Extracellular processing of dentin matrix protein in the mineralizing odontoblast culture.
Odontoblasts that we prepared from bovine incisors produced a dentin-specific protein, phosphophoryn, and accumulated it in mineralized nodules. The time course of mineralization was detected by measuring osteocalcin and mineral in the nodules. The sequence of developmental expression of proteins in this mineralizing dentin cell culture is very similar to that in bone cells, suggesting a common mechanism for matrix mineralization in bone and dentin. Casein kinase II, which phosphorylates bone phosphoproteins and dentin phosphorylates bone phosphoproteins and dentin phosphophoryn, also emerges coinciding with the initiation of mineralization. Furthermore, we have detected extracellular phosphorylation by casein kinase II of a dentin protein of M(r) 60,000, which we recovered from the phosphophoryn fraction in CaCl2 precipitate.


Gas/particle partitioning and global distribution of polycyclic aromatic hydrocarbons--a modelling approach.
The global atmospheric distribution and long-range transport (LRT) potential of three polycyclic aromatic hydrocarbons (PAH) - anthracene, fluoranthene and benzo[a]pyrene - are studied. The model used is a global aerosol-chemistry-transport-model, which is based on an atmospheric general circulation model. The model includes an in-built dynamic aerosol model coupled to two-dimensional surface compartments. Several parameterisations of gas/particle partitioning and different assumptions of degradation in the aerosol particulate phase were tested. PAHs are mostly distributed in the source regions but reach the Arctic and the Antarctic. The Canadian Arctic is predicted to be significantly less affected by mid-latitude PAH emissions than the European Arctic. Re-volatilisation is significant for semivolatile PAHs. Accumulation of semivolatile PAHs in polar regions, however, is not indicated. The model study suggests that gas/particle partitioning in air drastically influences the atmospheric cycling, the total environmental fate (e.g. compartmental distributions) and the LRT potential of the substances studied. A parameterisation which calculates the gas/particle partitioning assuming absorption into organic matter and adsorption to black carbon (soot) agrees best with the observations at remote sites. The study provides evidence that the degradation in the particulate phase must be slower than that in the gas-phase. The predicted concentrations of the semivolatile PAHs anthracene and fluoranthene in near-ground air at remote sites in mid and high northern latitudes are in line with measured concentrations, if adsorption of the substances to soot combined with absorption in particulate organic matter is assumed to determine gas/particle partitioning, but cannot be explained by adsorption alone (Junge-Pankow parameterisation of gas/particle partitioning). The results suggest that PAHs absorbed in the organic matrix of particulate matter is shielded from the gas-phase.


Stabilization of liquid interface and control of two-phase confluence and separation in glass microchips by utilizing octadecylsilane modification of microchannels.
We demonstrated a liquid/liquid and a gas/liquid two-phase crossing flow in glass microchips. A 250-microm-wide microchannel for aqueous-phase flow was fabricated on a top glass plate. Then, as a way to utilize the surface energy difference for stable phase confluence and separation, a 250-microm-wide microchannel for organic-phase (or gas-phase) flow was fabricated on a bottom glass plate and the wall was chemically modified by octadecylsilane (ODS) group. The top and bottom plates were sealed only by pressure. A microchannel pattern was designed so that the two phases made contact at the crossing point of the straight microchannels. The crossing point was observed with an optical microscope. Results showed that the ODS modification of the microchannel wall clearly improved stability of the interface between the two fluids. Pressure difference between fluids was measured and the interface of water and nitrobenzene was stable for the pressure difference from +300 Pa to -200 Pa. The pressure drop in a countercurrent flow configuration was also estimated, and the pressure difference required to realize the counter current flow was less than the allowable pressure range. Finally, we discussed the advantages of utilizing this approach.


Association between scanning frequency of flash glucose monitoring and continuous glucose monitoring-derived glycemic makers in children and adolescents with type 1 diabetes.
We assessed the association between scanning frequency of flash glucose monitoring (FGM) and continuous glucose monitoring (CGM)-derived glycemic markers in children and adolescents with type 1 diabetes. Subjects consisted of 85 children and adolescents with type 1 diabetes using FGM. We assessed the association between scanning frequencies of FGM- and CGM-derived metrics: Time in range (TIR) (70-180 mg/dL), time below range (TBR) (<70 mg/dL), time above range (>180 mg/dL), and other glycemic markers - laboratory-measured HbA1c and CGM-estimated glucose and HbA1c (eA1c) levels in the subjects. The mean number of scans was 11.5 ± 3.5 (5-20) times per day, and scanning was most frequently conducted during a period of 18-24 h. Scanning frequency showed significant positive correlation with TIR (r = 0.719, P < 0.0001) and inverse correlation with time above range (r = -0.743, P < 0.0001), but did not correlate with TBR. There were also significant inverse correlations between scanning frequency and glucose, HbA1c, and eA1c levels (r = -0.765, -0.815, and -0.793, respectively, P < 0.0001). Frequent glucose testing with FGM decreased hyperglycemia with increased TIR, but did not reduce TBR. Coping with a rapid fall of glucose and unexpected hypoglycemia with more advanced technology might contribute to a reduction in TBR.


Discovery of potent, cyclic calcitonin gene-related peptide receptor antagonists.
Calcitonin gene-related peptide (CGRP), a potent dilator of cerebral and dural vasculature, is known to be elevated in plasma and cerebral spinal fluid during migraine attacks. Selective blockade of the CGRP receptor offers the promise of controlling migraine headache more effectively and without the side-effects associated with the use of triptans. Our efforts to develop a novel, peptide-based CGRP antagonist focused on the C-terminal portion of the peptide which is known to bind the receptor but lack agonist properties. Extensive SAR studies of the C-terminal CGRP (27-37) region identified a novel cyclic structure: Bz-Val-Tyr-cyclo[Cys-Thr-Asp-Val-Gly-Pro-Phe-Cys]-Phe-NH(2) (23) with a kb value of 0.126 nM against the cloned human CGRP receptor. Additional SAR studies directed at enhancement of potency and improvement of physicochemical properties yielded a series of analogs with kb values in the 0.05-0.10 nM range.


Suicidal ideation and self-harm behavior in a community sample of preadolescent youth: a case-control study.
Research has focused on understanding risk factors associated with suicidal ideation and self-harm behaviors in older youth, but less is known regarding these behaviors in preadolescents. We examined characteristics associated with suicidal ideation and self-harm behavior in youth aged 10-13 years. A community sample of 387 youth was enrolled in a prospective study assessing precursors of risk behaviors. Twenty-three subjects endorsing items regarding suicidal ideation or self-harm behaviors (Achenbach's Youth Self-Report) (endorsers) were matched with 23 non-endorsers. Groups were compared on problem behaviors, impulsivity, neurocognitive function, risk behaviors, and other variables. Endorsers had higher levels of impulsivity, were more likely in borderline/clinical range on 5 of 8 Youth Self-Report Syndrome scales, and reported more risk taking. Endorsers and non-endorsers were similar in neurocognitive function. More non-endorsers were on stimulants, but groups were similar in parental monitoring and parental report of behavioral/emotional issues, socioeconomic status, and marital status. In this study, preadolescent endorsers report significantly more problem behaviors than non-endorsers. However, parental monitoring and parent report of problems were similar between groups. Given these findings, we suggest that at-risk youth may be underrecognized at young ages.


Extraoral bite-wing radiographs: A universally accepted paradox.
The development of specialized panoramic radiograph machine software has spawned the introduction of an innovative and promising dental radiographic examination type: extraoral bite-wings. But does this unconventional type of imaging belong in the bite-wing family? Is there any relationship at all to the conventional bite-wing radiograph? The purpose of this article is not to make a case for the diagnostic effectiveness of one system over the other; this is best left to further clinical evaluation. Instead, the authors intend to provide an outline of a few key and distinguishing elements of the intraoral bite-wing radiographic examination followed by those of the extraoral panoramic substitute and draw attention to the importance of reimagining the increasingly universal naming convention of this novel radiographic examination, the paradoxical "extraoral bite-wing radiograph", based on the fundamental principles of each of these imaging systems. The accuracy of clinical and technical terminology in oral radiography is of paramount importance to both the profession and patients, especially when considering emerging technologies.


Effects of lubricant oil and diesel on macrofaunal communities in marine sediments: A five year field experiment in Antarctica.
Hydrocarbons pose significant risks to marine ecosystems. A field experiment investigated the effects of four different hydrocarbon products (diesel fuel and three lubricating oils: Unused, Used and Biodegradable) on sediment macrofaunal communities over a five year period, in a shallow Antarctic marine embayment. Sediments were defaunated, treated with a hydrocarbon and deployed in trays (including a control) on the seabed. Diesel fuel had the biggest initial impact on communities, with strong effects at 5 weeks and 1 year, in particular on annelids, but also on amphipods, ostracods and cumaceans. By five years, however, the effect of diesel was less than that of lubrication oils and showed more recovery than oiled treatments and the biggest effect was from the Used oil. There was an effect of hydrocarbons on diversity, especially diesel, at 5 weeks and 1 year, but by 2 and 5 years diversity was not different or greater in hydrocarbon treatments than controls. Total abundance was always lower in hydrocarbon treatments than controls, especially for crustaceans, but annelids were more abundant in oil treatments than controls at 5 years. Oils, and in some cases diesel, enhanced the abundance of some taxa at 2-5 years, including molluscs, some polychaete families (capitellids, cirratulids, dorvilleids), oligochaetes, as well as ostracods, cumaceans and isopods. Amphipods and tanaids were most sensitive to hydrocarbons, and annelids were very sensitive to diesel. The Biodegradable oil had similar magnitude community effects to standard oil at 5 years, but annelids were more affected by Biodegradable oil, particularly at 1 and 2 years, and it did not enhance annelid or mollusc abundance at 5 years like the other oils, except for some polychaete families. Impacts of spilled hydrocarbons in Antarctica will persist well beyond 5 years, but diesel impacts will recover faster than oil.


The secretion of protein and of some electrolytes in response to alpha- and beta- adrenergic agonists by rat parotid and submandibular salivary glands enlarged by chronic treatment with isoproterenol.
In comparison with control rats. chronic administration of isoproterenol (IPR) caused enlargement of the parotid and submandibular glands and the synthesis of apparently new proteins, probably by acinar cells. The parotid and submandibular saliva secreted in response to methoxamine or IPR differed markedly in protein and electrolyte content. In addition, with each stimulus, the salivas secreted by control and experimental glands differed in flow rate, protein concentration, and in the concentrations of certain of the electrolytes.


Zeolitic imidazolate framework-8 decorated with gold nanoparticles for solid-phase extraction of neonicotinoids in agricultural samples.
A composite built with aminated zeolitic imidazolate framework and gold nanoparticles (AuNPs) for solid-phase extraction (SPE) of neonicotinoids in agricultural samples is presented. The composite was prepared through the assembly of AuNPs onto the surface of metal-organic framework based on the strong interaction between the amino group and AuNP. These metallic surfaces provided additional interactions based on the affinity of amino and cyano groups present in the target compounds. The composite was characterized by scanning electron microscopy, powder X-ray diffraction, Fourier-transform infrared spectroscopy, and surface area measurements. Regarding the SPE protocol, several parameters that can influence the extraction performance were optimized, such as sample volume or composition of elution solvent, among others. After elution, the analytes were determined via HPLC with diode-array detection. Under the selected conditions, satisfactory recoveries of five pesticides (thiamethoxan, clothianidin, imidacloprid, acetamiprid, and thiacloprid) were obtained (between 80 and 110%) in real samples, whereas the limits of detection ranged from 0.019 to 0.041 μg L-1 in aqueous samples and 0.3 to 0.8 μg g-1 in solid samples.


Prognosis of Single Early-Stage Hepatocellular Carcinoma (HCC) with CEUS Inconclusive Imaging (LI-RADS LR-3 and LR-4) Is No Better than Typical HCC (LR-5).
The American College of Radiology (ACR) released the Liver Imaging Report and Data System (LI-RADS) scheme, which categorizes hepatic nodules in risk classes from LR-1 to LR-5 (according to the degree of risk to be HCC) and LR-M (probable malignancy not specific for HCC). The aim of this study was to test whether HCC with different LR patterns on CEUS have different overall survival (OS) and recurrence-free survival (RFS). We retrospectively enrolled 167 patients with the first definitive diagnosis of single HCC (by using CT/MRI or histological techniques if CT/MRI were inconclusive) for whom CEUS examination was available. The median size of HCC lesions was 2.2 cm (range 1.0-7.2 cm). According to CEUS LI-RADS classification, 28 patients were in LR-3, 48 in LR-4, 83 in LR-5, and 8 in LR-M. Patient liver function and nodule characteristics were not statistically different between CEUS LI-RADS classes. Using univariate analysis, CEUS LI-RADS class was not found to be a predictor of survival (p = 0.347). In conclusion, HCC showing the CEUS LI-RADS classes LR-3 and LR-4 have no better clinical outcome than typical HCC. Such data support the EASL policy, aimed at conclusive diagnostic investigations of indeterminate nodules up to obtaining histological proof to avoid leaving aggressive HCC not timely treated.


The herbal preparation Padma® 28 protects against neurotoxicity in PC12 cells.
Padma® 28 is a multicompound herbal preparation based on the camphor formulas from traditional Tibetan medicine (TTM). It contains a variety of different secondary plant substances, which include terpenes and polyphenols such as flavonoids and tannins. As a rich source of antioxidant polyphenols, this herbal Padma 28 preparation seems to be a promising candidate for the treatment of degenerative diseases such as Alzheimer's disease (AD), a condition involving oxidative stress. Moreover, polyphenols have also been shown to mitigate AD neuropathology. The study investigated the protective effect of Padma 28 and of certain polyphenols on the neurotoxicity of PC12 cells induced by the neurotoxins: amyloid-beta (Aβ), glutamate, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 3-nitropropionate (3-NP), known to be involved in AD, Parkinson's disease (PD), amyotrophic-lateral-sclerosis (ALS) and Huntington's disease (HD), respectively. The decrease in cell viability induced by each of the toxins was significantly attenuated by Padma 28 treatment. Also, a decrease in the oxidative capacity of PC12 cells treated with Padma 28 was noted, indicating that the decrease in cell viability induced by the toxins might have been the result of an oxidative stress which could be attenuated by Padma 28 acting as a potent antioxidant. Padma 28, which is available in Europe and USA, seems to be a promising candidate for the treatment of CNS diseases.


Bacterial cellulose production by Komagataeibacter hansenii can be improved by successive batch culture.
Bacterial cellulose (BC) is a biopolymer principally synthetized by strains of the genus Komagataeibacter. However, high costs and low production yield make large-scale application difficult. The aim of this work was to evaluate the effects of successive batch culture before fermentation on the ability to increase the capacity of bacterial cellulose biosynthesis by a low-producing strain. The Komagataeibacter hansenii strain ATCC 23,769 was initially cultivated in fermentation broth for two periods of 35 or 56 days under static conditions. At the end of each period of time, they were transferred to new broth to be cultivated again (new batch culture cycle) for 35 or 56 days and carried out in parallel with a 10-day fermentation to determine the quantity of BC produced. As a result, a greater increase was observed after the end of the second and third batch cultures of 56 days (increases of 137% and 187% in relation to the nonbatch cultured strain, respectively). The produced samples presented higher crystallinity and thermal properties but lower water holding capacity. Through this work, it was concluded that the longer the batch culture time was, the greater the increase in the capacity of cellulose biosynthesis, which also depended on the number of successive batch culture cycles carried out.


[Surgical treatment of hemorrhage caused by rupture of esophageal varices. Circular sclerosis of the lower esophagus by a clip introduced by the oral approach and ligation by the thoracic approach to the peri-esophageal veins. Results of 108 cases surgically treated in the last 5 years].
This method of treating hemorrhage from ruptured esophageal varices gives excellent results in cases usually reserved for treatment by portocaval shunts, as well as patients with the usual contraindications to shunt operations. If it is possible without transfusion, and with a single assistant, to definitely stop hemorrhage from ruptured esophageal varices in one hour, then the method is of even greater merit, particularly knowing that the thoracotomy used leaves the untouched abdominal cavity accessible to any possible secondary operation due to progression of portal hypertension and/or hepatic insufficiency. At the request of numerous surgeons in France and from abroad, therefore, a demand has been made to manufacture the apparatus used at the present time after its development over 5 years.


The impact of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury on mortality and clinical outcomes: a meta-analysis.
Renal replacement therapy (RRT) is essential in the presence of life-threatening complications associated with acute kidney injury (AKI). In the absence of urgent indications, the optimal timing for RRT initiation is still under debate. This meta-analysis aims to compare the benefits between early and late RRT initiation strategies in critically ill patients with AKI. Studies were obtained from three databases [Medical Literature Analysis and Retrieval System Online (MEDLINE), Cochrane Central Register of Controlled Trials (CENTRAL) and Scopus], searched from inception to May 2021. The selected primary outcome was 28-day mortality. Secondary outcomes included overall mortality, recovery of renal function (RRF) and RRT-associated adverse events. A random-effects model was used for summary measures. Heterogeneity was assessed through Cochrane I 2 test statistics. Potential sources of heterogeneity for the primary outcome were sought using sensitivity analyses. Further subgroup analyses were conducted based on RRT modality and study population. A total of 13 randomized controlled trials including 5193 participants were analysed. No significant differences were found between early and late RRT initiation regarding 28-day mortality [risk ratio (RR) 1.00; 95% confidence interval (CI) 0.89-1.12, I² = 30%], overall mortality (RR 1.00; 95% CI 0.90-1.12, I² = 42%) and RRF (RR 1.02; 95% CI 0.92-1.13, I² = 53%). However, early RRT initiation was associated with a significantly higher incidence of hypotensive (RR 1.34; 95% CI 1.17-1.53, I² = 6%) and infectious events (RR 1.83; 95% CI 1.11-3.02, I² = 0%). Early RRT initiation does not improve the 28-day and overall mortality, nor the likelihood of RRF, and increases the risk for RRT-associated adverse events, namely hypotension and infection.


Evaluation of topical application and systemic administration of rosuvastatin in preventing epidural fibrosis in rats.
Epidural fibrosis is a major challenge in spine surgery, with some patients having recurrent symptoms secondary to excessive formation of scar tissue resulting in neurologic compression. One of the most important factors initiating the epidural fibrosis is assumed to be the transforming growth factor-1β (TGF-1β). Rosuvastatin (ROS) has shown to demonstrate preventive effects over fibrosis via inhibiting the TGF-1β. We hypothesized that ROS might have preventive effects over epidural fibrosis through the inhibition of TGF-1β pathways. Experimental animal study. Forty-eight adult male Wistar Albino rats were equally and randomly divided into four groups (laminectomy, spongostan, topical ROS, and systemic ROS). Laminectomy was performed at the L3 level in all rats. Four weeks later, the extent of epidural fibrosis was assessed both macroscopically and histopathologically. Our data revealed that topical application and systemic administration of ROS both were effective in reducing epidural fibrosis formation. Furthermore, the systemic administration of ROS yielded better results than topical application. Both topical application and systemic administration of ROS show meaningful preventive effects over epidural fibrosis through multiple mechanisms. The results of our study provide the first experimental evidence of the preventive effects of ROS over epidural fibrosis.


The importance of maternal BMI on infant's birth weight in four BMI groups for the period 1978-2001.
To study whether increased maternal weight and other factors of importance is associated with higher birth weights of the children over a period of almost 25 years. Retrospective cohort study. Delivery wards in southeast Sweden. A total of 4,330 delivered women and their children from the years 1978, 1986, 1992, 1997, and 2001. Analysis of covariance was used to evaluate the importance of the mother's body mass index (BMI) on the children's birth weights during the study years and smoking, parity, employment, gestational age, and the age of the mothers were adjusted for. Weight of the offspring in relation to maternal BMI and possible confounders such as smoking, parity, employment, gestational age, and the age of the mother. Between 1978 and 1992, there was an increase in birth weight in each of the four BMI categories (i.e. BMI<20, 20-24.9, 25-29.9 and > or =30, respectively) even after adjustments were made for relevant background characteristics (p<0.001). However, between 1992 and 2001, the birth weight for children whose mothers had a BMI of less than 20 or between 20 and 24.9 decreased (p<0.001). For almost every study year, the mothers' BMI was of significant influence on the children's birth weights. However, the proportion of variance explained by the models (i.e. the adjusted R(2)) was not substantially altered when the mother's BMI was excluded from the models. Maternal BMI is of significance to explain trends in infants' birth weight over time, but not of sole importance.


Mediastinal Myxofibrosarcoma Harboring Loss-of-Function MSH2 Variant in a Patient With Lynch Syndrome: A Case Report and Literature Review.
Myxofibrosarcoma is a malignant fibroblastic neoplasm that commonly arises in the extremities, with mediastinum being a very rare location. The development of sarcomas is uncommon in patients with Lynch syndrome. We present a Lynch syndrome patient with synchronous cecal adenocarcinoma and mediastinal myxofibrosarcoma with both harboring the same loss-of-function MSH2 alteration (c.2634 + 1G > A splice region variant). Metastatic myxofibrosarcoma in the left chest wall developed 6 months after the initial diagnosis. The clinical presentation, imaging findings, histopathology, and molecular studies along with differential diagnoses are presented and discussed.


Recyclable surface enhanced Raman scattering monitoring of nucleotides and their metabolites based on Au nanoflowers modified g-C3N4 nanosheets.
The effective monitoring of nucleotides and their metabolites is critical for the prevention of various genetic metabolic diseases. In this aspect, surface-enhanced Raman scattering (SERS) as an ultrasensitive and nondestructive sensing techniques has spurted an attractive prospect. Henceforth, an effective SERS-based analysis of adenosine monophosphate (AMP) as well as adenine was realized here by utilizing an innovative kind of self-cleaning substrate constructed with graphitic carbon nitride and Au nanoflowers (g-C3N4@Au NFs). Taking advantages of the numerous nanotip-triggered "hotspot" regions of Au NFs as well as the excellent photocatalytic degradation capability of g-C3N4 matrix, the hybrid substrate not only brought about a low limit of detection (LOD) of 5.01 × 10-10 M, but also yielded an attractive self-cleaning property. Particularly, these fascinating features of the proposed g-C3N4@Au NFs facilitated a recyclable monitoring of AMP and adenine in serum with reliable sensitivity and stability. The achieved wide linear range from 10-4 to 1 mg/mL together with the LOD values down to 10-5 mg/mL all envisioned that it is possible to monitor and investigate human metabolic processes by SERS protocol.


Monoaminergic network dysfunction and development of depression in multiple sclerosis: a longitudinal investigation.
Monoaminergic network dysfunction is thought to underpin depression in multiple sclerosis (MS) patients. However, longitudinal studies are lacking. Here, we investigated the association between development of depressive symptoms in MS and changes of resting-state functional connectivity (RS FC) within monoaminergic networks. Forty-nine MS patients without depression [Montgomery-Asberg Depression Scale (MADRS) ≤ 9] and 27 healthy controls underwent clinical and 3.0 T RS FC assessment at baseline and after a median follow-up of 1.6 years (interquartile range 1.0-2.1 years). Monoamine-related RS FC was derived by independent component analysis, constrained to PET atlases for dopamine, noradrenaline and serotonin transporters. Longitudinal changes of RS FC within monoaminergic networks and their correlations with MADRS scores were assessed. At baseline, MS patients showed decreased RS FC vs healthy controls in all PET-guided monoaminergic networks in frontal, cingulate and cerebellar cortices, and increased RS FC in parieto-occipital regions. Fourteen (29%) MS patients developed depressive symptoms (MADRS > 9) at follow-up (D-MS) and exhibited widespread RS FC decrease over time in the PET-guided dopamine network, mainly in orbitofrontal, occipital, anterior cingulate and precuneal cortices compared to patients who did not develop depressive symptoms. In D-MS, decreased RS FC over time was also observed in parahippocampal and occipital regions of the PET-guided noradrenaline network. Decreased RS FC over time in dopamine and noradrenaline PET-guided networks correlated with concomitant increased MADRS scores (r = range - 0.65/- 0.61, p < 0.001). The development of depressive symptoms in MS patients was associated with specific RS FC changes within the dopamine and noradrenaline networks.


Collagenase-1 (MMP-1), matrilysin-1 (MMP-7), and stromelysin-2 (MMP-10) are expressed by migrating enterocytes during intestinal wound healing.
Matrix metalloproteinases (MMPs) play a crucial role in wound healing of the skin, airways, and cornea, but data on MMPs in normal intestinal wound healing is limited. The aim of this study was to clarify the role of collagenase-1 (MMP-1), matrilysin-1 (MMP-7), and stromelysin-2 (MMP-10) in intestinal wound repair and to determine the effect of cytokines on the expression of these MMPs in intestinal epithelial cell lines. Surgical specimens from patients with ischemic colitis (n = 5) were used as an in vivo model of intestinal re-epithelialization. Fetal ileal explants were used as an ex vivo model. In situ hybridization for MMPs -1, -3, -7, and -10 was performed and immunohistochemical stainings were used to localize MMP-7 and -9 expressing cells. Stainings for cytokeratin and laminin-5 were performed to identify epithelial cells and migrating enterocytes, respectively. Caco-2, HT-29, and WiDr cell lines were treated for 6-48 h with different cytokines (e.g. EGF, KGF, IL-1 beta, TGF-alpha, TNF-alpha, and TGF-beta1) and Taqman real-time quantitative RT-PCR was used to investigate their effect on the expression of MMPs-1, -7, and -10. MMP-7, MMP-10, and MMP-1 were expressed by migrating enterocytes bordering intestinal ulcers in 5/5, 3/5, and 3/5 samples, respectively. In the fetal gut model, MMP-1 and MMP-10 were expressed by migrating enterocytes, but matrilysin-1 expression was not detected. Matrilysin-1 was up-regulated by TNF-alpha and IL-1 beta, and stromelysin-2 by TNF-alpha and EGF in Caco-2 and WiDr cell cultures. MMP-1 was up-regulated in Caco-2 cells by TGF-beta, EGF, and IL-1 beta, but only by EGF in WiDR cells. It is concluded that collagenase-1, stromelysin-2, and matrilysin-1 are involved in intestinal re-epithelialization in vivo and that they are up-regulated by cytokines relevant in wound repair.


Infiltrative myxoma of the stifle joint and thigh in a domestic rabbit (Oryctolagus cuniculus).
A 5-year-old male domestic rabbit had severe swelling of the left hindlimb. Radiographs demonstrated a proliferative, infiltrative lesion involving the stifle joint, femur and soft tissues of the thigh. Osteomyelitis or neoplasia was suspected and the limb was amputated. Grossly, there was a multilobular mass comprised of cystic spaces containing yellow mucinous material. Microscopically, the mass formed coalescing lobules of stellate to rounded cells embedded in varying amounts of myxoid to collagenous matrix, and some rimmed by narrow walls of metaplastic bone and/or cartilage, and some infiltrated by plasma cells, lymphocytes, heterophils and histiocytes. Immunohistochemically, neoplastic cells expressed vimentin but not cytokeratin, sarcomeric actin, Mac387 or BLA36. Cytokeratin was not detected in normal synovial cells. The radiographic, gross and histological findings were most consistent with synovial myxoma; however, because of the extensive involvement of the limb in the absence of confirmed metastatic disease, the term infiltrative synovial myxoma was applied.


The effect of heat shock on RNA synthesis in Drosophila tissues.
Total RNA from Drosophila imaginal discs, labeled under conditions of heat shock, is analyzed by hybridization in situ to salivary gland polytene chromosomes. Grain densities over the hybridizing bands are compared, showing that the response to heat shock is similar for several disc types and fly stocks. Alteration of the culture medium used for labeling during heat shock results in the specific induction (in discs, salvary glands, or fat body) of one of the heat-shock loci to a level far beyond that normally seen. We discuss the implications of this specific induction regarding the mechanism of response. We also discuss the observed difference between transcription labeling of salivary gland chromosomes and labeling by in situ hybridization.


Co-expression of alcohol dehydrogenase and aldehyde dehydrogenase in Bacillus subtilis for alcohol detoxification.
Alcoholic liver disease is a major cause of morbidity and mortality worldwide. In this work, a food-grade recombinant Bacillus subtilis co-expressing both alcohol dehydrogenase from Saccharomyces cerevisiae (scADH) and aldehyde dehydrogenase from Issatchenkia terricola (istALDH) were successfully constructed via double-crossover homologous recombination. When cultured at 37 °C for 48 h, the activities of scADH and istALDH were 57.56 ± 7.44 and 81.41 ± 8.26 U/mL, respectively. In pH 4.0, the alcohol degradation rate of recombinant B. subtilis fmb8 was 33% and the ΔLog10 was 0.1, indicating that fmb8 could be used as whole-cell biocatalysts for biodegradation of alcohols under low pH conditions. Mice experiments indicated that recombinant B. subtilis significantly alleviate recombinant alcohol-induced increases of mouse liver index, blood alcohol content, and serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities. Furthermore, recombinant B. subtilis significantly reduced liver malondialdehyde levels and increased total antioxidant capacity and superoxide dismutase levels in mouse liver. Overall, our findings suggested that food-grade B. subtilis fmb8 co-expressing scADH and istALDH could be used as a potential probiotic for alcohol detoxification and alleviation of alcoholic liver injury.


Right thyroid lobe agenesis and left thyroid colloid benign nodule discovered incidentally in female with breast carcinoma receiving chemotherapy for multiple metastases: Case report and review of the literature.
Thyroid hemiagenesis (THA) is the failure of embryologic development of a lobe of the thyroid gland and is a rare anomaly of uncertain incidence. The left lobe is more commonly absent than the right lobe. It is discovered incidentally during investigations. A 48 year old Egyptian female presented at the thyroid surgery clinic at our institution to follow up after a nodule left thyroid lobe accidently discovered on positron emission tomography (PET) scan undertaken to follow up on bone metastasis of breast cancer which was surgically removed about 14 years ago. The patient looked clinically well with no scar in the anterior of the neck, no palpable thyroid nodules, and no lymphadenopathy. Ultrasound imaging of the neck revealed absent right thyroid lobe tissue and a nodule was noted at the upper pole of the left thyroid. Laboratory tests unremarkable, with TSH (2.14 mIU/L), and FT4 (12.4 pmol/L) within normal range. Fine needle aspiration and cytology of the thyroid nodule revealed atypia of undetermined significance. THA is rare and right THA is even rarer. It is usually asymptomatic, and diagnosis is mostly incidental while investigating symptoms due to pathology of the other thyroid lobe or any of the parathyroid glands. In much rarer circumstances, right THA might be discovered when investigating conditions not related to the thyroid or parathyroid glands years after the initial pathology as in the current case. Etiology is inconclusive but genetic factors could play a role. No treatment is required if no symptoms are present.


Sural nerve harvest for infants: integrated with information based on anatomical dissections
The aim of the present study was to determine the course and possible variations of the sural nerve with all anatomical details in human fetal cadavers. This study was performed on 60 fetal cadavers. Formation type and level of the sural nerve was detected. According to trimesters, it was determined that the mean transverse and vertical distance between the lowest point of the LM and the SN varied between 1.1 and 2.9 mm and 1.54 and 3.58 mm, respectively. Type 2 was the most common seen type of sural nerve (35.83%). It was determined that the sural nerve was mostly formed at the middle third of the leg (42.5%). Sural nerve graft with the knowledge of the anatomical details may be used for peripheral nerve reconstruction is required in congenital lesions, such as facial paralysis, obstetric brachial paralysis, and posttraumatic lesions in infants and children.


Engagement with the North Wales Local Dental Committee - part 2: communication preferences.
Aims To gather the views of dentists practising within North Wales on their preferences as to how they would prefer to interact with the North Wales Local Dental Committee (LDC) (NWLDC).Design Descriptive cross-sectional survey.Setting Online electronic questionnaire.Materials and methods Survey circulated via the NWLDC's current communication channels, local professional groups, the local health board and Health Education and Improvement Wales' MaxCourse email distribution.Results A total of 167 unique responses were received from across North Wales, which included 132 responses from primary care dentists, yielding a response rate of 40.6%. Respondents would prefer to interact with the NWLDC via email notifications (88%), virtual meetings (52.1%) and via the LDC website (41.9%). Furthermore, 31.1% wanted a combination of both physical and virtual attendance at an LDC meeting to be an option and 43.7% of respondents did not want to attend LDC meetings as a preferred method of engaging with the LDC. The survey indicated that holding an educational event just before the LDC meeting will not have a positive impact on subsequent participation in the LDC meeting for 91.6% of respondents. The survey revealed that 70% had never visited the NWLDC's website, with only 20.4% of people visiting it more than once a year. Also, 83.8% stated that the pandemic had made no difference on them accessing the NWLDC website. The results allowed the identification of the top five 'core elements' for an ideal LDC website and which elements should have their access restricted only to LDC members.Conclusions The survey revealed that the respondents want greater communication from the NWLDC and that this is best achieved over a variety of different communication platforms, using the NWLDC website as a primary information resource to which the other communication methods are tethered. It is recognised that only a minority will want to, or be able to, attend the quarterly LDC meetings and so it is imperative that the NWLDC's communication strategy accommodates these individuals, both proactively and passively, by effective use of digital media and to continuously monitor its effectiveness so that it can adapt its strategy to maximise engagement and information delivery. There is a need to expand the representation of the LDC committee to encompass those who have newly entered the profession or are new to the area. The NWLDC recognises the need to reach out to dentists across North Wales who many feel isolated and disenfranchised to establish a constructive, mutually beneficial relationship.


Targeting the viral-entry facilitators of SARS-CoV-2 as a therapeutic strategy in COVID-19.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) infection, which has emerged as a global pandemic causing serious concerns. Lack of specific and effective therapeutics for the treatment of COVID-19 is a major concern and the development of vaccines is another important aspect in managing the infection effectively. The first step in the SARS-CoV-2 pathogenesis is the viral entry and it is mediated by its densely glycosylated spike protein (S-protein). Similar to the SARS-CoV, SARS-CoV-2 also engages angiotensin-converting enzyme 2 (ACE2) as the host cell entry receptor. In addition to ACE2, several recent studies have implicated the crucial role of cell surface heparan sulfate (HS) as a necessary assisting cofactor for ACE2-mediated SARS-CoV-2 entry. Furthermore, SARS-CoV-2 was also identified to use both endosomal cysteine proteases cathepsin B and L (CatB/L) and the transmembrane serine protease 2 (TMPRSS2) for the pivotal role of S-protein priming mediating viral entry. As the entry of SARS-CoV-2 into host cells is mandatory for viral infection, it becomes an extremely attractive therapeutic intervention point. In this regard, this review will focus on the therapeutic targeting of the crucial steps of SARS-CoV-2 viral entry like S-protein/ACE2 interaction and S-protein priming by host cell proteases. In addition, this review will also give insights to the readers on several therapeutic opportunities, pharmacological targeting of the viral-entry facilitators like S-Protein, ACE2, cell surface HS, TMPRSS2, and CatB/L and evidence for those drugs currently ongoing clinical studies.


Anterior temporal lobectomy for complex partial seizures: evaluation, results, and long-term follow-up in 100 cases.
We report evaluation and results in 100 patients who had undergone anterior temporal lobectomy for intractable complex partial seizures. Average follow-up was 9.0 years (range, 2 to 21 years). In the 2nd postoperative year, 63% were seizure free, 16% were significantly improved, and 21% were considered not significantly improved. Mean number of seizures in the last group was 27% of preoperative levels. Surgical results did not change significantly in subsequent postoperative years; good outcomes tended to persist over the longer term. We also examined the utility of continuous depth electrode monitoring in the evaluation of patients with independent bitemporal interictal epileptiform activity. Despite limited numbers of subjects in this category, there was a trend toward improved surgical outcome when such subjects were evaluated with depth electrodes.


Ferroptosis contributes to developmental cell death in rice blast.
Ferroptosis, an iron-dependent cell death process, was found to occur in Magnaporthe oryzae, and plays a key role in infection-related development therein. Ferroptosis in the rice-blast fungus was confirmed based on five basic criteria. We confirmed the dependence of ferroptosis on ferric ions, and optimized ratio-fluorescence imaging of C11-BODIPY581/591 as a precise sensor for lipid peroxides that mediate ferroptosis in M. oryzae. We uncovered an important regulatory function for reduced glutathione and NADPH oxidases in modulating the superoxide moieties required for ferroptotic cell death. We found ferroptosis to be necessary for the developmental cell death of conidia during appressorium maturation in rice blast. Such ferroptotic cell death initiated first in the terminal cell and progressed sequentially to the entire conidium. Iron chelation or chemical inhibition of ferroptosis caused conidial cells to remain viable, and led to strong defects in host invasion by M. oryzae. Ferroptosis induction exclusively in the host severely constrained the invasive growth of M. oryzae. We found inter-reliant and independent roles for ferroptosis and autophagy in controlling such precise cell death in M. oryzae during pathogenic differentiation. Our study provides significant molecular insights into the role of developmental cell death and iron homeostasis in fungal pathogenesis.


Localization of serotonin in cleavage embryos of Ophryotrocha labronica La Greca and Bacci.
Serotonin distribution in early Ophryotrocha embryos was investigated with fluorescence microscopy based on formaldehyde gas treatment of the embryos, and with light- and electron-microscopic autoradiography after the embryos had been treated with3H-5-hydroxytryptophan.Sections of early cleavage embryos showed serotonin-specific fluorescence all over the blastomeres, but it was mainly concentrated on yolk granules, and to a lesser degree on lipid drops and vacuoles. In 2-8 cell embryos, marked regional concentration of serotonin fluorescence was noticeable along the completed cleavage furrows.The autoradiographs confirmed the picture of the yolk granules as the principal site of serotonin formation and serotonin accumulation; considerable amounts were also associated with their decomposition products, i.e. lipid drops, vacuoles, and vesicles, whereas major cell organelles, e.g. mitochondria, were almost totally lacking. Of cytoplasmic structures in the blastomeres without apparent yolk granule origin, only microfilaments, particularly those amassed along the cleavage furrow, showed consistent and significant association with formed serotonin. This suggests a connexion between serotonin and microfilaments and might imply that in early embryo cells the fundamental contractile machinery is controlled by serotonin gradually released from the yolk granules.Within the blastomere nuclei, moderate amounts of serotonin were demonstrated with both fluorescence microscopy and autoradiography.The monoamine oxidase (MAO) inhibitor catron® (phenylisopropylhydrazine), used to intensify the autoradiographic picture of serotonin in the Ophryotrocha embryos, markedly increased intragranular serotonin accumulation, but also retarded yolk granule disintegration and delayed the cell cleavage process. In embryos barely able to cleave after treatment with catron®, ultrastructural analysis demonstrated that membrane formation at cell cleavage depends on influx of material from the nearby disintegrating yolk granules.


[Quality of life after subtotal resection and gastrectomy for gastric cancer].
Recently, quality of life has become a main objective in surgical therapy. Apart from the oncological consequences, the quality of results after gastric carcinoma resection are mainly determined by social and psychological aspects of life, early postoperative complications, and long-term nutritive/functional parameters. Of 338 patients who underwent gastric resection for adenocarcinoma of the stomach, quality of life was assessed in 73 recurrence-free patients by means of the Gastrointestinal Life Quality Index (GLQI). The median age was 71.9 years, and surgery had been carried out at least 1 year prior to the investigation (median follow-up 4.5 years). Patients with subtotal gastric resection displayed significantly higher GLQI scores (120 [97-138] points) than patients with gastrectomy (116 [70-139] points;p=0.047). Among partial parameters of the life quality index, physical functions were significantly better after subtotal resection (p=0.040), while the emotional status (p=0.147) and social activities (p=0.337) did not differ between the two groups. Abdominal symptoms (p=0.081) and the nutritional function (p=0.228) were insignificantly different. The number of meals (4 vs. 5 meals per day) and the loss of weight since surgery (5 vs. 10 kg) were less after subtotal resection than after gastrectomy. However, the latter parameter did not reach statistical significance.


Temporary suppression of tinnitus by modulated sounds.
Despite high prevalence of tinnitus and its impact on quality life, there is no cure for tinnitus at present. Here, we report an effective means to temporarily suppress tinnitus by amplitude- and frequency-modulated tones. We systematically explored the interaction between subjective tinnitus and 17 external sounds in 20 chronic tinnitus sufferers. The external sounds included traditionally used unmodulated stimuli such as pure tones and white noise and dynamically modulated stimuli known to produce sustained neural synchrony in the central auditory pathway. All external sounds were presented in a random order to all subjects and at a loudness level that was just below tinnitus loudness. We found some tinnitus suppression in terms of reduced loudness by at least one of the 17 stimuli in 90% of the subjects, with the greatest suppression by amplitude-modulated tones with carrier frequencies near the tinnitus pitch for tinnitus sufferers with relatively normal loudness growth. Our results suggest that, in addition to a traditional masking approach using unmodulated pure tones and white noise, modulated sounds should be used for tinnitus suppression because they may be more effective in reducing hyperactive neural activities associated with tinnitus. The long-term effects of the modulated sounds on tinnitus and the underlying mechanisms remain to be investigated.


Aconitate decarboxylase 1 suppresses cerebral ischemia-reperfusion injury in mice.
Immunometabolic changes have been shown to be a key factor in determining the immune cell response in disease models. The immunometabolite, itaconate, is produced by aconitate decarboxylase 1 (Acod1) and has been shown to inhibit inflammatory signaling in macrophages. In this study, we explore the role of Acod1 and itaconate in cerebral ischemia/reperfusion injury. We assessed the effect of global Acod1 knockout (Acod1KO, loss of endogenous itaconate) in a transient ischemia/reperfusion occlusion stroke model. Mice received a transient 90-min middle cerebral artery occlusion followed with 24-h of reperfusion. Stroke lesion volume was measured by MRI analysis and brain tissues were collected for mRNA gene expression analysis. Acod1KO mice showed significant increases in lesion volume compared to control mice, however no differences in pro-inflammatory mRNA levels were observed. Cell specific knockout of Acod1 in myeloid cells (LysM-Cre), microglia cells (CX3CR1, Cre-ERT2) and Endothelial cells (Cdh5(PAC), Cre-ERT2) did not reproduce lesion volume changes seen in global Acod1KO, indicating that circulating myeloid cells, resident microglia and endothelial cell populations are not the primary contributors to the observed phenotype. These effects however do not appear to be driven by changes in inflammatory gene regulation. These data suggests that endogenous Acod1 is protective in cerebral ischemia/reperfusion injury.


Identification of the CesA Subfamily and Functional Analysis of GhMCesA35 in Gossypium hirsutum L.
The cellulose synthase genes control the biosynthesis of cellulose in plants. Nonetheless, the gene family members of CesA have not been identified in the newly assembled genome of Gossypiumhirsutum (AD1, HEBAU_NDM8). We identified 38 CesA genes in G. hirsutum (NDM8) and found that the protein sequence of GhMCesA35 is 100% identical to CelA1 in a previous study. It is already known that CelA1 is involved in cellulose biosynthesis in vitro. However, the function of this gene in vivo has not been validated. In this study, we verified the function of GhMCesA35 in vivo based on overexpressed Arabidopsis thaliana. In addition, we found that it interacted with GhCesA7 through the yeast two-hybrid assay. This study provides new insights for studying the biological functions of CesA genes in G. hirsutum, thereby improving cotton fiber quality and yield.


Implications for the insulin signaling pathway in Snell dwarf mouse longevity: a similarity with the C. elegans longevity paradigm.
Mutation analyses in the nematode, Caenorhabditis elegans, and mice have identified genes that increase their life-span via hormonal signal transduction, i.e. the insulin/insulin-like growth factor-1 (IGF-1) pathway in nematodes, and the growth hormone (GH)-thyriod stimulating hormone (TSH)-prolactin system in Snell dwarf mouse mutants. We have shown that the GH deficiency due to Pit1 mutation in the long-lived Snell dwarf mice may decrease circulating insulin levels, thereby resulting in a decreased activity of the insulin/IGF-1 signaling pathway. The data presented are consistent with our hypothesis that the decreased circulating insulin levels resulting from the Pit1 mutation mimics a physiological state similar to that proposed to occur in the long-lived C. elegans, daf-2 mutant. Our studies demonstrate a series of changes in components of the insulin/IGF-1-signaling pathway that suggest a reduction-of-function of this pathway in the aged dwarf. These include a decreased IRS-2 pool level, a decrease in PI3K activity and its association with IRS-2 and decreased docking of p85alpha to IRS-2. Our data also suggest a preferential docking of IRS-2-p85 alpha -p110 alpha in the aged dwarf liver and IRS-2-p85 alpha -p110 beta in the aged control. We speculate that the preference for the p110 alpha-containing complex may be a specific characteristic of a downstream segment of the longevity-signaling cascade. We conclude that the Pit1 mutation may result in physiological homeostasis that favors longevity, and that the Snell dwarf mutant conforms to the nematode longevity paradigm.


Effect of Breathing Support in Very Preterm Infants Not Breathing During Deferred Cord Clamping: A Randomized Controlled Trial (The ABC Study).
To determine if providing respiratory support to very preterm infants who fail to breathe regularly during deferred cord clamping (DCC) decreased red cell transfusion. Infants less than 31 weeks of gestation undergoing DCC who were apneic or not breathing regularly at 15 seconds underwent stratified randomization. Pale, limp, and nonresponsive infants were excluded. The standard group received gentle stimulation in a neutral position for 50 seconds; the intervention group received intermittent positive pressure ventilation via face mask and T piece from 20 to 50 seconds of age with a fractional inspired oxygen of 0.3. The primary outcome was the proportion transfused, with a secondary composite outcome of death, severe intraventricular hemorrhage, or chronic lung disease. Of 311 assessed infants, 113 met the inclusion criteria and were studied; 57 received the intervention and 56 standard treatment. Patient characteristics were similar. Overall, 105 infants (93%) received the intended 50 seconds DCC (54 in the intervention group and 51 in the standard group). Rates of transfusion were similar (28% vs 30% in the intervention vs control groups), as were rates of the composite outcome (46% vs 38% in the intervention vs the control arms; P = .45). Providing breathing support during 50 seconds of DCC in this single-center cohort seemed to be safe and feasible, but did not decrease the transfusion rates or improve outcomes. http://www.anzctr.org.au/ACTRN12615001026516.aspx.


Traumatic brachial plexus lesions in the adult. Indications and results.
Several types of lesions in adults can be differentiated. The author discusses his experience with 810 operated cases from 1975 to 1994.


Building Critical Care Capacity in a Low-Income Country.
Critical illness is common throughout the world and is associated with high costs of care and resource intensity. The Corona virus disease 2019 (COVID-19) pandemic created a sudden surge of critically ill patients, which in turn led to devastating effects on health care systems worldwide and more so in Africa. This narrative report describes how an attempt was made at bridging the existing gaps in quality of care for critically ill patients at national and regional levels for COVID and the postpandemic era in a low income country.


Hematogenously disseminated skin disease caused by Mucor velutinosus in a patient with acute myeloid leukemia.
We report here a case of disseminated skin infection caused by Mucor velutinosus, a recently described new species. We believe this to be the first published report of a clinical case of mucormycosis due to M. velutinosus, as well as a rare case of dissemination from a deep site to skin.


Task-synchronized eye blink modulation neither requires visual stimulation nor active motor response and is modulated by task predictability.
It has been repeatedly shown that temporal task features are reflected in eye blink dynamics during attention tasks. Eye blinks occur with increased likeliness particularly when demands on external attention allocation are low. Both predictive, top-down and reactive, bottom-up processes were shown to be involved in blink regulation. However, whether temporal stimulus prediction is a generally active component of the attention system or rather specific to the visual domain has not been fully elaborated yet. By monitoring eye blinking of 99 students during an auditory attention task and analyzing particularly the dynamics of eye blink onsets relative to stimuli timings, we show here that prediction does, in principle, not require visual stimulation, and is also not merely a consequence of the involvement of manual responses during the task. We further show that both the inclusion of manual response to stimuli and elevated task predictability enhance the prediction component reflected in eye blink dynamics, whereas for the latter we experimentally manipulate objective task predictability by adjusting the frequency dependence of the power spectral densities of the series of inter-stimulus time intervals. This allows us finally to explain why, for specific choices of experimental conditions, the generally active and present prediction component involved in attention can become difficult to detect in non-visual, auditory tasks. Conversely, this comes with the important implication that, if tasks aim for elaborating particularly temporal prediction, distributing stimuli over time such that inter-stimulus-intervals conform to a sample of Gaussian noise represents a specifically unfavorable choice.


An NH2-terminal peptide from the vaccinia virus L1R protein directs the myristylation and virion envelope localization of a heterologous fusion protein.
The vaccinia virus L1R gene product is a late protein destined for insertion into the envelope of intracellular virus particles. Because this protein is co-translationally modified by the addition of myristic acid to the penultimate NH2-terminal glycine residue, it was of interest to identify the modification signal within the L1R protein and to assess the relevance of myristylation to protein localization. To this end, a family of chimeric reporter genes containing 0-13 codons from the NH2 terminus of the L1R open reading frame fused in-frame to the bacterial chloramphenicol acetyltransferase gene was constructed. The encoded proteins were tested as myristylation substrates in cell-free extracts and infected cells. The results obtained in vitro and in vivo were similar and suggested that although the NH2-terminal 5 amino acids of the L1R protein were the minimum signal required to observe modification by myristate, 12 amino acids were required to obtain wild type levels of myristylation with a modulating role played by the intervening amino acid residues. Furthermore, subcellular fractionation of infected cells expressing the fusion proteins indicated that the NH2 terminus of the L1R protein was capable of targeting the fusion proteins to membrane-containing fractions only if myristylated. In particular, the myristylated fusion protein containing the first 12 amino acids of the L1R protein abutted to the chloramphenicol acetyltransferase protein was found associated with the envelope of intracellular vaccinia virus particles.


Hepatitis B core antigen-based vaccine demonstrates cross-neutralization against heterologous North American Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2) strains.
The U.S. swine industry have been bearing the financial impact of Porcine Reproductive and Respiratory Syndrome (PRRS) for decades. Absent of a safe and efficacious vaccine to combat PRRS virus's genetic heterogeneity, it remains a costly disease on pig farms across the country. We have developed virus-like-particle (VLP) based vaccines that incorporate 4 PRRSV epitopes in the hepatitis B core antigen (HBcAg) backbone. Administration of the vaccines in female BALB/C mice resulted in extremely significant PRRSV epitope specific antibody response. One vaccine candidate GP3-4 was able to mount a significant viral neutralizing response against both parental PRRSV strain VR2385 and heterologous PRRSV strain NADC20, showing a promising potential for cross-protection against PRRSV.


The SnRK2 family in pepper (Capsicum annuum L.): genome-wide identification and expression analyses during fruit development and under abiotic stress.
Plant-specific SnRK2 (sucrose nonfermenting-1-related protein kinase 2) genes play crucial roles in the coordination of plant growth and development and responses to stress. However, comprehensive studies have not been performed for this gene family in pepper (Capsicum annuum), a very important Solanaceous vegetable worldwide. To fully understand the status of SnRK2s in chili pepper, a total of 9 putative SnRK2 genes (named CaSnRK2.1-2.9) were identified in pepper in the present study. These genes were located on 7 different chromosomes and classified into three subfamilies based on the phylogenetic tree. Their conserved motif compositions and exon-intron structures were systematically analyzed, and the results strongly supported the classification. Furthermore, a total of 81 putative cis-elements were found in the promoter regions, and the cis-elements related to hormone and stress signaling were abundant. Finally, the CaSnRK2 gene expression profiles among different tissues, especially developing fruit tissue, and under various abiotic stresses were investigated to identify tissue-specific or stress-responsive candidates. This study was the first to comprehensively investigate the SnRK2 family in pepper, and the results provide important clues for further functional analyses of fruit development and abiotic stress responses.


Determination of the labyrinth in different amphibian species and its correlation with determination of the other ectoderm derivatives.
The process of labyrinth determination has been studied in three urodelean and seven anuran species by means of homoplastic transplantation of ear region epidermis, defined as the piece of epidermal layer containing the material of the prospective ear vesicle (labyrinth rudiment). The ear region epidermis was grafted onto the abdominal wall of embryos of the same developmental stage. The earliest stage of operation resulting in ectopic ear vesicle formation was determined, suggesting the appearance of organ-specific properties in the ear ectoderm. These properties were enhanced in the further course of development, as indicated by the frequency of ear vesicle formation and by the volume and degree of complexity that the vesicles reached. The data obtained allowed us to arrange the species studied in a sequence, ranging from most Ranidae and Bufo viridis, in which organ-specific properties appear earlier and are most strongly expressed, to Triturus vulgaris in which their expression is least pronounced. Comparison of properties of the material giving rise to the ear vesicle or to several other ectodermal derivatives led to the conclusion that species-specific differences in determination of different ectodermal rudiments are due to species specific properties of the whole ectoderm. These differences appear to be determined by an evolutionary shift of the beginning of gastrulation towards later cleavage cycles.


The Long and Short of It: A Dwarf Neurexin Suffices for Synapse Assembly.
Neurexins have been established as a major coordinator of synapse assembly, functioning through interactions with postsynaptic cell adhesion molecules. Kurshan et al. (2018) now show that a C. elegans "dwarf neurexin" lacking its extracellular interaction domains can conduct synapse formation independent of postsynaptic partners.


UGT1A1 and UGT1A3 activity and inhibition in human liver and intestinal microsomes and a recombinant UGT system under similar assay conditions using selective substrates and inhibitors.
In vitro enzyme kinetics and inhibition data was compared for UGT1A1 and UGT1A3 isoforms under similar assay conditions using human liver microsomes (HLM), human intestinal microsomes (HIM) and recombinant UGT (rUGT) enzyme systems.UGT1A1 catalysed β-estradiol 3-β-D-glucuronide formation showed allosteric sigmoidal kinetics in all enzyme systems; while UGT1A3 catalysed CDCA 24-acyl-β-D-glucuronide formation exhibited Michaelis-Menten kinetics in HLM, substrate inhibition kinetics in HIM and rUGT systems. Corresponding Km or S50 concentrations of β-estradiol and CDCA were employed in the respective UGT inhibition studies.Atazanavir inhibited the production of β-estradiol 3-β-D-glucuronide with IC50 values of 0.54 µM and 0.16 µM in HLM and rUGT1A1, respectively. But its inhibition potential was not observed in HIM, indicating potential cross-talk with other high-affinity intestinal UGT isozymes. On the other hand, zafirlukast, a pan UGT inhibitor, exhibited moderate inhibition in HIM with an IC50 value of 16.70 µM. Lithocholic acid, inhibited the production of CDCA 24-acyl-β-D-glucuronide with IC50 values of 1.68, 1.84, and 12.42 µM in HLM, rUGT1A3, and HIM, respectively.These results indicated that HLM, HIM, and rUGTs may be used as complementary in vitro systems to evaluate hepatic and intestinal UGT mediated DDIs at the screening stage.


KR-32570, a novel Na+/H+ exchanger-1 inhibitor, attenuates hypoxia-induced cell death through inhibition of intracellular Ca2+ overload and mitochondrial death pathway in H9c2 cells.
A novel Na+/H+ exchanger-1 (NHE-1) inhibitor [5-(2-methoxy-5-chloro-5-phenyl)furan-2-ylcarbonyl]guanidine (KR-32570) has been previously demonstrated to elicit cardioprotective effect against ischemic injury in rat heart. In the present study, we examined the effects of KR-32570 on cell death induced by hypoxic insult in heart-derived H9c2 cells. Treatment with KR-32570 (1-10 microM) significantly reduced hypoxia-induced necrotic cell death (lactate dehydrogenase release) and apoptotic cell death (TUNEL-positivity, caspase-3 activity). KR-32570 also decreased the cytosolic and mitochondrial Ca2+ overload induced by hypoxia. Inhibition of mitochondrial Ca2+ overload by ruthenium red mimicked the anti-apoptotic effect of KR-32570. In addition, KR-32570 significantly recovered the large reduction in mitochondrial membrane potential (delta psi(m)) and cytochrome c release induced by hypoxia. Taken together, our results suggest that a new NHE-1 inhibitor KR-32570 elicits potent cardioprotective effects in H9c2 cells, and its effects may be mediated by inhibition of intracellular Ca2+ overload and mitochondrial death pathway during hypoxia.


Stereotactic radiosurgery for patients with solid brain metastases: current status.
The goal of this article is to provide a contemporary update on the use of stereotactic radiosurgery (SRS) for the treatment of intracranial metastatic disease. We discuss the rationale for employing SRS in brain metastases and describe the critical factors that predict outcome. We highlight the main clinical indications for SRS including treatment of recurrent brain metastases after previous whole brain radiation therapy (WBRT), as a boost after WBRT, and as sole therapy for newly diagnosed tumors. For each clinical scenario, we offer a treatment algorithm based on our clinical experience. The article also addresses the most common complications associated with SRS and their treatment.


An immunogenic Salmonella ghost confers protection against internal organ colonization and egg contamination.
The tightly regulated expression of the PhiX174 lysis gene E from a multi-copy plasmid led to the stable production of an Salmonella Enteritidis bacterial ghost. The present study was conducted to evaluate induction of the humoral and cell-mediated immune responses induced after single or double intramuscular immunization with the S. Enteritidis ghost and to assess its protective effect on colonization of the intestinal tract, visceral and reproductive organs, internal egg contamination, and egg production of laying chickens. A total of 60 chickens were equally divided into three groups (n=20); group A (non-immunized control), group B (immunized at 8 and 16 weeks of age) and group C (immunized at 16th week of age). Chickens from both immunized groups B and C demonstrated significant increases in plasma IgG, intestinal secretory IgA levels, and antigen-specific lymphocyte proliferative responses. The population of CD3+CD4+ positive T cells in the immunized chickens was also significantly increased after immunization and virulent challenge. In addition, the immunized groups B and C showed significantly higher egg production and a lower percentage of S. Enteritidis contaminated eggs after challenge compared to those of group A. A comparison of challenge strain isolation from the immunized-challenged and non-immunized-challenged layer hens showed that the double immunization group induced excellent protection against intestinal, liver, splenic, and ovarian Salmonella colonization; however, the single immunized chickens showed lower counts only in the splenic and ovarian organs. Overall, the data give compelling evidence that vaccination with the S. Enteritidis ghost induced robust protective immunity against experimental avian salmonellosis and may contribute to the reduce incidence of egg contamination.


Geophysical monitoring of simulated homicide burials for forensic investigations.
Finding hidden bodies, believed to have been murdered and buried, is problematic, expensive in terms of human resource and currently has low success rates for law enforcement agencies. Here we present, for the first time, ten years of multidisciplinary geophysical monitoring of simulated clandestine graves using animal analogues. Results will provide forensic search teams with crucial information on optimal detection techniques, equipment configuration and datasets for comparison to active and unsolved cold case searches. Electrical Resistivity (ER) surveys showed a naked burial produced large, low-resistivity anomalies for up to four years, but then the body became difficult to image. A wrapped burial had consistent small, high-resistivity anomalies for four years, then large high-resistivity anomalies until the survey period end. Ground Penetrating Radar (GPR) 110-900 MHz surveys showed the wrapped burial could be detected throughout. 225 MHz GPR data was optimal, but the naked burial was poorly imaged after six years. Results suggested conducting both ER and GPR surveys if the burial style was unknown when searching for interred remains. Surveys in winter and spring produced the best datasets, and, as post-burial time increases, surveying in these seasons became increasingly important. This multidisciplinary study provides critical new insights for law enforcement and families of the disappeared worldwide.


Overcontrolled, undercontrolled, and resilient personality styles among patients with eating disorders.
Personality has been suggested to be an important factor in understanding onset, maintenance, and recovery from eating disorders (ED). The objective of the current study was to evaluate personality style in different ED diagnostic groups as classified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth edition (DSM-5). The overcontrolled, undercontrolled, and resilient personality styles were compared in four groups of patients with EDs: anorexia nervosa restricting (ANr) (n = 34), anorexia nervosa binge eating/purging (ANbp) (n = 31), atypical anorexia nervosa (AAN) (n = 29), and bulimia nervosa (BN) (n = 76). These groups were compared with a group of patients with borderline personality disorder (BPD) (n = 108), and a non-clinical group (NC) (n = 444). Patient data were collected at two outpatient clinics in Uppsala, Sweden. NC control data were collected through convenience sampling. Participants filled out questionnaires assessing personality style. The main findings were more pronounced overcontrol reported by the ANr and AAN groups compared with the BN, BPD, and NC groups, and no significant difference in resilience between the ED and the NC groups. Considerable variability of over- and undercontrol was also found within each group. The results replicate previous findings when EDs are classified according to current diagnostic criteria (DSM-5). Taking personality styles into account may improve our understanding of certain characteristics in EDs, such as social deficits and rigidity that are attributed to poor treatment outcome.


[François Gros : an intelligent, kind-hearted man who couldn't say no].
Here I recall some privileged moments in my interactions with François: when he helped me obtain a grant for an NGO; when I participated in the work of COPED; when I returned to hospital medicine, his support for writing and publishing books that give patients a voice.


REVIEW: Efficacy and mechanisms of action of statins in the treatment of diabetic dyslipidemia.
The Adult Treatment Panel III recommends 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, as first-line lipid-altering therapy for all adult patients with diabetes mellitus. This is based on the well-characterized efficacy and safety profiles of this class of agents as well as several clinical trials demonstrating that statin treatment reduces the risk of cardiovascular events. This review provides an overview of the effectiveness and mechanisms of action of statins in patients with diabetes mellitus using small efficacy trials and large clinical outcomes trials as well as studies of the effects of statins on apolipoprotein B (apoB) metabolism. The major findings presented are a review of mechanistic studies of selected subjects with diabetes mellitus and dyslipidemia and a compilation of results from large-scale clinical trials of patients with diabetes. Statins are highly efficacious as low-density lipoprotein cholesterol-lowering agents and have more modest effects on very low-density lipoprotein triglyceride and high-density lipoprotein cholesterol levels. The effects of statins on plasma lipids and lipoproteins result from their ability to both increase the efficiency with which very low-density lipoprotein and low-density lipoprotein are cleared from the circulation and reduce the production of apoB-containing lipoproteins by the liver. Additional investigations are needed to clarify the mechanisms by which statins reduce apoB secretion from the liver.


Scanning electron microscopic assessment of coating irregularities and their precursors in unexpanded durable polymer-based drug-eluting stents.
To assess and quantify coating irregularities on unexpanded and expanded durable polymer-based drug-eluting stents (DES) to gain insights into the origin of coating irregularities. Previous scanning electron microscopy (SEM) studies in various expanded DES revealed differences in frequency and size of coating irregularities between DES types and specific distribution patterns, however, the origin of these irregularities is unclear. We assessed at bench side a total of 1,200 SEM images obtained in 30 DES samples (15 expanded and 15 unexpanded) of Cypher Select Plus, Taxus Liberté, Endeavor, Xience V, and resolute. For most coating irregularities seen on expanded DES (72%; 23/32), a matching irregularity (n = 18/23) and/or its precursor (n = 11/23) was observed in unexpanded DES. Unexpanded Cypher select showed (small) crater lesions and cracks together with precursors of "peeling." On unexpanded Taxus Liberté, thinning of polymer, small bare metal areas, wrinkles, and one precursor type were found. Unexpanded endeavor showed cracks, small bare metal areas, crater lesions, and precursors of the latter. Unexpanded Xience V and resolute mainly revealed crater lesions and their precursors. On unexpanded versus expanded DES, there was no difference in measured frequency of coating irregularities and precursors (P = ns) with the exception of more bare metal areas on expanded Taxus Liberte (P = 0.01). Most coating irregularities, or the potential to develop them, are inherent to the unexpanded DES. Important determinants of the formation of coating irregularities may be the stent geometry and the physical properties of the coating, while stent-balloon interaction plays no major role.


Synthesis of Modified Nucleoside Oligophosphates Simplified: Fast, Pure, and Protecting Group Free.
Phosphoramidite analogues of modified cyclotriphosphates provide a general and step-economical synthesis of nucleoside triphosphates and analogues on scale without the need for protecting groups. These reagents enable rapid access to pure nucleoside oligophosphates and a range of other analogues that were previously difficult to obtain (e.g., NH, CH2, CCl2, and CF2 replacements for O, phosphono- and phosphoimidazolides, -morpholidates, -azidates, and -fluoridates). DFT calculations demonstrate that the selectivity of the cyclotriphosphate opening reactions proceeds via an in-line substitution mechanism that displaces the least charged leaving group.


Phenotypic and behavioral defects induced by iron exposure can be transferred to progeny in Caenorhabditis elegans.
Previous work has showed that excess iron accumulation is harmful to reproduction and even promotes death; however, whether the multiple biological toxicity of iron (Fe) exposure could be transferred to progeny remains unknown. The present study used Caenorhabditis elegans to analyze the multiple toxicities of iron exposure and their possible transferable properties. Three concentrations of iron sulfate solution (2.5 micromol/L, 75 micromol/L, and 200 micromol/L) were used. The endpoints of lifespan, body size, generation time, brood size, head thrash and body bend frequencies, and chemotaxis plasticity were selected to investigate Fe toxicity and its effect on progeny in Caenorhabditis elegans. The Fe toxicity could cause multiple biological defects in a dose-dependent manner by affecting different endpoints in nematodes. Most of the multiple biological defects and behavior toxicities could be transferred from Fe-exposed Caenorhabditis elegans to their progeny. Compared to the parents, no recovery phenotypes were observed for some of the defects in the progeny, such as body bend frequency and life span. We further summarized the defects caused by Fe exposure into 2 groups according to their transferable properties. Our results suggest that Fe exposure could cause multiple biological defects, and most of these severe defects could be transferred from Fe exposed nematodes to their progeny.


Thin-layer chromatography, overlay technique and mass spectrometry: a versatile triad advancing glycosphingolipidomics.
Much effort is currently invested in the development of mass spectrometry-based strategies for investigating the entirety of glycosphingolipids (GSLs) of a certain cell type, tissue, organ or body encompassing the respective glycosphingolipidome. As part of the investigation of the vertebrate glycosphingolipidome, GSL analysis is undergoing rapid expansion owing to the application of novel mass spectrometry techniques acting as the linchpin in the network of collaborations challenged to unravel structural and functional aspects of GSLs. Difficulties may arise in the determination of the exact structures of GSLs due to the heterogeneity of the sugar moiety varying in the number and sequence of monosaccharides, and their anomeric configuration and linkage type, which make up the principal items of the glyco code of biologically active carbohydrate chains. The ceramide variability caused by the diversity of the long-chain amino alcohol and the fatty acid, which both may vary in chain length, degree of unsaturation, and type and number of substituents, further contributes to the increasing number of possible GSL species. In view of this heterogeneity, a single-method analytical mass spectrometry (MS) technique without auxiliary tools yields limited data, providing only partial structural information of individual GSLs in complex mixtures. Approaching this challenge, current advances on a triad system matching three complementary methods are described in this review: (i) silica gel based TLC separation of GSLs, (ii) their overlay detection on the TLC plate (mostly based on antibody-mediated recognition), and (iii) direct and indirect MS based structural characterization, i.e. directly on the TLC plate or in lipid extracts from silica gel. We will focus on recent improvements by employing antibodies, AB(5) toxins and bacteria for direct IR-MALDI-o-TOF MS and indirect ESI-QTOF MS analysis of GSLs. We believe that the combinatorial approach using conventional TLC and modern mass spectrometry provides a developmental advance in exploring the glycosphingolipidome of biological material.


Reconstruction of Interimplant Papilla by Demineralized Freeze-dried Bone Allograft Block Fixed by Titanium Screw in Maxillary Esthetic Zone.
To evaluate effectiveness of demineralized freeze-dried bone allograft (DFDBA) block fixed by titanium screw for reconstructing interimplant papilla in maxillary esthetic zone during one-stage early loading multiple implant procedure. A total of 20 implants were placed in 10 systemically healthy patients (2 implants per patient) for replacement of multiple teeth by early loading one-stage implants along with interimplant papilla reconstruction using DFDBA block fixed by titanium screw. At the baseline, 6 months, and at 1 year, clinical measurements (interimplant papillary height measurement, papilla contour) and radiographic measurements were recorded. At 1 year, mean gain in interimplant vertical crestal bone was 1.7 mm, and complete reconstruction of the papilla was observed in 90% cases. Demineralized freeze-dried bone allograft block fixed by titanium screw for reconstruction of interimplant papilla in maxillary esthetic zone during one-stage early loading multiple implant procedure is effective. Presence of interimplant papilla is of utmost importance for esthetically successful implant-supported restoration in the anterior region. This technique leads to reconstruction of interimplant papilla, thus providing esthetic appearance.


Molecular analysis of a cytotoxin-converting phage, phi CTX, of Pseudomonas aeruginosa: structure of the attP-cos-ctx region and integration into the serine tRNA gene.
The Pseudomonas aeruginosa ctx gene encoding cytotoxin is carried by a temperate phage phi CTX. The genome of phi CTX is a 35.5 kb double-stranded DNA with cohesive ends (cos). It is unique in that the ctx gene and attP site of phi CTX exist very close to the respective cohesive ends. In this study, we determined the structure of this attP-cos-ctx region. The termini of phi CTX are 21-base 5' extended-single-stranded DNAs. The ctx gene is located 361 bp downstream of the left end (cosL). The attP core sequence of 30 bp exists only 647 bp apart from the right end (cosR). The attP-cos-ctx region contains six kinds of repeats and integration host factor-binding sequences and showed sequence-directed static bends, suggesting its potential to form a highly ordered structure. In addition, phi CTX was found to integrate into the serine tRNA gene which was mapped to the 43-45 min region on the P. aeruginosa chromosome.


Carbon fixation gene expression in Skeletonema marinoi in nitrogen-, phosphate-, silicate-starvation, and low-temperature stress exposure.
Diatoms are unicellular algae with a set of extraordinary genes, metabolic pathways, and physiological functions acquired by secondary endosymbiosis, especially for their efficient photosynthetic carbon fixation mechanisms, which can be a reason for their successful environmental adaptation and great contribution to primary production. Based on the available genomic information, the expression patterns of carbon fixation genes were analyzed using transcriptomic sequencing and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in Skeletonema marinoi. Meanwhile, suitable reference genes applying to specific experimental treatments were selected. In our results, carbon fixation genes were standardized by actin and TATA box-binding protein-coding genes in growth phase samples and stress conditions, respectively. It was found that a series of carbon fixation genes, such as the pyruvate orthophosphate dikinase (PPDK)-coding gene, had significantly up-regulated expression in nitrogen-starvation, phosphate-starvation, and low-temperature conditions, but consistently down-regulated in silicate-starvation treatment. These carbon fixation genes exhibited variable expression levels in different conditions and will be useful for investigating gene expression mechanisms in S. marinoi and improve our understanding of diatom carbon fixation pathways.


Overexpression of circRNA SNRK targets miR-103-3p to reduce apoptosis and promote cardiac repair through GSK3β/β-catenin pathway in rats with myocardial infarction.
Ischemic cardiomyopathy seriously endangers human health leading to a poor prognosis. Acute myocardial infarction (AMI) is the primary etiology, and the pathophysiological process concludes with the death of cardiomyocytes caused by acute and persistent ischemia and hypoxia in the coronary arteries. We identified a circRNA (circSNRK) which was downregulated in rats with myocardial infarction (MI), however, the role it plays in the MI environment is still unclear. This study contained experiments to investigate the role of circSNRK in the regulation of cardiac survival and explore the mechanisms underlying circSNRK functions. Quantitative real-time PCR (qRT-PCR) was performed to determine the circSNRK expression patterns in hearts. Gain-of-function assays were also conducted in vitro and in vivo to determine the role of circSNRK in cardiac repair. qRT-PCR, western blot, and luciferase reporter assays were used to study circRNA interactions with micro RNAs (miRNAs). Overexpression of circSNRK in cardiomyocytes reduced apoptosis and increased proliferation. Adeno associated virus 9 (AAV9) mediated myocardium overexpression of circSNRK in post MI hearts reduced cardiomyocyte apoptosis, promoted cardiomyocyte proliferation, enhanced angiogenesis, and improved cardiac functions. Overall, upregulation of circSNRK promotes cardiac survival and functional recovery after MI. Mechanistically, circSNRK regulates cardiomyocyte apoptosis and proliferation by acting as a miR-103-3p sponge and inducing increased expression of SNRK which can bind GSK3β to regulate its phosphorylated activity. And thus circSNRK may be a promising therapeutic target for improving clinical prognosis after MI.


Culture medium density as a simple monitoring tool for cell integrity of Escherichia coli.
During the expression of recombinant proteins in the periplasm of Escherichia coli, the integrity of the outer membrane can change, so that product leaks to the medium. Additional stress can induce lysis, the complete disintegration of both inner and outer membrane, leading to release of both product and host cell proteins. Whether leakiness is unwanted or intentional, appropriate monitoring of leakiness and its distinction from lysis is necessary to ensure product quality and process performance. Here, we investigated a novel monitoring tool for leakiness and lysis based on the measurement of the culture supernatant density. The method benefits from short analysis time and low analytical error, simple result output, relatively low cost, low risk of operator errors and the option of easy on-line implementation. Although limitations exist regarding selectivity, we could show that the method is capable of detecting changes in cell integrity. This tool is therefore an interesting addition to the monitoring toolbox for industrial E. coli bioprocesses.


Cardiac arrest: a rare complication of pallid syncope?
Cardiac arrest is rare in children. Breath-holding, on the other hand, is fairly common. We report a case in which one complicated the other with serious consequences. A review of the literature on the subject was undertaken.


Feasibility of remotely assessing hormonal contraceptive use and smoking-related symptomatology: Evidence from a preliminary prospective cohort study.
Half of women who smoke cigarettes also use hormonal contraceptives (HCs). Prior research suggests that variations in ovarian hormones may undermine smoking cessation efforts made by premenopausal women. However, clinical findings of these hormonal effects are inconsistent, potentially due to methodological limitations. The goal of this preliminary prospective cohort study is to determine the feasibility and acceptability of a fully remote protocol to longitudinally examine changes in smoking-related behavior and symptoms in relation to hormone use in women of reproductive age. Eligible participants (n = 60) were biologically female, current age 18-35 years old, smokes ≥ 5 cigarettes/day, and classified into three groups: naturally-cycling (NC; n = 17), using a monophasic oral contraceptive (OC; n = 21), or using depot medroxyprogesterone acetate (DMPA; n = 22). Participants completed daily surveys and weekly dried blood spot collections. Overall, 92% (55/60) participants completed the study with 90% of daily surveys completed and 87% of participants collecting at least 5 of the 6 dried blood spot samples. Participants were "somewhat" (13%) or "extremely" (87%) likely to participate in the study again. Preliminary observations also suggested differences in self-reported cigarettes/day and premenstrual pain over time by study group. This study outlines a fully remote protocol that may be used to clarify the relationships between hormonal contraceptive use and smoking-related outcomes over time. Preliminary results add to existing evidence that HC use may reduce relapse risk for premenopausal women.


Mesectodermal leiomyosarcoma of the antrum and orbit.
A 39-year-old black man developed a left antral leiomyosarcoma that subsequently extended into the ipsilateral orbit. On light microscopic appearance of the antral tumor the presence of a distinctive myxoid and fibrillar cytoplasmic background suggested the diagnosis of a malignant Schwann's cell tumor. A second biopsy of the orbital extension displayed the same fibrillar character, but the emergence of tumor giant cells with cytoplasmic trichrome positivity also raised the possibility of a rhabdomyosarcoma. Electron microscopy demonstrated the smooth muscle derivation of the tumor, which probably originated from vascular smooth muscle elements. The atypical neural appearance of this myogenous tumor may have been caused by the extensive neural crest contribution to the cephalic connective tissues (mesectoderm). Radiation therapy and chemotherapy were ineffective.


LRP1b shows restricted expression in human tissues and binds to several extracellular ligands, including fibrinogen and apoE-carrying lipoproteins.
To investigate low-density lipoprotein receptor-related protein 1b (LRP1b) expression in human tissues and to identify circulating ligands of LRP1b. Using two independent RT-PCR assays, LRP1b mRNA was detected in human brain, thyroid gland, skeletal muscle, and to a lesser amount in testis but absent in other tissues, including heart, kidney, liver, lung, and placenta. Circulating ligands were purified from human plasma by affinity chromatography using FLAG-tagged recombinant LRP1b ectodomains and identified by mass spectrometry. Using this technique, several potential ligands (fibrinogen, clusterin, vitronectin, histidine rich glycoprotein, serum amyloid P-component, and immunoglobulins) were identified. Direct binding of LRP1b ectodomains to fibrinogen was verified by co-immunoprecipitation. ApoE-carrying lipoproteins were shown to bind to LRP1b ectodomains in a lipoprotein binding assay. Furthermore, binding as well as internalization of very low density lipoproteins by cells expressing an LRP1b minireceptor was demonstrated. LRP1b expression in humans appears to be confined to few tissues, which could point out to specialized functions of LRP1b in certain organs. Most of the newly identified LRP1b ligands are well-known factors in blood coagulation and lipoprotein metabolism, suggesting a possible role of LRP1b in atherosclerosis.


[Magnetic resonance tomography, endosonography and hydrosonography in staging stomach carcinoma].
Endosonography (EUS) results in greater accuracy in small gastric cancers (T1, T2) than MRI. The accuracy rate in correct lymph node staging is 82% (EUS) and 76% (MRI). Hydrosonography provides information but no significant staging.


Properties of ionic currents from isolated adult rat carotid body chemoreceptor cells: effect of hypoxia.
1. The electrical properties of chemoreceptor cells from neonatal rat and adult rabbit carotid bodies (CBs) are strikingly different. These differences have been suggested to be developmental and/or species related. To distinguish between the two possibilities, the whole-cell configuration of the patch-clamp technique was used to characterize the ionic currents present in isolated chemoreceptor cells from adult rat CBs. Since hypoxia-induced inhibition of O2-sensitive K+ currents is considered a crucial step in O2 chemoreception, the effect of hypoxia on the adult rat chemoreceptor cell currents was also studied. 2. Outward currents were carried mainly by K+, and two different components could be distinguished: a Ca(2+)-dependent K+ current (IK(Ca)) sensitive to Cd2+ and charybdotoxin (CTX), and a Ca(2+)-insensitive, voltage-dependent K+ current (IK(V)). IK(V) showed a slow voltage-dependent activation (time constant (tau) of 87.4 ms at -20 mV and 8.8 ms at +60 mV) and a very slow inactivation, described by the sum of two exponentials (tau 1 = 684 +/- 150 ms and tau 2 = 4.96 +/- 0.76 s at + 30 mV), that was almost voltage insensitive. The kinetic and pharmacological properties of IK(V) are typical of a delayed rectifier K+ channel. 3. Voltage-dependent Ca2+ currents (ICa) were present in nineteen of twenty-seven cells. TTX-sensitive Na+ currents were also observed in about 10% of the cells. 4. Low PO2 (< 10 mmHg) reduced the whole outward current amplitude by 22.17 +/- 1.96% (n = 27) at +20 mV. This effect was absent in the presence of Cd2+. Since low PO2 did not affect ICa, we conclude that hypoxia selectively blocks IK(Ca). 5. The properties of the currents recorded in adult rat chemoreceptor cells, including the specific inhibition of IK(Ca) by hypoxia, are similar to those reported in neonatal rat CB cells, implying that the differences between rat and rabbit chemoreceptor cells are species related.


Effect of sunflower cake supplementation on meat quality of indigenous goat genotypes of South Africa.
The effect of four castrated goat genotypes and sunflower cake supplementation on goat meat quality was determined. Supplemented Boer (BOR) and Xhosa-Boer cross (XBC) goats had significantly higher (P<0.05) SLW and CDM than non-supplemented groups. The Xhosa lop-eared (XLE) and Nguni (NGN) goats had higher pH24 (P<0.05) than BOR and XBC goats. For each genotype, the sunflower cake supplemented and non-supplemented goats had similar a* values, except for the XLE goats. In the XLE goats, the a* values were lower in the sunflower cake supplemented goats. Sunflower cake supplemented BOR goats had higher L*values than their non-supplemented counterparts (P<0.05). The sunflower cake supplemented BOR and NGN goats also had higher b* values as compared to their non-supplemented counterparts. In comparison with the Boer goat, the XLE and NGN goats had lower CDM, L* and WBF values but generally had higher CL and a* values. Sunflower cake supplementation improved meat quality attributes of the goats.


Periodontal implications of surgical-orthodontic treatment of an impacted dilacerated maxillary incisor: A case report with a 2-year follow-up.
The treatment of an 8-year-old girl with a dilacerated maxillary incisor began in the mixed dentition; a modified palatal arch attached to the molars served as anchorage for the forced eruption of the dilacerated tooth to prevent the intrusion of the adjacent teeth and reduce the risk of root resorption. Two surgical sessions were planned: the first to permit the closed eruption; the second was an apically positioned flap to add attached gingiva to the labial side of the erupting tooth. The result was an optimal periodontal outcome; moreover, the roots of the adjacent teeth did not show any sign of resorption at the end of the forced eruption. The tooth was vital at the end of the treatment, and the apex covered by alveolar mucosa. The root developed normally throughout the treatment, and the periodontium was healthy and esthetically acceptable at the 2-year follow-up. Further study is needed to assess the advantages of the combined surgical-orthodontic treatment.


Quality of sick child management by health extension workers: role of a complex improvement intervention.
Despite the expansion of the Integrated Community Case Management services for childhood illness, quality and utilization of services have remained low. To address the problem, the Government of Ethiopia introduced a complex intervention that included community engagement, capacity building of health workers and enhanced district-level ownership of sick child management. We examined whether this complex intervention was associated with improved management of sick children by health extension workers. The study was conducted in four Ethiopian regions. A baseline survey was conducted in 26 intervention and 26 comparison districts from December 2016 to February 2017, followed by an end-line survey 24 months later. We observed health extension workers' consultations of sick 2-59 months old children. The analysis has evaluated if children with pneumonia, diarrhoea and malnutrition were assessed, classified and treated according to guidelines, and included difference-in-difference analyses. We observed 1325 consultations of sick children. At baseline, 86% of the sick children with cough in the intervention areas and 85% in comparison areas were assessed according to the guidelines, without any change at end-line associated with the intervention (difference-in-difference = -21%, p = 0.55). Sixty-two percent of children were assessed for dehydration at baseline in intervention and 47% in comparison areas, with no improvement associated with the intervention. Similarly, 87% of sick children in intervention and 91% in comparison areas were assessed for malnutrition, with no change over time associated with the intervention (difference-in-difference = 5%, p = 0.16). Appropriate pneumonia treatment with antibiotics declined and diarrhea treatment increased in both areas. Half of the malnourished children received ready-to-use therapeutic foods without any improvement associated with the intervention. The intervention was not associated with improved quality of the health extension workers' management of sick children. The lack of association may be linked to low fidelity in the implementation of the intervention. Our findings suggest that training healthcare providers without continued clinical mentoring and support does not improve the quality of care. Community-based programs can be strengthened by ensuring high coverage and continued clinical mentorships, supportive supervision, and supply of medicines and other essential commodities. ISRCTN12040912, retrospectively registered on 19/12/ 2017.