[Determination of tropane alkaloid components in Przewalskia tangutica Maxim. by capillary electrophoresis with electrochemiluminescence detection].
Based on an Eu-PB modified platinum electrode as the working electrode, a method for the simultaneous determination of the four tropane alkaloids, anisodamine, scopolamine, atropine and anisodine, by capillary electrophoresis with electrochemiluminescence detection (CE-ECL) has been established. The effects of several factors, such as the detection potential, the acidity and concentration of the running buffer, and the content of the methanol additive were investigated for the improvement of separation ability and detection sensitivity. Under the optimized conditions, these four components could be fully separated from each other in a 20 mmol/L phosphate (pH 8.0) containing 7% (v/v) methanol buffer within 6 min. The relative standard deviations of the peak area and migration time were less than 5.0% and 1.1% (n = 12) respectively for all the four compounds. Thus, the method has been successfully applied to the determination of anisodamine, scopolamine in Przewalskia tangutica Maxim. The average amounts of 27.8 g/kg anisodamine and 4.43 g/kg scopolamine were found in the herbal root-stalk sample. The recoveries of the tropane alkaloids were 97.8% - 102%.


Regeneration and Cicatrization.
Cicatricial tissue, being the local center of sclerosis, replaces the wound or focus of cell death. Scarring is caused by various types of injuries, including operations, as well as by a number of diseases. Scarring often culminates in the formation of strictures and other complications. Integrated stimulation of regeneration that takes the role of the immune system into account, in conjunction with the prescription of enzyme preparations possessing proteolytic activity, can be used to reduce the severity of sclerosis of damaged tissues.


Circumferential Stenosis of the Second Part of the Duodenum Caused by Eosinophilic Gastroenteritis.
Isolated eosinophilic gastroenteritis (EGE) of the second part of the duodenum is rare. We herein report a case of EGE limited to the second part of the duodenum that caused circumferential stenosis due to massive wall thickening. A boring biopsy was useful to verify the accumulation of eosinophils. Induction of remission by prednisolone was accompanied by a marked reduction in the mRNA expression of IL-6, C-C motif chemokine ligand 17 (CCL17), and CCL26 without any reduction in prototypical EGE-associated T helper type 2 cytokines (IL-5, IL-13). Thus, the enhanced expression of IL-6, CCL17, and CCL26 might be involved in the development of EGE in this case.


Silencing the shutoff protein of Epstein-Barr virus in productively infected B cells points to (innate) targets for immune evasion.
During productive infection with Epstein-Barr virus (EBV), a dramatic suppression of cellular protein expression is caused by the viral alkaline exonuclease BGLF5. Among the proteins downregulated by BGLF5 are multiple immune components. Here, we show that shutoff reduces expression of the innate EBV-sensing Toll-like receptor-2 and the lipid antigen-presenting CD1d molecule, thereby identifying these proteins as novel targets of BGLF5. To silence BGLF5 expression in B cells undergoing productive EBV infection, we employed an shRNA approach. Viral replication still occurred in these cells, albeit with reduced late gene expression. Surface levels of a group of proteins, including immunologically relevant molecules such as CD1d and HLA class I and class II, were only partly rescued by depletion of BGLF5, suggesting that additional viral gene products interfere with their expression. Our combined approach thus provides a means to unmask novel EBV (innate) immune evasion strategies that may operate in productively infected B cells.


Intraoperative topical nimodipine after aneurysm clipping.
The lipophilic calcium antagonist Nimodipine (Bayer Pharma , Wuppertal ) was administered during aneurysm operations in 40 patients with ruptured intracranial aneurysm. Immediately after clipping of the aneurysm, a 2.4 X 10(-5) M solution of Nimodipine in 18 ml of Ringer's solution was injected into the subarachnoid space near the site of aneurysm clipping. Arterial vessels regularly dilated and spastic portions resumed their normal diameters. Since it is known from experimental work, that Nimodipine has stronger dilator capacity than papaverine and acts at least for several hours, two conclusions are drawn from the present preliminary study: Pre-operative vasospasm seen on angiograms is no longer a contraindication to early operation because spasm detected intraoperatively can be effectively treated. The long-lasting effect of Nimodipine prevents ischaemic complications in the first few days after operation and thereby seems to exert a protective effect against the onset of severe symptomatic vasospasm.


Low-intensity indocyanine-green laser phototherapy of acne vulgaris: pilot study.
Near infrared (NIR) diode laser low-intensity (soft) phototherapy with the topical application of indocyanine green (ICG) has been suggested for treatment of acne vulgaris. Twelve volunteers with acne lesions on their faces and/or backs were enrolled in the experiment. Skin areas of the subjects that were 4 x 5 cm2 were stained with ICG solution for 5 min before laser irradiation (803 nm) at a power density up to 50 mW/cm2 for 5 to 10 min. For 75% of the subjects, a single treatment was provided and for the other 25%, eight sequential treatments over a period of a month were carried out. Observations a month after the completion of the treatment showed that only the multiple treatments with a combination of ICG and NIR irradiation reduced inflammation and improved the state of the skin for a month without any side effects. A month after treatment, the improvement was about 80% for the group receiving multiple treatments. Single treatments did not have a prolonged effect.


Preparation and thermal-mechanical characterization of nanoclay-unsaturated polyester composites.
Recently polymer nanocomposites have attracted great interest as much as in industry as in research laboratories, due to they often show remarkable improvement in their mechanical and thermal properties when are compared with the virgin polymers. Among nanocomposites, nanoclay-reinforced polymers have been widely studied, specifically, those formed by a thermosetting polymer matrix, like unsaturated polyester crosslinked resin reinforced with layered silicates, like montmorillonite. In this work we have prepared nanocomposites formed by an isophtalic unsaturated polyester crosslinked resin (UP) reinforced with different contents (2-10 wt%) of organic modified montmorillonite (OMMT). The UP/OMMT nanocomposites have been prepared following different procedures and the structural characterization has been carried out by using X-ray diffraction (XRD). In all the cases an increase of the d-spacing between layers of the OMMT has been detected. The objective of this study is to analyze the thermal and mechanical behaviour of nanocomposites. For all of the reinforced systems, the glass transition temperatures values, Tg, obtained by differential scanning calorimetry (DSC) and dynamic-mechanical thermal analysis, (DMTA) are higher than the corresponding ones to neat UP. On the other hand, the OMMTP mechanical behaviour has been evaluated by DMTA and by tensile tests. Both techniques reveal an increase in Young modulus, however, a decrease of the tensile strength is observed in all the reinforced systems.


Serial electrophysiological studies in a young patient with recurrent ventricular fibrillation.
A 28-year-old male with recurrent episodes of ventricular fibrillation, which were initiated by very early ventricular premature depolarizations with a normal QT interval, was subjected to three consecutive electrophysiological studies. During the first study, which was carried out to test the efficacy of amiodarone treatment, no ventricular arrhythmias could be induced. While on amiodarone therapy, the patient experienced another syncopal episode and therefore a second electrophysiological study was done. In that study, ventricular fibrillation was induced by ventricular stimulation. During the third study, which was carried out in order to evaluate the effect of the addition of quinidine to the on-going amiodarone therapy, no more than three repetitive ventricular responses could be induced. The patient has been asymptomatic since the third study (fifteen months) with combined therapy of amiodarone and quinidine. The significance of the ability to induce ventricular fibrillation during an electrophysiological study is discussed as well as the value of such studies in determining the long-term efficacy of antiarrhythmic drug therapy.


Feasibility of measuring prostate perfusion with arterial spin labeling.
Prostate perfusion has the potential to become an important pathophysiological marker for the monitoring of disease progression or the assessment of the therapeutic response of prostate cancer. The feasibility of arterial spin labeling, an MRI approach for the measurement of perfusion without an exogenous contrast agent, is demonstrated in the prostate for the first time. Although various arterial spin labeling methods have been demonstrated previously in highly perfused organs, such as the brain and kidneys, the prospect of obtaining such measurements in the prostate is challenging because of the relatively low blood flow, long transit times, susceptibility-induced image distortion and local motion. However, despite these challenges, this study demonstrates that, with a whole-body transmit coil and external receiver array, global prostate perfusion can be measured with arterial spin labeling at 3 T. In five healthy subjects with a mean age of 44 years, the mean total prostate blood flow was measured to be 25.8 ± 7.1 mL/100 cm(3) /min, with an estimated bolus duration and arterial transit time of 884 ± 209 ms and 721 ± 131 ms, respectively.


Genomic organization and sequence dynamics of the AvrPiz-t locus in Magnaporthe oryzae.
Plants utilize multiple layers of defense mechanisms to fight against the invasion of diverse pathogens. The R gene mediates resistance, in most cases, dependent on the co-existence of its cognate pathogen-derived avirulence (Avr) gene. The rice blast R gene Piz-t corresponds in gene-for-gene fashion to the Magnaporthe oryzae Avr gene AvrPiz-t. In this study, we determined and compared the genomic sequences surrounding the AvrPiz-t gene in both avirulent and virulent isolates, designating as AvrPiz-t-ZB15 and avrPiz-t-70-15 regions, respectively. The sequence of the AvrPiz-t-ZB15 region is 120966 bp whereas avrPiz-t-70-15 is 146292 bp in length. The extreme sequence similarity and good synteny in gene order and content along with the absence of two predicted genes in the avrPiz-t-70-15 region were observed in the predicted protein-coding regions in the AvrPiz-t locus. Nevertheless, frequent presence/absence and highly dynamic organization of transposable elements (TEs) were identified, representing the major variation of the AvrPiz-t locus between different isolates. Moreover, TEs constitute 27.3% and 43.2% of the genomic contents of the AvrPiz-t-ZB15 and avrPiz-t-70-15 regions, respectively, indicating that TEs contribute largely to the organization and evolution of AvrPiz-t locus. The findings of this study suggest that M. oryzae could benefit in an evolutionary sense from the presence of active TEs in genes conferring avirulence and provide an ability to rapidly change and thus to overcome host R genes.


Development of severe pemphigus vulgaris following ChAdOx1 nCoV-19 vaccination and review of literature.
Vaccines are indeed a boon for tackling the present COVID-19 pandemic. In India, ChAdOx1 nCoV-19 (Covishield) is the most commonly used vaccine in the government vaccination program for adults more than 18 years of age. It is a recombinant vaccine developed by Oxford-Astra Zeneca and manufactured in India by Serum Institute of India (SSI). Here, we report a case of severe pemphigus vulgaris following the second dose of ChAdOx1 nCoV-19 vaccination in an adult male. The patient developed septicemia during the course of hospital stay, and he was managed with systemic steroids, parenteral antibiotics, and intravenous immunoglobulins (IVIg) along with proper wound care. Patient started improving within 1 month of therapy. This case is being reported in view of the rarity of pemphigus vulgaris following ChAdOx1 nCoV-19 vaccine.


Identification of Salmonella somatic and flagellar antigens by modified serological methods.
This report describes two modified methods for the identification of Salmonella somatic (O) and flagellar (H) antigens. Over a period of 2 years, both modified methods were found to be approximately three times less labor intensive than the standard methods while requiring no more technical skill. The modified methods were as accurate as the standard methods in identifying the O and H antigens of 350 Salmonella isolates. Furthermore, 43 O antisera reacted exclusively with organisms possessing homologous O antigens when the modified and two standard methods were used. At the antiserum dilutions used for H antigen identification, H antisera did not react with O antigens or heterologous H antigens by either the modified or the standard method. Compared with the standard method for H antigen identification, the modified method was approximately 20 times more economical with respect to antisera and usually generated a 1.5- to 4-fold higher titer. Since the antisera stored for use in the modified method for H antigen identification were usually 100-fold more dilute than the antisera stored for the standard method, an antibody-stabilizing buffer was incorporated in the diluted antisera, allowing these reagents to be used for at least 9 to 16 months.


[DNA tests for mutant genes coding for transthyretins Gly42, Arg50 and Cys114 in Japanese cases of familial amyloid polyneuropathy].
Four different genes encoding variant transthyretins (TTR) have been known in Japanese cases with familial amyloidotic polyneuropathy (FAP); TTR Met30, Gly42, Arg50 and Cys114. First three mutant genes can be detected by restriction fragment length polymorphism using NsiI, Cfr13I and MvaI, respectively. Since a single base change responsible for TTR Cys114 produces no new restriction site, RFLP is not directly applicable for the detection of this gene. In this study, TTR Cys114 gene was amplified by polymerase chain reaction using mismatch primer to produce a new restriction site for HgiAI. The enzyme digestion of the product resulted in the appearance of extra fragments in the presence of the normal fragment. The accurate detections of all the four mutant genes are hereafter possible by these procedures.


Deconstruction of the human connexin 26 hemichannel due to an applied electric field; A molecular dynamics simulation study.
Connexins are a 21-member membrane protein family constituting channels evolved in direct communication between adjacent cells by passaging cytoplasmic molecules and ions. Hexametrical assembly of connexin proteins in plasma membrane forms a wide aqueous pore known as connexin hemichannel. These hemichannels mediate cytoplasm and extracellular milieu communication both in many external tissues and in the central nervous system. In this study, a series of molecular dynamics simulations has been performed to investigate the effect of applied static and alternating electric fields on the stability and conformation of human connexin26 hemichannel. The root mean square deviations of C-alpha atoms, the dipole moment distribution, the number of inter-protein hydrogen bonds and the number of water-protein hydrogen bonds were used to assess connexin26 hemichannel stability. In the static field case, our results show that although the lowest field used in this study (0.1V/nm) does not lead to the hemichannel deconstruction, stronger fields (>0.1V/nm), however, disrupt the protein structure during the simulations time period. Furthermore, in the alternating case, compared to static field case, field effects on the connexin26 hemichannel conformation are reduced and consequently the protein maintains its native structure for longer times. Specifically, for the highest frequency used in this study (50GHz), the hemichannel keeps its structure even under the effect of the strongest field (0.4V/nm). According to our results, the protein secondary structure is preserved in the characteristic times determined for the protein deconstruction. Consequently, we suggest that the protein deconstruction is due to the tertiary and quaternary structure loss.


Ordered recruitment of histone acetyltransferases and the TRAP/Mediator complex to thyroid hormone-responsive promoters in vivo.
Transcriptional coactivators implicated in gene activation by the thyroid hormone receptor (TR) include members of the p160/steroid receptor coactivator (SRC) family of proteins, p300, and the multisubunit TR-associated protein (TRAP)/Mediator complex. We investigated the temporal recruitment of these cofactors to mammalian thyroid hormone (T3)-responsive promoters in vivo. We show that upon T3 treatment, TR recruits all three types of coactivators to specific promoters in at least two sequential steps: p160/SRC proteins and p300 are recruited first and rapidly induce histone acetylation, followed by the recruitment of the TRAP/Mediator complex. Interestingly, inhibition of histone deacetylase activity with trichostatin A elicited a more rapid promoter recruitment of the TRAP/Mediator complex but not p160/SRC proteins. T3-dependent gene expression assays indicate that all three coactivators are targeted to a promoter before significant activation occurs. These findings thus suggest that histone acetylation may be a prerequisite for TRAP/Mediator recruitment and function at specific T3-responsive mammalian promoters.


Renal Allograft Histology at 10 Years After Transplantation in the Tacrolimus Era: Evidence of Pervasive Chronic Injury.
Improving long-term renal allograft survival remains an important unmet need. To assess the extent of histologic injury at 10 years after transplantation in functioning grafts, we studied 575 consecutive adult solitary renal transplants performed between 2002 and 2005: 77% from living donors and 81% maintained on tacrolimus-based immunosuppression. Ten-year graft survival was 59% and death-censored graft survival was 74%. Surveillance allograft biopsies were assessed at implantation, 5 years, and 10 years from 145 patients who reached 10 years. At implantation, 5% of biopsies had major histologic abnormalities (chronic transplant glomerulopathy score > 0, other chronic Banff scores ≥ 2, global glomerulosclerosis > 20%, or mesangial sclerosis ≥ 2). This increased to 54% at 5 years and 82% at 10 years. Major lesions at 10 years included the following: arteriolar hyalinosis (66%), mesangial sclerosis (67%), and global glomerulosclerosis > 20% (43%), with 48% of grafts having more than one major lesion. Transplant glomerulopathy and moderate-to-severe interstitial fibrosis were uncommon (12% each). Major lesions were associated with increased proteinuria and decreased graft function. In patients with diabetes at baseline, 52% had diabetic nephropathy/mesangial sclerosis at 10 years. We conclude that almost all renal allografts sustain major histologic injury by 10 years after transplantation. Much damage appears nonimmunologic, suggesting that new approaches are needed to decrease late injury.


Regulatory Approaches and Considerations in Establishing Bioequivalence of Inhaled Compounds.
To be considered bioequivalent to their branded counterparts, generic drugs must meet the standards for bioequivalence (BE) described by the regulatory agencies. While BE of generic inhalational drugs can be evaluated using a similar approach as that for oral dosage from products or drugs that are delivered systemically, the approach is insufficient to address the complexities of inhalational products (e.g., localized site of action, device-patient interface). Therefore, more considerations are needed and caution should be applied when evaluating BE of inhaled compounds. The purpose of this review is to highlight the considerations and challenges in establishing BE of inhaled compounds by (1) outlining the current regulatory approaches (from Health Canada, the U.S. Food and Drug Administration, and the European Medicines Agency) to assess BE for subsequent entry inhaled products (SEIPs) and (2) reviewing the literature pertaining to testing considerations of SEIPs to establish BE.


Ouabain exacerbates botulinum neurotoxin-induced muscle paralysis via progression of muscle atrophy in mice.
Botulinum neurotoxin serotype A (BoNT/A) inhibits acetylcholine release at the neuromuscular junction in isolated muscles, and ouabain can partially block its effect. However, it is not clear whether ouabain attenuates BoNT/A-induced neuromuscular paralysis in vivo. In this work, we investigated the effects of ouabain on BoNT/A-induced neuromuscular paralysis in mice. Ouabain was administered to mice intraperitoneally immediately after a single injection of BoNT/A into skeletal muscle. The effects of ouabain on BoNT/A-induced muscle paralysis were assessed by quantitative monitoring of muscle tension and digit abduction via the digit abduction scoring (DAS) assay. A single administration of ouabain significantly prolonged BoNT/A-induced neuromuscular paralysis. Moreover, consecutive daily injection of ouabain exacerbated BoNT/A-induced neuromuscular paralysis, and led to a significant decrease in both twitch and tetanic forces as assayed in isolated BoNT/A-injected muscles. We next looked at the effects of ouabain on BoNT/A-induced muscle atrophy. Administration of ouabain led to a decrease in the myofibrillar cross-sectional area (CSAs) by 14 post-BoNT/A injection. In addition, repeated administration of ouabain increased mRNA expression levels of ubiquitin ligases, which are markers of muscle atrophy, in BoNT/A-injected muscle. These results suggest that ouabain exacerbates BoNT/A-induced neuromuscular paralysis via a marked progression of BoNT/A-induced muscle atrophy.


[Diabetic foot: new insights into pathophysiology and treatment].
A foot ulcer is a complication that is difficult to treat in people with diabetes mellitus. Over the past few years, both clinicians and scientists have been showing more interest in this condition. A number of factors are involved in the development and maintenance of a diabetic foot ulcer, including: polyneuropathy, mechanical overload, peripheral arterial disease and infection. The cornerstones of treatment are: relief of pressure, the restoration of perfusion ofthe foot, treatment of infection, wound care, optimum glucose regulation and education. New and effective methods of treatment have become available. These include a non-removable plaster cast that is modelled to the form of the foot (a 'total contact cast'), endovascular revascularisation procedures in the lower leg, and topical application of negative pressure.


Polynomial-time quantum algorithm for the simulation of chemical dynamics.
The computational cost of exact methods for quantum simulation using classical computers grows exponentially with system size. As a consequence, these techniques can be applied only to small systems. By contrast, we demonstrate that quantum computers could exactly simulate chemical reactions in polynomial time. Our algorithm uses the split-operator approach and explicitly simulates all electron-nuclear and interelectronic interactions in quadratic time. Surprisingly, this treatment is not only more accurate than the Born-Oppenheimer approximation but faster and more efficient as well, for all reactions with more than about four atoms. This is the case even though the entire electronic wave function is propagated on a grid with appropriately short time steps. Although the preparation and measurement of arbitrary states on a quantum computer is inefficient, here we demonstrate how to prepare states of chemical interest efficiently. We also show how to efficiently obtain chemically relevant observables, such as state-to-state transition probabilities and thermal reaction rates. Quantum computers using these techniques could outperform current classical computers with 100 qubits.


Radial basis function networks GPU-based implementation.
Neural networks (NNs) have been used in several areas, showing their potential but also their limitations. One of the main limitations is the long time required for the training process; this is not useful in the case of a fast training process being required to respond to changes in the application domain. A possible way to accelerate the learning process of an NN is to implement it in hardware, but due to the high cost and the reduced flexibility of the original central processing unit (CPU) implementation, this solution is often not chosen. Recently, the power of the graphic processing unit (GPU), on the market, has increased and it has started to be used in many applications. In particular, a kind of NN named radial basis function network (RBFN) has been used extensively, proving its power. However, their limiting time performances reduce their application in many areas. In this brief paper, we describe a GPU implementation of the entire learning process of an RBFN showing the ability to reduce the computational cost by about two orders of magnitude with respect to its CPU implementation.


Nociceptin/orphanin FQ increases anxiety-related behavior and circulating levels of corticosterone during neophobic tests of anxiety.
Intracranial administration of nociceptin/orphanin FQ (N/OFQ) increases circulating concentrations of adrenocorticotrophic hormone and corticosterone in unstressed rats, and elevates the responsiveness of these hormones during mild stress. Furthermore, N/OFQ and its cognate receptor are both abundant in a variety of limbic nuclei, and stress exposure decreases neuronal N/OFQ content in forebrain neurons. In light of these and other findings, we examined the potential involvement of N/OFQ in regulation of anxiety-related behaviors in rats. In the open field, elevated plus maze, and dark-light neophobic tests, intracerebroventricular N/OFQ (1.0 pmole-1.0 nmole) increased the expression of anxiety-related behaviors. Specifically, N/OFQ increased the latency to enter, decreased the number of entries into, and decreased the time spent in the exposed or brightly lit environments of all three tests. N/OFQ also enhanced thigmotactic responses in the open field test. The effects of diazepam and of the benzodiazepine inverse agonist FG 7142 were also assessed in independent groups of rats. In all three tests, the behavioral effects of N/OFQ resembled the anxiogenic actions of FG 7142, and contrasted with the anxiolytic actions of diazepam. N/OFQ administration also increased circulating concentrations of corticosterone during anxiety testing, in comparison with the concentrations in vehicle-treated controls. We conclude that N/OFQ administration is anxiogenic, and elevates responsiveness of the hypothalamic pituitary-adrenal axis during neophobic tests of anxiety. This supports the possibility that N/OFQ neurotransmission participates in processing of emotionally-salient and stressful stimuli, and suggests that normal functioning of the N/OFQ system may be important in physiological and psychological well-being.


Heritability of hypothyroidism in the Finnish Hovawart population.
The Hovawart is a working and companion dog breed of German origin. A few hundred Hovawart dogs are registered annually in Finland. The most common disease with a proposed genetic background in Hovawarts is hypothyroidism. The disease is usually caused by lymphocytic thyroiditis, an autoimmune disorder which destroys the thyroid gland. Hypothyroidism can be treated medically with hormone replacement. Its overall incidence could also be reduced through selection, provided that the trait shows an adequate genetic basis. The aim of this study was to estimate the heritability of hypothyroidism in the Finnish Hovawart population. The pedigree data for the study were provided by the Finnish Kennel Club and the hypothyroidism data by the Finnish Hovawart Club. The data included 4953 dogs born between 1990 and 2010, of which 107 had hypothyroidism and 4846 were unaffected. Prior to the estimation of heritability, we studied the effects of gender, birth year, birth month, and inbreeding on susceptibility to hypothyroidism. Heritability was estimated with the probit model both via restricted maximum likelihood (REML) and Gibbs sampling, using litter and sire of the dog as random effects. None of the studied systematic effects or level of inbreeding had a significant effect on susceptibility to hypothyroidism. The estimated heritability of hypothyroidism varied from 0.47 (SE = 0.18) using REML to 0.62 (SD = 0.21) using Gibbs sampling. Based on our analysis, the heritability of hypothyroidism is moderate to high, suggesting that its prevalence could be decreased through selection. Thus, breeders should notify the breed association of any affected dogs, and their use for breeding should be avoided.


GENOMICS OF PROSTATE CANCER: CLINICAL UTILITY AND CHALLENGES.
The studying of prostate cancer genomics is important for understanding prostate cancer biology, it can provide clinically relevant stratification into subtypes, the development of new prognostic and predictive markers in the context of precision medicine, and the development of new targeted therapies. Recent studies have provided detailed insight into genomics, epigenomics and proteomics of prostate cancer, both primary and metastatic castration-resistant (mCRPC). Many mutations have been discovered, both those that occur early in the carcinogenesis and progression as well as those responsible for the resistance to therapy occurring later under the influence of treatment. A large number of characteristic mutated signaling pathways has been identified, e.g. the mutations in DNA repair pathway were found in 23% of mCRPC, which suggests potential response to PARP inhibitors. Multifocality and intralesional genomic heterogeneity of prostate cancer make the clinical application of genomics complicated. Although a great progress was made in understanding prostate cancer genomic, and clinical studies related to its routine application are ongoing, prostate cancer genomics still needs to find its standard wide routine application in patients with prostate cancer.


Isolated benign primary cutaneous plasmacytosis in a child.
Isolated benign primary cutaneous plasmacytosis in a child is a very rare and benign disease. Herein we present a case of this condition occurring in a child who showed good response to topical corticosteroid.


cellCounts: an R function for quantifying 10x Chromium single-cell RNA sequencing data.
The 10x Genomics Chromium single-cell RNA sequencing technology is a powerful gene expression profiling platform, which is capable of profiling expression of thousands of genes in tens of thousands of cells simultaneously. This platform can produce hundreds of million reads in a single experiment, making it a very challenging task to quantify expression of genes in individual cells due to the massive data volume. Here, we present cellCounts, a new tool for efficient and accurate quantification of Chromium data. cellCounts employs the seed-and-vote strategy to align reads to a reference genome, collapses reads to Unique Molecular Identifiers (UMIs) and then assigns UMIs to genes based on the featureCounts program. Using both simulation and real datasets for evaluation, cellCounts was found to compare favourably to cellRanger and STARsolo. cellCounts is implemented in R, making it easily integrated with other R programs for analysing Chromium data. cellCounts was implemented as a function in R package Rsubread that can be downloaded from http://bioconductor.org/packages/release/bioc/html/Rsubread.html. Data and analysis code used in this study can be freely accessed via La Trobe University's Institutional Repository at https://doi.org/10.26181/21588276.


Abnormal structure of the Y chromosome detected in bovine gonadal hypoplasia (XY female) by FISH.
The structure of the Y chromosome was investigated by FISH and G banding in 3 cases of bovine XY females shown by PCR to lack the SRY gene. Although 2 different repeat-DNA sequences (BC1.2 and btDYZ-1) hybridized to the short arm of the Y chromosome in a normal bull, they hybridized to both arms of the Y chromosome in the XY females. In the Y chromosome from XY females, only the centromeric region was darkly stained by G banding, in comparison with dark staining on the long arm of a normal Y chromosome. From the results obtained, it seemed that the Y chromosome from the XY females was structurally abnormal, namely an isochromosome with an identical short arm. Our results also confirm that SRY is located on the long arm of the Y chromosome in bovine.


Superficial morphea: case report, look-alikes, pathogenesis, and treatment.
Superficial morphea, a rare variant of morphea, is characterized by hypopigmented to hyperpigmented skin lesions located predominantly in a symmetric fashion at intertriginous sites. These patches and plaques typically lack the significant induration, contractures, and atrophy seen in other subtypes of morphea. Histologic examination is key for accurate diagnosis considering the number of similar conditions which may clinically mimic superficial morphea. Herein, we present a case of a 25-year-old woman who re-presented for consultation in our clinic after gradual progression of her skin lesions. In addition, we review dermatologic look-alikes, as well as the pathophysiology and treatment options for superficial morphea.


The diagnostic and prognostic value of MRP8/MRP14 in intrahepatic cholangiocarcinoma.
Myeloid-related protein 8 (MRP8) and 14 (MRP14) are abundantly expressed in several kinds of benign and malignant tumors. However, little is known about their clinicopathological significance in intrahepatic cholangiocarcinoma (ICC), biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of bile duct (IPNB), or inflammatory hepatic biliary ducts epithelium (IHBD). This study aimed to investigate the diagnostic and prognostic values of MRP8 and MRP14 as new biomarkers for ICC. We examined MRP8 and MRP14 expression levels by immunohistochemistry in IHBD (n = 15), BilIN (BilIN1 = 24, BilIN2 = 9, BilIN3 = 5), IPNB (n = 18) and ICC (n = 416). The differential diagnostic and prognosis values were also evaluated. The results showed that the ratio of tumor-infiltrating MRP8 and MRP14 positive immune cells, relative to biliary epithelial cells, was significantly increased in ICC tissues compared with nonmalignant tissues, including IHBD, BilIN1, BilIN2, BilIN3, and IPNB (P value < 0.05). In addition, over-expression levels of MRP8 and MRP14 were correlated with overall survival (OS) and time to recurrence (TTR) by univariate analysis; MRP8/MRP14 combination was an independent prognostic factor for OS and TTR. MRP8 and MRP14 expression might help to identify the benign bile duct diseases from ICC, as high expression of MRP8 and MRP14 suggests a poor prognosis after surgical resection.


Fat embolism syndrome: a puzzling phenomenon.
Fat emboli are a life-threatening source of respiratory insufficiency. Whether they are of mechanical or chemical origin remains a subject of controversy. Fat embolism syndrome is most often seen after fracture of long bones, and immobilization of the fracture site may decrease risk of its development. Adequate oxygenation is the most important aspect of therapy; most patients given vigorous supportive treatment recover with no residual lung injury.


In vitro nuclear magnetic resonance spectroscopy metabolic biomarkers for the combination of temozolomide with PI3K inhibition in paediatric glioblastoma cells.
Recent experimental data showed that the PI3K pathway contributes to resistance to temozolomide (TMZ) in paediatric glioblastoma and that this effect is reversed by combination treatment of TMZ with a PI3K inhibitor. Our aim is to assess whether this combination results in metabolic changes that are detectable by nuclear magnetic resonance (NMR) spectroscopy, potentially providing metabolic biomarkers for PI3K inhibition and TMZ combination treatment. Using two genetically distinct paediatric glioblastoma cell lines, SF188 and KNS42, in vitro 1H-NMR analysis following treatment with the dual pan-Class I PI3K/mTOR inhibitor PI-103 resulted in a decrease in lactate and phosphocholine (PC) levels (P<0.02) relative to control. In contrast, treatment with TMZ caused an increase in glycerolphosphocholine (GPC) levels (P≤0.05). Combination of PI-103 with TMZ showed metabolic effects of both agents including a decrease in the levels of lactate and PC (P<0.02) while an increase in GPC (P<0.05). We also report a decrease in the protein expression levels of HK2, LDHA and CHKA providing likely mechanisms for the depletion of lactate and PC, respectively. Our results show that our in vitro NMR-detected changes in lactate and choline metabolites may have potential as non-invasive biomarkers for monitoring response to combination of PI3K/mTOR inhibitors with TMZ during clinical trials in children with glioblastoma, subject to further in vivo validation.


Healing in periodontal defects treated by decalcified freeze-dried bone allografts in combination with ePTFE membranes. Assessment by computerized densitometric analysis.
This study quantitatively assessed radiographic changes in alveolar bone density by computer-assisted densitometric image analysis (CADIA) in periodontal defects that were treated with decalcified freeze dried bone allograft (DFDBA) alone or in combination with interproximal expanded polytetrafluroethylene membranes (ePTFE). The radiographic changes where then analyzed for correlation with the clinically assessed changes. The radiographic changes were evaluated on standardized radiographs of treated sites treated prior to, 1 week after surgery, and 6 months post-operatively. 15 patients with one pair of bilateral interproximal periodontal defects of similar morphology and > or = 6 mm in pocket depth participated. Analysis of the changes 6 months after treatment showed that the increases in density in the defect areas that received the graft were significantly greater than the adjacent areas (p < 0.001). These adjacent areas, in contrast, demonstrated significantly larger loss in radiographic density than the defect area (p < 0.001). The placement of DFDBA into the defects produced in itself significant increases in radiographic density, as illustrated by the results of one week which remained at six months. Utilization of ePTFE addition to DFDBA did not lead to additional radiographic gains in the defect area. While at one week the analysis suggested increased resorption by the combined treatment over grafting alone, such differences did not persist at 6 months post-surgery. Analysis comparing CADIA derived values for change with those of the clinical assessment revealed some associations.(ABSTRACT TRUNCATED AT 250 WORDS)


Subpicosecond Photoinduced Hole Transfer from a CdS Quantum Dot to a Molecular Acceptor Bound Through an Exciton-Delocalizing Ligand.
This paper describes the enhancement of the rate of hole transfer from a photoexcited CdS quantum dot (QD), with radius R = 2.0 nm, to a molecular acceptor, phenothiazine (PTZ), by linking the donor and acceptor through a phenyldithiocarbamate (PTC) linker, which is known to lower the confinement energy of the excitonic hole. Upon adsorption of PTC, the bandgap of the QD decreases due to delocalization of the exciton, primarily the excitonic hole, into interfacial states of mixed QD/PTC character. This delocalization enables hole transfer from the QD to PTZ in <300 fs (within the instrument response of the laser system) when linked by PTC, but not when linked by a benzoate group, which has a similar length and conjugation as PTC but does not delocalize the excitonic hole. Comparison of the two systems was aided by quantification of the surface coverage of benzoate and PTC-linked PTZ by (1)H NMR. This work provides direct spectroscopic evidence of the enhancement of the rate of hole extraction from a colloidal QD through covalent linkage of a hole acceptor through an exciton-delocalizing ligand.


Generation and Stability of Bulk Nanobubbles.
Recently, extremely small bubbles, referred to as nanobubbles, have drawn increased attention due to their novel properties and great potential for various applications. In this study, a novel method for the generation of bulk nanobubbles (BNBs) was introduced, and stability of fabricated BNBs was investigated. BNBs were created from CO2 gas with a mixing method; the chemical identity and phase state of these bubbles can be determined via infrared spectroscopy. The presence of BNBs was observed with a nanoparticle tracking analysis (NTA). The ATR-FTIR spectra of BNBs indicate that the BNBs were filled with CO2 gas. Furthermore, the BNB concentration and its ζ-potential were about 2.94 × 108 particles/mL and -20 mV, respectively (24 h after BNB generation with a mixing time of 120 min). This indicates the continued existence and stability of BNBs in water for an extended period of time.


Is sudoscan a reliable tool in detecting small fiber neuropathy in Parkinson's disease patients?
Aim: Previous studies have revealed uncertainties concerning the utility of sudoscan in identifying small fiber neuropathy in Parkinson's disease (PD). Patients & methods: We searched for a significant reduction of electrochemical skin conductance (ESC) in 67 PD patients versus 66 controls with similar characteristics. We conducted analysis of the subgroups of PD patients without diabetes using sudoscan technology. Results: There is no discrimination between patients and controls relative to feet ESC, the modified Hoehn and Yahr Scale and/or Unified Parkinson's Disease Rating Scale. ESC in patients did not differ significantly according to the Unified Parkinson's Disease Rating Scale score. The oldest PD patients with cardiovascular risk factors have more marked small fibers dysfunction. Conclusion: The sudoscan procedure did not show advantage in the diagnosis of small fiber neuropathy. Its diagnostic value increases in some subgroups of patients with cardiovascular co-morbidity.


Characterization of 2 linear peptides without disulfide bridges from the venom of the spider Lycosa poonaensis (Lycosidae).
Spider venom is a complex mixture of bioactive components, in which peptides play an important role by showing neurotoxicity or cytotoxicity. Disulfide-rich peptides are major components in the venom, but linear peptides without disulfide bridges are also present and often show antimicrobial activity. In this study, we analyzed the venom of the spider Lycosa poonaensis (Lycosidae) to find novel antimicrobial peptides using mass spectrometry. The result revealed that 120 out of 401 detected components were nondisulfide-bridged peptides. From them, the sequence of 2 peptides (lyp2370 and lyp1987) were determined by MS/MS analysis. The biological activity test revealed that lyp2370 has only weak antibacterial activity. On the other hand, lyp1987, which is identical to M-lycotoxin-Ls3b from the Lycosa singoriensi venom, showed significant antibacterial activity. The weak activity of lyp2370 was found to be due to the presence of a Glu residue on the hydrophilic face of its amphipathic α-helical structure.


Effect of topical nepafenac in prevention of macular edema after cataract surgery in patients with non-proliferative diabetic retinopathy.
To determine the efficacy of topical Nepafenac (0.1%), administered post-operatively in prevention of Macular Edema (ME), after cataract surgery in patients with Non-Proliferative Diabetic Retinopathy (NPDR). This randomized control trial was conducted at Armed Forces Institute of Ophthalmology (AFIO), Rawalpindi from Sep 2015 to Sep 2016. Sixty eyes of 60 patients with NPDR underwent phacoemulsification with intraocular lens implantation. Group 1 received 0.1% Nepafenac, 8-hourly, in operated eye after cataract surgery for three months, along with routine post-operative medications. Group-2 received only routine post-operative medications. ME was defined as increase in Central Macular Thickness (CMT) of >10% from pre-operative baseline, measured using spectral domain optical coherence tomography. Mean age of study population was 60.97±4.91 years. Out of 60 patients, 34 (56.7%) were males and 24 (43.3%) were females. Mean pre-operative CMT, 3 months post-operative CMT, mean change in CMT and mean frequency change in CMT of Group-1 was 226.5±10.86µm, 228.83±14.56 µm, 2.33±10.45 µm and 1.05% respectively. Mean pre-operative CMT, three months post-operative CMT, mean change in CMT and mean frequency change in CMT in Group-2 was 223.93±11.69µm, 236.17±16.16 µm, 12.23±12.40µm and 5.51% respectively. ME was observed in one patient (3.3%) in Group-1, and seven patients (23.3%) in Group 2. The difference of mean change in CMT and frequency change in CMT between groups was statistically significant (p<0.05). 0.1% topical Nepafenac is effective in prevention of macular edema after cataract surgery in patients with non-proliferative diabetic retinopathy (NPDR).


Mutations in the SLC2A10 gene cause arterial abnormalities in mice.
Glucose transporter 10 (GLUT10), encoded by the SLC2A10 gene, is a member of the class III facilitative glucose transporter family. Mutations in the SLC2A10 gene cause arterial tortuosity syndrome (ATS) in humans. To further study the pathogenesis of the disease, we generated mice carrying GLUT10 mutations. Using a gene-driven N-ethyl-N-nitrosourea (ENU)-mutagenesis approach, we generated mice carrying GLUT10 mutations c.383G>A and c.449C>T, which resulted in missense mutations of glycine to glutamic acid (p.G128E) and serine to phenylalanine (p.S150F), respectively. Both mutant strains appeared normal at birth, gained weight appropriately and survived to adulthood (>18 months). Blood and urine glucose were normal. Echocardiogram and electrocardiogram were also normal and brain magnetic resonance angiography revealed normal cerebral arteries without tortuosity, stenosis/dilatation, or aneurysm. Histopathology revealed thickening and irregular vessel wall shape of large and medium size arteries characterized by markedly increased elastic fibres, both in number and size. There was also intima endothelial hypertrophy and deranged elastic fibres that resulted in disruption of internal elastic lamina in the aorta of older mice. Abnormal elastogenesis with early elastic fibre proliferation provides a clue to the pathogenesis of arterial tortuosity in human ATS. Availability of this mouse model will allow testing of the relationship between diabetes and its vascular complications, including diabetic retinopathy, nephropathy and peripheral vascular disease.


Unusual dendritic keratitis.
Bilateral pseudo-dendritic keratitis in infancy can be due to tyrosinemia, a rare metabolic disorder. Ocular involvement may be the earliest presenting manifestation of this disease. Early diagnosis is essential because dietary modifications can result in complete reversal of the manifestations of this disorder. This disease must be suspected in all cases of non-responsive dendritic keratitis in the pediatric age group, especially if it is associated with cutaneous lesions such as patmoplantar keratosis. Serum tyrosine levels must be done in these cases.


Graves' disease coexisting with probable autoimmune hypoparathyroidism.
Organ-specific autoimmune endocrine disorders may present as single diseases or may occur together in polyendocrine syndromes. We present a report of 23-year-old female with Graves' disease and concurrent hypocalcemia. As she lacked other specific features of autoimmune polyendocrine syndromes, the most likely diagnosis was Graves' disease coexisting with autoimmune hypoparathyroidism.


Perceptions and Attitudes of Egyptian Health Professionals and Policy-Makers towards Pharmaceutical Sales Representatives and Other Promotional Activities.
Pharmaceutical promotion activities in low and middle-income countries are often neither regulated nor monitored. While Egypt has the highest population and per capita use of medicines in the Arab world, we know very little about pharmaceutical companies promotional activities in the country. To explore and analyze the perceptions of physicians towards promotional and marketing activities of pharmaceutical companies among physicians and pharmacists in Egypt. Perspectives of different healthcare system stakeholders were explored through semi-structured, in-depth interviews conducted in 2014 in Cairo, Egypt. Interviewees were chosen via purposive sampling and snowball technique. Each interview was recorded and transcribed. Then qualitative, thematic analysis was conducted with the help of NVIVO software. The majority of physicians and pharmacists acknowledged exposure to pharmaceutical promotion. It was commonly believed that interaction with the pharmaceutical industry is necessary and both associated risks and benefits were acknowledged. The interviewed physicians considered themselves competent enough to minimize risks and maximize benefits to their prescribing habits. Views diverged on the extent and magnitude of the risks and benefits of pharmaceutical promotion, especially in regard to the influence on patients' health. Pharmaceutical promotion in Egypt is intensely directed at prescribers and dispensers. Physicians, pharmacists and policymakers expressed little skepticism to the influence of promotion towards their individual prescribing. Raising awareness of the pitfalls of pharmaceutical promotion is necessary, especially among the less experienced physicians.


Structural and magnetic properties of iron nanowires and iron nanoparticles fabricated through a reduction reaction.
The main goal of this work is to study the structural and magnetic properties of iron nanowires and iron nanoparticles, which have been fabricated in almost the same processes. The only difference in the synthesis is an application of an external magnetic field in order to form the iron nanowires. Both nanomaterials have been examined by means of transmission electron microscopy, energy dispersive X-ray spectrometry, X-ray diffractometry and Mössbauer spectrometry to determine their structures. Structural investigations confirm that obtained iron nanowires as well as nanoparticles reveal core-shell structures and they are composed of crystalline iron cores that are covered by amorphous or highly defected phases of iron and iron oxides. Magnetic properties have been measured using a vibrating sample magnetometer. The obtained values of coercivity, remanent magnetization, saturation magnetization as well as Curie temperature differ for both studied nanostructures. Higher values of magnetizations are observed for iron nanowires. At the same time, coercivity and Curie temperature are higher for iron nanoparticles.


Role of Long Noncoding RNAs in Parkinson's Disease: Putative Biomarkers and Therapeutic Targets.
Parkinson's disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigidity, and tremor. Age is the main risk factor. Long noncoding RNAs (lncRNAs) are novel RNA molecules of more than 200 nucleotides in length. They may be involved in the regulation of many pathological processes of PD. PD has a variety of pathophysiological mechanisms, including alpha-synuclein aggregate, mitochondrial dysfunction, oxidative stress, calcium homeostasis, axonal transport, and neuroinflammation. Among these, the impacts of lncRNAs on the pathogenesis and progression of PD need to be highlighted. lncRNAs may serve as putative biomarkers and therapeutic targets for the early diagnosis of PD. This study aimed to investigate the role of lncRNAs in various pathological processes of PD and the specific lncRNAs that might be used as putative diagnostic biomarkers and therapeutic targets of PD.


Motor planning in primates.
Vaesen asks whether goal maintenance and planning ahead are critical for innovative tool use. We suggest that these aptitudes may have an evolutionary foundation in motor planning abilities that span all primate species. Anticipatory effects evidenced in the reaching behaviors of lemurs, tamarins, and rhesus monkeys similarly bear on the evolutionary origins of foresight as it pertains to tool use.


Development of fetal growth charts in twins stratified by chorionicity and mode of conception: a retrospective cohort study in China.
Twin pregnancies continue to increase worldwide; however, the current clinical prenatal evaluation for the intrauterine growth of twins still relies on the growth standards of singletons. We attempted to establish a set of fetal biometric references for Chinese twin pregnancies, stratified by chorionicity and conception mode as spontaneously conceived monochorionic diamniotic (SC-MCDA), spontaneously conceived dichorionic diamniotic (SC-DCDA), and assisted reproductive technology dichorionic diamniotic (ART-DCDA) twins. From 2016 to 2019, the ultrasonographic fetal biometric measurements were longitudinally collected in pregnant women, including fetal weight, biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length. The linear mixed models were used to test the difference of growth patterns between groups, and the growth curve of each biometric parameter was modeled by a generalized additive model for location scale and shape. A total of 929 twin pregnant women and 2019 singleton pregnant women, met the inclusion criteria. Among twin pregnancies, 148 were SC-MCDA, 215 were SC-DCDA, and 566 were ART-DCDA twins. Overall, SC-DCDA twins grew faster than SC-MCDA twins, while slower than ART-DCDA twins (all P < 0.05), and all of the three groups showed significant differences comparing with singletons, especially during the third trimester. Hence, the customized fetal growth charts of each fetal biometric parameter were, respectively, constructed for SC-MCDA, SC-DCDA, and ART-DCDA twins. The fetal biometric trajectories demonstrated characteristic patterns according to chorionicity and conception mode. To fill the gap, we modeled fetal biometric parameters for Chinese SC-MCDA, SC-DCDA, and ART-DCDA twin pregnancies, hoping to provide a reference for the further establishment of fetal growth reference values for Chinese twin fetuses.


Identifiable grief responses in persons with Alzheimer's disease.
Various dementias alter many aspects of the life and interactions between older adults and their families. This is particularly true even in a context in which the emotion is one that is expected. One such experience is the grief related to the loss of a family member. Physicians, nurses, and family members in long-term care report that they frequently have residents for whom a primary loved one, such as a spouse, has died. Questions quickly surface as to whether or not to tell the senior with dementia, how to tell the person, and how that person's response will impact the family. In two separate focus groups these questions were discussed with a group of family members and an interdisciplinary group of physicians, nurses, nurse aides, and social workers connected to long-term care facilities in one mid-sized community. Three patterns of resident response were identified. "Self-threat" describes situations in which the individual responds to the announcement of the death by questioning who will take care of them now; substitution refers to the individual's inability to remember who has died and substitution with a relative who died years ago; and metaphone, substitution of an object or unrelated item for the loss of a loved one. The authors suggest that persons with dementia should be told in most circumstances that their loved one has died, but that behavioral interventions need to be designed to address the confusion that this announcement can initiate. Families need to be prepared that the senior may not respond in the ways they once would have to this loss.


Differences in spousal influence on smoking cessation by gender and education among Japanese couples.
Previous studies have reported that spousal non-smoking has a spillover effect on the partner's cessation. However, discussion is lacking on the factors modifying that association. We examined whether the spillover effect of spousal non-smoking was associated with the couple's educational attainment. We used paired marital data from the Japanese Study on Stratification, Health, Income, and Neighborhood (J-SHINE), which targeted residents aged 25-50 years in four Japanese municipalities. We selected a spouse smoker at the time of marriage (target respondent), and set his/her smoking status change (continued or quit smoking after marriage) as an outcome, regressed on the counterpart's smoking status (continued smoking or non-smoking) and combinations of each couple's educational attainment as explanatory variables using log-binomial regression models (n =1001 targets; 708 men and 293 women). Regression results showed that a counterpart who previously quit smoking or was a never-smoker was associated with the target male spouse's subsequent cessation. However, for women, the association between husband's non-smoking and their own cessation was significant only for couples in which both spouses were highly educated. Our findings suggest that a spouse's smoking status is important for smoking cessation interventions in men. For women, however, a couple's combined educational attainment may matter in the interventions.


Fine-needle aspiration biopsy findings in marginal zone B cell lymphoma.
Marginal zone B cell lymphomas (MZBCLs) represent a category of non-Hodgkin's lymphoma which may arise in a wide variety of extranodal organs where they are termed low grade B cell lymphomas of mucosa-associated lymphoid tissue (MALT). MZBCLs may involve primarily lymph nodes and or spleen where they are designated monocytoid B cell lymphoma or splenic marginal zone lymphoma, respectively. Recognition of this category of lymphoma, in particular, extranodal MALT lymphoma, is clinically significant in determining optimal therapy. Although there have been recent case reports describing the cytologic findings in low grade MALT lymphoma in various extranodal organs, this category of lymphoma has not been widely recognized or discussed in the cytology literature. The cytologic findings in seven fine-needle aspirations and two bronchial washings of histologically confirmed marginal zone lymphoma (five extranodal MALT lymphomas and four nodal marginal zone lymphomas) are described. In all of the cases, the cytologic specimens showed a polymorphous proliferation comprising a predominant population of intermediate sized lymphoid cells with centrocyte-like or monocytoid features, transformed cells, and variable numbers of plasma cells. These findings, while highly suggestive of MALT lymphoma in extranodal proliferations, may be more difficult to distinguish from reactive conditions in lymph nodes.


[Hemapheresis using vesicular plant separation materials].
The present paper deals with the separation of cells from soluble compounds of blood by means of exclusion chromatography using a recently described vesicular packing material made from the cell wall framework of the small duckweed Wolffia arrhiza. The cells of the periphere blood are hardly retarded in passing through a packing of the vesicular material and eluted as sharp peak at an elution volume which is near to 30% of the column volume. The behavior of cells is similar to that of the excluded high molecular weight plasma proteins (e.g. serumalbumin). Low molecular weight solutes (e.g. salts, glucose, urea, kreatinin), but also substances of considerable molecular weight (e.g. myoglobin and Vitamin B12) which are usually difficult to separate by dialysis from serum, are eluted at nearly 100% of the packing volume and may be separated completely from cells and high molecular weight proteins. In vitro-Tests did not show a reduced vitality of eluted blood cells.


The effects of hydroxyapatite/calcium phosphate glass scaffold and its surface modification with bovine serum albumin on 1-wall intrabony defects of beagle dogs: a preliminary study.
The purpose of this study was to evaluate the effects of biphasic hydroxyapatite/calcium phosphate glass (HA/CPG) scaffold and its surface modification with bovine serum albumin (BSA) on periodontal regeneration. 1-wall intrabony defects were surgically created on five beagle dogs. HA/CPG scaffolds, with a hydroxyapatite (HA)/calcium phosphate glass (CPG) ratio of 95:5 by weight (%) and surface modification done by 2% bovine serum albumin, were used. The control group received surgical flap operation, and the experimental groups were filled with HA/CPG scaffolds and HA/CPG(BSA) scaffolds. The animals were sacrificed eight weeks after surgery. Histological findings revealed better space maintenance in the experimental groups than the control group, and showed new bone formation intermittently in between the residual material particles. The newly formed bone was mostly woven bone and the residual particles were undergoing resorption. Cementum regeneration was observed with limited root resorption in all the groups. Histometric analysis also revealed greater mean values in new bone formation, cementum regeneration and bone area than the control group in both experimental groups. However, similar findings were presented between HA/CPG and HA/CPG(BSA). The result of the present study revealed the newly fabricated HA/CPG scaffold to have a potential use as a bone substitute material.


Chronic asthma and improvement with relaxation induced by hypnotherapy.
Sixteen chronic asthmatic patients inadequately controlled by drugs had, after one year of hypnotherapy, a fall in admissions from 44 in the year before starting therapy to 13 in the year after. Duration of stay was reduced for 13 patients by 249 days; prednisolone was withdrawn in 6, reduced in 8 and increased in none. Side effects of drugs were reduced. Although 62% reported improvement on a visual analogue scale, observations of air flow gave variable results.


Immunodeficiencies and haematological disorders--direct connections to cellular signalling pathways.
Extracellular signals, such as cytokines and foreign antigens, regulate the development and activation of haematopoietic cells through receptor-mediated transcriptional responses. Investigation of the biochemical events that transduce receptor activation to intracellular signal transduction have revealed a general mechanism for both the antigen receptor and the cytokine receptor nuclear signalling. Receptor stimulation is coupled to down-stream signalling cascades through activation of cytoplasmic tyrosine kinases but both receptor types utilize distinct signalling proteins. Antigen receptors employ protein tyrosine kinases of the Src, Syk, and Tec families which phosphorylate and activate cytoplasmic signalling proteins leading to activation of NF-AT, AP-1 and NF-kappaB transcription factors, while the principal signal transducers for cytokine receptors are the Jak tyrosine kinases and Stat transcription factors. The molecular basis for several immune and haematological disorders has been characterized during the last few years and they have been found to be caused by defects in various signalling proteins. In this review the aetiology of immune and haematological disorders is discussed in the light of the recent developments in signal transduction.


Emergency oesophageal transection for uncontrolled variceal haemorrhage.
Continued haemorrhage from oesophageal varices despite adequate injection sclerotherapy and tamponade has a high mortality rate. Such patients are usually referred for surgery. Over a 10-year period, 30 patients (21 men and nine women of median age 52 (range 21-70) years) with acute variceal haemorrhage uncontrolled by initial treatment underwent early emergency oesophageal transection. Portal hypertension was caused by alcoholic cirrhosis in 22 patients; other forms of cirrhosis were present in seven and portal vein thrombosis in one. Hepatic function immediately before operation was Pugh grade A in two patients, B in six and C in 22. Deterioration between admission and transection from grade A to B occurred in one patient and from B to C in five. Oesophageal transection stopped variceal haemorrhage in 29 of the 30 patients. Rebleeding from gastric varices within 35 days of surgery occurred in five patients. Postoperative haemorrhage also occurred from perioesophageal vessels (two patients), a gastrotomy (one) and oesophageal ulceration (two). Hepatic failure developed in seven patients, renal failure in five and both hepatic and renal failure in four. Mortality at 30 days occurred in neither of the two patients with liver function of grade A, in one of six of grade B and in 18 of 22 of grade C. The overall 30-day mortality rate was thus 63 per cent. Mortality was related to the preoperative Pugh grade (hazard ratio 3.95 per grade; P = 0.013) and preoperative blood transfusion (hazard ratio 1.37 per unit; P = 0.035). Four of six patients with grade B liver function died within 3 months and 21 of 22 with grade C disease within 1 year. Oesophageal transection is effective at stopping variceal bleeding but does not modify the underlying disease. Caution is urged for patients with grade C hepatocellular impairment proceeding to acute oesophageal transection after initial sclerotherapy. Such patients may benefit more from treatment with somatostatin or an intrahepatic porta-systemic stent shunt while awaiting definitive therapy.


Sonoelastography of the trunk and lower extremity muscles in a case of Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a rare genetic disorder typically presenting with muscle weakness and reduced tone of trunk and lower extremities. The sonoelastographic properties of DMD are poorly understood. We describe sonoelastographic characteristics of a patient's trunk and lower extremity musculature. An 8-year-old male presented with a 5-year history of DMD. Sonoelastographic measures of the gluteus maximus and medius, lumbar erector spinae, rectus abdominis, rectus femoris, biceps femoris, tibialis anterior, medial and lateral gastrocnemius muscles were obtained. Sonoelastography demonstrated increased elasticity by elevated kiloPascals (kPa) across all muscles, except the lumbar erector spinae. Patient values were compared to an age-matched healthy control. These abnormal sonoelastographic findings reflected the pathological mechanical properties of DMD. Sonoelastography was valuable for characterizing the mechanical properties of normal and abnormal muscle tissue. There is limited information on the sonoelastography application to DMD. Sonoelastography may serve as a useful measure for diagnosis and monitoring clinical outcomes for DMD.


The ethics of compulsory removal under section 47 of the 1948 National Assistance Act.
Orders for removal under Section 47 of the 1948 National Assistance Act are little discussed. However, they involve severe infringements of the civil liberties of those affected. It is argued that all previously presented justifications for the use of these orders fail. Repeal of the act is called for. The Law Commission has drafted alternative legislation, but this has not been enacted. Until this occurs local authorities, the Faculty of Public Health Medicine and individual public health physicians should refuse to be involved in its use.


A pair of dopamine neurons target the D1-like dopamine receptor DopR in the central complex to promote ethanol-stimulated locomotion in Drosophila.
Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol.


Substance abuse prevention: the role of the school nurse across the continuum of care.
As a health care provider, health educator, and school/family/community liaison, the school nurse is in a unique position to act as a change agent for youth substance abuse prevention. This article discusses the roles of the school nurse as they apply to the prevention of substance abuse among school-age children, across a continuum of care model first introduced by the Institute of Medicine (IOM) in 1994. Through careful assessment, identification of substance abuse risk factors, and promoting the enhancement of protective factors of students, both in and out of the school setting, the school nurse can play a vital role in the prevention of substance abuse. Existing tools, including the IOM Mental Health Intervention Spectrum Model, can be easily adapted to nursing practice and may prove helpful in assisting school nurses in the evaluation and implementation of effective prevention interventions in the school setting.


Adipocytes-released Peptides Involved in the Control of Gastrointestinal Motility.
The present review focuses on adipocytes-released peptides known to be involved in the control of gastrointestinal motility, acting both centrally and peripherally. Thus, four peptides have been taken into account: leptin, adiponectin, nesfatin-1, and apelin. The discussion of the related physiological or pathophysiological roles, based on the most recent findings, is intended to underlie the close interactions among adipose tissue, central nervous system, and gastrointestinal tract. The better understanding of this complex network, as gastrointestinal motor responses represent peripheral signals involved in the regulation of food intake through the gut-brain axis, may also furnish a cue for the development of either novel therapeutic approaches in the treatment of obesity and eating disorders or potential diagnostic tools.


Otitis media in the Tgif knockout mouse implicates TGFβ signalling in chronic middle ear inflammatory disease.
Otitis media with effusion (OME) is the most common cause of hearing loss in children and tympanostomy to alleviate the condition remains the commonest surgical intervention in children in the developed world. Chronic and recurrent forms of OM are known to have a very significant genetic component, however, until recently little was known of the underlying genes involved. The identification of mouse models of chronic OM has indicated a role of transforming growth factor beta (TGFβ) signalling and its impact on responses to hypoxia in the inflamed middle ear. We have, therefore, investigated the role of TGFβ signalling and identified and characterized a new model of chronic OM carrying a mutation in the gene for transforming growth interacting factor 1 (Tgif1). Tgif1 homozygous mutant mice have significantly raised auditory thresholds due to a conductive deafness arising from a chronic effusion starting at around 3 weeks of age. The OM is accompanied by a significant thickening of the middle ear mucosa lining, expansion of mucin-secreting goblet cell populations and raised levels of vascular endothelial growth factor, TNF-α and IL-1β in ear fluids. We also identified downstream effects on TGFβ signalling in middle ear epithelia at the time of development of chronic OM. Both phosphorylated SMAD2 and p21 levels were lowered in the homozygous mutant, demonstrating a suppression of the TGFβ pathway. The identification and characterization of the Tgif mutant supports the role of TGFβ signalling in the development of chronic OM and provides an important candidate gene for genetic studies in the human population.


[Knockdown of DNA-PKcs inhibits cell cycle and its mechanism of drug-resistant Bel7402/5-Fu hepatocellular carcinoma cells].
Objective To study the effect of the knock-down of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) on the cell cycle of the multidrug-resistant (MDR) Bel7402/5-Fu hepatocellular carcinoma cells and its MDR mechanism. Methods After cationic liposome-mediated siDNA-PKcs oligonucleotide transfection, the drug sensitivity of Bel7402/5-Fu cells to 5-fluorouracil (5-Fu) and adriamycin (ADM) was determined by MTT assay; the cell cycle were detected by flow cytometry; meanwhile, the protein expressions of cell cycle-related proteins P21, cell cycle protein B1 (cyclin B1), cell cycle division protein 2 (CDC2) were tested by Western blotting; the expressions of ataxia telangiectasia mutated (ATM) and p53 at both mRNA and protein levels were detected by real-time PCR and Western blot analysis. Results The MTT results showed siDNA-PKcs increased the chemotherapeutic sensitivity of Bel7402/5-Fu cells to 5-Fu and ADM. The flow cytometric analysis showed siDNA-PKcs decreased the percentage of S-phase cells but increased the percentage of G2/M phase cells. Western blotting showed siDNA-PKcs increased the protein expression of P21 but decreased cyclinB1 and CDC2 proteins. In addition, siDNA-PKcs also increased the expressions of ATM and p53. Conclusion DNA-PKcs silencing increases P21 while decreases cyclin B1 and CDC2 expressions, and finally induces G2/M phase arrest in Bel7402/5-Fu cells, which may be related to ATM-p53 signaling pathway.


Phylogenetic rooting using minimal ancestor deviation.
Ancestor-descendent relations play a cardinal role in evolutionary theory. Those relations are determined by rooting phylogenetic trees. Existing rooting methods are hampered by evolutionary rate heterogeneity or the unavailability of auxiliary phylogenetic information. Here we present a rooting approach, the minimal ancestor deviation (MAD) method, which accommodates heterotachy by using all pairwise topological and metric information in unrooted trees. We demonstrate the performance of the method, in comparison to existing rooting methods, by the analysis of phylogenies from eukaryotes and prokaryotes. MAD correctly recovers the known root of eukaryotes and uncovers evidence for the origin of cyanobacteria in the ocean. MAD is more robust and consistent than existing methods, provides measures of the root inference quality and is applicable to any tree with branch lengths.


Delayed puberty.
Puberty is the acquisition of secondary sexual characteristics associated with a growth spurt and resulting in the attainment of reproductive function. Delayed puberty is diagnosed when there is no breast development by 13.4 years of age in a girl and no testicular enlargement by 14.0 years in a boy. The aetiologies are: (i) pubertal delay, either with constitutional delay of growth and puberty or secondary to chronic illness, and (ii) pubertal failure, with hypogonadotrophic (defect in the hypothalamo-pituitary region) or hypergonadotrophic (secondary to gonadal failure) hypogonadism, or both (secondary to radio/chemotherapy). The investigation includes: history, auxological data and pubertal development examination. Boys usually require treatment and, if they do not respond, investigation. In girls it is appropriate to measure the thyroid function and karyotype first and, if necessary, to offer treatment. If they present with dysmorphic features, or positive familial history, an assessment is required before treatment.


A case for community psychiatric nurses.
The author reviews the development of community psychiatric nursing services since the Mental Health Act 1959. In particular, the community services to her own catchment population are discussed, analysed and evaluated. A claim is made that community care is cost-effective and makes a contribution to prevention. It is also agreed that the presence of community psychiatric nurses in the community fosters greater tolerance and acceptance of the mentally sick by the community at large.


Finding defects in glasses through machine learning.
Structural defects control the kinetic, thermodynamic and mechanical properties of glasses. For instance, rare quantum tunneling two-level systems (TLS) govern the physics of glasses at very low temperature. Due to their extremely low density, it is very hard to directly identify them in computer simulations. We introduce a machine learning approach to efficiently explore the potential energy landscape of glass models and identify desired classes of defects. We focus in particular on TLS and we design an algorithm that is able to rapidly predict the quantum splitting between any two amorphous configurations produced by classical simulations. This in turn allows us to shift the computational effort towards the collection and identification of a larger number of TLS, rather than the useless characterization of non-tunneling defects which are much more abundant. Finally, we interpret our machine learning model to understand how TLS are identified and characterized, thus giving direct physical insight into their microscopic nature.


Intra-arterial blood pressure response in hypertensive subjects during low- and high-intensity resistance exercise.
The aim of this study was to describe blood pressure responses during resistance exercise in hypertensive subjects and to determine whether an exercise protocol alters these responses. Resistance exercise has been recommended as a complement for aerobic exercise for hypertensive patients. However, blood pressure changes during this kind of exercise have been poorly investigated in hypertensives, despite multiple studies of normotensives demonstrating significant increases in blood pressure. Ten hypertensive and ten normotensive subjects performed, in random order, two different exercise protocols, composed by three sets of the knee extension exercise conducted to exhaustion: 40% of the 1-repetition maximum (1RM) with a 45-s rest between sets, and 80% of 1RM with a 90-s rest between sets. Radial intra-arterial blood pressure was measured before and throughout each protocol. Compared with normotensives, hypertensives displayed greater increases in systolic BP during exercise at 80% (+80 +/-3 vs. +62 +/-2 mmHg, P<0.05) and at 40% of 1RM (+75 +/-3 vs. +67 +/-3 mmHg, P<0.05). In both exercise protocols, systolic blood pressure returned to baseline during the rest periods between sets in the normotensives; however, in the hypertensives, BP remained slightly elevated at 40% of 1RM. During rest periods, diastolic blood pressure returned to baseline in hypertensives and dropped below baseline in normotensives. Resistance exercise increased systolic blood pressure considerably more in hypertensives than in normotensives, and this increase was greater when lower-intensity exercise was performed to the point of exhaustion.


The effect of the selective activation of different peripheral nerve fiber groups on the somatosensory evoked potentials in the cat.
Contralateral and ipsilateral cortical somatosensory evoked potentials to selective activation of different diameter sural nerve fiber groups were recorded in cats. Activation of alpha fibers evoked a well defined positive-negative primary potential at the contralateral somatosensory area II. Activation of delta fibers in addition to alpha fibers resulted in another positive-negative wave of comparable amplitude with a latency approximately twice that of the early component. Isolation of the peripheral input to the delta fibers alone, by blocking the alpha fiber activity with the use of triangular pulses, caused the complete disappearance of the initial wave, leaving the second with no latency or amplitude changes. This demonstrated that the latter potential was evoked by delta fibers. Ipsilateral responses followed the same pattern, however with higher peripheral thresholds, longer latencies and smaller amplitudes. No cortical potentials could be recorded to activation of C fibers. The results of this study are at variance with previous observations about the cortical responses to small myelinated nerve fiber activity. The rationale of the use of triangular pulses for selectively activating nerve fiber groups is also discussed.


Diffusion chamber culturing of haematopoietic cells: methodological investigations and improvement of the technique.
Mouse bone marrow cells were cultured to determine some basic characteristics of the diffusion chamber (DC) technique. The main findings were as follows: (i) Incorporated 3H-thymidine was conveniently measured after deposition of a cell sample on glass fibre discs followed by methanol washing. Varying the specific activity from approximately 2-approximately 20 Ci/mmole did not affect the relationship between DC cellularity and isotope incorporation. Isotope uptake was similar regardless of whether 3H-thymidine of high or low specific activity had been used. (ii) Higher cell yields were obtained when Millipore or Acropor filters were heat-sealed rather than glued to the plastic rings, when Millipore filters were moistened before DC filling, when we omitted gluing the closing plugs, and when we used an average pore size of 0.22 mum for the DC walls rather than one of 0.10 mum or 0.45 mum. Varying the ring thickness from 2.0-2.5 mm did not impair the cell growth, nor did removal of a softening agent from the plastic rings improve it. (iii) More cells were retrieved from DC carried by young rather than by older mice. Results were not influenced by sex or strain differences between the donor and the host or by the number of implants, whether single or double, within an individual host. (iv) Adding Ficoll to the pronase solution increased the yield of viable CFU-C. (V) Diffusion rate through the DC walls declined with increasing period of culturing, so that i.p. 3H-thymidine is not a flash label for 7-day cultures, for example. The great variability of 3H-thymidine diffusion into i.p. DC was markedly reduced by in vitro exposure to the unopened DC to the isotope. (vi) DC could be incubated in vitro in a medium devoid of protein for at least 6 hours without a fall in 3H-thymidine incorporation rate or CFU-C content, provided that pH was kept constant.


Functional characterization of complement proteases C1s/mannan-binding lectin-associated serine protease-2 (MASP-2) chimeras reveals the higher C4 recognition efficacy of the MASP-2 complement control protein modules.
C1s and mannan-binding lectin-associated serine protease-2 (MASP-2) are the proteases that trigger the classical and lectin pathways of complement, respectively. They have identical modular architectures and cleave the same substrates, C2 and C4, but show markedly different efficiencies toward C4. Multisite-directed mutagenesis was used to engineer hybrid C1s/MASP-2 molecules where either the complement control protein (CCP) modules or the serine protease (SP) domain of C1s were swapped for their MASP-2 counterparts. The resulting chimeras (C1s(MASP-2 CCP1/2) and C1s(MASP-2 SP), respectively) were expressed and characterized chemically and functionally. Whereas C1s(MASP-2 SP) was recovered as an active enzyme, C1s(MASP-2 CCP1/2) was produced in a proenzyme form and was susceptible to activation by C1r, indicating that the activation properties of the chimeras were dictated by the nature of their SP domain. Similarly, each activated chimera had an esterolytic activity characteristic of its own SP domain and cleaved C2 with an efficiency comparable with that of their parent C1s and MASP-2 proteases. Both chimeras cleaved C4, but whereas C1s(MASP-2 SP) and C1s had Km values in the micromolar range, C1s(MASP-2 CCP1/2) and MASP-2 had Km values in the nanomolar range, resulting in 21-27-fold higher kcat/Km ratios. Thus, the higher C4 cleavage efficiency of MASP-2 arises from a higher substrate recognition efficacy of its CCP modules. Remarkably, C1s(MASP-2 CCP1/2) retained C1s ability to associate with C1r and C1q to form a pseudo-C1 complex and to undergo activation within this complex, indicating that the C1s-CCP modules have no direct implication in either function.


Assessing the influence of preconception diet on female fertility: a systematic scoping review of observational studies.
Preconception diet is a proposed modifiable risk factor for infertility. However, there is no official guidance for women in the preconception period as to which dietary approaches may improve fertility. A comprehensive synthesis of the relevant evidence is key to determine the potentially effective dietary patterns and components as well as evidence gaps, and to provide information for nutritional recommendations for couples planning a pregnancy. In this systematic scoping review, four electronic databases (Medline and EMBASE via Ovid processing, CAB Direct, and CINAHL via EBSCO) were searched for observational studies (prospective and retrospective cohort, cross-sectional, and case-control studies) from inception to 27 September 2021. Eligible studies included women of reproductive age during the preconception period, and evaluated exposures related to preconception diet and outcomes related to fertility. Results were synthesized using a descriptive approach. A total of 36 studies were eligible for inclusion (31 prospective, 3 cross-sectional, and 2 case-control studies) and were published between 2007 and 2022. Of the assessed dietary exposures, increased adherence to the Mediterranean diet displayed the strongest and most consistent association with improved clinical pregnancy rates. Reducing trans fatty acids (TFAs), saturated fatty acids, and discretionary food intake (fast food and sugar-sweetened beverages) were associated with improvements in live birth, clinical pregnancy rates, and related ART outcomes. The dietary components of seafood, dairy, and soy demonstrated inconsistent findings across the few included studies. Due to heterogeneity and the limited available literature on most exposures, there is insufficient evidence to support any specific dietary approach for improving fertility. However, following some of the dietary approaches outlined in this review (anti-inflammatory diets, reducing TFA, and discretionary food intake) are consistent with broad healthy eating guidelines, have little to no associated risk, and offer a plausible set of possible benefits. This warrants further exploration in randomized controlled trials.


Performance and Cost Comparisons for Continuous Rearing of Arma chinensis (Hemiptera: Pentatomidae: Asopinae) on a Zoophytogenous Artificial Diet and a Secondary Prey.
The impact of a zoophytogenous, insect-free artificial diet and a secondary prey, pupae of Chinese oak silk moth Antheraea pernyi (Guérin-Méneville) (Lepidoptera: Saturniidae), on the developmental rate, life history parameters, and fertility was examined for F6, F9, and F12 consecutive generations for domesticated Arma chinensis (Fallou) (Heteroptera: Pentatomidae). This study showed that when fed an insect-free artificial diet during both the nymphal and adult stages, developmental times were prolonged, and fecundity, egg viability, net reproductive rates (R0), and intrinsic rates of increase (rm) declined. As a result, the cost to rear A. chinensis on the artificial diet approached 1.7 times the cost of rearing A. chinensis on pupae of A. pernyi. Future diet improvements should attempt to reduce developmental time, increase fecundity, and egg viability and use less costly nutrient sources.


Biomaterial-based strategies for maxillofacial tumour therapy and bone defect regeneration.
Issues caused by maxillofacial tumours involve not only dealing with tumours but also repairing jaw bone defects. In traditional tumour therapy, the systemic toxicity of chemotherapeutic drugs, invasive surgical resection, intractable tumour recurrence, and metastasis are major threats to the patients' lives in the clinic. Fortunately, biomaterial-based intervention can improve the efficiency of tumour treatment and decrease the possibility of recurrence and metastasis, suggesting new promising antitumour therapies. In addition, maxillofacial bone tissue defects caused by tumours and their treatment can negatively affect the physiological and psychological health of patients, and investment in treatment can result in a multitude of burdens to society. Biomaterials are promising options because they have good biocompatibility and bioactive properties for stimulation of bone regeneration. More interestingly, an integrated material regimen that combines tumour therapy with bone repair is a promising treatment option. Herein, we summarized traditional and biomaterial-mediated maxillofacial tumour treatments and analysed biomaterials for bone defect repair. Furthermore, we proposed a promising and superior design of dual-functional biomaterials for simultaneous tumour therapy and bone regeneration to provide a new strategy for managing maxillofacial tumours and improve the quality of life of patients in the future.


Increased insulin sensitivity in patients with anorexia nervosa: the role of adipocytokines.
Anorexia nervosa (AN) is characterized by self-induced starvation leading to severe weight and fat loss. In the present study, we measured fasting plasma levels of adiponectin, leptin, resistin, insulin and glucose in 10 women with a restrictive type of AN and in 12 healthy women (C). Insulin sensitivity was determined according to homeostasis model assessment of insulin resistance (HOMA-R). Plasma resistin, leptin and insulin levels were significantly decreased, whereas plasma adiponectin levels were significantly increased in patients with AN compared to the C. HOMA-R was significantly decreased in patients with AN compared to the C group. Plasma adiponectin and leptin concentrations negatively and positively correlated with the body mass index and percentage body fat in both groups. Plasma adiponectin levels were negatively related to plasma insulin levels in the AN group only. In conclusion, we demonstrated that AN is associated with significantly decreased plasma leptin and resistin levels, markedly increased plasma adiponectin levels and increased insulin sensitivity. Plasma leptin and adiponectin levels were related to the body size and adiposity. Hyperadiponectinemia could play a role in increased insulin sensitivity of patients with AN. Neither body size and adiposity nor insulin sensitivity are the major determinants of plasma resistin levels in AN.


Interrogation of Milk-Driven Changes to the Proteome of Intestinal Epithelial Cells by Integrated Proteomics and Glycomics.
Bovine colostrum is a rich source of bioactive components which are important in the development of the intestine, in stimulating gut structure and function and in preparing the gut surface for subsequent colonization of microbes. What is not clear, however, is how colostrum may affect the repertoire of receptors and membrane proteins of the intestinal surface and the post-translational modifications associated with them. In the present work, we aimed to characterize the surface receptor and glycan profile of human HT-29 intestinal cells after exposure to a bovine colostrum fraction (BCF) by means of proteomic and glycomic analyses. Integration of label-free quantitative proteomic analysis and lectin array profiles confirmed that BCF exposure results in changes in the levels of glycoproteins present at the cell surface and also changes to their glycosylation pattern. This study contributes to our understanding of how milk components may regulate intestinal cells and prime them for bacterial interaction.


The Rho-kinase (ROCK) inhibitor Y-27632 protects against excitotoxicity-induced neuronal death in vivo and in vitro.
Rho-associated coil kinase (ROCK) inhibitors reportedly prevent neurodegeneration, and abnormal ROCK activation in the central nervous system induces neurite collapse and retraction. However, it is unclear whether the ROCK inhibitor Y-27632 directly protects hippocampal neurons from excitotoxicity. Here, we determined the effects of Y-27632 on neuroprotection following kainic acid (KA)-induced seizures in mice and during glutamate-induced excitotoxicity in HT22 cells. One day after Y-27632 injection, mice were treated with KA and killed 1-2 days later. Fluoro-Jade B and rapid Golgi staining showed that Y-27632 protected against KA-induced neurodegeneration and neurite dystrophy. Y-27632 inhibited increases in hippocampal RhoA and ROCK2 in KA-treated mice as determined by western blot analysis. Immunohistochemical analysis revealed ROCK2-positive neurons and astrocytes in the KA-treated hippocampus. In HT22 cells, Y-27632 also protected neurons and neurite formation during glutamate-induced excitotoxicity in vitro. These results indicate that ROCK inhibition modulates neurite growth and protects neurons from excitotoxicity-induced cell death.


[Anterior pituitary hypersecretion syndromes].
Anterior pituitary hypersecretion can be due to abnormal hypothalamic regulation, decreased peripheral hormone feedback or pituitary tumor. In some cases hypersecretion gives rise to a typical clinical syndrome involving acromegaly, hyperprolactinemia, and excess corticotropin (ACTH). The etiology of acromegaly is a growth hormone (GH)-secreting pituitary tumor in the vast majority of cases. Hyperprolactinemia and excess cortisol, however, may be due to many causes among which prolactin (PRL)- and ACTH-secreting pituitary tumors are not frequent. Glycoprotein-secreting pituitary tumors, especially gonadotropin (LH and FSH) and free subunits usually do not cause a typical excess hormone syndrome. Perhaps for this reason they are seldom recognized clinically, although histopathological studies are increasingly disclosing the gonadotrope nature of many pituitary tumors. Mixed hormonal secretions are common. When pituitary hormone secretion can be selectively suppressed by medical therapy, a significant reduction of tumor size is by no means rare. In other cases, pituitary irradiation or surgery, or even treatment aimed at a peripheral target gland, may be necessary.


NO2 Solvation Structure in Choline Chloride Deep Eutectic Solvents-The Role of the Hydrogen Bond Donor.
Deep eutectic solvents (DESs) are promising candidates as alternate media for industrial gas sequestration processes, such as denitrification via NO2 adsorption. Here, quantum chemical methods are employed to characterize the NO2 solvation structure and adsorption mechanism in choline chloride DES with urea, methylurea, and thiourea hydrogen bond donors. Our results show that the solvation structure of NO2 in bulk choline chloride DES is determined by the type of the hydrogen bond donor present. Changing the structure of the hydrogen bond donor not only changes its NO2 coordination mechanism but also changes that between NO2 and the choline and chloride ions in the DES. By using an energy decomposition analysis scheme, we show that the principle forces stabilizing NO2 in these DES are dispersion and polarization interactions and, consequently, that NO2 adsorption is most favorable in the choline chloride-thiourea DES. These results highlight a potential route for the optimization of choline chloride DES for denitrification, by modulating the hydrogen bond donor structure.


Mission impossible: upholding successfully a charge of infanticide in the Albanian legal practice.
Infanticide is a horrendous crime universally condemned from all ethical, juridical and moral standpoints. However, legislation on infanticide foresees mitigating circumstances for infanticidal mothers, with sentences by far disproportionate to the severity of the crime. The main justification for this abstaining from severe punishments has been the so-called post puerperal psychosis, whose diagnostic criteria and existence are still very confusing. Psychiatric experts and even jurors show excessive feelings of empathy toward defendant mothers, and fair verdicts under this setting and with this judicial tradition are questionable. Albanian courts have in some cases even denied defendant mothers the unwilling albeit necessary psychiatric treatment, thus exposing them to recidivism and to other social difficulties. Upholding the charge of infanticide in an Albanian court is hereby an impossible enterprise, with high chances for defendants to achieve acquittal on mental insanity grounds. Through describing three cases of infanticide and filicide in recent years of Albanian judicial proceedings, authors raise the concern formulated from other sources regarding the excessive empathy surrounding infanticidal mothers, a deleterious obstacle toward achieving justice.


Effects of double encapsulation and coating on synthetic seed conversion in M.26 apple rootstock.
Encapsulated vitro-derived apical buds of M.26 apple rootstock (Malus pumila Mill) can be employed for the formation of the synthetic seed. Satisfactory levels of conversion (plantlets from synthetic seed) can be achieved if there are adequate (i) rooting induction treatment, (ii) protocol of encapsulation, and (iii) nutritive and environmental conditions. For capsule manufacturing, sodium alginate is largely used; however, this is excessively permeable with loss of the nutritive substances (artificial endosperm) and/or dehydration risks during conservation and transport causing detrimental effects on the synthetic seed conversion and on the plantlet's growth. In order to overcome these problems, two experiments were carried out comparing simple encapsulation in alginate with double encapsulation, and with encapsulation-coating procedures. The presence of a second layer of alginate (double encapsulation) and of a thin external coating layer over the alginate (encapsulation-coating) did not show any detrimental effects on viability, sprouting and regrowth of the encapsulated microcuttings. Satisfactory conversion (70%) was reached with the encapsulation-coating procedure, whereas the double and simple encapsulation converted less than 40% of the synthetic seed. The effect of the addition to the capsule of an anti-microbial substance (Plant Preservative Mixture - PPM) was examined: it did not compromise the conversion of the encapsulated microcuttings sown in ex-vitro non-aseptic conditions.