Andrographolide promotes skeletal muscle regeneration after acute injury through epigenetic modulation.
Myopathy is a muscle disease in which muscle fibers do not function properly, and eventually cause severe diseases, such as muscular dystrophy. The properly regeneration of skeletal muscle plays a pivotal role to maintain the muscle function after muscle injury. The aim of this study is to determine whether andrographolide plays an effect role on regulating skeletal muscle regeneration. Mouse satellite cells, C2C12 cells and Cardiotoxin (CTX) intramuscular injection induced acute skeletal muscle injury model were used to evaluate whether andrographolide is essential for skeletal muscle regeneration. The underling mechanism detected using immunohistochemistry stain, western blot, real time PCR. Andrographolide promotes mouse skeletal muscle regeneration. In cardiotoxin induced skeletal muscle injury model, andrographolide treatment enhanced myotube generation and promoted myotube fusion. Andrographolide treatment dramatically increased expression of myotube differentiation related genes, including Desmin, MyoD, MyoG, Myomaker, Tnni2, Dmd, Myoz1 and Myoz3. For the mechanism studies, we observed that andrographolide treatment significantly promoted histone modification, such as H3K4Me2, H3K4Me3 and H3K36Me2, both in vivo and in vitro. Treatment with DZNep, a Lysine methyltransferase EZH2 inhibitor, significantly attenuated andrographolide-induced expression of Myf5, Myomaker, Skeletal muscle α-actin, MyoD and MyoG. Taken together, our data in this study demonstrate andrographolide epigenetically drives differentiation and fusion of myotube, eventually promotes skeletal muscle regeneration. This should be a therapeutic treatment for skeletal muscle regeneration after muscle damage.


Oxidative stress causes epigenetic alteration of CDX1 expression in colorectal cancer cells.
The intestine-specific transcription factor, caudal type homeobox-1 (CDX1), is a candidate tumor suppressor gene that plays key roles in regulating intestinal epithelial differentiation and proliferation. It is aberrantly down-regulated in colorectal cancers and colon cancer-derived cell lines by promoter hypermethylation. Since the effects of oxidative stress on the transcription of tumor suppressor genes are largely unknown, this study explored the epigenetic alterations that occur during reactive oxygen species (ROS)-induced silencing of CDX1 in colorectal cancer cells. Oxidative stress by hydrogen peroxide (H2O2) down-regulated CDX1 mRNA levels and protein expression in the human colorectal cancer cell line, T-84. This down-regulation was abolished by pretreatment with the ROS scavenger, N-acetylcysteine. In addition, the DNA methylation inhibitor, 5-aza-2-deoxycytidine (5-Aza-dC) markedly attenuated the decrease in mRNA and protein expression levels induced by H2O2. Moreover, methylation-specific PCR data revealed that H2O2 treatment increased CDX1 promoter methylation, and treatment with 5-Aza-dC reversed this effect, suggesting that an epigenetic regulatory mechanism triggered by ROS-induced methylation may be involved in CDX1 expression. Furthermore, H2O2 treatment resulted in up-regulation of DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1) expression and activity, and enhanced the association between DNMT1 and HDAC1. Taken together, these results suggest that ROS-induced oxidative stress silences the tumor suppressor CDX1 through epigenetic regulation, and may therefore be associated with the progression of colorectal cancer.


[Hepatoduodenal ligament teratoma followed by hypertensive syndrome of the portal vein].
A rare localization of teratoma was observed in the hepatoduodenal ligament. In a 6-year-old child, the tumor blocked the partial vein followed by the hypertensive syndrome that resulted in death.


Small-molecule theranostics in Alzheimer's disease.
Alzheimer's Disease (AD) remains one of the most challenging health-related issues for our society. It is becoming increasingly prevalent, especially in developed countries, due to the rising life expectancy and, moreover, represents a considerable economic burden worldwide. All efforts at the discovery of new diagnostic and therapeutic tools in the last decades have invariably met with failure, making AD an incurable illness and underscoring the need for new approaches. In recent years, theranostic agents have emerged as an interesting strategy. They are molecules able to simultaneously provide diagnostic information and deliver therapeutic activity, allowing for the assessment of the molecule activity, the organism response and the pharmacokinetics. This makes these compounds promising for streamlining research on AD drugs and for their application in personalized medicine. We review here the field of small-molecule theranostic agents as promising tools for the development of novel diagnostic and therapeutic resources against AD, highlighting the positive and significant impact that theranostics can be expected to have in the near future in clinical practice.


Reflecting Size Differences of Exosomes by Using the Combination of Membrane-Targeting Viscosity Probe and Fluorescence Lifetime Imaging Microscopy.
Exosomes are cell-secreted membrane-coated vesicles with their sizes variable from 30 to 150 nm. So far, there is no simple, fast, and economical way to evaluate the sizes of exosomes in living systems. Here, we put forward a hypothesis in which the sphere sizes (resulting in different curvature) may affect the local mobility/viscosity of exosome membranes. Based on this hypothesis, we propose a novel method to evaluate the exosome sizes by quantifying the membrane viscosity. For this sake, we design a membrane-targeting molecular rotor with its fluorescence lifetime sensitive to viscosity and use it under a fluorescence lifetime imaging microscope (FLIM). Through a multiple-step ultrafiltration technique, we isolate three individual size distributions (10-50, 50-100, and 100-220 nm) with exosomes from HeLa and MCF-7 cell culture media and then perform the FLIM assay on the above two groups. In both cases, we indeed find a regular pattern in which the membrane viscosity reflected by lifetime decreases with exosome sizes. We then perform the assay on exosomes from cancer cells, corresponding normal tissue cells, and serum of breast cancer patients. We find that exosomes from cancer cells have a fluorescence lifetime (larger viscosity) longer than that of normal tissue cells. The average fluorescence lifetime of exosomes from a triple-negative breast cancer patient is longer (or the viscosity is larger) than that of a HER2 positive one. Therefore, our new and simple method may hold application prospects in future cancer diagnosis.


Extraction by reversed micelles of the intracellular enzyme xylose reductase.
Xylose reductase enzyme (EC 184.108.40.206) produced by Candida guilliermondii in sugarcane bagasse was extracted by reversed micelles of N-benzyl-N-dodecyl-N-bis (2-hydroxyethyl) ammonium chloride cationic surfactant. An experimental design was employed to evaluate the influences of the following factors on the enzyme extraction: temperature, cosolvent, and surfactant concentration. A model was used to represent the enzyme recovery and fit of the experimental data. The extraction yielded a total recovery of 130%, and the purity increased 4.8-fold. This study demonstrates that liquid-liquid extraction by reversed micelles is a process able to recover and increase the enzymatic activity and purity of XR produced by C. guilliermondii.


Predicting risk for large-for-gestational age neonates at term: a population-based Bayesian theorem study.
To evaluate the prediction of large-for-gestational age (LGA) term neonates using the routine third-trimester ultrasound examination and to investigate whether the prediction could be further improved by adding information on maternal characteristics. Information on 56,792 singleton term pregnancies with a routine ultrasound examination at 32-34 weeks' gestation was retrieved from a population-based perinatal register. Estimated fetal weights (FW) were expressed as gestational age-specific standard deviation scores (Z-scores). The prediction of LGA was assessed by receiver-operating characteristics (ROC) curves, with LGA defined as birth weight Z-score > + 2. The data set with complete clinical information (n = 48,809) was divided into a development and a validation set. Using the development set, multiple logistic regression analysis was performed to identify maternal characteristics associated with LGA. The odds ratios obtained were converted into likelihood ratios. These were then applied to the validation set and the probability for LGA for each infant was estimated using the Bayesian theorem. The FW Z-score showed a high predictive ability for LGA (area under the ROC curve (AUC) 0.89 (95% CI, 0.89-0.90)). Prediction was further improved by using the model that included both FW Z-scores and maternal variables (AUC 0.91 (95% CI, 0.90-0.92)) (P for difference < 10(-6) ). The corresponding AUC for a model including maternal characteristics only was 0.74 (95% CI, 0.73-0.76). Routine third-trimester ultrasound FW estimation is effective in the prediction of LGA neonates at term. The prediction of LGA might be further improved by using a model including maternal characteristics.


Low-frequency wavelength modulation spectroscopy with D2 transition of atomic cesium by use of an external-cavity diode laser.
Low-frequency wavelength modulation spectroscopy is acquired with an external-cavity diode laser. The wavelength modulation is achieved with voltage tuning by means of scanning with the piezoelectric stepper motor, which rotates the end mirror in the laser cavity. With optimum 1-kHz frequency modulation and harmonic detection, direct absorption experiments for the 6S(1/2)(F = 4) --> 6P(3/2) transition of the cesium D(2) line were carried out. We found that 6f-harmonic detection is best here with a signal-to-noise voltage ratio of 460.


SEM analysis of sensilla on the mouthparts and antennae of Asian larch bark beetle Ips subelongatus.
The Asian larch bark beetle, Ips subelongatus, is a severe pest of larches in Northeastern China. The gustatory and olfactory systems of I. subelongatus play important roles in host location, mating, and feeding. In this study, we examined the types, distributions, and abundances of various sensilla associated with the mouthparts and antennae of I. subelongatus using scanning electron microscopy (SEM). On the mouthparts, five types of sensilla are present: sensilla trichodea (S.t.1-3), sensilla chaetica (S.c.1-3), sensilla basiconica (S.b.1-2), sensilla twig basiconica (S.tb.1-3), and sensilla placodea (S.p). S.t.3 are the most abundant sensilla subtype on the mouthparts in both sexes, while S.b.1 are the least abundant. Most sensilla on the mouthparts are located on the maxillae and labium, and the apex of each maxillary and labial palp carry the same sensilla subtypes (S.b.2 and S.tb.1-3). However, the total number of sensilla on the apex of each maxillary palp is higher than that on the labial palp. On the antennae, five types of sensilla are present: sensilla trichodea (S.t.1-3), sensilla chaetica (S.c.1-2), sensilla basiconica (S.b.1-3), Böhm bristles (B.b), and sensilla coeloconica (S.co). Antennal sensilla are mostly situated on the anterior surface of the antennal club, particularly on the two dense sensory bands. S.b.1 are the most abundant sensilla subtype on the antennae in both sexes, while S.t.1 are the least abundant. No sexual dimorphism in sensilla type or distribution on the mouthparts or antennae is observed between the sexes of I. subelongatus. However, S.t.3 (on mouthparts) and S.c.1 (on antennae) were significantly more abundant in males than in females, while more S.t.1 (on mouthparts) were observed in females than in males. Finally, the putative functions of each kind of sensilla with respect to their fine structures, distributions, and abundances on the mouthparts and antennae are discussed.


[Assessment of in vitro activity and stability of antifungal suspensions for mouthrinses: to a reappraisal of empiric practices?].
Establishment of an effective prophylaxis against oral candidiasis by local treatment is essential for immunocompromised patients. The aim of the study is to assess effectiveness and stability of antifungal suspensions for mouthrinses. The assessed suspensions are compounded by one solvent among sterile water, spring water or sodium bicarbonate associated with amphotericin B (Fungizone®) or nystatine (Mycostatine®). Two others mixes are assessed: Mycostatine®-bicarbonate and Mycostatine®-Hextril®-bicarbonate as well as the two straight antifungal. In vitro activity is tested on five Candida species (C. albicans, C. glabrata, C. krusei, C. parapsilosis, C. tropicalis) after a five minutes contact between yeasts and the assessed suspension. A galenic study is realized during 3 days. Mixes associating a polyene with sodium bicarbonate have no effectiveness on Candida albicans, others mixes shows intermediate effectiveness (the percentage of yeast growth inhibition lies between 35% and 68%). Effectiveness results of Hextril®-based mixes are not explainable because of alcohol in its composition. Spring water-based mixes must be evicted due to microbiologic contaminations after 48hours. Mycostatine®-Hextril®-bicarbonate mix is not stable during 3 days. All those mouthrinses, poorly effective, excepted on C. glabrata, should be avoided. Straight Mycostatine® shows a good antifungal effectiveness excepted on C. krusei and its use should be recommended.


Passive immunity in the prevention of rabies.
Prevention of clinical disease in those exposed to viral infection is an important goal of human medicine. Using rabies virus infection as an example, we discuss the advances in passive immunoprophylaxis, most notably the shift from the recommended polyclonal human or equine immunoglobulins to monoclonal antibody therapies. The first rabies-specific monoclonal antibodies are undergoing clinical trials, so passive immunisation might finally become an accessible, affordable, and routinely used part of global health practices for rabies. Coupled with an adequate supply of modern tissue-culture vaccines, replacing the less efficient and unsafe nerve-tissue-derived rabies vaccines, the burden of this disease could be substantially reduced.


Evaluation of community-wide interventions: the ecologic case-referent study design.
In a setting of long-standing, community-wide and generally accepted prevention activities like youth health care services in The Netherlands, evaluative research in the form of experimental studies is hardly possible. Furthermore, as most interventions will bear fruit only after several years and the effects are often described in rather vague terms, even non-experimental study designs are fraught with possible difficulties. Although a study design using aggregate data is generally considered inferior or 'incomplete', in many cases, especially in health services research, this approach can be the only one feasible to evaluate the effectiveness of preventive programmes and interventions. In this article we present the ecologic case-referent design as a potentially expedient and valid method for estimating the ecologic effect of a population-wide intervention on the outcome rate in those populations. In this case-referent design, many variables are measured at the individual level, whereas the main exposure variable is measured at an aggregate or ecologic level. Using recently published studies as an example, the advantages and drawbacks of the design are discussed using the randomised controlled trial design as the referent study design.


Introducing taxes, subsidies or both: the effects of various food pricing strategies in a web-based supermarket randomized trial.
Fiscal policies may form a solution in improving dietary intake. This study aimed to examine the effectiveness of varying taxing and subsiding schemes to stimulate healthier food purchases. A randomized controlled trial with three levels of price reduction on healthy foods (no; 25%; 50%)×three levels of price increase on unhealthy foods (5%; 10%; 25%) factorial design was used. 150 participants were randomized into one of nine conditions and were asked to purchase groceries at a web-based supermarket. Data were collected in the Netherlands in January-February 2010 and analyzed using analysis of covariance. Subjects receiving 50% discount purchased significantly more healthy foods than subjects receiving no (mean difference=6.62 items, p<0.01) or 25% discount (mean difference=4.87 items, p<0.05). Moreover, these subjects purchased more vegetables (mean difference=821 g;p<0.05 compared to no discount). However, participants with the highest discount also purchased significantly more calories. No significant effects of the price increases on unhealthy foods were found. Price decreases are effective in stimulating healthy food purchases, but the proportion of healthy foods remains unaffected. Price increases up to 25% on unhealthier products do not significantly affect food purchases. Future studies are important to validate these results in real supermarkets and across different countries.


Fifty years of headache care evolution: from a few interested doctors to certified specialists and comprehensive systems.
Headache care has evolved dramatically during the lifetime of the American Headache Society. Dr. Saper charts the most important developments and recognizes those instrumental in influencing current thought and practice.


Intravesical Mucoadhesive Hydrogel Induces Chemoresistant Bladder Cancer Ferroptosis through Delivering Iron Oxide Nanoparticles in a Three-Tier Strategy.
Bladder cancer (BCa) is the most costly solid tumor owing to its high recurrence. Relapsed cancer is known to acquire chemoresistant features after standard intravesical chemotherapy. This cancer state is vulnerable to ferroptosis, which occurs when lipid peroxides generated by iron metabolism accumulate to lethal levels. Increasing the labile iron pool (LIP) by iron oxide nanoparticles (IONPs) promises to inhibit chemoresistant BCa (CRBCa), but systemically administered IONPs do not sufficiently accumulate at the tumor site. Therefore, their efficacy is weakened. Here, we present a three-tier delivery strategy through a mucoadhesive hydrogel platform conveying hyaluronic acid-coated IONPs (IONP-HA). When instilled, the hydrogel platform first adhered to the interface of the tumor surface, sustainably releasing IONP-HA. Subsequently, the tumor stiffness and interstitial fluid pressure were reduced by photothermal therapy, promoting IONP-HA diffusion into the deep cancer tissue. As CRBCa expressed high levels of CD44, the last delivery tier was achieved through antibody-mediated endocytosis to increase the LIP, ultimately inducing ferroptosis. This three-tiered strategy delivered the IONPs stepwise from anatomical to cellular levels and increased the iron content by up to 50-fold from that of systematic administration, which presents a potential regimen for CRBCa.


Response to an Escherichia coli K88 oral challenge and productivity of weanling pigs receiving a dietary nucleotides supplement.
Dietary nucleotides, considered as antibiotics alternative, were shown to have positive effects on intestinal hyperaemia, systemic immunity, small-intestinal growth, and hepatic composition in pigs. However, there is no previous research on nucleotide supplementation in weanling pigs under an oral challenged E. coli K88. Therefore, 2 experiments were conducted to investigate the effects of dietary nucleotides on weanling pig growth performance, nutrient digestibility, fecal score, and blood profile after being orally challenged with E. coli K88. In Exp. 1, a total of 140 weanling pigs [8.33 ± 0.33 kg of body weight (BW), 28-d old] were used in this 42-d feeding trial. Pigs were distributed into 1 of 4 treatments, 5 pigs/pen (3 barrows and 2 gilts) and 7 pens/treatment. Treatments were a control basal diet (CON) or the CON supplemented with 150 (R150), 220 (R220), or 275 (R275) mg/kg to give the three treatment diets. In Exp. 2, 28 weanling pigs (BW = 8.40 ± 0.22 kg, 28-d old) were distributed into 1 of 4 treatments to give 1 pig/pen and 7 pens/treatment in a 42-d feeding and challenge trial. Dietary treatments were the same as in Exp. 1. On d 14, all those pigs (BW = 13.3 ± 0.15 kg, 42-d old) were orally dosed with 1.5 mL suspension containing 10(10) cfu/mL of E. coli K88. Twenty four hours after challenge, blood and excreta samples were collected from each pigs for analysis. Fecal scores were measured on d 7, 14, 21, and 28 of the study. In Exp. 1, overall BW, average daily gain (ADG), gain/feed (G/F) ratio, and nutrient digestibilities were lower (P < 0.05) in CON group compared with the nucleotides fed pigs. In Exp. 2, after challenge, IgA, IgM, and IGF-I were higher (P < 0.05) in the nucleotide groups compared with CON. However, the nucleotide groups had lower (P < 0.05) cortisol and TNF-α compared with CON. Fecal E. coli counts and fecal score for the nucleotide groups were lower (P < 0.05) than for CON. In conclusion, dietary nucleotides supplementation could improve growth performance, nutrient digestibility, immune status, microbial balance, reduce diarrhea, and provide protection against enterotoxigenic E. coli K88 infection in weanling pigs.


Antiplasmodial and cytotoxic activity of galipinine and other tetrahydroquinolines from Galipea officinalis.
The antimalarial and toxicological properties of four tetrahydroquinoline alkaloids from Galipea officinalis trunk bark were studied. Crude extracts and pure alkaloids were tested for in vitro antimalarial activity on Plasmodium falciparum. The IC50 were evaluated after 24 and 72 h contact between compounds and the parasite culture, and ranged from 1.8 to 40 microg/ml for the chloroquine-sensitive strain (CQS) and from 0.09 to 38 microg/ml for the chloroquine-resistant strains (CQR). Galipinine yielded the best antimalarial effect (IC50: 0.09 - 0.9 microg/ml on CQR strain) and this compound interacted particularly between the 32(nd) and the 40(th) hour of the P. falciparum erythrocytic cycle. The cytotoxicity of the extracts and pure tetrahydroquinoline alkaloids was assessed on the HeLa cell line and showed IC50 values ranging from 5.8 to above 50 microg/ml.


Reverse Breech Extraction Vs Head Pushing For Delivery Of Deeply Impacted Fetal Head In Emergency Caesarean Section.
Obstructed labour is considered a negligible component of maternal mortality in developed countries but it is a major mortality burden in developing countries. This study was done to compare maternal outcome associated with reverse breech extraction and vaginal head pushing method for the deeply impacted foetal head in emergency caesarean section. It was done at the Department of Obstetrics and Gynaecology Military Hospital, Rawalpindi from May to Nov 2014. A total of 110 patients meeting our inclusion criteria were randomly divided into two groups, i.e., Group A (delivered by reverse breech extraction) and Group B (delivered by hand push method). Patient demographic data and maternal outcomes were compared among both groups. Data was analysed using SPSS-21. Mean age of the patients was 27.51±6.60 and 27.91±6.85 years in Group-A and B respectively with an age range of 15-45 years while the mean gestational age was 39.93±0.87 weeks and 40.05±0.62 weeks in Group A and B respectively. 27 (49.1%) from Group A and 26 (47.3%) from Group B were primigravida. Extension of uterine incision was observed in 5 (9.1%) patients of group-A and 25 (45.5%) patients of group-B. Mean operative duration was 42.47±3.00 min and 51.73±2.14 min in Group A and B respectively. More blood loss was observed in Group-B when compared with Group-A (1542.36±188.27 ml vs 1090.36±130.08 ml). A statistically significant difference was seen in both groups regarding maternal outcomes (p<0.001). Reverse breech extraction for delivery of deeply impacted foetal head during the emergency caesarean section is a safe and quick technique as compared to the push method.


Progesterone to ovariectomized mice enhances cognitive performance in the spontaneous alternation, object recognition, but not placement, water maze, and contextual and cued conditioned fear tasks.
Research on how steroid hormones mediate mnemonic processes have focused on effects of 17beta-estradiol (E(2)); yet, progesterone (P(4)) co-varies with E(2) across endogenous hormonal milieu, and itself may influence cognitive processes. We investigated the hypothesis that acute P(4) treatment enhances cognitive performance compared to vehicle. Ovariectomized (OVX) c57/BL6J mice were randomly assigned to be subcutaneously injected with oil vehicle or P(4) (10mg/kg). Mice were trained in the spontaneous alternation, object recognition, object placement, water maze, or fear conditioning tasks, and injected with vehicle or P(4) before training or immediately post-training, and then were tested 1, 4, or 24h later. The data obtained from these experiments supported our hypothesis. P(4) increased the percentage of spontaneous alterations made in a T-maze more so than did vehicle. P(4), compared to vehicle, increased the percentage of time spent exploring the novel object in the object recognition task, but did not alter performance in the object placement task. P(4), compared to vehicle, decreased latencies to reach the location in the water maze where the platform had been during training in a probe trial, but did not alter performance in the control, cued trial. Compared to vehicle, P(4) treatment increased freezing in contextual and cued fear testing. Thus, acute P(4) treatment to OVX mice can improve cognitive performance across a variety of tasks.


Three cases of platelet alloimmunisation associated with the presence of a novel platelet-specific antibody.
In three cases of platelet alloimmunisation, a platelet-specific alloantibody was detected which could not be classified within the known human platelet alloantigen or HLA systems. The first case was of a family in which two siblings suffered neonatal alloimmune thrombocytopenia at birth. In the second case, the newborn was suffering from phocomelia with hypoplastic thrombocytopenia. The third case was a male who became refractory to transfusions of HLA-matched platelets after a related bone marrow transplantation. The serum samples were investigated by: enzyme-linked immunosorbent assay, platelet suspension immunofluorescence test (PSIFT), monoclonal antibody immobilisation of platelet antigens assay (MAIPA), and by the lymphocytotoxicity test. The antibody gave positive reactions with 26% of normal donor platelets. Surprisingly, no platelet-specific antibody was detected by PSIFT or by MAIPA and there was no evidence found to support classifying the antibody within the HLA system. The reactivity pattern of the antibody detected and the clinical presentation of the three cases described, strongly suggest the presence of an additional platelet-specific alloantigen system.


Metabolic disturbances in cystinuria.
Metabolic investigations were made in 21 cystinuric patients. The results showed a low output of urinary phosphorus and an increase of plasma IgG. These findings and the presence of uric acid in the urine, even in normal values, could play an important role in pathogenesis and stone formation, and also in cystinuria.


External reversible control of recognition behavior of alpha-peptide ribonucleic acid (alpha-PRNA) through anti-syn orientational switching of the nucleobase induced by borate esterification of the cis-2',3'-diol.
A novel nucleic acid model using peptide ribonucleic acid (PRNA), which contains 5'-amino-5'-deoxypyrimidine ribonucleoside as a recognition site for nucleic acids, has been designed, synthesized and applied to the external reversible control of recognition behavior of the complementary polynucleotide through the orientational switching of the nucleobase induced by borate.


Pulp ECM-derived macroporous scaffolds for stimulation of dental-pulp regeneration process.
Recent studies suggest xenogeneic extracellular matrices as potential regenerative tools in dental pulp regeneration. This study aimed to fabricate and characterize a novel three-dimensional macroporous pulp-derived scaffold that enables the attachment, penetration, proliferation and differentiation of mesenchymal stem cells. Bovine pulp was decellularized and characterized with histological and DNA content methods. This scaffold was prepared using finely milled lyophilized decellularized pulp extracellular matrix (ECM) digested with pepsin. Three different concentrations of ECM (1.50, 2.25 and 3.00mg/ml) were freeze-dried and were tested with/without chemical crosslinking. The specimens were subjected to physicochemical characterization, cell viability and quantitative real time polymerase chain reaction assessments with human bone marrow mesenchymal stem cells (hBMMSCs). All scaffolds were subcutaneously implanted in rats for two weeks and histological and immunostaining analyses were performed. Histological and DNA analysis confirmed complete decellularization. All samples demonstrated more than 97% porosity and 1.50mg/ml scaffold demonstrated highest water absorption. The highest cell viability and proliferation of hBMMSCs was observed on the 3.00mg/ml crosslinked scaffolds. The gene expression analysis showed a significant increase of dmp-1 and collagen-I on 3.00mg/ml crosslinked scaffolds compared to the other scaffolds. Histological examination of subcutaneous implanted scaffolds revealed low immunological response, and enhanced angiogenesis in cross-linked samples compared to non-crosslinked samples. The three-dimensional macroporous pulp-derived injectable scaffold developed and characterized in this study displayed potential for regenerative therapy. While the scaffold biodegradability was decreased by crosslinking, the biocompatibility of post-crosslinked scaffold was significantly improved.


How to avoid premature decay of your macromolecular crystal: a quick soak for long life.
Radiation damage to biological samples is currently one of the major limiting factors in macromolecular X-ray crystallography, since it severely and irreversibly affects the quality of the data that can be obtained from a diffraction experiment. However, radiation damage can effectively be reduced by utilizing the electron and radical scavenging potential of certain small-molecule compounds. We propose an approach to protect macromolecular crystals prior to data collection by quick soaking with scavengers. This, in favorable cases, can more than double crystal lifetime in the X-ray beam. The approach has the potential to yield diffraction data of superior quality and hence to increase the amount of high-quality diffraction data and of structural information attainable from a single crystal.


Effect of gender on in vivo cartilage magnetic resonance imaging T2 mapping.
To determine if gender is a significant variable for in vivo magnetic resonance imaging (MRI) T2-mapping of knee articular cartilage in young asymptomatic volunteers. Cartilage MRI T2 mapping was performed in a young healthy population consisting of seven male and 10 female volunteers, 22 to 29 years of age. High-resolution in vivo T2 maps were obtained of patellar, tibial, and weight-bearing femoral articular cartilage. Spatial dependency of cartilage T2 between groups was evaluated through a comparison of cartilage T2 as a function of normalized distance from bone. Bulk cartilage T2 values were similar at all three anatomic sites, and between male and female volunteers. All volunteers demonstrated similar spatial variation in cartilage MRI T2 values, with a minimum located in the radial zone and increasing T2 values toward the articular surface. There was no difference in spatial dependency of cartilage T2 between males and females. In young, healthy volunteers, the magnitude and spatial dependency of cartilage T2 does not differ with gender.


Evaluation of intralesional Candida antigen in diabetic patients with multiple warts.
Treatment of warts in diabetic patients with ablative modalities poses a significant risk owing to increased possibility of secondary infection, slow healing, and recurrence. Intralesional immunotherapy has gained popularity in the treatment of warts due to its proven efficacy and good tolerability compared with destructive methods. To evaluate the intralesional Candida antigen injection for the treatment of multiple warts in diabetic patients. Fifty diabetic patients with multiple genital/nongenital warts were divided into two groups. The first group (30 patients) received intralesional Candida antigen, and the second group (20 patients) had intralesional saline as control. The treatments were injected into the largest wart every 2 weeks until complete clearance of warts or for a maximum of five sessions. Complete clearance of warts was observed in 80% of the diabetic patients in the Candida antigen group compared with 15% in the control group (P < .001). Side effects to Candida antigen included pain during injection in all patients, flu-like symptoms, and localized reaction at the injection site in few patients. Intralesional Candida antigen injection can be a promising effective and safe therapeutic option for the treatment of warts in diabetic patients.


Heterogeneity of the serine synthetic pathway in Entamoeba species.
Phosphoserine phosphatase (PSP) catalyzes the third step of the phosphorylated serine biosynthetic pathway, and occurred multiple times in evolution, while enzymes catalyzing the first and second steps in the pathway have single respective origins. In the present study, we examined the existence of PSP among genus Entamoeba including a human enteric parasite, Entamoeba histolytica. E. histolytica as well as majority of Entamoeba species have the first and second enzymes, but lacks PSP. In contrast, a reptilian enteric parasite, Entamoeba invadens possesses canonical PSP. Thus, there are variations in the existence of the serine biosynthetic ability among Entamoeba species.


Early and late results following repair of partial atrioventricular (AV) canal.
Since 1961, 35 patients have undergone correction of partial AV canal. The mean age was 9.8 years (2 to 56 years). At cardiac catheterization, the ratio of pulmonary to systemic blood flow was greater than 2.5: 1 in 26 patients (74%) while pulmonary artery pressure was greater than 30 mmHg in 18 patients (51%). Mitral regurgitation was mild in 14 patients, moderate in 8 and severe in 3. The defect was closed with a patch in all patients. Mitral valvuloplasty was performed in 23 patients (68%) and no patient required valve replacement. There were no hospital or late deaths. Postoperatively, 22 patients were asymptomatic (NYHA I) while 13 were class II. There was no progression of mitral regurgitation in 8 years mean follow-up.


Effect of exercise training on insulin sensitivity, mitochondria and computed tomography muscle attenuation in overweight women with and without polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is an insulin resistant (IR) state. Increased skeletal muscle lipid content and impaired mitochondrial biogenesis have been implicated in the pathogenesis of IR. We investigated whether differences in these variables explain the IR of women affected by PCOS and whether improvements in IR with exercise are reflected by changes in these variables. Sixteen PCOS and 13 non-PCOS overweight women were assessed, and eight PCOS and seven non-PCOS women were reassessed after 12 weeks of moderate and vigorous exercise training. Outcomes included insulin sensitivity (glucose infusion rate [GIR]), skeletal muscle gene expression and protein abundance, enzyme activity of selected mitochondrial components, and computed tomography (CT) attenuation-estimated muscle lipid. GIR was lower in women with PCOS versus those without (p = 0.01) and increased with exercise in both groups. Baseline CT muscle attenuation suggested a trend to less muscle lipid in PCOS, which increased with exercise training, with a difference in the change in muscle lipid (p = 0.01, age-corrected), compared with non-PCOS women. GIR correlated with PGC1A gene expression across the whole group; skeletal muscle expression of mitochondrial biogenesis markers was not different between groups at baseline, or after training. Neither lipid changes nor mitochondrial changes correlated with changes in GIR. Differences in IR in women with and without PCOS were not explained by differences in skeletal muscle lipid or mitochondrial parameters. Improvements in IR with exercise were dissociated from mitochondrial parameters. CT muscle attenuation suggested a differential capacity of PCOS muscle to store lipid compared with non-PCOS. Clinicaltrials.gov ISRCTN84763265. National Health & Medical Research Council (Grant number 606553), Monash University and The Jean Hailes Foundation.


Ventricular Arrhythmias and Sudden Death Following Percutaneous Pulmonary Valve Implantation in Pediatric Patients.
Reports have suggested a transient increase in ventricular ectopy early after percutaneous pulmonary valve implantation (PPVI). Little is known about the potential for more serious ventricular arrhythmias (VA) in children who undergo PPVI. We sought to evaluate the incidence of severe VA following PPVI in a pediatric population and to explore potential predictive factors. A retrospective cohort study was conducted of patients who underwent PPVI under 20 years of age in our institution from January 2007 to December 2019. The primary outcome of severe VA was defined as sustained and/or hemodynamically unstable ventricular tachycardia (VT), inducible sustained VT, or sudden death of presumed arrhythmic etiology. A total of 21 patients (mean age 16.2 ± 2.1 years; 66.7% male) underwent PPVI. The majority of patients (N = 15; 71.4%) had tetralogy of Fallot (TOF) or TOF-like physiology, with the most common indication being pulmonary insufficiency (N = 10; 47.6%). During a median follow-up of 29.6 months (IQR 10.9-44.0), severe VA occurred in 3 (14.3%) patients aged 15.6 (IQR 14.7-16.1) a median of 12.3 months (IQR 11.2-22.3) after PPVI. All events occurred in patients with TOF-like physiology following Melody valve implant. In conclusion, severe VA can occur long after PPVI in a pediatric population, particularly in those with TOF-like physiology. Further studies are required to elucidate underlying mechanisms and assess strategies to mitigate risks.


Short-chain fatty acids (SCFAs) as potential resuscitation factors that promote the isolation and culture of uncultured bacteria in marine sediments.
Many marine bacteria are difficult to culture because they are dormant, rare or found in low-abundances. Enrichment culturing has been widely tested as an important strategy to isolate rare or dormant microbes. However, many more mechanisms remain uncertain. Here, based on 16S rRNA gene high-throughput sequencing and metabolomics technology, it was found that the short-chain fatty acids (SCFAs) in metabolites were significantly correlated with uncultured bacterial groups during enrichment cultures. A pure culture analysis showed that the addition of SCFAs to media also resulted in high efficiency for the isolation of uncultured strains from marine sediments. As a result, 238 strains belonging to 10 phyla, 26 families and 82 species were successfully isolated. Some uncultured rare taxa within Chlorobi and Kiritimatiellaeota were successfully cultured. Amongst the newly isolated uncultured microbes, most genomes, e.g. bacteria, possess SCFA oxidative degradation genes, and these features might aid these microbes in better adapting to the culture media. A further resuscitation analysis of a viable but non-culturable (VBNC) Marinilabiliales strain verified that the addition of SCFAs could break the dormancy of Marinilabiliales in 5 days, and the growth curve test showed that the SCFAs could shorten the lag phase and increase the growth rate. Overall, this study provides new insights into SCFAs, which were first studied as resuscitation factors in uncultured marine bacteria. Thus, this study can help improve the utilisation and excavation of marine microbial resources, especially for the most-wanted or key players. The online version contains supplementary material available at 10.1007/s42995-023-00187-w.


Relation between estrogen receptor concentration and clinical and histological factors: their relative prognostic importance after radical mastectomy for primary breast cancer.
After modified radical mastectomy, 490 primary breast cancer patients were followed for a median of 75 months. Bloom grade was measured in 340 patients and ER status in 341. Follow-up of these patients has yielded the following results: (a) The value of traditional indices has been reaffirmed. (Cox's multivariate analysis identified, in order of decreasing importance, the number of invaded lymph nodes, the initial tumor size and the histological grade. Other variables were found to be of lesser importance and were correlated with the three main indices.) (b) The value of ER status disappeared after more than 3 years of follow-up. (c) ER positive patients fared better after recurrence. This was interpreted as being a consequence of their responsiveness to hormonal treatment.


The expression of CD44v6 in colon: from normal to malignant.
CD44v6, an integral transmembrane protein belonging to a family of adhesion molecule receptors, plays an important role in tumor growth, progression and metastasis. The purpose of this study was to evaluate the expression of CD44v6 in normal, hyperplastic, adenomatous, and malignant colonic epithelium and to determine its correlation with tumor pathologic stage and lymph node metastasis. We examined the immunohistochemical expression of CD44v6 in normal colonic tissue (n = 25), hyperplastic polyps (n = 45), tubular adenomas (n = 57), tubulovillous adenomas (n = 25), villous adenomas (n = 9), adenocarcinomas stage I (n = 26), adenocarcinomas stage III (n = 26), and lymph node metastasis (n = 26). The percentage of positive cells and the staining intensity were assessed and scored. Statistical analysis was performed using logistic regression and McNemar test. All normal colonic tissue and hyperplastic polyps showed CD44v6 staining confined to the base of the crypt. In tubular adenomas, the dysplastic surface adenomatous epithelium expressed CD44v6 in 49 (86%) cases. CD44v6 was expressed in the glandular areas of tubulovillous adenomas in 21 (84%) cases and in the villous portion in 18 (72%) cases. All villous adenomas expressed CD44v6. CD44v6 was expressed in 23 (88%) cases of stage I adenocarcinomas, in 24 (92%) cases of stage III adenocarcinomas, and in 9 (35%) cases of metastatic adenocarcinomas. We concluded that the gain of CD44v6 expression in premalignant and malignant colonic lesions suggests that CD44v6 may be functionally involved in the adenoma-to-carcinoma progression. CD44v6 did not correlate to tumor pathologic stage and is lost during the acquisition of migratory function by metastatic tumor cells.


In Vitro Cytotoxicity and Oxidative Stress Evaluation of Valerian (Valeriana officinalis) Methanolic Extract in Hepg2 and Caco2 Cells
Traditional treatment methods are becoming popular and commonly used in many societies and have become the first treatment option for most people. While some of these methods are helpful, they can interact with medications the patient is taking for another disease and cause a variety of life-threatening risks. Valerian (catweed) plant is used in traditional medicine as a sleep aid due to its sedative effects. Valerian may also exert anticancer effect in vitro. In this study, the cytotoxicty and oxidative stress effects of valerian root extract were evaluated in human liver hepatocellular carcinoma (Hepg2) and human colorectal adenocarcinoma (Caco2) cell lines. The cytotoxicity was evaluated via the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Total reactive oxygen species analysis was performed via a 2',7'-dichlorodihydrofluorescein diacetate assay in flow cytometry. Inhibition concentration 50 values were calculated as 936.6 and 1097.5 µg/mL in the Hepg2 and Caco2 cell lines, respectively. It was observed that valerian root extract did not induce oxidative stress in HepG2 and Caco2 cell lines. These results indicate that the use of valerian root extract as an alternative method in cancer treatment may not be effective and may cause a risk for public health. On the other hand, it may be safe at recommended tolerated concentrations since it does not cause oxidative stress.


Selective pressure governs the composition, antibiotic, and heavy metal resistance profiles of Aeromonas spp. isolated from Ba River in Northwest China.
The selective pressure of the living surroundings is a key factor in the development of resistance profiles in pathogenic bacteria such as Aeromonas spp. In this study, Aeromonas species were isolated from the Ba River, and their composition, resistance profiles to antibiotics, and heavy metals (HMs) were investigated. The discovery revealed that selective pressure altered the diversity of Aeromonas spp., with Aeromonas veronii being more adaptable to contaminated waters. Long-term exposure to antibiotics or HMs exerts persistent selective pressure on Aeromonas species, leading to the increase in multiple antibiotic resistance (MAR) index and multidrug-resistant (MDR) strains. Furthermore, HMs could drive the co-selection of antibiotic resistance via co-resistance or cross-resistance. blaTEM, blaSHV, blaCTX-M, sul1, czcA, mexA, and mexF were detected at high frequencies in Aeromonas species. Among these resistance phenotypes conferred genes, blaTEM may be intrinsic in the genome of Aeromonas spp., while mexA and mexF may have been acquired from surrounding environments owing to selective pressure. Resistance genes evolved as a consequence of selective pressure and have been shown to be positively correlated with their prevalence. Our study suggests that the selective pressure of living surroundings significantly contributes to the composition and resistance profiles of Aeromonas spp. in the riverine ecosystem.


Percutaneous transluminal angioplasty and stenting vs aggressive medical management on stroke or intracranial atherosclerotic stenosis: a systematic review and meta-analysis.
There are currently two main treatment strategies mainly for high-risk patients: percutaneous transluminal angioplasty and stenting (PTAS) and aggressive medical management (AMM). However, the choice between PTAS or AMM remains controversial for patients with stroke or intracranial atherosclerotic stenosis (ICAS). The investigators searched the PubMed, Web of Science, Embase, Scopus, and Cochrane library databases. Randomized controlled trial (RCT) comparing PTAS and AMM for patients with stroke or ICAS were selected. RevMan 5.3 was used to analyze the results and assess risk of bias. The primary endpoints are stroke and death within 30 days after enrollment, or ischemic stroke in the territory of the qualifying artery beyond 30 days, and entire follow-up endpoints. The secondary outcomes were the disabling or fatal stroke, and incidence of death within 3 years. Four studies, 989 patients were included in this article. The AMM group was superior in the entire follow-up endpoint (OR 0.56; 95% CI 0.40, 0.79). The AMM also better in primary endpoint within 30 days (OR 0.32; 95% CI 0.17, 0.61). There was no significant difference beyond 30 days (OR 1.08; 95% CI 0.63, 1.86). The remaining outcomes, such as stroke and death, were not significantly different (P > 0.05). This meta-analysis shows AMM is significantly more effective than PTAS in subjects with ICAS due to the high rate of periprocedural stroke (OR 0.32; 95% CI 0.17, 0.61) and stroke during the entire follow-up (OR 0.56; 95% CI 0.40, 0.79) associated with PTAS. Furthermore, PTAS offers no additional benefits over AMM beyond 30 days (OR 1.08; 95% CI 0.63, 1.86).


International exchange programs in dermatology: a prescription for the present, a hope for the future.
Little has been written about the various types and availability of international exchange programs in dermatology. These opportunities comprise medical student electives, mentorships for dermatology residents, international residencies, and clinical and research fellowships. For qualified dermatologists, there are opportunities for teaching and volunteering in emerging countries and career-development visiting fellowships to academic centers and private practices to learn specific techniques or to focus on particular areas. Exchange programs in dermatology, although minimal now, soon may be accessible to most dermatologists worldwide, thereby promoting the advancement of scientific and clinical dermatologic information. The tables summarize funding sources for these exchanges.


Objective measurement of hepatic encephalopathy by means of automated EEG analysis.
Automated analysis of the electroencephalogram as an objective measurement of hepatic encephalopathy for the individual patient was investigated. The mean dominant frequency of patients with grades 0 and 1 hepatic encephalopathy was in the normal range (greater than or equal to 6.4 Hz); grade 1 hepatic encephalopathy, however, was characterized by abnormal relative power of theta activity of more than 35%. Twelve out of 34 patients with clinical grade 0 hepatic encephalopathy also had an elevated power of theta activity and probably therefore latent hepatic encephalopathy. Patients with grades 2, 3 and 4 hepatic encephalopathy had a low mean dominant frequency (less than 6.4 Hz) and could be identified by a biphasic power spectrum (theta and delta peaks, grade 2) or by a high power of delta activity (greater than or equal to 70%, grade 3-4). We conclude that automated EEG analysis based on the parameters mean dominant frequency and the relative powers of the delta and theta band is very suitable for objective classification of hepatic encephalopathy in individual patients.


Ameliorative effect of pioglitazone on glucose induced glycation of α-crystallin: Management of complications associated with diabetic retinopathy.
The glycation and aggregation of lens proteins significantly contribute to the onset of diabetic cataracts as well as the retinopathy. The glycation exerts numerous alterations in the tertiary structural of proteins. Moreover, the covalent crosslinking of lens crystallins also contribute to the cataract formation. In this article, the effect of pioglitazone on glucose induced glycation and aggregation α-crystallin was examined. A remarkable inhibition of early glycation products (~80%) and advanced glycation products (~75%) was recorded by the treatment of pioglitazone. There was >75% recovery in biochemical marker (carbonyl content). The presence of 150 μM of pioglitazone reduced the free lysine modifications to 35%. Treatment of pioglitazone also protected the secondary structural alterations induced by glycation and inhibited the formation of protein aggregates. The interaction studies showed that pioglitazone interacted with α-crystallin via moderate binding affinity. The interaction between pioglitazone interacted and α-crystallin was energetically and entropically favourable. The complex of pioglitazone with studied protein stable in which RMSF, Rg, SASA, RMSD, and the secondary structural components was not affected. The findings show antiglycation activity of pioglitazone along with its mechanism of action highlighting the ability of drug to be possibly developed novel as glycation inhibitor.


Surgical handicraft: teaching and learning surgical skills.
Surgeons choose their profession with a strong desire to excel at manual therapeutic skills. Although we mime our mentors, we have often received the torch of technique in the absence of a systematic program to optimally develop our manual dexterity. The operating room is the ultimate arena to refine one's technical ability, but a surgical skills laboratory should assume increasing importance in introducing the trainee to the many nuances of the fine manual motor skills necessary for optimal surgical technique. Surgical educators should address the science of surgical handicraft in a manner similar to the science of preoperative and postoperative surgical principles that have been espoused over the past 40 years. Although it has been euphemistically said that "you can teach a monkey to operate," few of us have broken the process down into the basic elements to accomplish such a goal. In view of the increasing complexity of operations and equipment, the constraints on animal laboratories and teaching caseloads, and the mounting economic and medico-legal pressures, the development of optimal surgical skills should be a major objective of every surgical training program. By developing novel programs and scientifically evaluating the results of such endeavors, surgical faculties may find increased academic rewards for being a good teacher.


Sleep problems and emotional dysregulation mediate the relationship between childhood emotional abuse and suicidal behaviors: A three-wave longitudinal study.
Suicide is a major public health safety concern among youth. Childhood emotional abuse is one of the most widely recognized risk factors for suicidal behaviors. However, little is known about the role of sleep problems and emotion dysregulation in this relationship. This study is part of a large-scale health-related cohort among Chinese college students. A total of 7434 participants who completed the first three waves of data collection were used for data analysis. All participants completed questionnaires regarding childhood emotional abuse (Wave 1), sleep problems and emotional dysregulation (Wave 2), and suicidal behaviors (Wave 3). Mediation analyses with bootstrapping were conducted to investigate the mediating role of sleep problems and emotional dysregulation in the relationship between childhood emotional abuse and suicidal behaviors. The results showed that the prevalence of childhood emotional abuse and suicidal behaviors were 8.7% and 5.9%, respectively. Findings from mediation analysis showed that sleep problems and emotional dysregulation served both parallel and sequential mediating roles in the relationship between childhood emotional abuse and suicidal behaviors. All measures were based on self-report instead of objective assessments or clinical diagnostic evaluations. Psychological interventions aimed at developing healthy sleep habits and emotion regulation skills may be helpful in decreasing the risk of suicidal behaviors, especially for suicide ideators with childhood emotional abuse.


Hyperbaric oxygenation reduces long-term brain injury and ameliorates behavioral function by suppression of apoptosis in a rat model of neonatal hypoxia-ischemia.
Neonatal hypoxia-ischemia (HI) produces neurodegeneration and brain injury, and leads to behavioral and cognitive dysfunction. Hyperbaric oxygen (HBO) treatment may potentially be neuroprotective in HI injury. The aim of this study was to examine any neuroprotection by HBO treatment on long-term neurological function in the rat model of neontatal HI. Seven-day-old rats were subjected to HI or sham surgery. HBO treatment was administered (2.5 ATA for 90 min) 1h after hypoxia exposure. Sensorimotor (grip test and rota-rod) and cognitive tests (inhibitory avoidance and Morris water maze) were performed at postnatal day 28 to day 60. The extent of brain damage was determined by histological evaluation. Apoptosis, caspase-3 and apoptosis inducing factor (AIF) expression were assessed by immunohistochemistry 12, 24, and 48 h after HI. HI-treated animals had significantly worse sensorimotor and cognitive performances than those in the Sham group. HBO treatment led to significant improvements in neurobehavioral functions compared to the HI group, especially for cognitive performances. Morphological evaluation revealed a remarkable recovery of brain injury in the HBO group. Furthermore, the improvements in neurobehavioral impairments were correlated with the reduction in lesion size of the hippocampus and cerebral cortex. The proportion of apoptotic cells significantly increased with time after HI, and HBO significantly inhibited apoptotic cell death. The proportion of caspase-3 positive cells and nuclear AIF translocation increased and peaked at 24h after HI injury. HBO-treated rats showed decreased expression of these proteins compared to HI-treated animals. In conclusion, our results suggested that HBO treatment was effective in promoting long-term functional and histological recovery against neonatal HI brain injury. HBO-induced neuroprotection was associated with suppression of apoptosis by inhibiting caspase-3 and AIF-mediated pathways. Further studies evaluating its associated molecular and cellular mechanism are needed.


Altered intrinsic brain activity and functional connectivity in COVID-19 hospitalized patients at 6-month follow-up.
Although most patients can recover from SARS-CoV-2 infection during the short-term, the long-term effects of COVID-19 on the brain remain explored. Functional MRI (fMRI) could potentially elucidate or otherwise contribute to the investigation of the long COVID syndrome. A lower fMRI response would be translated into decreased brain activity or delayed signal transferring reflecting decreased connectivity. This research aimed to investigate the long-term alterations in the local (regional) brain activity and remote (interregional) functional connection in recovered COVID-19. Thirty-five previously hospitalized COVID-19 patients underwent 3D T1weighed imaging and resting-state fMRI at 6-month follow-up, and 36 demographic-matched healthy controls (HCs) were recruited accordingly. The amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity (FC) was used to assess the regional intrinsic brain activity and the influence of regional disturbances on FC with other brain regions. Spearman correlation analyses were performed to evaluate the association between brain function changes and clinical variables. The incidence of neurosymptoms (6/35, 17.14%) decreased significantly at 6-month follow-up, compared with COVID-19 hospitalization stage (21/35, 60%). Compared with HCs, recovered COVID-19 exhibited higher ALFF in right precuneus, middle temporal gyrus, middle and inferior occipital gyrus, lower ALFF in right middle frontal gyrus and bilateral inferior temporal gyrus. Furthermore, setting seven abnormal activity regions as seeds, we found increased FC between right middle occipital gyrus and left inferior occipital gyrus, and reduced FC between right inferior occipital gyrus and right inferior temporal gyrus/bilateral fusiform gyrus, and between right middle frontal gyrus and right middle frontal gyrus/ supplementary motor cortex/ precuneus. Additionally, abnormal ALFF and FC were associated with clinical variables. COVID-19 related neurological symptoms can self heal over time. Recovered COVID-19 presented functional alterations in right frontal, temporal and occipital lobe at 6-month follow-up. Most regional disturbances in ALFF were related to the weakening of short-range regional interactions in the same brain function.


Identification of the cells of origin of a central pathway which sprouts following lesions in mature rats.
Following unilateral destruction of the entorhinal cortical region of the adult rat, the denervated granule cells of the dentate gyrus are reinnervated as a result of the proliferation of a pathway from the surviving contralateral entorhinal area. The present study investigates the cells of origin of this lesion-induced pathway. Following HRP injections into the reinnervated dentate gyrus, heavily labeled cells were evident in layers II and III of the contralateral entorhinal area, in marked contrast to the pattern of labeling in normal animals, where labeled cells are restricted almost entirely to layer III. The atypically labeled cells in the operated animals were found predominantly in the dorsal half of the entorhinal area, and were concentrated in the medial most portion of layer II. These atypically labeled cells in layer II of the operated animals were an average of 16% larger than their unlabeled neighbors in the same lamina. This was not related to the loading with HRP, however, since in normal animals, cells in layer II which are labeled with HRP were no different in size than unlabeled cells. The atypically labeled cells in layer II of operated animals could also be identified at the electron microscopic level, and could be distinguished from the cells in layer III which normally project to regio superior of the contralateral hippocampal formation. While labeled cells were evident in layers II and III following injections into the reinnervated dentate gyrus, no labeled cells were found in the presubiculum or parasubiculum. In combination, these results suggest (1) the pathway which reinnervates the dentate gyrus from the contralateral entorhinal area originates predominantly, if not exclusively, from the cells in layer II, (2) these cells in layer II have the same preferential distribution within the entorhinal area as the rare lightly labeled cells which can be found contralateral to an injection in normal animals and (3) cells which participate in the reinnervation are larger than their unlabeled neighbors which presumably do not give rise to fibers which reinnervate the contralateral dentate gyrus. Since the cells in layer II which sprout following lesions can be identified at both the light and elctron microscopic level, a potentially valuable model system is available in which to analyze cellular changes during sprouting.


Artificial intelligence-based identification of octenidine as a Bcl-xL inhibitor.
Apoptosis plays an essential role in maintaining cellular homeostasis and preventing cancer progression. Bcl-xL, an anti-apoptotic protein, is an important modulator of the mitochondrial apoptosis pathway and is a promising target for anticancer therapy. In this study, we identified octenidine as a novel Bcl-xL inhibitor through structural feature-based deep learning and molecular docking from a library of approved drugs. The NMR experiments demonstrated that octenidine binds to the Bcl-2 homology 3 (BH3) domain-binding hydrophobic region that consists of the BH1, BH2, and BH3 domains in Bcl-xL. A structural model of the Bcl-xL/octenidine complex revealed that octenidine binds to Bcl-xL in a similar manner to that of the well-known Bcl-2 family protein antagonist ABT-737. Using the NanoBiT protein-protein interaction system, we confirmed that the interaction between Bcl-xL and Bak-BH3 domains within cells was inhibited by octenidine. Furthermore, octenidine inhibited the proliferation of MCF-7 breast and H1299 lung cancer cells by promoting apoptosis. Taken together, our results shed light on a novel mechanism in which octenidine directly targets anti-apoptotic Bcl-xL to trigger mitochondrial apoptosis in cancer cells.


The use of intravenous cholangiography in teaching hospitals: a survey.
Thirty academic radiology departments active in biliary imaging were surveyed to document how frequently intravenous cholangiography (IVC) was being performed. Over a 10-year period the number of examinations has decreased precipitously from approximately 1728 in 1976 to 8 in 1986. This coincides with the increased availability of alternative procedures. The availability of new contrast agents with improved diagnostic yield and decreased toxicity suggests that its use may have been prematurely abandoned.


Sequence of motor nerve terminal involvement in acrylamide neuropathy.
Acrylamide neuropathy is characterized by distal multifocal axonal degeneration. In this condition long and large myelinated fibers are affected more than sort and thin fibers. The purpose of the present study was to investigate the sequence of nerve terminal involvement. The study was limited to axons that belonged to one type of neuron, of approximately equal diameter but differing in length. Axon terminals from alpha motor neurons were investigated in five muscles from rats. The results show that the initial motor nerve terminal degeneration is widespread and not restricted to terminals of the longest axons with the largest volumes. It is suggested that the variation in degree of involvement of the motor nerve terminals is determined both by differences between endplates and the regenerative capacity of neurons.


Bump2Baby and Me: protocol for a randomised trial of mHealth coaching for healthy gestational weight gain and improved postnatal outcomes in high-risk women and their children.
Gestational diabetes (GDM) impacts 8-18% of pregnancies and greatly increases both maternal and child risk of developing non-communicable diseases such as type 2 diabetes and obesity. Whilst lifestyle interventions in pregnancy and postpartum reduce this risk, a research translation gap remains around delivering implementable interventions with adequate population penetration and participation. Impact Diabetes Bump2Baby is an implementation project of an evidence-based system of care for the prevention of overweight and obesity. Bump2Baby and Me is the multicentre randomised controlled trial investigating the effectiveness of a mHealth coaching programme in pregnancy and postpartum for women at high risk of developing GDM. Eight hundred women will be recruited in early pregnancy from 4 clinical sites within Ireland, the UK, Spain, and Australia. Women will be screened for eligibility using the validated Monash GDM screening tool. Participants will be enrolled from 12 to 24 weeks' gestation and randomised on a 1:1 basis into the intervention or control arm. Alongside usual care, the intervention involves mHealth coaching via a smartphone application, which uses a combination of synchronous and asynchronous video and text messaging, and allows for personalised support and goal setting with a trained health coach. The control arm receives usual care. All women and their children will be followed from early pregnancy until 12 months postpartum. The primary outcome will be a difference in maternal body mass index (BMI) of 0.8 kg/m2 at 12 months postpartum. Secondary maternal and infant outcomes include the development of GDM, gestational weight gain, pregnancy outcomes, improvements in diet, physical activity, sleep, and neonatal weight and infant growth patterns. The 5-year project is funded by the EU Commission Horizon 2020 and the Australian National Health and Medical Research Council. Ethical approval has been received. Previous interventions have not moved beyond tightly controlled efficacy trials into routine service delivery. This project aims to provide evidence-based, sustainable support that could be incorporated into usual care for women during pregnancy and postpartum. This study will contribute evidence to inform the early prevention of non-communicable diseases like obesity and diabetes in mothers and the next generation. Australian New Zealand Clinical Trials Registry ACTRN12620001240932 . Registered on 19 November 2020.


Hydrogen Proton Magnetic Resonance Spectroscopy (MRS) in Differential Diagnosis of Intracranial Tumors: A Systematic Review.
Meningioma, glioma, and metastases are the most common intracranial tumors in clinical practice. In order to improve the prognosis of patients, timely diagnosis and early treatment are crucial. Hydrogen proton magnetic resonance spectroscopy (1H-MRS) imaging can noninvasively display the biochemical information of tissues in vivo and has been applied to identify and diagnose intracranial tumors. We want to comprehensively evaluate 1H-MRS identify and diagnose intracranial tumors by meta-analysis. Some databases such as PubMed and Cochrane Library were used to systematically search articles that were about identifying and diagnosing intracranial tumors with 1H-MRS. Then, weighted mean difference (WMD) was used as an effect size to conduct meta-analysis. There are altogether nine articles, including 533 patients. Results of meta-analysis: The Cho/Cr and Cho/NAA ratios in the LGG group were significantly lower than those in the HGG group (WMD = -0.69, 95% CI (-0.92, -0.45), P < 0.001, WMD = -0.76, 95% CI (-1.03, -0.48), P < 0.001). The Cho/Cr ratio of tumor and peritumor in the HGG group was significantly different from that in the metastasis group (0.68, 95% CI (-1.27, 2.62), P < 0.001, WMD = 0.94, 95% CI (0.41, 1.47), P < 0.001). There was no significant difference in the tumor and peritumor NAA/Cr ratio between the HGG group and metastasis group (WMD = -0.64, 95% CI (-1.63, 0.34), P=0.31, WMD = -0.22, 95% CI (-0.59, 0.15), P=0.24). 1H-MRS can provide metabolic information of different intracranial tumors and can effectively diagnose and differentiate glioma and metastasis. 1H-MRS can also provide a reliable basis for the classification of glioma, and has certain clinical application value.


The risk and timing of acute ischemic stroke after electrical cardioversion for atrial fibrillation in Taiwan: A nationwide population-based cohort study.
There is a positive association between electrical cardioversion (ECV) and acute ischemic stroke (AIS). Although 4 weeks of anticoagulation therapy after ECV in atrial fibrillation (AF) patients is generally suggested by current guidelines to reduce the risk of AIS, limited studies have been conducted in Asian populations to determine the risk and timing of AIS after ECV for AF in recent years. Therefore, we aim to use the National Health Insurance Research Database (NHIRD) in Taiwan to determine the risk and timing of AIS after ECV for AF. The data analyzed in this nationwide population-based retrospective cohort study were obtained from the NHIRD in Taiwan. The outcome in this study was the cumulative incidence of AIS in patients with AF during 7-day and 30-day follow-up periods after the patients underwent ECV. Our analysis included 39,697 patients with AF, of whom 5723 received ECV and 5723 were propensity score-matched controls. Compared to the controls, patients who received ECV exhibited a significantly increased incidence of 7-day AIS development (adjusted hazard ratio [HR] = 1.524, p = 0.003). In contrast, the incidence of 30-day AIS development showed no significant increase (adjusted HR = 1.301, p = 0.426). AF patients who underwent ECV had a higher incidence of 7-day AIS development but not 30-day AIS development. Considering the timing of AIS development after ECV in AF patients, the optimal duration of antithrombotic therapy after ECV deserves further investigation.


Seminal lead and copper in fertile and infertile men.
Lead and copper concentrations were determined by atomic absorption spectroscopy in semen from 18 fertile and 172 infertile men. Significant correlations between copper concentrations in semen and sperm concentration (r = 0.32, P less than 0.001), percentage progressive motility (r = 0.23, P less than 0.005) and normal morphology (r = 0.22, P less than 0.005) were observed, while no such correlation existed for lead. However, semen copper concentrations of infertile men (194.99 +/- 5.70 micrograms l-1) and fertile men (183.39 +/- 14.37 micrograms l-1) did not differ significantly. Mean lead concentration in semen of fertile men was 11.18 +/- 0.62 micrograms l-1 and significantly higher than lead concentration in semen of fertile men (5.61 +/- 0.53 micrograms l-1, P less than 0.006). Reinvestigation of 18 infertile men after 2 years showed a significant drop of lead concentrations in semen from 17.31 +/- 1.41 to 6.94 +/- 1.32 micrograms l-1 (P less than 0.0002), which might be related to the decreasing use of leaded petrol in the Federal Republic of Germany.


Disseminated herpes simplex virus and varicella zoster virus co-infection in a patient with idiopathic thrombocytopenic purpura.
Concomitant disseminated herpes simplex virus (HSV) and varicella zoster virus (VZV) infection is a rare event. We describe a case of disseminated HSV and VZV infection in an 80-year-old patient many years after splenectomy for idiopathic thrombocytopenic purpura (ITP). This is the first case of disseminated HSV-1 and VZV infection with molecular evidence of the simultaneous presence of both viruses in two different body sites (the skin and cerebrospinal fluid). This adds to the three reports of patients developing cutaneous disseminated herpes zoster multiple years after splenectomy for ITP.


Mapping of polyadenylated transcripts of a monkey lymphotropic papova virus.
Polyadenylated transcripts of a monkey lymphotropic papovavirus (LPV), which can be propagated in monkey and human lymphoblastoid cell lines, were identified and mapped. Polyadenylated RNA was purified from cells of the human line BJA/B infected with LPV, and was hybridized with various LPV DNA fragments. The hybrids were treated with S1 endonuclease and analyzed by alkaline gel electrophoresis. This analysis revealed two groups of RNA molecules encoded in two regions of the LPV genome. One group includes four colinear transcripts of 2.3, 2.1, 1.85, and 1.2 kb, whose polyadenylated termini map at a single site on the LPV DNA. The second group includes two less-abundant transcripts of 1.8 and 1.95 kb. The polarities of the LPV transcripts were determined by hybridizing cDNA complementary to their 3' termini with LPV DNA fragments. The two groups were found to have opposite polarities. It is shown that the four major transcripts can be aligned with, and may be functionally related to, SV40 and polyoma virus "late" mRNAs. It is also inferred that the 1.8- and 1.95-kb RNA species may be functionally related to the "early" transcripts of these papovaviruses.


Efficacy and safety of Android artificial pancreas system use at home among adults with type 1 diabetes mellitus in China: protocol of a 26-week, free-living, randomised, open-label, two-arm, two-phase, crossover trial.
Do-it-yourself artificial pancreas system (DIY APS) is built using commercially available insulin pump, continuous glucose monitoring (CGM) and an open-source algorithm. Compared with commercial products, DIY systems are affordable, allow personalised settings and provide updated algorithms, making them a more promising therapy for most patients with type 1 diabetes mellitus (T1DM). Many small and self-reported observational studies have found that their real-world use was associated with potential metabolic and psychological benefits. However, rigorous-designed studies are urgently needed to confirm its efficacy and safety. In this 26-week randomised, open-label, two-arm, two-phase, crossover trial, participants aged 18-75 years, with T1DM and glycated haemoglobin (HbA1c) 7-11%, will use AndroidAPS during one 12-week period and sensor-augmented pump during another 12-week period. This study will recruit at least 24 randomised participants. AndroidAPS consists of three components: (1) real-time CGM; (2) insulin pump; (3) AndroidAPS algorithm implemented in Android smartphone. The primary endpoint is time in range (3.9-10.0 mmol/L) derived from CGM. The main secondary endpoints include percentage of sensor glucose values below, within and above target range; mean sensor glucose value; measures of glycaemic variability and centralised HbA1c. Safety endpoints mainly include the frequency of hypoglycaemia events, diabetic ketoacidosis and other serious adverse events. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University. There will be verbal and written information regarding the trial given to each participant. The study will be disseminated through peer-reviewed publications and conference presentations. Recruiting. 11 February 2023. 31 July 2024. ClinicalTrials.gov Registry (NCT05726461).


Localization of hyaluronan in normal breast tissue, radial scar, and tubular breast carcinoma.
Hyaluronan (hyaluronic acid [HYA]) is one of the extracellular matrix components involved in normal cell physiology and is localized mainly in bodily fluids and connective tissues. Increased amounts of HYA in serum have been demonstrated in a number of neoplastic and inflammatory conditions, among them breast cancer. Tubular breast carcinoma (TC) and radial scar (RS) are two breast lesions that microscopically display characteristic stromal alterations and possess gross and microscopic similarities. Due to the importance of HYA as a component of the extracellular matrix, we investigated its presence in these lesions and in normal breast tissue. Using a biotinylated HYA-binding region for the in situ detection of HYA, we noted an increased amount of HYA in both TC and RS as compared with that in normal breast tissue specimens. A strong reactivity was observed predominantly around glandular structures and in the interlobular stroma of both TC and RS. Perivascular HYA staining also was distinctly observed in these lesions (TC and RS). Some HYA was observed in the connective tissue of the intralobular regions, around small blood vessels, and in the perivascular connective tissue of the normal breast. The distribution of HYA adjacent to the epithelium in the normal breast suggests a role for HYA in the interaction between epithelium and stroma of the normal breast. Its increase in the connective tissue of both TC and RS reflects the derangement of the stroma commonly observed in these conditions and supports the notion that these lesions may be associated.


The PPARγ2 P12A polymorphism is not associated with all-cause mortality in patients with type 2 diabetes mellitus.
The high mortality risk of patients with type 2 diabetes mellitus may well be explained by the several comorbidities and/or complications. Also the intrinsic genetic component predisposing to diabetes might have a role in shaping the risk of diabetes-related mortality. Among type 2 diabetes mellitus SNPs, rs1801282 is of particular interest because (i) it is harbored by peroxisome proliferator-activated receptor-γ2 (PPARγ2), which is the target for thiazolidinediones which are used as antidiabetic drugs, decreasing all-cause mortality in type 2 diabetes mellitus, and (ii) it is associated with insulin resistance and related traits, risk factors for overall mortality in type 2 diabetes mellitus. We investigated the role of PPARγ2 P12A, according to a dominant model (PA + AA vs. PP individuals) on incident all-cause mortality in three cohorts of type 2 diabetes mellitus, comprising a total of 1672 patients (462 deaths) and then performed a meta-analysis of ours and all available published data. In the three cohorts pooled and analyzed together, no association between PPARγ2 P12A and all-cause mortality was observed (HR 1.02, 95 % CI 0.79-1.33). Similar results were observed after adjusting for age, sex, smoking habits, and BMI (HR 1.09, 95 % CI 0.83-1.43). In a meta-analysis of ours and all studies previously published (n = 3241 individuals; 666 events), no association was observed between PPARγ2 P12A and all-cause mortality (HR 1.07, 95 % CI 0.85-1.33). Results from our individual samples as well as from our meta-analysis suggest that the PPARγ2 P12A does not significantly affect all-cause mortality in patients with type 2 diabetes mellitus.


Cyclosporine-steroid combination therapy in 84 cadaveric renal transplants.
Sixty-three primary and 21 retransplant cadaver kidney allografts were placed in 77 patients over a one-year period with three- to six-month follow-up. Eight primary grafts (12.7%) and six retransplants (28.6%) were lost to rejection. Patient mortality was 3.9%. There were no grafts lost and no deaths due to opportunistic infections. Renal function at 6 months after transplantation was similar in all primary transplant recipients regardless of risk factors, including advanced age, diabetes, or the need for postoperative dialysis.


Role of gamma-subunit N- and C-termini in assembly of the mitochondrial ATP synthase in yeast.
The gamma-subunit is required for the assembly of ATP synthases and plays a crucial role in their catalytic activity. We stepwise shortened the N-terminus and the C-terminus of the gamma-subunit in the mitochondrial ATP synthase of yeast and investigated the relevance of these segments in the assembly of the enzyme and in the growth of the cells. We found that a deletion of 9 residues at the N-terminus or 20 residues at the C-terminus still allowed efficient import of the subunit into mitochondria; however, the assembly of both monomeric and dimeric holoenzymes was partially impaired. gamma-Subunits lacking 13 N-terminal residues or 30 C-terminal residues were not assembled. Yeast strains expressing either of the truncated gamma-subunits did not grow on non-fermentable carbon sources, indicating that non-assembled parts of the ATP synthase accumulated and impaired essential mitochondrial functions.


An Audio-Based 3D Spatial Guidance AR System for Blind Users.
Augmented reality (AR) has great potential for blind users because it enables a range of applications that provide audio information about specific locations or directions in the user's environment. For instance, the CamIO ("Camera Input-Output") AR app makes physical objects (such as documents, maps, devices and 3D models) accessible to blind and visually impaired persons by providing real-time audio feedback in response to the location on an object that the user is touching (using an inexpensive stylus). An important feature needed by blind users of AR apps such as CamIO is a 3D spatial guidance feature that provides real-time audio feedback to help the user find a desired location on an object. We have devised a simple audio interface to provide verbal guidance towards a target of interest in 3D. The experiment we report with blind participants using this guidance interface demonstrates the feasibility of the approach and its benefit for helping users find locations of interest.


Do discharge codes underestimate hospitalisation due to heart failure? Validation study of hospital discharge coding for heart failure.
Discharge codes are frequently used to describe hospital activity related to heart failure (HF). To determine whether discharge codes for HF underestimated or overestimated hospital activity related to HF. Patients with atrial fibrillation (AF), who commonly have HF, were identified and their case notes reviewed to identify cases of HF missed by discharge codes. Patients admitted between November 1997 and January 1998 with either HF or AF. Identification of HF and AF by ICD10 hospital discharge codes. Identification of additional cases of AF from a central hospital-wide ECG database. We identified 330 cases with an ICD 10 code for HF, of which 43 (13%) were deemed to be miscoded, 32 patients (10%) were classified as possible, 39 (12%) as probable and 216 (65%) as definite HF. Results were similar whether or not HF was the primary discharge diagnosis. We identified 452 patients with AF, of whom 45 (10%) were classified as probable and 193 (43%) as definite HF. 129 (54%) of these cases had no diagnostic discharge code for HF. ICD 10 discharge codes for HF were correct in 77% of cases but identified only 66% of patients with probable or definite HF in this analysis. Screening of other diagnoses would have identified further cases of HF. Hospital discharge codes substantially underestimate hospital events related to HF in the UK.


Detection and Molecular Characterization of Zoonotic Poxviruses Circulating in the Amazon Region of Colombia, 2014.
During 2014, cutaneous lesions were reported in dairy cattle and farmworkers in the Amazon Region of western Colombia. Samples from 6 patients were analyzed by serologic and PCR testing, and results demonstrated the presence of vaccinia virus and pseudocowpox virus. These findings highlight the need for increased poxvirus surveillance in Colombia.


Adrenoceptor supersensitivity in the isolated rat vas deferens during barbital withdrawal.
Long-term treatment with sodium barbital did not alter significantly the responsiveness of the isolated rat vas deferens to noradrenaline. However, three days after barbital withdrawal there was a 4.5-fold increase in the sensitivity and an enhanced maximum response to the neurotransmitter. Pharmacological analysis of the affinity of postjunctional adrenoceptors showed no alteration of the pA2 of phentolamine, a decrease in the apparent dissociation constant (KA) for noradrenaline and an increase in the fraction of adrenoceptors (q) remaining active after exposure to phenoxybenzamine. Comparison between ED50 and KA indicates the presence of spare receptors in the rat vas deferens. There was also a decrease in the blocking activity of phenoxybenzamine, in vasa deferentia obtained from rats three days after barbital withdrawal. These results suggest that an increased affinity of postjunctional adrenoceptors could be responsible, at least partially, for this supersensitivity to noradrenaline. The increased maximum response to the neurotransmitter could be the consequence of an improved coupling of adrenoceptor occupation to the final contractile response.


Mucolipidosis type II with evidence of a novel storage site.
In a case of infantile mucolipidosis type II (I-cell disease), storage was identified at autopsy in serous-type secretory cells in exocrine pancreas, in the tracheal and sublingual salivary glands and in the chief (zymogenic) cells of the gastric oxyntic glands, suggesting a systemic involvement of this type of secretory cells. The content of specific secretory granules was inversely proportional to the intensity of the storage process. The mucus-producing cells were not affected. The serous glandular system is a novel storage site in I-cell disease. Review of archival material in three further cases confirmed the findings.


Sensitivity of lateral view cervical spine radiographs taken in the neutral position in atlantoaxial subluxation in rheumatic diseases.
The value of lateral view cervical spine radiography in various positions of the neck was assessed in patients with rheumatoid atlantoaxial subluxation (AAS). We wanted to find out how much information is lost if only neutral position radiographs are used. The series consisted of 65 rheumatoid patients with unstable AAS. Lateral view cervical spine radiographs were taken in the neutral position and during flexion and extension. Neutral position radiographs would have failed to confirm the diagnosis of AAS in 31 cases (48%) and would have failed to record its true severity in 43 cases (66%); their diagnostic sensitivity was 52%. The sensitivity of the neutral radiographs in showing the reversibility of AAS was 48%. Routine cervical spine radiography of rheumatoid patients should include lateral view radiographs taken during flexion and extension. The result may be applied to magnetic resonance imaging, which is usually performed in the neutral position.


Local therapies for liver metastases of rare head and neck cancers: a monoinstitutional case series.
Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are established procedures for treating hepatocellular cancer and selected malignancies with liver metastasis. The aim of this study is to describe a monoinstitutional case series of local approaches in patients with liver metastases from rare head and neck cancers (HNCs). This is a retrospective series of adult patients with HNC treated with liver locoregional approaches (TACE or RFA) at our institution from 2007 to 2018. In case of chemoembolization, the preferred chemotherapeutic drug was doxorubicin. Response according to RECIST (Response Evaluation Criteria in Solid Tumors) was assessed with contrast-enhanced computed tomography scans. Thirty-four patients were treated (20 men, median age 58 years) with TACE (27), transarterial embolization (2), or RFA (7). Primary tumours were salivary gland (21), thyroid (6), nasopharyngeal (5), and sinonasal cancers (2). Seventeen patients (50%) had a single metastatic liver nodule; 70% of the remaining 17 patients had at least three liver metastases. The median diameter of the metastatic liver mass undergoing treatment was 39 mm (range 11-100 mm). Median follow-up was 27.6 months. Response rate was 35% (3% complete, 32% partial response). Median progression-free survival and overall survival were 6.9 and 19.6 months, respectively. Treatment-related adverse events occurred in 59% of patients (21% grade ⩾ 3; no grade 5). This retrospective case series demonstrates that locoregional radiologic approaches for rare HNCs with liver metastases are feasible. These procedures deserve further prospective studies before being considered safe and active in these malignancies where the availability of effective systemic treatments is lacking.


Amino acids determination using capillary electrophoresis with on-capillary derivatization and laser-induced fluorescence detection.
Free amino acids have been derivatized on-capillary with 3-(2-furoyl)quinoline-2-carboxaldehyde (FQ) and analyzed using a laboratory-made capillary electrophoresis apparatus with laser-induced fluorescence detection. Several parameters that control on-capillary derivatization of amino acids, including pH, mixing time, reaction time, concentration of the derivatization reagents (potassium cyanide and FQ) and solvent of FQ, as well as the temperature of mixing and reaction were optimized. Repeatabilities better than 1.8% for migration time and 7.8% for peak height were obtained. Assay detection limits for the different amino acids ranged from 23 nM for glycine to 50 nM for lysine and glutamic acid. The methods developed were applied to the analysis of several amino acids in pharmaceutical preparations and plasma samples. Results showed a good agreement with those obtained using an amino acid autoanalyzer for the same samples.


Effects of chemical elements in the trophic levels of natural salt marshes.
The relationships between the bioaccumulation of Na, K, Ca, Mg, Fe, Zn, Cu, Mn, Co, Cd, and Pb, acidity (pH), salinity (Ec), and organic matter content within trophic levels (water-soil-plants-invertebrates) were studied in saline environments in Poland. Environments included sodium manufactures, wastes utilization areas, dumping grounds, and agriculture cultivation, where disturbed Ca, Mg, and Fe exist and the impact of Cd and Pb is high. We found Zn, Cu, Mn, Co, and Cd accumulation in the leaves of plants and in invertebrates. Our aim was to determine the selectivity exhibited by soil for nutrients and heavy metals and to estimate whether it is important in elucidating how these metals are available for plant/animal uptake in addition to their mobility and stability within soils. We examined four ecological plant groups: trees, shrubs, minor green plants, and water macrophytes. Among invertebrates, we sampled breastplates Malacostraca, small arachnids Arachnida, diplopods Diplopoda, small insects Insecta, and snails Gastropoda. A higher level of chemical elements was found in saline polluted areas (sodium manufactures and anthropogenic sites). Soil acidity and salinity determined the bioaccumulation of free radicals in the trophic levels measured. A pH decrease caused Zn and Cd to increase in sodium manufactures and an increase in Ca, Zn, Cu, Cd, and Pb in the anthropogenic sites. pH increase also caused Na, Mg, and Fe to increase in sodium manufactures and an increase in Na, Fe, Mn, and Co in the anthropogenic sites. There was a significant correlation between these chemical elements and Ec in soils. We found significant relationships between pH and Ec, which were positive in saline areas of sodium manufactures and negative in the anthropogenic and control sites. These dependencies testify that the measurement of the selectivity of cations and their fluctuation in soils provide essential information on the affinity and binding strength in these environments. The chemical elements accumulated in soils and plants; however, further flow is selective and variable. The selectivity exhibited by soil systems for nutrients and heavy metals is important in elucidating how these metals become available for plant/animal uptake and also their mobility and stability in soils.


Does the length of the biliary limb influence medium-term laboratory remission of type 2 diabetes mellitus after Roux-en-Y gastric bypass in morbidly obese patients?
The Roux-en-Y gastric bypass (RYGB) is an effective treatment of morbid obesity leading to type 2 diabetes mellitus (T2DM) resolution. However, evidence demonstrates that standard limb lengths can have a limited impact on long-term weight loss and durable T2DM remission. The authors evaluated the impact of biliary limb (BL) length on the T2DM laboratory markers in 2-year follow-up. The data of 93 obese patients with T2DM who underwent RYGB between 2008 and 2010 were collected from prospectively designed database. The length of BL was standard in one group of 51 patients (S-BL: 50-75 cm) and longer in another group of 42 patients (L-BL: 100-150 cm). The laboratory parameters defining T2DM remission - fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) - were measured 3, 6, 12 and 24 months after surgery. The average level of FPG and HbA1c remained non-diabetic 24 months after the RYGB in both groups. A statistical difference was not observed in direct FPG, HbA1c, ΔFPG and ΔHbA1c comparisons at any follow-up point. However, a significantly higher proportion of patients in L-BL than in S-BL reached the laboratory remission criteria without anti-diabetic medicaments. Additional analysis revealed a strong correlation between the measured T2DM parameters and length of the common limb (CL) in both groups. A longer BL can intensify the anti-diabetic effect of RYGB. The length of CL rather than BL influences the medium-term T2DM remission. Long-term observation is needed to fully assess whether introduced technical aspects of RYGB provide a durable effect of T2DM resolution.


Consensus and recommendations on vaginal-cuff Brachytherapy of the Spanish Brachytherapy Groups of SEOR and SEFM.
On October 5, 2018, a meeting of the Spanish Society of Radiation Oncology (SEOR) Brachytherapy Group was held, in collaboration with the Spanish Society of Medical Physics (SEFM), with the aim of preparing a consensus document on postoperative vaginal-cuff brachytherapy (VCBT). A survey including 42 questions was sent to Spanish Radiation Oncology Centres before the meeting. The survey items included: experience in VCBT, technique indications, previous patient preparation, applicator type, implant procedure, computerized tomography (CT) simulation, definition of target volumes and organs at risk (OAR), dose prescription, fractionation, treatment planning, dosimetric parameters and constraints to OAR. Thirty-three centres answered the survey. Statistical analysis of the survey considered that there was consensus when there was ≥ 85% of agreement related to a survey item, otherwise an item with < 85% of agreement would be discussed during the meeting to reach consensus. The results of the survey are reported here. The mean number of patients treated per centre in 2017 was 52 ± 41 (range 7-175), and the mean number of procedures per centre was 175 ± 150 (range 24-701).There was consensus on: the indications, applicator type, the OAR to be considered, the prescription point, standardisation and dosimetric quality parameters. There was no consensus on: patient preparation for the implant, the need for performing CT simulation and the frequency, the length of the vagina to be treated, if CTV should be delimited, the definition of the clinical target volume, fractionation, overall EQD2, active source length, separation between dwelling stepping source positions, if considering the uniformity/maximum values for dwelling stepping sources, the optimization mode, and the limiting doses to the OAR. After presenting the results of the survey, the consensus meeting discussion focused on the issues for which there was no consensus. A consensus document on postoperative VCBT of the Spanish Brachytherapy Groups of SEOR-SEFM was elaborated.


Rationally designed calix[4]arene-pyrrolotetrathiafulvalene receptors for electron-deficient neutral guests.
Four upper rim bis-monopyrrolotetrathiafulvalene-calix[4]arene conjugates 2a,b and 3a,b have been efficiently synthesized using a modular construction approach. The new compounds feature a molecular tweezer architecture with a quasi-parallel arrangement of redox-active tetrathiafulvalene (TTF) arms, which serve as the guest binding centers. Complexation studies using UV/vis binding titrations revealed a high affinity of the calixarene-TTF receptors for planar electron-deficient guests, leading to formation of deeply colored charge-transfer complexes in solution. The binding efficiency of the receptors depends on the flexibility of the calixarene scaffolds and the electronic nature of the TTF arms: the highest binding efficiency is shown by receptor 2b, featuring a highly preorganized molecular structure and an electron-rich TTF moiety.


MRI and CT findings of infected cephalhaematoma complicated by skull vault osteomyelitis, transverse venous sinus thrombosis and cerebellar haemorrhage.
We present the CT and MRI findings of an 8-day-old infant with an infected cephalhaematoma complicated by skull osteomyelitis, venous sinus thrombosis and left cerebellar haemorrhage.


Physicochemical studies of chemosensor imidazole derivatives: DFT based ESIPT process.
A series of substituted imidazoles have been synthesized in very good yield under a solvent free condition using molecular iodine as the catalyst. An excited state intramolecular proton transfer (ESIPT) process in hydroxy imidazole has been studied using emission spectroscopy. DFT calculations on energy, dipole moment, charge distribution of the rotamers in the ground and excited states of the imidazole derivatives have been performed and discussed. DFT analysis about HOMO, HOMO-1, LUMO and LUMO+1 has been carried out and discussed. The energy barrier for the interconversion of two rotamers is too high in the excited state than the ground state that is shown by PES calculation. The molecular electrostatic potential surface (MEP) has also been employed to show the higher electron density at N(3) nitrogen. Fluorescence enhancement has been found in the presence of transition metal ions and this may result from the suppression of radiationless transitions from the n-π* state in the chemosensors.