intravenous treprostinil (off selexipag). The mean right atrial pressure, the ratio of pulmonary arterial pressure (PAP) to systemic arterial pressure (SAP) (mean PAP/mean SAP, diastolic PAP/diastolic SAP: -17%), and transpulmonary pressure gradients (TPG) (mean TPG: -17%; p < 0.01; diastolic TPG: -6 mm Hg; p < 0.05) were improved after the therapy (n = 10). Selexipag therapy was associated with a better right ventricular systolic function (tricuspid annular plane systolic excursion: +14.5%; p < 0.01) and functional class. Improvement was seen in non-invasive and combined invasive/non-invasive PH risk scores (lower risk: +18%-22%, higher risk: -35%-37%; p < 0.05). Overall, the efficacy of selexipag was variable, often with a better response in less sick patients. Oral selexipag use in children with PAH is well tolerated and safe when closely monitored. Add-on selexipag therapy improved several outcome-relevant variables in about 50% of patients and prevented disease progression in additional 27% of patients. The novel EPPVDN pediatric PH risk score indicated these drug effects properly, can be useful in clinical follow-up, and should be validated in larger prospective studies.


Ganoderic Acid A Alleviates OVA-Induced Asthma in Mice.
The aim of this study is to investigate the effects of ganoderic acid A (GAA) on OVA-induced asthma in mice. Mouse asthma model was established by ovalbumin (OVA) in vitro. Diff-Quik staining was used to observe the total numbers of cells and the number of classification cells in each group, and HE staining was used to observe lung inflammation in lung tissue sections. ELISA was used to detect the effect of GAA on the levels of interleukin-4 (IL-4), IL-5, and IL-13 in serum and lung tissue. The expression levels of TLR/NF-κB were detected by Western blot. Immunohistochemistry was used to observe the expression changes of TLR4 and P-P65. Compared with the normal group, the inflammatory cell count, IL-4, IL-5, and IL-13 expression in the model group increased, and TLR/NF-kB signal protein expression increased. Compared with the model group, in GAA group, the number of inflammatory cells, the expression of IL-4, IL-5, and IL-13 decreased, and the expression of TLR/NF-kB signaling protein decreased. GAA regulated lung inflammation in asthmatic mice by inhibiting TLR/NF-kB signaling pathway.


GSH-responsive SN38 dimer-loaded shape-transformable nanoparticles with iRGD for enhancing chemo-photodynamic therapy.
Accurate tumor targeting, deep penetration and superb retention are still the main pursuit of developing excellent nanomedicine. To achieve these requirements, a stepwise stimuli-responsive strategy was developed through co-administration tumor penetration peptide iRGD with shape-transformable and GSH-responsive SN38-dimer (d-SN38)-loaded nanoparticles (d-SN38@NPs/iRGD). Upon intravenous injection, d-SN38@NPs with high drug loading efficiency (33.92 ± 1.33%) could effectively accumulate and penetrate into the deep region of tumor sites with the assistance of iRGD. The gathered nanoparticles simultaneously transformed into nanofibers upon 650 nm laser irradiation at tumor sites so as to promote their retention in the tumor and burst release of reactive oxygen species for photodynamic therapy. The loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm, which consequently resulted in SN38 release and excellent chemo-photodynamic effect on tumor. In vitro, co-administering iRGD with d-SN38@NPs+laser showed higher cellular uptake, apoptosis ratio and multicellular spheroid penetration. In vivo, d-SN38@NPs/iRGD+laser displayed advanced penetration and accumulation in tumor, leading to 60.89% of tumor suppression in 4T1 tumor-bearing mouse model with a favorable toxicity profile. Our new strategy combining iRGD with structural transformable nanoparticles greatly improves tumor targeting, penetrating and retention, and empowers anticancer efficacy.


A novel flower-shaped Ag@ZIF-67 chemiluminescence sensor for sensitive detection of CEA.
In this work, a chemiluminescence (CL) aptasensor for sensitive carcinoembryonic antigen (CEA) detection was constructed based on the CL system of luminol-H2O2-NaOH. Magnetic carbon nanotubes (MCNTs), as the base material, was modified with CEA-aptamer and DNA1, and was combined with the novel flower-shaped Ag@ZIF-67 of modified with DNA2 through the principle of base complementary pairing. CEA combined with aptamer when it existed in the solution. At the same time, MCNTs was adsorbed at the bottom of the container under the influence of external magnetic field, and Ag@ZIF-67 enhanced the CL signal. The CL aptasensor demonstrated high selectivity and sensitivity for CEA in human serum sample with (1-4): a detection limit of 4.53 × 10-3 ng/mL in case the detection range was 0.05-500 ng/mL. Furthermore, the proposed method had been shown great potential in cancer diagnosis.


Adaptive cardiorespiratory changes to chronic continuous and intermittent hypoxia.
This chapter reviews cardiorespiratory adaptations to chronic hypoxia (CH) experienced at high altitude and cardiorespiratory pathologies elicited by chronic intermittent hypoxia (CIH) occurring with obstructive sleep apnea (OSA). Short-term CH increases breathing (ventilatory acclimatization to hypoxia) and blood pressure (BP) through carotid body (CB) chemo reflex. Hyperplasia of glomus cells, alterations in ion channels, and recruitment of additional excitatory molecules are implicated in the heightened CB chemo reflex by CH. Transcriptional activation of hypoxia-inducible factors (HIF-1 and 2) is a major molecular mechanism underlying respiratory adaptations to short-term CH. High-altitude natives experiencing long-term CH exhibit blunted hypoxic ventilatory response (HVR) and reduced BP due to desensitization of CB response to hypoxia and impaired processing of CB sensory information at the central nervous system. Ventilatory changes evoked by long-term CH are not readily reversed after return to sea level. OSA patients and rodents subjected to CIH exhibit heightened CB chemo reflex, increased hypoxic ventilatory response, and hypertension. Increased generation of reactive oxygen species (ROS) is a major cellular mechanism underlying CIH-induced enhanced CB chemo reflex and the ensuing cardiorespiratory pathologies. ROS generation by CIH is mediated by nontranscriptional, disrupted HIF-1 and HIF-2-dependent transcriptions as well as epigenetic mechanisms.


Advances in fish vaccine delivery.
Disease prevention is essential to the continued development of aquaculture around the world. Vaccination is the most effective method of combating disease and currently there are a number of vaccines commercially available for use in fish. The majority of aquatic vaccines are delivered by injection, which is by far the most effective method when compared to oral or immersion deliveries. However it is labor intensive, costly and not feasible for large numbers of fish under 20 g. Attempts to develop novel oral and immersion delivery methods have resulted in varying degrees of success but may have great potential for the future.


Precise high-throughput online near-infrared spectroscopy assay to determine key cell wall features associated with sugarcane bagasse digestibility.
Sugarcane is one of the most crucial energy crops that produces high yields of sugar and lignocellulose. The cellulose crystallinity index (CrI) and lignin are the two kinds of key cell wall features that account for lignocellulose saccharification. Therefore, high-throughput screening of sugarcane germplasm with excellent cell wall features is considered a promising strategy to enhance bagasse digestibility. Recently, there has been research to explore near-infrared spectroscopy (NIRS) assays for the characterization of the corresponding wall features. However, due to the technical barriers of the offline strategy, it is difficult to apply for high-throughput real-time analyses. This study was therefore initiated to develop a high-throughput online NIRS assay to rapidly detect cellulose crystallinity, lignin content, and their related proportions in sugarcane, aiming to provide an efficient and feasible method for sugarcane cell wall feature evaluation. A total of 838 different sugarcane genotypes were collected at different growth stages during 2018 and 2019. A continuous variation distribution of the near-infrared spectrum was observed among these collections. Due to the very large diversity of CrI and lignin contents detected in the collected sugarcane samples, seven high-quality calibration models were developed through online NIRS calibration. All of the generated equations displayed coefficient of determination (R2) values greater than 0.8 and high ratio performance deviation (RPD) values of over 2.0 in calibration, internal cross-validation, and external validation. Remarkably, the equations for CrI and total lignin content exhibited RPD values as high as 2.56 and 2.55, respectively, indicating their excellent prediction capacity. An offline NIRS assay was also performed. Comparable calibration was observed between the offline and online NIRS analyses, suggesting that both strategies would be applicable to estimate cell wall characteristics. Nevertheless, as online NIRS assays offer tremendous advantages for large-scale real-time screening applications, it could be implied that they are a better option for high-throughput cell wall feature prediction. This study, as an initial attempt, explored an online NIRS assay for the high-throughput assessment of key cell wall features in terms of CrI, lignin content, and their proportion in sugarcane. Consistent and precise calibration results were obtained with NIRS modeling, insinuating this strategy as a reliable approach for the large-scale screening of promising sugarcane germplasm for cell wall structure improvement and beyond.


Contamination of human gingival crevicular fluid by plaque and saliva.
Dental plaque and saliva are both possible contaminants of gingival crevicular fluid (GCF). Plaque samples from 12 sites in four subjects who had allowed plaque to accumulate for 24-48 h were quantified using the Plaque Index and then transferred to filter paper strips for fluid volume determination using the Periotron 6000. The mean volume of fluid for plaque scores of 0 was 0.02 (+/- 0.01) microliter, whereas for plaque scores of 3 the mean volume was 0.15 (+/- 0.07) microliters. In a clinical study, GCF samples, from 19/184 subjects (10.4%) were assessed as contaminated or suspected to be contaminated with saliva, but only 28/1740 strips (1.6%) were placed in these categories of contamination. An assay to confirm salivary contamination was established, using an immunochemical, double-antibody method with sheep anti-human salivary alpha-amylase followed by peroxidase-conjugated rabbit anti-sheep immunoglobulin. The detection threshold of the assay was 7.5 ng of alpha-amylase, which represents approx. 15-25 nl of saliva. The assay was evaluated on 90 GCF samples categorized as 'known' (n = 16), 'suspected' (n = 16), or 'not' contaminated (n = 58) with saliva; 81.25, 50-61.5 and 5.2-8.6%, respectively, were positive for salivary alpha-amylase. In some GCF samples salivary contamination was in excess of 50%. It was concluded that GCF samples seen to be contaminated with saliva should be discarded, whereas samples considered free from contamination may be used with confidence. Samples suspected of contamination may require an alpha-amylase assay before further analysis.


Risk factors and microbial profile of central venous catheter related blood stream infection in medical cardiac care units, National Heart Institute, Egypt.
Catheter related blood stream infection (CRBSI) is the main complication of central venous catheter (CVC) use. The aim of the study is to improve the safety of patients with central venous catheter in National Heart Institute (NHI) medical cardiac care units. A Prospective cohort study was conducted on one hundred and eleven cardiac patients in (NHI) cardiac care units from August 2017 to February 2018. All patients subjected to central venous catheter (CVC) in cardiac care units, NHI, were included except: 1. Patients with obvious source of infection, 2. Immunocompromised patients, 3. patients having infective endocarditis, 4. patients whose catheter was put outside NHI. Noncompliance of health care providers to care bundle elements of CVC of Centers for Disease Control and Prevention (CDC) represents a risk factor for CRBSI occurrence. Coagulase negative staphylococci was the most common isolated organism. Health care providers should adhere care bundle elements recommended by CDC during insertion and handling of CVC. This will in turn decrease CRBSI.


High virucidal potential of novel ceramic-metal composites fabricated via hybrid selective laser melting and spark plasma sintering routes.
In this work, we combine selective laser melting (SLM) and spark plasma sintering (SPS) to fabricate new materials with high virucidal potential. Various bioactive disc-shaped ceramics, metal alloys, and composites were fabricated and tested against bacteriophage Phi6-a model system for RNA-enveloped viruses. We prepared silver-doped titanium dioxide (TiO2 + 2.5‒10% Ag), copper-doped titanium dioxide (TiO2 + 2.5‒10% Cu), Cu2NiSiCr, and Cu15Ni8Sn composite materials (metal lattices filled with ceramics). The virucidal tests of the ceramic and metal powders were performed in buffered suspensions, while the surfaces of the discs were tested by swabbing. The results show that the virus titer on the TiO2 + 10% Ag ceramic and CuNi2SiCr metal discs decreased by 4 logs after 15 min of exposure to the surfaces compared to the control ceramic and steel discs. We show that SLM 3D printed pre-alloyed CuNi2SiCr filled with bioactive TiO2 + 10% Ag nanopowders and sintered by the SPS process combines the simplicity of printing with the strength and virucidal properties of Ag and Cu materials. The proposed new virucidal materials were also used for the fabrication of prototype elevator buttons.


DEPTOR as a novel prognostic marker inhibits the proliferation via deactivating mTOR signaling pathway in gastric cancer cells.
Aberrantly activated mTOR signaling pathway is commonly found in malignancies including gastric cancer (GC). DEPTOR, as a naturally occurred inhibitor of mTOR, functions in the pro- or anti-tumor manner depending on distinct tumor contexts. However, the roles of DEPTOR in GC remain largely unknown. In this study, DEPTOR expression was identified to be significantly decreased in GC tissues compared with matched normal gastric tissues, and reduced DEPTOR level was indicative of poor prognosis in patients. Restored DEPTOR expression inhibited the propagation in AGS and NCI-N87 cells, whose DEPTOR levels are low, via deactivating mTOR signaling pathway. Likewise, cabergoline (CAB) attenuated the proliferation in AGS and NCI-N87 cells via partially rescuing DEPTOR protein level. Targeted metabolomics analysis showed that several key metabolites, such as l-serine, significantly changed in AGS cells with DEPTOR restoration. These results revealed the anti-proliferation function of DEPTOR in GC cells, suggesting that restored DEPTOR expression using CAB may be a potential therapeutic approach for patients with GC.


Acute alcohol intoxication paired with aversive reinforcement: ethanol odor as a conditioned reinforcer in rat pups.
Previous research has suggested that infant rats process ethanol sensory properties during acute alcohol intoxication. The present study was designed in order to examine if alcohol odor could act as an aversive conditioned stimulus after the organism experiences the state of intoxication paired with nociceptive stimulation (footshock). In a first experiment 11-day-old pups received intragastric alcohol administration (1.5 g/kg). At different postabsorptive intervals footshock was presented (0-30, 30-60, 60-90, or 90-120 min). An explicitly unpaired control group which experienced footshock prior to the state of intoxication was also employed. All animals were subsequently tested in terms of alcohol intake and ethanol locational odor preferences. Both assessments indicated that pups which were exposed to the unconditioned peripheral stimulus 30-60 min after receiving ethanol expressed strong alcohol aversions. In a second experiment pups were exposed to footshock during this postabsorptive interval. Twenty four hours later, pups experienced ambient ethanol odor paired with soft or rough texture surfaces. Differential texture aversions were registered in experimental animals when compared with controls which suffered the state of intoxication explicitly unpaired with footshock, or unpaired presentations of ethanol odor and the tactile stimuli under consideration. These results appear to support the hypothesis concerning orosensory processing during an acute state of intoxication. Additionally it seems that the hedonic value of sensory attributes of this drug varies as a function of associative processes occurring during such a state.


High molecular weight adiponectin as a biomarker of hypertension in children and adolescents with obesity.
Lower HMW (high molecular weight) adiponectin levels are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents. However, data on HMW levels in pediatric population with hypertension are lacking. This study aimed to examine the association and predictive capacity of HMW levels, HMW/HOMA-IR, and HMW/APN ratio with hypertension in obese children and adolescents. The 299 pediatric subjects were grouped in obese hypertensive (OH), obese normotensive (ON), and normal weight normotensive (NN). Plasma concentrations of HMW were investigated by ELISA. ANOVA was used to compare study groups, and a binary logistic regression analysis was used to verify if HMW, HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, and HOMA-IR are associated to hypertension regardless obesity in children and adolescents. To compare the strength and performance of each biomarker to classify individuals with and without hypertension, the receiver-operating characteristic (ROC) curve, area under the curve (AUC), and Youden index (J) were evaluated. Both HMW plasma levels and the HMW/HOMA-IR ratio were significantly lower in the OH group when compared to the ON group (HMW: 2.00 ± 1.33 µg/mL vs 2.48 ± 1.48 µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 1.27 ± 1.2; P < 0.05) and NN weight groups (HMW: 2.00 ± 1.33 µg/mL vs 4.02 ± 1.99 µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 2.62 ± 1.86; P < 0.05). Hypertension was associated with lowest HMW (OR = 4.50; 95% CI = 1.41-15.84) and HMW/HOMA-IR (OR = 12.13; 95% CI = 2.51-92.93) regardless of obesity. However, HOMA-IR or the HMW/APN was not significant (P > 0.05). In the ROC curve analyses, the HMW and HMW/HOM-IR were more sensitive to detect hypertension in children and adolescents with obesity. Conclusion: Low levels of HMW oligomer and HMW/HOM-IR are associated with hypertension in childhood obesity. Thus, these biomarkers could be clinically useful in identifying hypertension in childhood obesity. What is Known: • HMW has previously been reported as the most biologically active isoform of adiponectin, and lower HMW concentrations are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents. • HMW/HOMA-IR ratio is a sensitive predictor for metabolic syndrome in adults. What is New: • HMW levels are associated with hypertension in children and adolescents, independently of presence of obesity. • HMW was more sensitive to detect hypertension in children and adolescents with obesity when compared to HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, or HOMA-IR.


Can gingival crevicular blood effectively screen for diabetes in Chinese patients with moderate to severe periodontitis? A pilot study.
The early diagnosis of diabetes is essential for the prevention of complications. Periodontitis has been identified as the sixth complication of diabetes and chair-side screening may improve diagnosis of diabetes. This study evaluated whether gingival crevicular blood (GCB) available during routine periodontal examination can be used to screen for diabetes in Chinese patients with moderate to severe periodontitis. Finger-stick blood (FSB) and GCB were collected from patients (18 with diabetes and 42 without diabetes) during routine periodontal probing and analyzed for glucose and hemoglobin A1c (HbA1c) levels. In the diabetic group, the mean glucose levels in GCB and FSB were 12.21 ± 3.86 and 12.61 ± 4.19 mmol/L respectively, while those of the non-diabetic group were 6.14 ± 0.85 and 6.15 ± 0.87 mmol/L, respectively. The average HbA1c values of the diabetic group were 7.72% ± 1.71% and 7.89% ± 1.78% in GCB and FSB, respectively, while those of the non-diabetic group were 5.28% ± 0.31% and 5.23% ± 0.32%, respectively. Highly significant correlations were found between GCB and FSB glucose levels (r = 0.993 for the diabetic group, and r = 0.977 for the non-diabetic group) and between GCB and FSB HbA1c levels (r = 0.977 for the diabetic group, and r = 0.829 for the non-diabetic group). Our study results indicate that GCB available during routine periodontal examination may be acceptable for the analyses of blood glucose and HbA1c levels. The approach is suitable for screening undiagnosed diabetes in a dental setting.


Online support of patients and survivors of cancer.
To provide information on current use of a type of online support, Internet cancer support groups, by patients and survivors of cancer, and the factors that influence their usages. The literature systematically searched and retrieved through the PUBMED, PsycInfo, and CINAHL databases. This literature review indicated five factors that influence the use of Internet cancer support groups (disease, background, cultural, need, and Internet use). Health care providers need to give careful attention to multiple factors that may influence the use of online support.


A single-centre study of treatment outcomes and survival in 120 patients with peripheral T-cell non-Hodgkin's lymphoma.
We conducted a retrospective study of treatment outcomes and survival in 120 consecutive, unselected patients with peripheral T-cell non-Hodgkin's lymphoma, presenting at a single centre over a 20-year period. Cases met the criteria of the Revised European-American Lymphoma (REAL) Classification and patients with peripheral T-cell lymphoma of the following subtypes were included: anaplastic large T-cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AILD), peripheral T-cell lymphoma unspecified (PTCLu), and intestinal T-cell lymphoma (ITCL). The study population consisted of 120 patients with a presenting diagnosis of peripheral T-cell lymphoma. Cases that had been previously confirmed as T-cell lymphoma at formal pathology review were identified from the lymphoma database of this institution. Staging investigations, treatment type and outcomes were taken from patient records. For each subtype, clinical characteristics, response to initial treatment, duration of response and any subsequent relapse were recorded. Overall, relapse, and progression-free survival figures were calculated. The ALCL group had the best response rate to first line treatment 19 of 22 (86 percent) while the AILD group had the lowest response 12 of 29 (41 percent). Relapse rates were PTCLu 13 of 35 (37 percent), ITCL 10 of 34 (29 percent), ALCL 6 of 22 (27 percent) and AILD 7 of 29 (24 percent). In terms of median overall survival, a significantly superior survival was demonstrated for the ALCL group (7.05 years) compared to the remaining three groups. The ALCL group had the lowest risk of death while the ITCL group had the highest risk (hazard ratio: 2.82). Five-year survival rates were estimated to be ALCL 60 percent, PTCLu 40 percent, AILD 30 percent and ITCL 25 percent. This single-centre study demonstrated different outcomes for each group with significant differences in overall survival rates. These findings support the clinical utility of the REAL lymphoma classification in respect to the PTCL subgroups included in this study.


Identification of novel metabolic signatures potentially involved in the pathogenesis of COPD associated pulmonary hypertension.
Chronic obstructive pulmonary disease (COPD) associated pulmonary hypertension (COPD-PH), one of the most prevalent forms of PH, is a major burden on the healthcare system. Although PH in COPD is usually of mild-to-moderate severity, its presence is associated with shorter survival, more frequent exacerbations and worse clinical outcomes. The pathophysiologic mechanisms responsible for PH development in COPD patients remain unclear. It is envisioned that a better understanding of the underlying mechanism will help in diagnosis and future treatment strategies. The present study aims to determine metabolomic alterations in COPD-PH patients as compared to healthy controls. Additionally, to ensure that the dysregulated metabolites arise due to the presence of PH per se, an independent COPD cohort is included for comparison purposes. Paired serum and exhaled breath condensate (EBC) samples were collected from male patients with COPD-PH (n = 60) in accordance with the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines. Age, sex and BMI matched healthy controls (n = 57) and COPD patients (n = 59) were recruited for comparison purposes. All samples were characterized using 1H nuclear magnetic resonance (NMR) spectroscopy. Fifteen serum and 9 EBC metabolites were found to be significantly altered in COPD-PH patients as compared to healthy controls. Lactate and pyruvate were dysregulated in both the biofluids and were further correlated with echocardiographic systolic pulmonary artery pressure (sPAP). Multivariate analysis showed distinct class separation between COPD-PH and COPD. The findings of this study indicate an increased energy demand in patients with COPD-PH. Furthermore, both lactate and pyruvate correlate with sPAP, indicating their importance in the clinical course of the disease.


Long-term career transition in the surgical workforce of Japan: a retrospective cohort study using the nationwide survey of physicians data from 1972 to 2006.
A surgical workforce is essential for providing surgical services to the community. However, little is known about surgeons' career changes in circumstances where physicians can freely choose their specialty. Differing career transitions among surgical specialties were hypothesized. Longitudinal data were obtained for all physicians in Japan, giving a total of 4,302,844 items of data (for 390,368 physicians) from 1972 to 2006. Descriptive statistics for all physicians and surgeons were calculated in 1976, 1986, 1996, and 2006. "Active surgeons" (working at hospitals), "primary care surgeons" (working at clinics), and "retired surgeons" were analyzed among physicians licensed in 1972, 1982, and 1992 for the subspecialties of general surgery, orthopedic surgery, neurosurgery, urology, and "other" surgeries. Survival analysis and Cox's proportional hazard analysis were conducted to examine factors affecting career changes. During the study period, the greatest change was observed in the increased number of surgeons per 100,000 physicians. The percentage of female surgeons and surgeons registered in a surgical subspecialty also increased greatly. Significant differences, by sex, age, and subspecialty, were shown in survival analyses for surgeons' career changes in the transition from active surgeons to primary care surgeons or retired surgeons. Surgical specialty was still a significant factor for predicting career transition, even after adjustment for the surgeons' characteristics. The current study elucidated the differences in career transitions among surgical specialties. Given the observed findings, policy makers should consider more detailed and effective measures for retaining surgeons in active practice.


Impact of Scaling and Periodontal Treatment during Pregnancy on the Risk of Adverse Birth Outcomes.
Adverse pregnancy outcomes (APOs) are associated with periodontal disease owing to the induction of a chronic systemic inflammatory response. Hence, knowledge of periodontal status during pregnancy is important in order to reduce the risk of APOs. The aim of this study was to compare the risk of APOs in women with and without periodontal disease to ascertain whether regular scaling performed prior to pregnancy improves the risk of APOs. This case-control study enrolled1,386,887 pregnant women from the National Health Insurance Research Database who gave birth to their first child between 1 January 2004 and 31 December 2014. The study population included mothers who gave birth to low birth weight (LBW) and non-LBW newborns, totaling 86,958 and 1,299,929, respectively. Scaling and periodontal emergency treatment during and before pregnancy were assessed. Univariable and multivariable logistic regression analyses were performed to identify the associations between periodontal treatment and LBW risk. Compared with the comparison cohort, the pregnant women who didnot have periodontal emergency treatment or scaling treatment during pregnancy exhibited a significantly increased risk of LBW than those who had treatment. Women who underwent scaling within the2 years before pregnancy or during pregnancy had a lower risk of delivering a LBW baby (odds ratio (OR), 0.93; 95% confidence interval (CI), 0.91-0.94). In the normal group, the mothers who had periodontal emergency treatment within the2 years before pregnancy or during pregnancy had a higher risk of delivering a LBW baby (OR, 1.05; 95% CI, 1.02-1.08). In those who had scaling treatment, a lower risk of delivering a LBW baby was noted (OR, 0.95; 95% CI, 0.93-0.97). The risk of LBW was significantly increased in women who underwent periodontal treatment, and our findings suggested that periodontal disease is an important risk factor for preterm LBW babies in an East Asian population.


Examining corruption risks in the procurement and distribution of COVID-19 vaccines in select states in Nigeria.
Public health emergencies raise significant concerns about corruption and accountability; however, these concerns can manifest in different ways across diverse locations. For instance, more developed countries with a stronger rule of law may experience more corruption in vaccine procurement, whereas developing countries may experience more corruption at the point of distribution and delivery to end users. This research focuses on corruption concerns in Nigeria, specifically examining the procurement and distribution of COVID-19 vaccines. This paper utilizes a scoping review and a qualitative research approach. Key informants (n = 40) involved in the procurement and distribution of COVID-19 vaccines across two states in Nigeria were interviewed. Findings from the scoping review were summarized, and collected data were inductively coded and analysed in themes, revealing clear examples of implementation irregularities and corruption in the country's COVID-19 vaccination processes. Vaccination programme budgeting processes were unclear, and payment irregularities were frequently observed, resulting in vaccinators soliciting informal payments while in the field. Recruitment and engagement of vaccination personnel was opaque, while target vaccination rates incentivized data falsification during periods of vaccine hesitancy. Accountability mechanisms, such as health worker supervision, vaccination data review, and additional technical support provided by donors were implemented but not effective at preventing corruption among frontline workers. Future accountability measures should be evidence-driven based on findings from this research. Personnel recruitment, contracting, budgeting, and remuneration should focus on transparency and accountability.


Efficient engraftment and viral transduction of human hepatocytes in an FRG rat liver humanization model.
Humanized liver rodent models, in which the host liver parenchyma is repopulated by human hepatocytes, have been increasingly used for drug development and disease research. Unlike the leading humanized liver mouse model in which Fumarylacetoacetate Hydrolase (Fah), Recombination Activating Gene (Rag)-2 and Interleukin-2 Receptor Gamma (Il2rg) genes were inactivated simultaneously, generation of similar recipient rats has been challenging. Here, using Velocigene and 1-cell-embryo-targeting technologies, we generated a rat model deficient in Fah, Rag1/2 and Il2rg genes, similar to humanized liver mice. These rats were efficiently engrafted with Fah-expressing hepatocytes from rat, mouse and human. Humanized liver rats expressed human albumin and complement proteins in serum and showed a normal liver zonation pattern. Further, approaches were developed for gene delivery through viral transduction of human hepatocytes either in vivo, or in vitro prior to engraftment, providing a novel platform to study liver disease and hepatocyte-targeted therapies.


Characterization of the complete chloroplast genome of basswood (Tilia mongolica maxim.).
Herein, we report the complete chloroplast genome of Tilia mongolica Maxim. from Tiliaceae. The chloroplast genome of T. mongolica is 162,804 bp, with a large single copy region of 91,255 bp, small single copy region of 20,355 bp, and two inverted-repeat regions of 25,597 bp. The chloroplast genome contains 130 genes, including 85 protein-coding, 8 rRNA, and 37 tRNA. The total GC content is 36.46%. The phylogenetic analysis of T. mongolica showed a relatively close relationship with Tilia taishanensis.


Topographical distribution of trabecular bone strength in the human os calcanei.
Mechanical properties of twenty human os calcanei were determined by uniaxial compression testing of bone specimens from facies articularis talaris posterior, facies articularis cuboidea, and tuber calcanei. Specimens were taken oriented perpendicular to the planes of the facies articularis, and in tuber along the presumed loading axis throughout the gait cycle. Young's modulus and strength at facies articularis cuboidea and facies articularis talaris posterior were about three times those at the tuber calcanei. The variation of the relationship between Young's modulus and apparent density indicated differences in the orientation of the trabecula, in relation to the direction of evaluation between these locations. A more detailed analysis of the topographical variation of strength within each location was made using penetration testing of a further nineteen specimens. The results of both types of measurements indicated that the major part of the load during walking is carried by facies articularis talaris posterior and facies articularis cuboidea.


Characterization of the ATP-binding cassette transporter gene expression profile in Y79: a retinoblastoma cell line.
Chemotherapy failure was reported in treatment of retinoblastoma suggesting a role for ATP-binding cassette (ABC) proteins. Little is known about the expression pattern of ABC proteins in this cancer type. We investigated the gene expression profile of 47 ABC proteins in the human retinoblastoma cell line Y79 by TaqMan low-density array. Analysis revealed 31 ABC transporter genes expressed in this tumor cell line. Y79 cells demonstrate high gene expression of ABCA7, ABCA12, ABCB7, ABCB10, ABCC1, ABCC4, ABCD3, ABCE1, ABCF1, ABCF2, and ABCF3 (more than twofold compared to pooled RNA from different tissues). Moreover, we show that Y79 cells exhibit an active calcein efflux pointing to multidrug resistance protein (MRP)-like transporter activity. In summary, we present for the first time an ABC transporter gene expression profile in cells derived from retinoblastoma. Most of the highly expressed ABC transporter genes are typical markers of cancer cells and might exhibit potential targets for medical treatment of retinoblastoma.


Compassionate and respectful care among outpatient clients at public health facilities in Northwest Ethiopia: A mixed-methods study.
Compassionate and respectful care is a pillar for improving health-seeking behaviour. It has given much attention globally, following the concerns that healthcare often falls significantly; however, less research emphasis was paid in the last decade. Therefore, this study aims to assess compassionate and respectful care and associated factors among outpatient clients at public health facilities in Northwest Ethiopia, 2020. A facility-based quantitative cross-sectional study supplemented with the qualitative findings was conducted from 30 February to 30 March 2020. A semi-structured interviewer-administered questionnaire was used to collect the quantitative data among 593 participants. Systematic and purposive sampling techniques were used to select the quantitative and qualitative participants, respectively. A semi-structured interview guide was also employed for the qualitative data collection. Epi-Data version 4.6 and SPSS version 25 were used for data entry and analysis, respectively. The bi-variable and multivariable logistic regression model was fitted to identify the factors associated with each outcome variable (compassionate and respectful care separately). Adjusted odds ratio (AOR) with 95% confidence interval (CI) and p-value less than 0.05 were used to declare the strength and factors statistically associated with the outcome variables. Overall, 72.8% and 82.6% of the respondents experienced compassionate and respectful care, respectively. Patients attending primary or above education (AOR: 0.35; 95% CI: 0.21-0.59), attending at the hospital (AOR: 0.59; 95% CI: 0.39-0.88), new clients (AOR: 0.33; 95% CI: 0.16-0.70) and service users who had three or more visits (AOR: 0.34; 95% CI: 0.17-0.71) were negatively associated with compassionate care. On the other hand, female patients (AOR = 0.53; 95% CI: 0.32-0.87), aged over 36 years (AOR = 0.43; 95% CI: 0.20-0.90), primary or above school attended clients (AOR = 0.18; 95% CI: 0.09-0.36), waiting two or more hours (AOR = 0.28; 95% CI: 0.13-0.62), and use public or private transport access (AOR: 0.49; 95% CI: 0.29-0.83) were negatively associated with a respectful care. Compassionate and respectful care provided to the outpatient clients in public health facilities of northwest Ethiopia was high. However, our result suggests that immediate actions are necessary to address respectful and compassionate care at hospitals, and hospital management should adopt mitigation measures. Consideration should be given to foster patient-centric services and educate the health care workers about compassionate and respectful care.


Embryo transfer is equally effective at cleavage stage and blastocyst stage: a randomized prospective study.
To compare the implantation and pregnancy rates after cleavage stage embryo transfer (ET) with transfer of blastocyst-stage (days 5-6) embryos. Prospective randomized trial at an assisted reproduction unit in a university hospital. Women with six or more follicles at the last ultrasound scan before oocyte aspiration were randomized for transfer of a maximum of two embryos after 2-3 days (n = 80) or after 5-6 days (n = 64) of culture. Embryo quality, implantation and pregnancy rates were evaluated. Statistical significance was tested with the Chi-square test and Fisher's exact test. No significant difference was observed in implantation rates (21.1% versus 20.9%, respectively) and clinical pregnancy rates (36.7% versus 32.5% respectively) after blastocyst and cleavage stage transfers for the two groups. The pregnancy rate among subjects who had at least one good quality embryo transferred was 37.5% per day 2-3 ET and 60% per day 5-6 ET. The overall implantation and pregnancy rates after embryo transfer at cleavage stage and at blastocyst stage transfer were not statistically different. Women who had at least one good quality blastocyst (n = 25) had a high pregnancy rate (60% per ET). Blastocyst transfer is a good alternative for couples with many good quality embryos on day 2 after insemination.


The use of toxicokinetics for the safety assessment of drugs acting in the brain.
Pharmacological and toxicological studies undertaken on drugs that affect the brain are frequently performed in disparate species under various experimental conditions, at doses often greatly in excess of those expected to be administered to humans, and the findings are extrapolated implicitly or explicitly with scant regard to differences in the biodisposition of the drugs. Such considerations are necessary since: 1. Species; 2. Strain; 3. Gender; 4. Route; 5. Dose; 6. Frequency and time of administration; 7. Temperature; 8. Coadministration of drugs; and 9. Surgical manipulation are but some of the factors that have been shown to influence the kinetics and metabolism of drugs. This article, using MDMA and other phenylethylamines as examples, provides evidence for the need to measure the exposure of the drugs and their active metabolites in blood and brain (toxicokinetics) in order that conclusions based only on dynamic, biochemical, or histological evidence are more pertinent. Further, the combined use of toxicokinetic-dynamic modeling can lead to a better appreciation of the mechanisms involved and a more useful approach to the calculation of safety margins.


Painful subungual keratotic tumors in incontinentia pigmenti.
We report a case of dyskeratotic subungual tumor in a 28-year-old woman. The patient presented achromic lineal lesions, typical of residual incontinentia pigmenti (IP), on her legs. Furthermore, the physical examination showed anodontia of the right incisor tooth. The familial background demonstrated miscarriages of male fetuses and characteristic dental abnormalities of IP in female siblings. The patient's daughter presented a typical background of IP and dyschromic splashed lesions. Light and electron microscopic studies of the subungual tumors were made. The analogy between subungual tumors of IP and keratoacanthoma is emphasized.


An uncommon cause of nerve stimulator's malfunction during a dual guidance lumbar plexus block: A technical brief report and an algorithm for prevention of complications.
Posterior Lumbar plexus block (PLPB) combined with an ipsilateral sacral plexus block is a valuable anaesthetic technique in patients undergoing hip fracture surgery. PLPB is performed through the acoustic window of the lumbar ultrasound trident and the position of the needle tip, before injection of LA, was confirmed by observing quadriceps femoris muscle contraction to peripheral nerve stimulation (i.e., dual guidance). We report an uncommon cause of nerve stimulator malfunction that might impair block performance and promote complications. We add an algorithm to limit the risk of complications.


Prevalence and outcome of HIV infected children admitted in a tertiary hospital in Northern Tanzania.
Provider Initiated Testing and Counseling (PITC) among hospitalized children have shown to increase the probability of identifying HIV-infected children and hence be able to link them to HIV care. We aimed at determining the prevalence, clinical characteristics and outcome of HIV-infected children admitted at Bugando Medical Centre (BMC) after active provision of PITC services. A cross-sectional study with follow up at three months post enrollment was done. Children with unknown HIV status were tested for HIV infection as per 2012 Tanzanian algorithm. Questionnaires were used to collect demographic, clinical and follow up information. Data was statistically analyzed in STATA v13. A total of 525 children were enrolled in the study. Median [IQR] age was 28 [15-54] months. Males consisted of 60.2% of all the participants. HIV prevalence was 9.3% (49/525). Thirty-three (67.3%) of HIV-infected children were newly diagnosed at enrolment. Thirty-nine (79.6%) of all HIV-infected patients had WHO HIV/AIDS clinical stage four disease, 10 (20.4%) had WHO clinical stage three and none qualified in stage one or two. About 84% (41/49) of HIV infected children had severe immunodeficiency at the time of the study. Factors that were independently associated with HIV infection were, cough (OR 2.40 [1.08-5.31], p = 0.031), oral thrush (OR 20.06[8.29-48.52], p < 0.001), generalized lymphadenopathy (OR 5.61 [1.06-29.56], p = 0.042), severe acute malnutrition (OR 6.78 [2.28-20.12], p = 0.001), severe stunting (OR 9.09[2.80-29.53], p = 0.034) and death of one or both parents (OR 3.62 [1.10-11.87], p = 0.034). The overall mortality (in-hospital and post-hospital) was 38.8% among HIV-infected children compared with 14.0% in HIV-uninfected children. Within three months period after discharge from the hospital, 71.4% (25/35) of discharged HIV-infected children reported to have attended HIV clinic at least once and 60.0% (21/35) were on antiretroviral medications. PITC to all admitted children identified significant number of HIV-infected children. Mortality among HIV-infected children is high compared to HIV-uninfected. At the time of follow up about 30% of discharged HIV-infected children did not attend to any HIV care and treatment clinics. Therefore effective efforts are needed to guarantee early diagnosis and linkage to HIV care so as to reduce morbidity and mortality among these children.


Studies of osteoporosis in Japan.
Calcium deficiency appears to play a central role in the development of involutional osteoporosis, especially in Japan, where calcium intake has been traditionally low, never reaching the current recommended daily allowance (RDA) of 600 mg/d. Compromised 1,25(OH)2 vitamin D synthesis in the aging kidney and age-bound changes of the intestine itself lead to calcium malabsorption; in addition, decreasing dietary intake of fat-soluble vitamins and reduced solar exposure associated with inadequate physical activity may contribute to calcium deficiency in old age. High salt intake and increasing protein and phosphate intake tend to aggravate such a tendency. These factors appear to underlie, in part, the widespread use of vitamin D derivatives for the treatment of osteoporosis in Japan. In 1981, a large-scale, double-blind clinical trial established the superior effect of 1 alpha(OH) vitamin D3 in maintaining bone density over that of placebo. The effect of 0.5 micrograms/d 1,25-(OH)2D3 (calcitriol) in two divided doses compared favorably with that of 1 micrograms/d of 1 alpha(OH) vitamin D3 in a recently conducted multicenter, double-blind study on 596 patients with involutional osteoporosis. Spinal fracture rate was also reduced to one-half by administration of the vitamin D derivative for 1 year to 800 patients with osteoporosis.


The Diversity Bonus in Oral and Maxillofacial Surgery.
The diversity bonus theorem developed by Scott Page postulates that in specific environments, diversity is an absolute necessity to creating the most successful team. The theorem dispels the myth that institutions must choose between diversity and excellence. Within oral and maxillofacial surgery, this bonus is captured through expanded access to care, more equitable and relevant research, and attracting the best and brightest to the specialty. To capture the bonus, oral and maxillofacial surgery must invest in policy changes to admissions and hiring practices, and offer training in communication, cultural competency, and implicit bias.


Improved delivery of rate-adaptive pacing using an impedance-derived contractility sensor in high-intensity exercise: A case report.
Effective rate-adaptive pacing may be difficult in the presence of atrial fibrillation (AF), and is important during high-intensity exercise. This case presents a 74-year-old elite cyclist with AF and a biventricular pacemaker after atrioventricular (AV) node ablation. He reported sudden breathlessness due to heart rate drops, caused by breaching the artefact threshold on the minute-ventilation sensor. He was exchanged to a generator with an impedance-derived contractility sensor (closed-loop stimulation), resulting in resolution of symptoms, and no further rate drops. This is the first description of the utility of closed-loop stimulation in high-intensity exercise.


Aerobic fitness testing in 6- to 9-year-old children: reliability and validity of a modified Yo-Yo IR1 test and the Andersen test.
This study analysed the reliability and validity of two intermittent running tests (the Yo-Yo IR1 test and the Andersen test) as tools for estimating VO(2max) in children under the age of 10. Two groups, aged 6-7 years (grade 0, n = 18) and 8-9 years (grade 2, n = 16), carried out two repetitions of a modified Yo-Yo IR1 test (2 × 16 m) and the Andersen test, as well as an incremental treadmill test, to directly determine the VO(2max). No significant differences were observed in test-retest performance of the Yo-Yo IR1 test [693 ± 418 (±SD) and 670 ± 328 m, r (2) = 0.79, CV = 19%, p > 0.05, n = 32) and the Andersen test (988 ± 77 and 989 ± 87 m, r (2) = 0.86, CV = 3%, p > 0.05, n = 31). The Yo-Yo IR1 (r (2) = 0.47, n = 31, p < 0.002) and Andersen test performance (r (2) = 0.53, n = 32, p < 0.001) correlated with the VO(2max). Yo-Yo IR1 performance correlated with Andersen test performance (r (2) = 0.74, n = 32, p < 0.0001). In conclusion, the Yo-Yo IR1 and the Andersen tests are reproducible and can be used as an indicator of aerobic fitness for 6- to 9-year-old children.