Association of MEK1 with p21ras.GMPPNP is dependent on B-Raf.
We have previously reported that immobilized p21ras forms a GMPPNP-dependent complex with a MEK activity. Furthermore, the association of the MEK activity was found to be independent of the presence of Raf-1. We have extended those observations to show that MEK1 is the MEK activity previously described to associate with immobilized p21ras.GMPPNP. The association between MEK1 and immobilized p21ras.GMPPNP increased its specific activity towards p42MAPK. We detected the specific association of B-Raf with immobilized p21ras.GMPPNP. In contrast to Raf-1-immunodepleted lysates, preclearance of the cytosolic B-Raf significantly reduced, by 96%, the amount of MEK1 activity associated with immobilized p21ras.GMPPNP. The decrease in MEK1 activity correlated with complete loss in the binding of both B-Raf and MEK1 proteins with immobilized p21ras.GMPPNP. These data suggest that the p21ras.GMPPNP-dependent activation of MEK1 in brain extracts is dependent on the presence of the B-Raf protein kinase.


Prolonged intermittent adjuvant chemotherapy with CCNU and hydroxyurea after resection of carcinoma of the lung.
Eight hundred sixty-five patients with a microscopically curative resection for carcinoma of the lung were accepted for study, none of whom were excluded from analysis. Adjuvant therapy was randomly assigned about the tenth to 14th postoperative day; 432 patients (treated) were to receive CCNU and hydroxyurea for one year, while 433 patients (controls) were to receive no adjuvant therapy. Toxic reactions to therapy were reported, but only 1% were severe enough to require stopping therapy. No evidence of improved survival or delayed recurrence of disease was seen in treated patients as a whole or when examined by cell type and by postsurgical TNM category. On the contrary, survival beyond the second year of follow-up may have been impaired by the drugs when administered to patients without evidence of tumor spread to the lymph nodes.


Combined effects of diamines and carboxylate bridges on structural and magnetic properties of a series of polynuclear copper(II) complexes with 1,1-cyclobutanedicarboxylic acid.
Six new copper(II) complexes of formula [Cu(mu-cbdca)(H2O)]n (1) (cbdca = cyclobutanedicarboxylate), [Cu2(mu-cbdca)2(mu-bipy)2]n (2) (bipy = 4,4'-bipyridine), [Cu(mu-cbdca)(mu-bpe)]n (3) (bpe = 1,2-bis(4-pyridyl)ethane), [Cu(mu-cbdca)(bpy)]2 (4) (bpy = 2,2'-bipyridine), [Cu(terpy)(ClO4)]2(mu-cbdca).H2O (5) (terpy = 2,2':6',2' '-terpyridine), and [Cu(cbdca)(phen) (H2O)].2H2O (6) (phen = 1,10-phenanthroline) were obtained and structurally characterized by X-ray crystallography. Complex 1 is a two-dimensional network with a carboxylate bridging ligand in syn-anti (equatorial-equatorial) coordination mode. Complexes 2 and 3 are formed by chains through syn-anti (equatorial-apical) carboxylate bridges, linked to one another by the corresponding amine giving two-dimensional nets. Complexes 4 and 5 are dinuclear, with the copper ions linked by two oxo (from two different carboxylate) bridging ligands in 4 and with only one carboxylate showing the unusual bis-unidentate mode in complex 5. Complex 6 is mononuclear, with the carboxylate linked to copper(II) in a chelated form. Intermolecular hydrogen bonds and pi-pi stacking interactions build an extended two-dimensional network. Magnetic susceptibility measurements of complexes 1-5 in the temperature range 2-300 K show the occurrence of weak ferromagnetic coupling for 1 and 4 (J = 4.76 and 4.44 cm(-1), respectively) and very weak antiferromagnetic coupling for 2, 3, and 5 (J = -0.94, -0.67, and -1.61 cm(-1), respectively). Structural features and magnetic values are compared with those reported for the similar copper(II) malonate and phenylmalonate complexes.


Prevalence of thyroid diseases in two samples of Czech population. A preliminary study.
Two preliminary pilot studies of prevalence of thyroid disorders in Central Bohemia (with mild endemy before the onset of iodine prophylaxis in 1948) were made: 1. Questionary survey of adult persons in Praha (1559 persons); 2. Clinical and laboratory investigation of 2015 employees of SKODA automobile works in Mladá Boleslav. Prevalence of thyroid disorders in Praha was 11.99%. In randomly selected subjects from Mladá Boleslav (evaluated in two periods after 10 years) the prevalence of clinically manifested thyroid disorders was 0.35% in men and 2.32% in women, respectively, the presence of positive titres of antithyroglobulin antibodies, varied from 2.43-6.11% of high titres and from 2.35 to 17.33% of low titres. However, the prevalence of goiter was markedly higher than expected, since diffuse goitre was found in 8.36% of men and in 11.34% of women. Even more striking was the prevalence of nodular goitre which was 5.59% in men and 22.96% in women thus making the total goitre prevalence of 13.95% in men and 34.30% in women. In addition, an unfavourable increase of prevalence of nodular goitre was found in younger women in comparison with older group. These results, although preliminary, pointed out the necessity of further more extensive and intensive studies of prevalence of thyroid disorders and of methodology of iodine prophylaxis.


Effect of ring substitution on the metabolic fate and anti-inflammatory activity of some prodolic acid analogs.
Prodolic acid, 1-n-propyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid, exhibits potent anti-inflammatory activity in adjuvant arthritic rats. The potency of prodolic acid is enhanced by indole ring substitution. This increase correlated well with higher and sustained drug concentrations in the serum of normal animals. Pharmacokinetic studies demonstrated that ring substitution prolonged the serum half-life without affecting the absorption or volume of distribution. Because, in the rat, indole ring hydroxylation is a major pathway for the disposition of prodolic acid, we ascribe the increased pharmacological activity of ring substituted derivatives to the interference of substituents with the hydroxylation reaction.


Superior sagittal sinus flow as a proxy for tracking global cerebral blood flow dynamics during wakefulness and sleep.
Sleep, a state of reduced consciousness, affects brain oxygen metabolism and lowers cerebral metabolic rate of oxygen (CMRO2). Previously, we quantified CMRO2 during sleep via Fick's Principle, with a single-band MRI sequence measuring both hemoglobin O2 saturation (SvO2) and superior sagittal sinus (SSS) blood flow, which was upscaled to obtain total cerebral blood flow (tCBF). The procedure involves a brief initial calibration scan to determine the upscaling factor (fc), assumed state-invariant. Here, we used a dual-band sequence to simultaneously provide SvO2 in SSS and tCBF in the neck every 16 seconds, allowing quantification of fc dynamically. Ten healthy subjects were scanned by MRI with simultaneous EEG for 80 minutes, yielding 300 temporal image frames per subject. Four volunteers achieved slow-wave sleep (SWS), as evidenced by increased δ-wave activity (per American Academy of Sleep Medicine criteria). SWS was maintained for 13.5 ± 7.0 minutes, with CMRO2 28.6 ± 5.5% lower than pre-sleep wakefulness. Importantly, there was negligible bias between tCBF obtained by upscaling SSS-blood flow, and tCBF measured directly in the inflowing arteries of the neck (intra-class correlation 0.95 ± 0.04, averaged across all subjects), showing that the single-band approach is a valid substitute for quantifying tCBF, simplifying image data collection and analysis without sacrificing accuracy.


First Infestation Case of Sarcoptic Mange from a Pet Rabbit Oryctolagus Cuniculus in Republic of Korea.
In November 2019 a 5-month-old mixed-breed rabbit presented to Chungbuk National University Veterinary Teaching Hospital, Cheongju-si, Chungbuk, Republic of Korea (Korea) with symptoms comprising pruritus, crusts on skin, poor appetite and reduced defecation. The rabbit was purchased 2 months prior from a pet shop located in a big market, and that the symptoms were first observed about 2 weeks prior to the hospital visit. Physical examination revealed that the patient had crust formation and alopecia on the nose together with lesions on the digits. A skin scraping test was performed using mineral oil and a high density of mites was observed by microscopy. Each mite showed a round, tortoise-like body with 4 comparatively short pairs of legs. The anus was located at the terminal unlike with suspected pathogen, Notoedres cati. Based on morphological characteristics, we identified the mite as Sarcoptes sp. Ivermectin was administered weekly by subcutaneous injection at a dosage of 0.4 mg/kg, and 4 weeks of follow-up study revealed the patient was fully recovered. And no more mites were detected from the case. This is the first case report of sarcoptic mange in a pet rabbit in Korea.


[Retroperitoneal fibrosis and chronic peri-aortitis--new hypothesis].
Retroperitoneal fibrosis is characterised by the development of fibrotic mass surrounding the abdominal aorta and its branches. In the one third of cases, the causes of this disease include ergot-derivative drugs, retoperitoneal haemorrhage or urine extravasation and desmoplastic response to a variety of tumours. Retroperitoneal fibrosis is idiopathic in two thirds of cases and is found most commonly as an isolated fibrotic plague centered over the lumbar spine and entrapping one or both ureters. It has been postulated that fibrosis in idiopathic cases is caused by a chronic inflammatory or autoimmune response to antigens leaking into retroperitoneum from atheromatous plagues in the aorta or common iliac arteries. Many findings indicate the active nature of aortic adventitial chronic inflammation associated with human advanced atherosclerosis ("chronic periaortitis") and show its possible progressive potential to the clinically important disease termed "idiopathic retroperitoneal fibrosis" and "inflammatory aneurysm". A definitive differential diagnosis requires not only CT and NMR but also histologic confirmation. Treatment may be surgical or medical, with the best outcome observed in patient receiving both.


Structure determination of disordered materials from diffraction data.
We show that the information gained in spectroscopic experiments regarding the number and distribution of atomic environments can be used as a valuable constraint in the refinement of the atomic-scale structures of nanostructured or amorphous materials from pair distribution function (PDF) data. We illustrate the effectiveness of this approach for three paradigmatic disordered systems: molecular C60, a-Si, and a-SiO2. Much improved atomistic models are attained in each case without any a priori assumptions regarding coordination number or local geometry. We propose that this approach may form the basis for a generalized methodology for structure "solution" from PDF data applicable to network, nanostructured and molecular systems alike.


DeepAc4C: a convolutional neural network model with hybrid features composed of physicochemical patterns and distributed representation information for identification of N4-acetylcytidine in mRNA.
N4-acetylcytidine (ac4C) is the only acetylation modification that has been characterized in eukaryotic RNA, and is correlated with various human diseases. Laboratory identification of ac4C is complicated by factors, such as sample hydrolysis and high cost. Unfortunately, existing computational methods to identify ac4C do not achieve satisfactory performance. We developed a novel tool, DeepAc4C, which identifies ac4C using convolutional neural networks (CNNs) using hybrid features composed of physicochemical patterns and a distributed representation of nucleic acids. Our results show that the proposed model achieved better and more balanced performance than existing predictors. Furthermore, we evaluated the effect that specific features had on the model predictions and their interaction effects. Several interesting sequence motifs specific to ac4C were identified. The webserver is freely accessible at https://ac4c.webmalab.cn/, the source code and datasets are accessible at Zenodo with URL https://doi.org/10.5281/zenodo.5138047 and Github with URL https://github.com/wangchao-malab/DeepAc4C. Supplementary data are available at Bioinformatics online.


[Risk factors for bone mineral density changes in patients with rheumatoid arthritis and fracture risk assessment].
To verify the fracture risk assessment tool (FRAX) to estimate the probability of osteoporotic fracture in patients with rheumatoid arthritis (RA) with or without bone mineral density (BMD), and identify associated risk factors of osteoporosis. In the study, 200 patients with rheumatoid arthritis aged more than 40 years in Peking University First Hospital from Dec. 2009 to Dec. 2012 were recruited. Clinical information was obtained from a questionnaire of their case history and medical records. FRAX tool was administered. Their lumber spine and left femoral BMD were determined by dual energy X ray absorptiometry. The gender, age, disease duration, menopause status, body mass index (BMI) and accumulative dose of glucocorticoid were obtained in retrospect. Correlation analysis was conducted between the BMD and clinical information. The study population (female, 77.5%) had a mean age of 59.4 years, in which 10 (13%) patients showed a normal BMD, 67 (87%) were osteopenia or osteoporosis, while 32 patients (16%) had fragile fracture. Compared with the patients with normal BMD, the subjects with low BMD had significantly older age, longer period for corticoids usage, higher day dose and accumulated dose of corticoids.The 10-year fracture risk of sustaining major osteoporotic fractures and hip fracture was higher. No significant difference was observed between the 10-year fracture risks calculated with BMD and without BMD. The values of the different area under the receiver operating characteristic (ROC) curve (AUC) for major and hip fractures calculated in three ways: without BMD, with the femoral neck BMD, and with T-score. The best result was for FRAX tool for hip fracture with the T-score (AUC 0.899). A stepwise multivariate linear regression model was constructed to explore the relationship between the different clinical factors studied and a low BMD. Three statistically significant variables for lumber BMD were pain on visual assessment scale (VAS) (P=0.02), fracture history (P=0.003) and a higher steroid accumulated dose (P=0.008). Three statistically significant variables for left hip BMD were age (P<0.001), fracture history (P=0.05) and lower BMI (P=0.03). Low BMD is a common complication in RA patients. Risk factors for major fracture and hip fracture are increased. There is a positive correlation between FRAX calculated with and without BMD or T score. FRAX with the femoral neck T score or BMD presents a discriminatory capacity better than FRAX without BMD, according to the AUC ROC.


TLR ligand loaded exosome mediated immunotherapy of established mammary Tumor in mice.
Tumor-derived exosomes (TEXs) could be harnessed as an immunotherapeutic cancer vaccine. These nanovesicles are inherently possesses rich tumor antigen reservoirs. Due to their undesirable features such as poor or limited immunogenicity as well as facilitation of cancer development via mediating communication between tumor cells TEXs could be transformed into an effective immune adjuvant delivery system that initiates a strong humoral and cell-mediated tumor-specific immune response. Engineering TEXs to harbor immunostimulatory molecules still remains a challenge. Previously, we demonstrated that nucleic acid ligand encapsulated liposomes could trigger synergistic strong humoral, and cell mediated immune responses and provokes tumor regression to that of their standalone counterparts. In this study, we evaluated to immunogenicity of 4T1/Her2 cell-derived exosomes upon loading them with two potent immuno adjuvant, a TLR9 ligand, K-type CpG ODN and a TLR3 ligand, p(I:C). Engineered TEXs co-encapsulating both ligands displayed boosted immunostimulatory properties by activating antigen-specific primary and memory T cell responses. Furthermore, our exosome-based vaccine candidate elicited robust Th1-biased immunity as evidenced by elevated secretion of IgG2a and IFNγ. In a therapeutic cancer model, administration of4T1 tumor derived exosomes loaded with CpG ODN and p(I:C) to animals regress tumor growth in 4T1 tumor-bearing mice. Taken together this work implicated that an exosome-based therapeutic vaccine promoted strong cellular and humoral anti-tumor immunity that is sufficient to reverse established tumors. This approach offers a personalized tumor therapy strategy that could be implemented in the clinic.


Combination Strategies to Enhance the Efficacy of Antimicrobial Peptides against Bacterial Biofilms.
The great clinical significance of biofilm-associated infections and their inherent recalcitrance to antibiotic treatment urgently demand the development of novel antibiofilm strategies. In this regard, antimicrobial peptides (AMPs) are increasingly recognized as a promising template for the development of antibiofilm drugs. Indeed, owing to their main mechanism of action, which relies on the permeabilization of bacterial membranes, AMPs exhibit a strong antimicrobial activity also against multidrug-resistant bacteria and slow-growing or dormant biofilm-forming cells and are less prone to induce resistance compared to current antibiotics. Furthermore, the antimicrobial potency of AMPs can be highly increased by combining them with conventional (antibiotics) as well as unconventional bioactive molecules. Combination treatments appear particularly attractive in the case of biofilms since the heterogeneous nature of these microbial communities requires to target cells in different metabolic states (e.g., actively growing cells, dormant cells) and environmental conditions (e.g., acidic pH, lack of oxygen or nutrients). Therefore, the combination of different bioactive molecules acting against distinct biofilm components has the potential to facilitate biofilm control and/or eradication. The aim of this review is to highlight the most promising combination strategies developed so far to enhance the therapeutic potential of AMPs against bacterial biofilms. The rationale behind and beneficial outcomes of using AMPs in combination with conventional antibiotics, compounds capable of disaggregating the extracellular matrix, inhibitors of signaling pathways involved in biofilm formation (i.e., quorum sensing), and other peptide-based molecules will be presented and discussed.


Ethics and rural healthcare: what really happens? What might help?
Relatively few articles discuss the ethical issues that accompany healthcare in rural areas. This article presents and discusses the key findings obtained from multi-method research studies conducted over a 9-year period of time in a multi-state rural area. It challenges the efficacy of current models for bioethics, shows what kinds of ethical issues develop in rural communities, and offers a framework for envisioning resources and approaches that may be more appropriate.


First report of Grapevine enamovirus 1 in Vitis vinifera cultivar 'Meunier' in France.
Grapevine enamovirus 1 (GEV-1) is a member of the genus Enamovirus in the family Solemoviridae. GEV-1 was first described in 2017 in a few grapevine cultivars in Brazil (Silva et al. 2017) and subsequently in China (Ren et al. 2021). We first identified GEV-1 using high throughput sequencing (Illumina, NOVASeq SP, TruSeq mRNA stranded 2*150 bp) of ribosomal RNA depleted total RNAs extracts using RNeasy Plant mini kit) (Qiagen) from a Vitis vinifera 'Meunier' leaf sample collected in a more than 20 year old commercial vineyard in the Champagne region of France in 2019. Analyses of the 47,573,330 total reads were performed using CLC Genomics Workbench 12.0 software (Qiagen) as previously described (Hily et al. 2018). The GEV-1 genome, determined only from the HTS data (isolate GEV-1-Fr; GenBank accession No. MW760844), is 6 262 nucleotides (nt) long and fully covered with 5,706 reads (mapping parameters of 0,5 in length and 0,7 in similarity fractions using CLC). Compared with the previously determined sequences (NC_034836 and KX645875) from Brazil, the GEV-1-Fr sequence contain a few indels, including a deletion of 9 nt in the 5' untranslated region (UTR), an insertion of 3 nt located in the overlapping region of the open reading frame (ORF)1 and ORF2, and a single nt insertion in the non-coding region between ORF2 and ORF3. These indels also exist within the sequence of isolate SD-CG from China (MT536978). However, GEV-1-Fr contains a unique 45 nt insertion in the 3'-UTR, although this needs to be verified using standard assays. Overall, GEV-1-Fr exhibits 88.7, 89.1 and 93.3 % identity at the nt level with isolates from Brazil (NC_034836, KX645875) and China (MT536978), respectively. The GEV-1-infected 'Meunier' grapevine showed symptoms of light chlorotic patterns on the leaves that were probably due to the presence of other co-infecting viruses, including Grapevine fanleaf virus, Grapevine Pinot gris virus, Grapevine rupestris stem pitting-associated virus and Grapevine fleck virus. The detection of GEV-1 was further confirmed in the 'Meunier' grapevine via RT-PCR using newly designed primer pairs Fwd_GEV_5600: GCAAGGAGCAGCCCTATAATGCT and Rev_GEV_6075: CTAGTCGATACGATCTATAGGCGAGG that amplified a 474 bp fragment of ORF5. We also designed a TaqManTM assay in OFR5 with the following primers and probe; Fwd_GEV_5662: ACAAGTGCCYGTTTCCATAG, Probe_GEV_5724-FAM: TTTACCGAGGACTATGACGCCGC, Rev_GEV_5772: CACCGGCTCCATAACCATT. Among all the samples from different grapevine cultivars and geographic regions in France that were tested with the TaqMan assay (N=188), only the original 'Meunier' plant from Champagne was positive for GEV-1. To our knowledge, this is the first report of GEV-1 in France and in European vineyards in general. Although many aspects of the virus biology are yet to be elucidated, our results expand its geographical range. New GEV-1 detection primers can be developed, considering its genetic diversity, to facilitate its detection and further define its evolutionary history. Compared to the original sequences (NC_034836 and KX645875) in Brazil a few indels have been identified, including a deletion of 9nt located in the 5' untranslated region (UTR), an insertion of 3nt located in the overlapping region of the open reading frame (ORF)1 and ORF2 and a single nucleotide insertion in the non-coding region between ORF2 and ORF3. All indels were already described in the Chinese sequence (MT536978). However, this new GEV-1-Fr isolate is the only one that displays a 45nt insertion in the 3'-UTR. Overall, GEV-1-Fr exhibits 88.7, 89.1 and 93.3 % identity with isolates from Brazil (NC_034836, KX645875) and China (MT536978), respectively. No specific symptoms were observed in the GEV-1-infected 'Meunier' grapevine other than light chlorotic patterns on the leaves that were probably due to the presence of other virus, as this plant was co-infected with grapevine fanleaf virus (GFLV), grapevine Pinot gris virus (GPGV), grapevine rupestris stem pitting-associated virus (GRSPaV) and grapevine fleck virus (GFkV). The detection of GEV-1 was further confirmed via RT-PCR using newly designed primer pairs located in the 'aphid transmission protein' producing a 474 nt amplicon; Fwd_GEV_5600: GCAAGGAGCAGCCCTATAATGCT; Rev_GEV_6075: CTAGTCGATACGATCTATAGGCGAGG. GEV-1 was detected in all cuttings (N=15) obtained from the original plant. We also designed a tool for a TaqManTM-based detection in the same genome region as mentioned above; Fwd_GEV_5662: ACAAGTGCCYGTTTCCATAG; Probe_GEV_5724-FAM: TTTACCGAGGACTATGACGCCGC; Rev_GEV_5772: CACCGGCTCCATAACCATT. Among all the samples from different grapevine cultivars and geographic regions in France that were tested with the TaqMan assay (N=188), only the original 'Meunier' plant from Champagne was found positive for GEV-1 in gapevine in France.


[Ultrasound assisted the enzymolysis of ginsenosides to prepare pare ginseng saponin Compound K].
To prepare ginseng saponin Compound K with ultrasound-assisted total zymolytic ginseng saponins. The conversion rate was taken as the index to detect the pre-treatment factors such as ultrasonic power and ultrasonic time, as well as the impact of enzymatic factors, such as pH value, temperature, concentration of substrate, dosage of enzyme and reaction time, on the conversion rate. The response surface method was used to optimize the preparation conditions. The enzymolytic products were identified with MS, 1H-NMR and 13C-NMR. The results showed that the optimum conditions of the ultrasound-assisted enzymolysis were 250 W for ultrasonic power, 15 min for ultrasonic time, 5.5 for enzymolytic pH, 50 degrees C for enzymolytic temperature, 36 h for enzymolytic time, 4:5 for enzymolytic dosage: substrate and 1.0 g x L(-1) for concentration of substrate. The relative molecular mass of reaction products was 622.4. Therefore, the nuclear magnetic map verified that the reaction product was rare ginseng saponin Compound K. Under the above conditions, based on the total zymolytic ginseng saponins, the conversion rate of rare ginseng saponin Compound K was 6.91% in proportion to the total of ginsenosides. The process features gentle reaction conditions, high conversion rate and simple and reliable process, which is suitable for industrial production.


Regulation of Redox Homeostasis Through DNA/RNA Methylation and Post-Translational Modifications in Cancer Progression.
Significance: Aberrant redox homeostasis, characterized by the enhancement of intracellular reactive oxygen species (ROS) and antioxidant defenses, is among the well-known cancer hallmarks. Understanding the regulatory mechanisms of redox homeostasis in cancer cells has become the focus of many studies. Epigenetic and post-translational modifications (PTMs), as pivotal regulators of multiple biological processes, play critical roles in tumorigenesis and development. Recent Advances: DNA and RNA methylation are important forms of epigenetic modifications. Recent evidence suggests that DNA/RNA methylation and PTMs can modulate redox homeostasis in multiple manners including affecting key molecules in ROS production, elimination, and redox-related signaling, thereby participating in tumor progression. Critical Issues: The regulatory effects of DNA/RNA methylation and PTMs on ROS are of crucial importance for tumor progression. In this review, we introduce the dual role of ROS in cancer, and then focus on the mechanistic role of DNA/RNA methylation and PTMs, especially ubiquitination and acetylation, in regulating redox homeostasis to involve in cancer progression. Future Directions: A complete understanding of how epigenetics and PTMs function in the regulation of redox homeostasis in cancer progression might expand a new direction for the progression mechanisms and therapeutic targets of cancer. Antioxid. Redox Signal. 39, 531-550.


[Molecular bases of diseases caused by mutations in genes encoding subunits of ATP synthase].
ATP synthase is the last enzyme of the OXPHOS system synthesizing ATP. Mutations in either mitochondrial or nuclear genes encoding subunits of this enzyme (17 polypeptides) cause neurodegenerative diseases. The ATP synthase subunits 8 (ATP8, alias A6L) and a (ATP6) are encoded by the MT-ATP8 and MT-ATP6 mitochondrial genes, respectively. 17 diseases associated mutations were identified in five nuclear genes coding for subunits of this enzyme. 58 mutations were described in the MT-ATP6 and MT-ATP8 genes, among them 36 were deposited in MITOMAP database. For most of them neither their pathogenic character nor the mechanisms are known. This review summarizes what is known about the molecular basis of the ATP synthase deficiencies. We review the mutations in the ATP synthase genes as well as biochemical data obtained from studies of patient's cells and cybrid or yeast models. We include yeast research about drugs selection and their mechanism of action. Moreover we position the mutations into a recently published structural model of the Fo complex and discuss their structural/functional consequences.


Efficient adenovirus-mediated gene transfer into primary T cells and thymocytes in a new coxsackie/adenovirus receptor transgenic model.
Gene transfer studies in primary T cells have suffered from the limitations of conventional viral transduction or transfection techniques. Replication-defective adenoviral vectors are an attractive alternative for gene delivery. However, naive lymphocytes are not readily susceptible to infection with adenoviruses due to insufficient expression of the coxsackie/adenovirus receptor. To render T cells susceptible to adenoviral gene transfer, we have developed three new murine transgenic lines in which expression of the human coxsackie/adenovirus receptor (hCAR) with a truncated cytoplasmic domain (hCAR(Delta)cyt) is limited to thymocytes and lymphocytes under direction of a human CD2 mini-gene. hCAR(Delta)cyt.CD2 transgenic mice were crossed with DO11.10 T cell receptor transgenic mice (DO11.hCAR(Delta)cyt) to allow developmental studies in a defined, clonal T cell population. Expression of hCAR(Delta)cyt enabled adenoviral transduction of resting primary CD4+ T cells, differentiated effector T cells and thymocytes from DO11.hCAR(Delta)cyt with high efficiency. Expression of hCAR(Delta)cyt transgene did not perturb T cell development in these mice and adenoviral transduction of DO11.hCAR(Delta)cyt T cells did not alter their activation status, functional responses or differentiative potential. Adoptive transfer of the transduced T cells into normal recipients did not modify their physiologic localization. The DO11.hCAR(Delta)cyt transgenic model thus allows efficient gene transfer in primary T cell populations and will be valuable for novel studies of T cell activation and differentiation.


Raman Amplification with a Flying Focus.
We propose a new laser amplifier scheme utilizing stimulated Raman scattering in plasma in conjunction with a "flying focus"-a chromatic focusing system combined with a chirped pump beam that provides spatiotemporal control over the pump's focal spot. Pump intensity isosurfaces are made to propagate at v=-c so as to be in sync with the injected counterpropagating seed pulse. By setting the pump intensity in the interaction region to be just above the ionization threshold of the background gas, an ionization wave is produced that travels at a fixed distance ahead of the seed. Simulations show that this will make it possible to optimize the plasma temperature and mitigate many of the issues that are known to have impacted previous Raman amplification experiments, in particular, the growth of precursors.


Proteomic changes of the porcine small intestine in response to chronic heat stress.
Acute heat stress (HS) negatively affects intestinal integrity and barrier function. In contrast, chronic mild HS poses a distinct challenge to animals. Therefore, this study integrates biochemical, histological and proteomic approaches to investigate the effects of chronic HS on the intestine in finishing pigs. Castrated male crossbreeds (79.00 ± 1.50 kg BW) were subjected to either thermal neutral (TN, 21 °C; 55% ± 5% humidity; n=8) or HS conditions (30 °C; 55% ± 5% humidity; n=8) for 3 weeks. The pigs were sacrificed after 3 weeks of high environmental exposure and the plasma hormones, the intestinal morphology, integrity, and protein profiles of the jejunum mucosa were determined. Chronic HS reduced the free triiodothyronine (FT3) and GH levels. HS damaged intestinal morphology, increased plasma d-lactate concentrations and decreased alkaline phosphatase activity of intestinal mucosa. Proteome analysis of the jejunum mucosa was conducted by 2D gel electrophoresis and mass spectrometry. Fifty-three intestinal proteins were found to be differentially abundant, 18 of which were related to cell structure and motility, and their changes in abundance could comprise intestinal integrity and function. The down-regulation of proteins involved in tricarboxylic acid cycle (TCA cycle), electron transport chain (ETC), and oxidative phosphorylation suggested that chronic HS impaired energy metabolism and thus induced oxidative stress. Moreover, the changes of ten proteins in abundance related to stress response and defense indicated pigs mediated long-term heat exposure and counteracted its negative effects of heat exposure. These findings have important implications for understanding the effect of chronic HS on intestines.


Topological effects of a rigid chiral spacer on the electronic interactions in donor-acceptor ensembles.
Two triads (donor-spacer-acceptor), exTTF-BN-C60 (6) and ZnP-BN-C60 (7), in which electron donors (i.e., exTTF or ZnP) are covalently linked to C60 through a chiral binaphthyl bridge (BN), have been prepared in a multistep synthetic procedure starting from a highly soluble enantiomerically pure binaphthyl building block (1). Unlike other oligomeric bridges, with binaphthyl bridges, the conjugation between the donor and the acceptor units is broken and geometric conformational changes are facilitated. Consequently, distances and electronic interactions between the donor and C60 are drastically changed. Both donor-spacer-acceptor (D-s-A) systems (i.e., 6 and 7) exhibit redox processes that correspond to all three constituent electroactive units, namely, donor, BN, and C60. Appreciable differences were, however, observed when comparing triad 6, in which no significant exTTF-C60 interactions were noted, with D-s-A 7, whose geometry favors donor-acceptor and pi-pi interactions that result in ZnP-C60 electronic communication. This through-space interaction is, for example, reflected in the redox potentials. Excited-state studies, carried out by fluorescence and transient absorption spectroscopy, also support through-space rather than through-bond interactions. Although both triads form the corresponding radical-ion pair, that is, exTTF*+-BN-C60*- and ZnP*+-BN-C60*-, dramatic differences were found in their lifetimes: 165 micros and 730 ns, respectively.


Red meat consumption: an overview of the risks and benefits.
Red meat is long established as an important dietary source of protein and essential nutrients including iron, zinc and vitamin B12, yet recent reports that its consumption may increase the risk of cardiovascular disease (CVD) and colon cancer have led to a negative perception of the role of red meat in health. The aim of this paper is to review existing literature for both the risks and benefits of red meat consumption, focusing on case-control and prospective studies. Despite many studies reporting an association between red meat and the risk of CVD and colon cancer, several methodological limitations and inconsistencies were identified which may impact on the validity of their findings. Overall, there is no strong evidence to support the recent conclusion from the World Cancer Research Fund (WCRF) report that red meat has a convincing role to play in colon cancer. A substantial amount of evidence supports the role of lean red meat as a positive moderator of lipid profiles with recent studies identifying it as a dietary source of the anti-inflammatory long chain (LC) n-3 PUFAs and conjugated linoleic acid (CLA). In conclusion, moderate consumption of lean red meat as part of a balanced diet is unlikely to increase risk for CVD or colon cancer, but may positively influence nutrient intakes and fatty acid profiles, thereby impacting positively on long-term health.


[The cement-free modular revision prosthesis MRP-hip revision stem prosthesis in clinical follow-up].
We present prospective medium-term results of the modular revision prostheses "MRP-TITANIUM". 45 patients (n = 48 prostheses) were evaluated. The mean follow-up was 4.7 years (min.-max.: 1.0-9.0 years). Pre- and postoperatively the Harris hip score (differentiated to Paprosky I-III) was examined. 66.67 % of the cases had extensive bony defects (> or = Paprosky II b). By means of X-ray examinations, the stability of the prostheses, periprosthetic bone remodelling, the presence of radiolucent lines as well as bone defect regeneration were assessed postoperatively. The mean Harris hip score improved from 25.6 preoperative to 71.4 postoperative (p < or = 0.05). In 44 cases the X-ray showed stable fixation without secondary migration. In one case the stem (stand time 2.36 years) was revised due to secondary migration (> or = 5 mm). The survival rate (Kaplan-Meier) was 97 %. Bone transplantation with consecutive defect regeneration was (n = 30) complete in all cases. In six cases (12.5 %) a postoperative dislocation occurred with subsequent successful closed reposition four times (8.3 %). In two cases (4.2 %) an open reposition was done with correction of the antetorsion angle of the prostheses. The "MRP-TITANIUM modular revision prostheses" has proved to be reliable in cases of revision surgery with extensive bony defects. The failure rate was 2.1 % for 48 prospectively examined prostheses.


Soluble human leukocyte antigen-G (SHLA-G) in Tunisian kidney transplantation.
To investigate the relationship between the soluble HLA-G (sHLA-G) and the appearance of acute renal rejection (AR) episodes we have quantify in this study the level of sHLA-G by enzyme-linked immunosotrbent assay in 42 kidney transplant patients classified in two groups: G1: 17patients with acute rejection (AR+) and G2: 25 patients without AR (AR-). To establish our normal sHLA-G ranges, serum samples from 18 healthy controls were tested. Pre-transplantation sHLA-G levels were significantly increased in patients (mean +/- standard error of the mean, 60.48 +/- 12.18 units/ml) than healthy subjects (19.11 +/- 4.9 units/ml) (p = 0.001). Although the difference was not statistically significant, G1 patients (AR+) revealed lower levels of sHLA-G (mean +/- standard error of the mean, 31.25 +/- 6.71 units/ml) compared to G2 patients (AR-) (53.43 +/- 1721 units/ml). Nevertheless, the course of total sHLA-G levels was nearly identical in patients with and without rejection. Nonparametric analysis revealed that pre-transplantation levels of sHLA-G < 18.00 units/ ml (sensitivity: 87.8% and specificity of 72.2%) were not related to rejection. Also, multivariate analysis regarding anti-HLA antibody status, recipient age and gender showed that sHLA-G could not be an independent risk factor for renal graft rejection. However, a higher sera levels of sHLA-G seemed to contribute to better kidney allograft survival rate after 10 years of follow-up (significance tendency: p = 0.091) as shown by the survival analysis. Because of the small number of subjects studied, these results must be treated with caution. A much larger cohort of kidney transplant patients according to acute rejection would seem necessary to confirm these findings.


Success of dental implants placed in intraoral block bone grafts.
The purpose of this study was to evaluate the survival and success of dental implants placed in alveolar bone following augmentation using intraoral block bone grafts. A consecutive retrospective study was conducted on patients who had onlay bone grafts for vertical or horizontal augmentations followed by dental implantation from 1999 to 2001. Files of 50 healthy patients who received 129 implants in augmented sites were reviewed. Implant survival, radiologic implant success (marginal bone loss), and complications were recorded. Follow-up from time of implantation ranged from 6 to 67 months (mean: 24.3 +/- 11.2 months). Ranges of implant widths and lengths were 3.25 to 4.7 mm and 10 to 16 mm, respectively. The overall survival rate was 96.9% (four implants were removed). Marginal bone loss around implants ranged from 0 to 3.3 mm (average: 0.22 +/- 0.45 mm). Only 5% of the implants presented marginal bone loss > or =1.5 mm over the follow-up time. Intraoral bone block graft surgery is a predictable operation for the use of dental implants. Implant placement in augmented areas presents high survival and radiologic success rates with minimal bone loss.


Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis.
The majority of eukaryotic cells synthesize neutral lipids and package them into cytosolic lipid droplets. In vertebrates, triacylglycerol-rich lipid droplets of adipocytes provide a major energy storage depot for the body, whereas cholesteryl ester-rich droplets of many other cells provide building materials for local membrane synthesis and repair. These lipid droplets are coated with one or more of five members of the perilipin family of proteins: adipophilin, TIP47, OXPAT/MLDP, S3-12, and perilipin. Members of this family share varying levels of sequence similarity, lipid droplet association, and functions in stabilizing lipid droplets. The most highly studied member of the family, perilipin, is the most abundant protein on the surfaces of adipocyte lipid droplets, and the major substrate for cAMP-dependent protein kinase [protein kinase A (PKA)] in lipolytically stimulated adipocytes. Perilipin serves important functions in the regulation of basal and hormonally stimulated lipolysis. Under basal conditions, perilipin restricts the access of cytosolic lipases to lipid droplets and thus promotes triacylglycerol storage. In times of energy deficit, perilipin is phosphorylated by PKA and facilitates maximal lipolysis by hormone-sensitive lipase and adipose triglyceride lipase. A model is discussed whereby perilipin serves as a dynamic scaffold to coordinate the access of enzymes to the lipid droplet in a manner that is responsive to the metabolic status of the adipocyte.


Topiramate Pharmacotherapy for Alcohol Use Disorder and Other Addictions: A Narrative Review.
: Topiramate is a non-benzodiazepine anticonvulsant medication with multi-faceted pharmacologic action. It has emerged as an efficacious pharmacotherapeutic option for the treatment of addiction, especially alcohol use disorder (AUD). We present a broad narrative review of the putative mechanism of action and clinical utility of topiramate with regard to AUD and other substance use disorders. Collective evidence suggests topiramate is an effective treatment option in AUD, with notable efficacy in reducing harmful drinking patterns in AUD. Though not currently approved by the United States Food and Drug Administration for the indication of AUD, topiramate should be considered as a pharmacological treatment option with high utility among AUD patients. Early pharmacogenetic studies raise the intriguing possibility of identifying patients likely to respond to topiramate using genetic testing, and initial studies show that topiramate may also be useful in treating cocaine use disorder, smoking cessation and behavioral addictions. However, further research is needed in all these areas.


Exploring the Successions in Microbial Community and Flavor of Daqu during Fermentation Produced by Different Pressing Patterns.
Daqu can be divided into artificially pressed daqu (A-Daqu) and mechanically pressed daqu (M-Daqu) based on pressing patterns. Here, we compared the discrepancies in physicochemical properties, volatile metabolites, and microbiota features between A-Daqu and M-Daqu during fermentation and further investigated the factors causing those differences. A-Daqu microbiota was characterized by six genera (e.g., Bacillus and Thermoactinomyces), while five genera (e.g., Bacillus and Thermomyces) dominated in M-Daqu. The flavor compounds analysis revealed that no obvious difference was observed in the type of esters between the two types of daqu, and M-Daqu was enriched with more alcohols. The factors related to differences between the two types of daqu were five genera (e.g., Hyphopichia). The functional prediction of microbial communities revealed that the functional discrepancies between the two types of daqu were mainly related to ethanol metabolism and 2,3-butanediol metabolism. This study provided a theoretical basis for understanding the heterogeneity of daqu due to the different pressing patterns.


Association of Lymphocyte to Monocyte Ratio and Risk of in-Hospital Mortality in Patients with Cardiogenic Shock: A Propensity Score Matching Study.
Lymphocyte to monocyte ratio (LMR) has been long implicated in the prediction of many inflammatory-related diseases. However, the possible value as prognostic marker of LMR have not been evaluated in cardiogenic shock (CS) patients. The aim of the study was to assess the relationship between LMR on admission and in-hospital mortality in CS patients. Data on patients diagnosed with CS were extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database. We performed a single-institution, retrospective study of 1487 CS patients and determined the optimal cut-off for LMR by X-tile software. Propensity score matching (PSM) and inverse probabilities of treatment weighting (IPTW) were conducted to control confounders. Cox proportional hazards model was performed to evaluate the relationship between LMR and in-hospital mortality. Kaplan-Meier curves and receiver operating characteristics (ROC) analysis were applied to assess the prognostic value of LMR. The optimal cut-off value for LMR was 0.9. Cox proportional hazards model demonstrated that lower LMR (< 0.9) was independently associated with in-hospital mortality with hazard ratio (HR) of 1.40 (1.12-1.74, P = 0.003). The results were consistent with survival analyses (P < 0.001, Log rank test). Adding LMR< 0.9 to the sequential organ failure assessment (SOFA) score improved discrimination and risk stratification for in-hospital mortality. Lower level of LMR is related to higher risk of in-hospital mortality of patients with CS. As an easily available biomarker, LMR can independently predict the in-hospital mortality in CS patients.


Feline cuterebrosis caused by a lagomorph-infesting Cuterebra spp. larva.
Native species of rodents and lagomorphs in the Americas are the typical hosts of Cuterebra spp. larvae. Although these bot flies are relatively host specific, they occasionally parasitize other native and introduced mammals (including domestic animals and humans), an affliction termed cuterebrosis. Cuterebra spp. larvae generally cause benign, subcutaneous lesions (warbles), but when infesting domestic cats, they can invade the eyes, respiratory tract, and cerebral tissues, causing severe, and in some cases fatal, injury. Despite more than 2 dozen published reports of feline cuterebrosis, the type (rodent- or lagomorph-infesting) or species parasitizing domestic cats has rarely been determined. Here, I identify a larva removed from a kitten in southern Wisconsin as belonging to a lagomorph-infesting Cuterebra species, most likely C. abdominalis, based especially on features of the cuticular platelets covering its exterior, and its geographic location. This seems to be only the third substantiated report of feline cuterebrosis in more than 50 yr in which a larva has been identified beyond "Cuterebra spp." In each case, lagomorph-infesting species were involved, suggesting that domestic cats may not be susceptible to rodent-infesting Cuterebra species. However, because these studies are limited in number and geographic area, additional research is required to establish the spectrum of Cuterebra species involved in feline cuterebrosis.


Trypanosoma cruzi and Its Soluble Antigens Induce NET Release by Stimulating Toll-Like Receptors.
Neutrophils release fibrous traps of DNA, histones, and granule proteins known as neutrophil extracellular traps (NETs), which contribute to microbicidal killing and have been implicated in autoimmunity. The role of NET formation in the host response to nonbacterial pathogens is not well-understood. In this study, we investigated the release of NETs by human neutrophils upon their interaction with Trypanosoma cruzi (Y strain) parasites. Our results showed that human neutrophils stimulated by T. cruzi generate NETs composed of DNA, histones, and elastase. The release occurred in a dose-, time-, and reactive oxygen species-dependent manner to decrease trypomastigote and increase amastigote numbers of the parasites without affecting their viability. NET release was decreased upon blocking with antibodies against Toll-like receptors 2 and 4. In addition, living parasites were not mandatory in the release of NETs induced by T. cruzi, as the same results were obtained when molecules from its soluble extract were tested. Our results increase the understanding of the stimulation of NETs by parasites, particularly T. cruzi. We suggest that contact of T. cruzi with NETs during Chagas's disease can limit infection by affecting the infectivity/pathogenicity of the parasite.


Celecoxib versus a non-selective NSAID plus proton-pump inhibitor: what are the considerations?.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are extensively used worldwide. However, associated adverse gastrointestinal effects (NSAID gastropathy) such as bleeding, perforation and obstruction result in considerable morbidity, mortality, and expense. Although it is essential to employ gastroprotective strategies to minimize these complications in patients at risk, controversy remains on whether celecoxib alone or a non-selective NSAID in conjunction with a proton-pump inhibitor (PPI) is a superior choice. Recent concerns regarding potential cardiovascular toxicities associated with cox-2 selective inhibitors may favor non-selective NSAID/PPI co-therapy as the preferred choice. Concomitant use of low-dose aspirin with any NSAID increases the risk of gastrointestinal complications and diminishes the improved gastrointestinal safety profile of celecoxib; whereas use of ibuprofen plus PPI regimens may negate aspirin's antiplatelet benefits. Evidence shows that concurrent use of a non-selective NSAID (such as naproxen) plus a PPI is as effective in preventing NSAID gastropathy as celecoxib, and may be more cost-effective. Patients failing or intolerant to this therapy would be candidates for celecoxib at the lowest effective dose for the shortest duration of time. Potential benefits from using low-dose celecoxib with a PPI in patients previously experiencing bleeding ulcers while taking NSAIDs remains to be proven. An evidence-based debate is presented to assist clinicians with the difficult decision-making process of preventing NSAID gastropathy while minimizing other complications.


Iatrogenic cardiac herniation: post mortem case.
A case is presented in which sudden cardiac death was caused by herniation of the heart through a pericardial incision following a gunshot wound to the chest, resulting in acute compression of the coronary arteries. At autopsy the heart protruded through the pericardial incision, which appeared to have elongated, and the cause of death was thought to be acute myocardial infarction secondary to coronary artery constriction.


[The citizen sentinel paradigm meets epidemiology].
The Basilicata Region (Southern Italy) is a European hub for oil extraction. Complex interests over time have stimulated poor extraction practices, affecting the environment and the health of residents. For years, the people have complained about environmental contamination and human illnesses. Some inhabitants started carrying out 'civic monitoring' activities to gather evidence to support their complaints. The study offers an analysis of the motivations for the 'civic sentinels' to take action and explores potential applications of the data collected, including in the field of epidemiology. A specific initiative is explored as case study on the basis of findings from field research. The analysis emphasises the essential need people have to access reliable information in the face of environmental distress. It also highlights the growing trend of civic actors using the collected data to demand or orient interventions from competent authorities. It concludes by reflecting on the socio-legal implications of the study, proposing civic monitoring as a means of addressing and possibly mediating environmental conflicts.


Misregulated Wnt/beta-catenin signaling leads to ovarian granulosa cell tumor development.
Misregulation of the Wnt/beta-catenin signaling pathway is a hallmark of several forms of cancer. Components of the Wnt/beta-catenin pathway are expressed in ovarian granulosa cells; nevertheless, its potential involvement in granulosa cell tumorigenesis has not been examined. To this end, human (n = 6) and equine (n = 18) granulosa cell tumors (GCT) were analyzed for beta-catenin expression by immunohistochemistry. Unlike granulosa cells of normal ovaries, most (15 of 24) GCT samples showed nuclear localization of beta-catenin, suggesting that activation of the Wnt/beta-catenin pathway plays a role in the etiology of GCT. To confirm this hypothesis, Catnb(flox(ex3)/+); Amhr2(cre/+) mice that express a dominant stable beta-catenin mutant in their granulosa cells were generated. These mice developed follicle-like structures containing disorganized, pleiomorphic granulosa by 6 weeks of age. Even in older mice, these follicle-like lesions grew no larger than the size of antral follicles and contained very few proliferating cells. Similar to corpora lutea, the lesions were highly vascularized, although they did not express the luteinization marker Cyp11a1. Catnb(flox(ex3)/+); Amhr2(cre/+) females were also found to be severely subfertile, and fewer corpora lutea were found to form in response to exogenous gonadotropin compared with control mice. In older mice, the ovarian lesions often evolved into GCT, indicating that they represent a pretumoral intermediate stage. The GCT in Catnb(flox(ex3)/+); Amhr2(cre/+) mice featured many histopathologic similarities to the human disease, and prevalence of tumor development attained 57% at 7.5 months of age. Together, these studies show a causal link between misregulated Wnt/beta-catenin signaling and GCT development and provide a novel model system for the study of GCT biology.


Malignant tumor in the mummy of Ferrante Ist of Aragon, King of Naples (1431-1494).
Ferdinand Ist of Aragon was king of Naples and an important figure in the Italian Renaissance. He died in 1494 at the age of 63 and his preserved mummy was recently exhumed in the Basilica of S. Domenico Maggiore in Naples. During the autopsy part of a hollow organ came to light which was labelled probable rectum. After re-hydration and cutting, the specimen appeared a dark brown colour with numerous whitish areas of varying diameter (0.5-3mm). Immuno histological studies together with electron microscope analysis clearly demonstrate that.


[Effects of wheat bran fiber on lipid metabolism in ApoE~(-/-) mice].
To explore the effect and mechanism of wheat bran fiber on lipid metabolism in ApoE~(-/-)mice fed a high fat diet. Twenty 7-week-old male ApoE~(-/-)mice were randomly divided into two groups and fed either a high fat diet as AS model group or a high fat diet adding 0. 8% wheat bran fiber as W-fiber group. And five C57 BL/6 mice with the same genetic background were used as control group. After 18 weeks feeding, HE staining were performed for atherosclerotic lesions from transverse section of the aorta and hepatic histological examination. Liver homogenate total cholesterol(TC), triglyceride(TG)and free fatty acids(FFAs)were analyzed. Western blot was used to determine the protein expressions involved in hepatic lipid metabolism, including sterol regulatory element binding protein 1(SREBP-1), fatty acid synthase(FAS), acetyl-coA carboxylase(ACC), sterol regulatory element binding protein 2(SREBP-2), low-density lipoproteins receptor(LDLR) and scavenger receptor B1(SR-B1). At the end of the experiment, compared with control group, atherosclerotic plaque of the aorta and hepatic steatosis was obvious in the mice of AS model group, and wheat bran fiber alleviated the area of atheromatous plaque and hepatic lipid accumulation. Compared with AS model group, wheat bran fiber decreased liver homogenate TC level((60. 56±13. 49) μmol/g vs. (51. 10±5. 94) μmol/g)(P<0. 05), reduced protein expression of SREBP-1, FAS and ACC(P<0. 05), increased protein expression of SREBP-2SR-B1(P<0. 05). Taken together, wheat bran fiber can delay the occurance of AS by regulating the related protein expressions involved in lipid metabolism and improving hepatic lipid metabolism.


Prevalence and correlates of herpes simplex virus type 2 infection: evaluation of behavioural risk factors.
To examine the prevalence and correlates of infection with herpes simplex virus type 2 (HSV-2) among sexually transmitted disease (STD) clinic attenders, we studied the prevalence of antibodies to HSV-2 and their association with risk behaviour. Data were collected in a cross-sectional study among STD clinic attenders in Amsterdam. Seropositivity for HSV-2 was determined in 1798 serum samples by means of a monoclonal antibody-blocking enzyme-linked immunoassay. The prevalence of HSV-2 antibodies was higher than expected: 32.3% in a population in which 3% had current genital herpes and 8% gave a history of genital herpes. Of those with HSV-2 antibodies, only 18% had a history of genital herpes. A strong independent association with the presence of HSV-2 antibodies was found for sexual behaviour, more specifically: homosexual orientation, increasing number of years of sexual activity, increasing number of lifetime partners, number of past gonococcal infections, having receptive anal and (or) vaginal contact. The presence of HSV-2 antibodies had a strong association with past sexual behaviour and, for both sexes, with receptive anal intercourse. HSV-2 antibodies may be used as a surrogate marker of sexual risk behaviour in comparing different populations over time.


The European LABDEL project and its relevance to the prevention and treatment of allergies.
In March 2001, the European Commission funded a 3-year project (contract no. QLK3-CT-2000-00340) under the fifth Framework Programme to develop and test prototype products based on the oral delivery of vaccine and therapeutic agents using harmless lactic acid bacteria (LAB). The project, best known under its acronym LABDEL (for LAB delivery) also included research on LAB fermentation and technological innovations aimed at enhancing the efficiency of LAB delivery systems (1). One of the key scientific objectives was to investigate the possibility to prevent or treat a type I allergic disease using mucosal administration of LAB expressing the pollen allergen Bet v 1. The aim of this paper was to describe the background of the project with reference to a limited selection of articles and recent reviews as well as the results and major conclusions arising from this part of the project.


Combining Acute Kidney Injury with Gastrointestinal Pathology: A Clue to Acute Oxalate Nephropathy.
Acute oxalate nephropathy (AON) is an increasingly recognized cause of acute kidney injury (AKI). Herein, we present two cases of biopsy-proven acute oxalate nephropathy in patients with gastrointestinal malabsorption, coincidentally both stemming from cholangiocarcinoma. The first is a 73-year-old male who presented with syncope and was found to have severe, oliguric AKI in the setting of newly diagnosed, nonresectable cholangiocarcinoma. The second is a 64-year-old man with remote resection of cholangiocarcinoma who presented after routine laboratory monitoring showed significant AKI. Temporary dialysis was required in both cases before renal recovery occurred. Together, these cases should increase physicians' suspicion of AON in the presence of malabsorption. By doing so, the workup of oxalate nephropathy can be expedited with prompt initiation of treatment.


Fractalkine upregulates intercellular adhesion molecule-1 in endothelial cells through CX3CR1 and the Jak Stat5 pathway.
Fractalkine (FKN) is a membrane-bound chemokine that can be released by proteolysis to produce soluble FKN (s-FKN). FKN and its receptor, CX3CR1, are believed to be important factors in atherosclerosis and may play a role in acute inflammatory responses. Although FKN is expressed on endothelial cells (ECs), CX3CR1 is reported to reside mainly on certain leukocyte populations. RT-PCR and Western blotting demonstrated that both human coronary artery and umbilical vein ECs expressed CX3CR1 mRNA and protein. Confocal microscopy showed that CX3CR1 was located at the cell membrane and to a lesser extent in the cytoplasm. Following exposure of both types of ECs to hypoxia and reoxygenation, FKN expression increased rapidly and s-FKN was shed into the culture medium. The addition of s-FKN protein to cultured ECs resulted in a dose-dependent increase in intercellular adhesion molecule (ICAM)-1 mRNA. Perfusion of mouse hearts with s-FKN protein increased expression of ICAM-1 protein in vascular endothelium. Transfection of ECs with CX3CR1-interfering RNA to knockdown the receptor resulted in decreased ICAM-1 expression after s-FKN stimulation. In addition, when ECs were stimulated with s-FKN, greater adhesion of human neutrophils to the ECs was observed. This increase was ICAM-1 dependent and was blocked by CX3CR1 knockdown. Following exposure to s-FKN, ECs exhibited increased phosphorylation of Jak2 and Stat5 and the ICAM-1 expression induced by s-FKN was blocked by silencing of Stat5 with small interfering RNA. Vascular ECs express both FKN and its receptor CX3CR1. s-FKN is shed from ECs following hypoxia/reoxygenation and acts through CX3CR1 on ECs to increase ICAM-1 expression and promote neutrophil adhesion through activation of the Jak-Stat5 pathway.


Measuring the severity of Clostridium difficile infection: implications for management and drug development.
The appropriate management of Clostridium difficile infection (CDI) has become a growing clinical and economic issue, as a new epidemic strain with enhanced virulence is causing increased morbidity and mortality. Presently, only two antibiotics (metronidazole and vancomycin) are routinely used to treat CDI. Both increasing disease severity and recurrent infections have been an impetus not only to develop new agents, but also to better recognize which patients are at highest risk for treatment failure and/or recurrence so that treatments can be optimized from the outset. The availability of a standardized and validated system for stratifying CDI severity could improve patient management and potentially accelerate the development of new treatment agents.


[Not Available].
A review is made of the more important works, issued during the years of Soviet rule, and concerning the life and activities of the most outstanding physicians--classicists of the world medical science (Hyppocrate, Galen, Avizena, Leonardo da Vinci etc). It is stressed that the works of the great representatives of the medico-biological sciences are an effective means for the correct ideologic and theoretic education of the modern generations of medical doctors and for the enrichment of research and investigation methods.


Lateral cephalothoracopagus: a case report.
A case of lateral cephalothoracopagus with posterior auricles is presented and compared with similar cases previously reported. This case is the first, to our knowledge, which exhibits both unequivocal lateral juncture of the faces and posterior auricles. Thus, it may represent a pattern of juncture intermediate between janiceps and lateral cephalothoracopagus.


Expression of human apolipoprotein A-I in transgenic mice results in reduced plasma levels of murine apolipoprotein A-I and the appearance of two new high density lipoprotein size subclasses.
In Western societies high density lipoprotein (HDL) levels correlate inversely with the risk for coronary heart disease. The primary protein component of both human and mouse HDL is apolipoprotein A-I (apoAI), which comprises greater than 70% of HDL protein and 30% of HDL mass. Human HDLs include particles of several distinct size subpopulations, whereas HDLs from inbred C57BL/6 mice contain a single population of particles. To study the regulation of apoAI expression and its role in HDL assembly, we created transgenic C57BL/6 mice containing the human apoAI gene. Two independent lines of transgenic mice with approximately twice the normal plasma levels of total apoAI were studied. The level of mouse apoAI is reduced greater than 4-fold in both transgenic lines, comprising only 4% of total plasma apoAI levels in one transgenic line and 13% in the other. We demonstrate that the mechanism responsible for the decrease in mouse apoAI is posttranscriptional. Parallel to the replacement of mouse with human apoAI, the single HDL species normally present in the plasma of C57BL/6 is replaced by two HDL subclasses similar in size to human HDL2b and HDL3a. The changes in murine apolipoprotein levels and HDL subclass size are inherited by all transgenic offspring of the two founder animals. These results suggest a dominant role of apoAI in determining the HDL particle size distribution and a mechanism involving expression of human apoAI transgenes that alters the plasma levels of mouse apoAI.


The Healthy Nurse: Identifying Barriers to Healthy Eating at Work.
To identify the barriers to healthy eating in a nurse's work environment by utilizing the PhotoVoice method, a self-report survey, and semi-structured interviews. Recruitment of participants consisted of friends and acquaintances (i.e., convenience sample) that are current nurses in the field. Research design comprised of three parts: photo collection, a self-report survey, and individual semi-structured interviews. Participants used PhotoVoice to take pictures of their experiences and environment. This tool focused on barriers, strengths and weaknesses. Participants were allotted two weeks to collect pictures, and used personal devices such as a cell phone. Pictures were then sent directly to the researcher via email and securely stored. Surveys were administered by Qualtrics to each participant to complete on their own time. The self-report survey was a compilation of variables the researcher sought to analyze: nutrition habits, mental and emotional health, physical health, and demographics. During the interviews, the participants explained and discussed their photographs. A list of follow-up questions were constructed to provide supplemental information. Each interview was completed under 30 minutes. Participants were informed the interviews were audio recorded, and were later transcribed verbatim by the researcher. The final sample size concluded 6 participants. Over half the nurses worked in a hospital setting. Common themes to barriers comprised of inconsistent break patterns, lack of availability and quality of food, and the abundance of accessible unhealthy options. Participant recommendations included bringing in healthier options, easier access and availability to healthy food, a nurse buddy system and accountability among staff. Attention and research are lacking in this area and further studies are necessary to shine light on the importance of a nurse's health. Future organizational support for nurses involves an extension on cafeteria hours to allow all shifts to obtain quality food, ordering healthier options, allow for water bottles or dispensers to be heavily present and to implement a plan for sufficient breaks. There was not a need for funding.


Investigation of micro-injection molding based on longitudinal ultrasonic vibration core.
An ultrasound-assisted micro-injection molding method is proposed to improve the rheological behavior of the polymer melt radically, and a micro-injection molding system based on a longitudinal ultrasonic vibration core is developed and employed in the micro-injection molding process of Fresnel lenses. The verification experiments show that the filling mold area of the polymer melt is increased by 6.08% to 19.12%, and the symmetric deviation of the Fresnel lens is improved 15.62% on average. This method improved the filling performance and replication quality of the polymer melt in the injection molding process effectively.


Effect of diazepam on ventilatory responses.
To investigate the effects of diazepam on ventilatroy control, hypoxic and hypercapnic ventilatory responses were studied in 8 normal subjects before and after 10 mg of intramuscular diazepam. There was no significant change in either resting minute ventilation or resting end-tidal CO2 tension, but depression of hypoxic ventilatory response was observed 15 (60% of control) and 30 min (53% of control) after diazepam (p less than 0.05). No significant depression of hypercapnic ventilatory response was noted 70 to 130 min after diazepam. In view of the depression of hypoxic ventilatory response by diazepam in normal subjects, adverse responses along these lines should be considered in patients with impaired ventilatory function, such as chronic airways obstruction, and in those encountering acute hypoxemia.


Charge-coupled-device based scanner for tomography of fluorescent near-infrared probes in turbid media.
We present a novel tomographer for three-dimensional reconstructions of fluorochromes in diffuse media. Photon detection is based on charge-coupled device technology that allows the implementation of a large parallel array of detection channels with high sensitivity. Using this instrument we studied the response and detection limits of near-infrared fluorochromes in diffuse media as a function of light intensity and for a wide range of biologically relevant concentrations. We further examined the resolution of the scanner and the reconstruction linearity achieved. We demonstrate that the instrument attains better than 3 mm resolution, is linear within more than two orders of magnitude of fluorochrome concentration, and can detect fluorescent objects at femto-mole quantities in small animal-like geometries. These measurements delineate detection and reconstruction characteristics associated with imaging of novel classes of fluorescent probes developed for in vivo molecular and functional probing of tissues.


Innovative Health and Social Integrated Care Model Effectiveness to Improve Quality Care for Chronic Patients: A Single Group Assignment Clinical Trial.
Patients with chronic disease have become one of the major challenges for health and social protection systems in developed countries. Integrated care models (ICM) have demonstrably improved the quality of care of chronic patients. However, new models of integration need further evaluation of its effectiveness and outcomes. The ICM studied promoted coordination between the health and social sectors during a 6-month period, through an ad hoc developed application (app) that enabled a constant flow of communication between professionals from both sectors. Patients' quality of life, treatment adherence, chronic patient experience and caregiver overload were assessed by questionnaires at baseline, at the end of the intervention and 6 months post-intervention. The implementation of the new health and social ICM permitted new case detection and medical and social services offered to chronic patients. Furthermore, the quality of life and treatment adherence of patients and caregiver overload were significantly improved. These positive effects lasted at least 6 months after the intervention. Integrated care may facilitate access to care services, increase perceived patient quality of life and treatment adherence. Enhanced access to medical and social services from complex chronic patients may have important implications for caregivers and the care systems who are struggling to adapt to an expanding demand.


Ligation of Intersphincteric Fistula Tract Is Suitable for Recurrent Anal Fistulas from Follow-Up of 16 Months.
Since 2007, ligation of the intersphincteric fistula tract (LIFT) for the management of anal fistula was all introduced with initial success and excitement. It remains controversial which surgical procedure is suitable for transsphincteric fistula, especially to complex anal fistula. This retrospective study was designed to evaluate the results in patients with recurrent anal fistula by LIFT. A retrospective study of 55 complex fistula patients who underwent LIFT procedure in a single medical center was analyzed. Patients and fistula characteristics, complications, and recurrences were reviewed. All 55 patients underwent the procedure with a median follow-up of 16 months. Median operative time was 44 (range 23-88) minutes. Of the 55 patients, 33 (60%) healed completely and did not require any further surgical treatment at end of follow-up. Twenty-two (40%) recurrences and six complications were observed. Compared with patients who had undergone more than two surgical procedures, LIFT was more suitable for patients who had undergone one to two surgical procedures, and significant difference was observed in number of operations before LIFT (p = 0.002). Clinicians can consider the use of LIFT for the treatment of recurrent anal fistulas. A larger number of patients and prospective study are needed to be performed.


Muscle membrane integrity in Duchenne muscular dystrophy: recent advances in copolymer-based muscle membrane stabilizers.
The scientific premise, design, and structure-function analysis of chemical-based muscle membrane stabilizing block copolymers are reviewed here for applications in striated muscle membrane injury. Synthetic block copolymers have a rich history and wide array of applications from industry to biology. Potential for discovery is enabled by a large chemical space for block copolymers, including modifications in block copolymer mass, composition, and molecular architecture. Collectively, this presents an impressive chemical landscape to leverage distinct structure-function outcomes. Of particular relevance to biology and medicine, stabilization of damaged phospholipid membranes using amphiphilic block copolymers, classified as poloxamers or pluronics, has been the subject of increasing scientific inquiry. This review focuses on implementing block copolymers to protect fragile muscle membranes against mechanical stress. The review highlights interventions in Duchenne muscular dystrophy, a fatal disease of progressive muscle deterioration owing to marked instability of the striated muscle membrane. Biophysical and chemical engineering advances are presented that delineate and expand upon current understanding of copolymer-lipid membrane interactions and the mechanism of stabilization. The studies presented here serve to underscore the utility of copolymer discovery leading toward the therapeutic application of block copolymers in Duchenne muscular dystrophy and potentially other biomedical applications in which membrane integrity is compromised.


An efficient reagent for the phosphorylation of deoxyribonucleosides, DNA oligonucleotides, and their thermolytic analogues.
[reaction: see text] The phosphoramidite 11 was prepared in three steps from methyl 2-mercaptoacetate and demonstrated efficiency in the synthesis of conventional 5'-/3'-phosphate/thiophosphate monoester derivatives of 2'-deoxyribonucleosides and DNA oligonucleotides. Moreover, the use of 11 has enabled the preparation of the dinucleoside phosphorothioate analogue 26 in high yields (>95%) with minimal cleavage (<2%) of the thermolytic thiophosphate protecting group.


[Neoplastic residues in the trocar tract in oncologic laparoscopic surgery].
The laparoscopic approach to malignant diseases runs up against both old and new problems: respect for the principles of radicality, operating times, the postoperative course and surgical complications, long-term oncological results in terms of survival and recurrence of the disease. One of the problems which has received most attention regards the onset of a metastasis on a trocar scar or a mini-laparotomy recurrence. Trocar site tumor recurrences have been described in the literature following laparoscopic surgery in almost all abdominal malignant pathologies (colorectal, gynaecological, pancreatic, etc.) and even after thoracoscopy. The real frequency is currently of the order of 1% (0-2%) in colic surgery and of 14% (10-17%) after cholecystectomy for occult gallbladder carcinoma. A retrospective survey was carried out of our laparoscopic experience; between 1994 and 2002 213 colic resections were carried out for cancer; we also observed 18 occult carcinomas of the gallbladder in 2386 laparoscopic cholecystectomies for lithiasis. Respectively 2 cases (11%) of trocar site neoplastic recurrences in gallbladder carcinoma and 2 cases (0.9%) from colon carcinoma were observed. The real extent of the problem would appear to be on a much lesser scale at the moment than was initially thought, especially as regards colic surgery. The multifactorial aetiology of the problem explains the importance of their prevention, on the basis above all of rigorous respect for the rules and protocols of laparoscopic technique.


Binding interaction between (-)-epigallocatechin gallate causes impaired spreading of cancer cells on fibrinogen.
Green tea and tea catechins, especially (-)-epigallocatechin gallate (EGCG), have been shown to have various health benefits including anti-cancer, anti-metastasis, and anti-cardiovascular disease effects. Our previous studies demonstrated that three plasma proteins, fibronectin, histidine-rich glycoprotein, and fibrinogen were bound by EGCG, and that one specific domain in fibronectin was responsible for its binding interaction with EGCG. Fibrinogen consists of 6 chains linked by the disulfide bonds of two each of the α-, β-, and γ-chains. The present study examined whether fibrinogen had a specific domain interacting with EGCG. The results of affinity chromatography under reducing conditions demonstrated that each of the α-, β-, and γ-subunit chains of fibrinogen was bound by EGCG. We also demonstrated that several peptides generated by treatment with cyanogen bromide or thermolysin were bound by EGCG. The amino acid sequences analyzed revealed that these peptides included those derived from the α-, β-, and γ-chains of fibrinogen. EGCG inhibited the spreading of mouse metastatic LL2-Lu3 lung cancer cells on the fibrinogen substratum, which suggested an impairment in the interaction between cancer cells and fibrinogen. Since the interaction between cancer cells and fibrinogen plays an important role in metastasis, the present results suggest, at least partially, that EGCG inhibited metastasis in the mouse models reported previously by inhibiting such an interaction.


Poor communications, cultural barriers impacting quality of health care for minorities.
A new survey released last month by the Commonwealth Fund shows that for a range of health care quality factors--such as patient/provider communications, cultural and linguistic barriers, and access to health care and insurance coverage--minority Americans are not faring as well as whites.


A case of occupational rhinitis caused by rice powder in the grain industry.
Rice is the major staple food in a large part of the world, especially in Asia. Hypersensitivity reactions to rice are rare. Moreover, cases of occupational allergies induced by inhalation of rice powder are uncommon. We report a 31-year-old male with work-related rhinitis and conjunctivitis symptoms caused by occupational exposure to rice powder in the grain industry. He showed positive responses to rice extracts on a skin prick test, and a high level of serum specific IgE to rice was detected by ELISA. Occupational rhinitis was confirmed by a nasal provocation test with rice extracts. An IgE ELISA inhibition test showed cross-creativity between rice and various grass pollen extracts. These findings suggest that the inhalation of rice powder can induce IgE-mediated occupational rhino-conjunctivitis, which may be derived from cross-reactivity to major grass pollens.


Influence of Diet on Development and Survival of Thanatophilus rugosus (Coleoptera: Silphidae).
This study examined the effects of various diets on the development time and survival of the carrion beetle Thanatophilus rugosus (Fabricius, 1775). We attempted to find the best diet for rearing the species in laboratory conditions for entomological research and forensic purposes, and to further understand its feeding habits. The larval stages were monitored while feeding on three types of meat under a constant temperature. We discovered that the shortest development time in total was achieved in larvae fed with pork liver, followed closely by pork muscle. The longest development and lowest survival rates were observed when introducing a chicken diet. We were also able to identify specific stages during which the diet significantly affected the development.


Topiramate in the treatment of substance-related disorders: a critical review of the literature.
To critically review the literature on topiramate in the treatment of substance-related disorders. A PubMed search of human studies published in English through January 2009 was conducted using the following search terms: topiramate and substance abuse, topiramate and substance dependence, topiramate and withdrawal, topiramate and alcohol, topiramate and nicotine, topiramate and cocaine, topiramate and opiates, and topiramate and benzodiazepines. 26 articles were identified and reviewed; these studies examined topiramate in disorders related to alcohol, nicotine, cocaine, methamphetamine, opioids, Ecstasy, and benzodiazepines. Study design, sample size, topiramate dose and duration, and study outcomes were reviewed. There is compelling evidence for the efficacy of topiramate in the treatment of alcohol dependence. Two trials show trends for topiramate's superiority over oral naltrexone in alcohol dependence, while 1 trial suggests topiramate is inferior to disulfiram. Despite suggestive animal models, evidence for topiramate in treating alcohol withdrawal in humans is slim. Studies of topiramate in nicotine dependence show mixed results. Human laboratory studies that used acute topiramate dosing show that topiramate actually enhances the pleasurable effects of both nicotine and methamphetamine. Evidence for topiramate in the treatment of cocaine dependence is promising, but limited by small sample size. The data on opioids, benzodiazepines, and Ecstasy are sparse. Topiramate is efficacious for the treatment of alcohol dependence, but side effects may limit widespread use. While topiramate's unique pharmacodynamic profile offers a promising theoretical rationale for use across multiple substance-related disorders, heterogeneity both across and within these disorders limits topiramate's broad applicability in treating substance-related disorders. Recommendations for future research include exploration of genetic variants for more targeted pharmacotherapies.


Osteoporosis-pseudoglioma syndrome: description of 9 new cases and beneficial response to bisphosphonates.
Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal recessive disorder of severe juvenile osteoporosis and congenital blindness, due to mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. Approximately fifty cases of OPPG have been reported. We report 9 new cases of OPPG, in three related nuclear families of Conservative Mennonites in Pennsylvania. All 9 children with OPPG were blind and had osteoporosis. Four of six parents had low bone mineral density (BMD) or osteoporosis; 2 were normal. Sequence analysis from genomic DNA revealed homozygosity for a nonsense mutation of exon 6 of LRP5 (W425X) in four OPPG cases tested in families A and C. In family B, OPPG cases were compound heterozygotes for the exon 6 W425X LRP5 mutation and a second exon 6 mutation (T409A); bone phenotype was milder than in family A. Neither of these mutations was present in an unrelated normal. The four treated OPPG patients all responded to bisphosphonates (duration 1.5-6.5 years) with improvement in Z-scores. One patient had a negligible response to teriparatide. In summary, we report 9 new cases of OPPG due to two novel LRP5 mutations, note a milder bone phenotype but similar ocular phenotype in LRP5 W425X/T409A compound heterozygotes than in W425X homozygotes and describe positive response to bisphosphonate treatment in four cases.


A dentin sialophosphoprotein mutation that partially disrupts a splice acceptor site causes type II dentin dysplasia.
The dentin sialophosphoprotein (DSPP) gene on chromosome 4q21.3 encodes the major noncollagenous protein in tooth dentin. DSPP mutations are the principal cause of dentin dysplasia type II, dentinogenesis imperfecta type II, and dentinogenesis imperfecta type III. We have identified a DSPP splice junction mutation (IVS2-6T>G) in a family with dentin dysplasia type II. The primary dentition is discolored brown with severe attrition. The mildly discolored permanent dentition has thistle-shaped pulp chambers, pulp stones, and eventual pulp obliteration. The mutation is in the sixth nucleotide from the end of intron 2, perfectly segregates with the disease phenotype, and is absent in 200 normal control chromosomes. An in vitro splicing assay shows that pre-mRNA splicing of the mutant allele generates wild-type mRNA and mRNA lacking exon 3 in approximately equal amounts. Skipping exon 3 might interfere with signal peptide cleavage, causing endoplasmic reticulum stress, and also reduce DSPP secretion, leading to haploinsufficiency.


Short communication: Human blood dendritic cells are infected separately from monocytes in HIV type 1 patients.
Monocytes serve as a systemic reservoir of myeloid precursors for the renewal of tissue macrophages and dendritic cells (DCs). Both monocytes and dendritic cells can be infected with HIV-1. Circulating DCs are believed to be derived from a common precursor of monocytes, or, in the case of inflammatory challenge, from monocytes directly. Because there are fewer infected blood monocytes than infected cells after differentiation, we hypothesized that the majority of HIV-1 infection in circulating DCs occurs via direct viral binding to their CD4 and coreceptors after differentiation. We isolated monocytes at one time point and circulating dendritic cells at a second time point from the blood of HIV-1-infected patients. Proviral DNA was isolated from DCs and monocytes, and the C2-V4 region of the HIV-1 env gene was cloned and sequenced. Phylogeny, nucleotide distances, and glycosylation patterns of the env gene were performed. The phylogenetic trees revealed that viral forms from the monocytes clustered distantly from the quasispecies derived from circulating DCs. The nucleotide distances and differing glycosylation patterns suggest that the infection of DCs is independent of the infection of the monocytes.


Association between urinary phthalate metabolites and chronic obstructive pulmonary disease incidence in US adults: results from NHANES 2007-2018.
Despite associations between urinary phthalates and respiratory symptoms and disorders have been investigated, knowledge about their impact on COPD incidence remains limited. Using data of 8242 adults (aged 20-80 years) from the 2007-2018 National Health and Nutrition Examination Survey (NHANES), the association of mixed urinary phthalate metabolites with COPD incidence was evaluated. Among them, 789 were COPD patients, and the rest were non-COPD participants. In the single-pollutant models, a variety of phthalate metabolites were identified as independent positive factors for COPD incidence, including mono-(carboxynonyl) phthalate (MCNP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-n-butyl phthalate (MnBP), mono-(3-carboxylpropyl) phthalate (MCPP), mono-ethyl phthalate (MEP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-benzyl phthalate (MBzP). Multi-pollutant models, including weighted quantile sum (WQS) regression, quantile-based g computation (qgcomp), and Bayesian kernel machine regression (BKMR) approaches consistently revealed the positive association between phthalates co-exposure and COPD incidence, and MCPP was recognized as the dominant positive driver. The positive association was more evident in the youth group and the male group. The interactions between certain phthalate metabolites in COPD were also observed. Given the limitations of the cross-sectional design of NHANES study, well-designed longitudinal studies are needed to verify or disprove these findings.


Isolation of an amoeba naturally harboring a distinctive Legionella species.
There are numerous in vitro studies documenting the multiplication of Legionella species in free-living amoebae and other protozoa. It is believed that protozoa serve as host cells for the intracellular replication of certain Legionella species in a variety of environmental settings. This study describes the isolation and characterization of a bacterium initially observed within an amoeba taken from a soil sample. In the laboratory, the bacterium multiplied within and was highly pathogenic for Acanthamoeba polyphaga. Extracellular multiplication was observed on buffered charcoal yeast extract agar but not on a variety of conventional laboratory media. A 16S rRNA gene analysis placed the bacterium within the genus Legionella. Serological studies indicate that it is distinct from previously described species of the genus. This report also describes methods that should prove useful for the isolation and characterization of additional Legionella-like bacteria from free-living amoebae. In addition, the characterization of bacterial pathogens of amoebae has significant implications for understanding the ecology and identification of other unrecognized bacterial pathogens.


Oblique frozen modes in periodic layered media.
We study the classical scattering problem of a plane electromagnetic wave incident on the surface of semi-infinite periodic stratified media incorporating anisotropic dielectric layers with special oblique orientation of the anisotropy axes. We demonstrate that an obliquely incident light, upon entering the periodic slab, gets converted into an abnormal grazing mode with huge amplitude and zero normal component of the group velocity. This mode cannot be represented as a superposition of extended and evanescent contributions. Instead, it is related to a general (non-Bloch) Floquet eigenmode with the amplitude diverging linearly with the distance from the slab boundary. Remarkably, the slab reflectivity in such a situation can be very low, which means an almost 100% conversion of the incident light into the axially frozen mode with the electromagnetic energy density exceeding that of the incident wave by several orders of magnitude. The effect can be realized at any desirable frequency, including optical and UV frequency range. The only essential physical requirement is the presence of dielectric layers with proper oblique orientation of the anisotropy axes. Some practical aspects of this phenomenon are considered.


Bilateral Plantar Fibromatosis
Aim To describe an uncommon clinical finding and raise awareness of its manifestation and associated conditions. Methods This case describes a gentleman with bilateral plantar fibromatosis caused by type 2 Diabetes Mellitus and previous alcohol excess. Results Treatment options include physiotherapy, steroid and collagenase injection therapy. Surgical intervention can be considered for persistently symptomatic or recurrent cases. Discussion In conclusion, plantar fibromatosis is an under-recognised and disabling condition which should prompt intervention and optimisation of co-morbidities.


Understanding perspectives on major system change: A comparative case study of public engagement and the implementation of urgent and emergency care system reconfiguration.
Major changes have been made to how emergency care services are configured in several regions in the Republic of Ireland. This study investigated the hypothesis that engagement activities undertaken prior to these changes influenced stakeholder perspectives on the proposed changes and impacted on the success of implementation. A comparative case-study approach was used to explore the changes in three regions. These regions were chosen for the case study as the nature of the proposals to reconfigure care provision were broadly similar but implementation outcomes varied considerably. Documentary analysis of reconfiguration planning reports was used to identify planned public engagement activities. Semi-structured interviews with 74 purposively-sampled stakeholders explored their perspectives on reconfiguration, engagement activities and public responses to reconfiguration. Framework analysis was used, integrating inductive and deductive approaches. Approaches to public engagement and success of implementation differed considerably across the three cases. Regions that presented the public with the reconfiguration plan alone reported greater public opposition and difficulty in implementing changes. Engagement activities that included a range of stakeholders and continued throughout the reconfiguration process appeared to largely address public concerns, contributing to smoother implementation. The presentation of reconfiguration reports alone is not enough to convince communities of the case for change. Genuine, ongoing and inclusive engagement offers the best opportunity to address community concerns about reconfiguration.


Comparative Study on the Clinical Efficacy and Safety of Acitretin and MTX in the Treatment of Pustular Psoriasis by TLR7/MyD88/CXCL16 Pathway.
To investigate the clinical efficacy and safety of acitretin and MTX with TLR7/MyD88/CXCL16 in the treatment of pustular psoriasis. A total of 54 patients with pustular psoriasis were randomly divided into control group (n = 14) and study group (n = 40). MTX was used in the control group, and different doses of acitretin were used in the study group, which were divided into low-dose group (n = 13), medium-dose group (n = 13), and high-dose group (n = 14). Symptom relief time, recurrence rate, GPPASI improvement rate, treatment response rate, BSA, DLQI score, and TLR7 and CXCL16 levels were compared among four groups. The erythema, fever, and pustules disappeared in the low-dose group, the medium-dose group, and the high-dose group for a shorter time than control group, and it is shortest for the high-dose group. The low-dose, medium-dose, and high-dose groups had relatively lower recurrence rates at 1 month and 3 months (P < 0.05). The improvement rates of GPPASI50 of the four groups (the control group, low-dose group, medium-dose group, and high-dose group in turn) were 71.4%, 78.3%, 80.2%, and 80.8%; GPPASI75 of the four groups were 73.5%, 74.3%, 79.4%, and 80.9%; and GPPASI90 were 12.9%, 13.1%, 13.4%, and 13.8%. After treatment, the BSA and DLQI scores of the four groups were reduced. The BSA and DLQI scores of the study group decreased more significantly, and the high-dose group had the most significant improvement (P < 0.05). The incidence of adverse reactions in the four groups was 16.2%, 8.1%, 10.3%, and 14.7%, respectively. The high-dose group had a higher incidence of adverse reaction than the low-dose group (P < 0.05). The effective rates of treatment of the four groups were 69.1%, 86.9%, 88.2%, and 91.9%, respectively. The study group had higher treatment efficiency than the control group, and the high-dose group had the highest treatment efficiency (P < 0.05). After treatment, the level of serum TLR7 and CXCL16 was significantly reduced, but which in the study group decreased more significantly (P < 0.05). The clinical effect of a high dose of acitretin on pustular psoriasis is remarkable. It can reduce the recurrence rate and improve the quality of life and clinical symptoms. Therefore, a high dose of acitretin is worth popularizing and applying.


Protection by Ethanolic Extract from Ulva lactuca L. against Acute Myocardial Infarction: Antioxidant and Antiapoptotic Activities.
Reactive oxygen species (ROS) play a major role in myocardial damage during acute myocardial infarction (AMI). This study aimed to determine the antioxidant and antiapoptotic activities of an ethanolic extract from Ulva lactuca L. (EEUL) against AMI. Thirty-six male Wistar rats were divided into six groups: one control group and five treatment groups. Treatment group II was given 85 mg/kg body weight (BW) of isoproterenol (ISO). Group III, IV and V were given ISO and EEUL at 250, 500 and 750 mg/kg BW, respectively. Group VI were given 10 mg/kg BW of ISO and melatonin. EEUL and melatonin were orally administered for 28 days. ISO was injected subcutaneously on day 29 and 30 to chemically induce AMI. On day 31, blood was collected for antioxidant assay and heart tissues were collected for histological examination. The activity of catalase (CAT), an endogenous antioxidant, in the EEUL-treatment groups was significantly increased compared to the ISO-treatment group (P < 0.001). The EEUL-treatment groups showed significantly decreased expression of caspase-3 (P < 0.001) and better myocardial tissue morphology. EEUL possibly protects against AMI because of its antioxidant and antiapoptotic properties.


The role of cell-associated virus in mother-to-child HIV transmission.
Mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) continues to contribute to the global burden of disease despite great advances in antiretroviral (ARV) treatment and prophylaxis. In this review, we discuss the proposed mechanisms of MTCT, evidence for cell-free and cell-associated transmission in different routes of MTCT, and the impact of ARVs on virus levels and transmission. Many population-based studies support a role for cell-associated virus in transmission and in vitro studies also provide some support for this mode of transmission. However, animal model studies provide proof-of-principle that cell-free virus can establish infection in infants, and studies of ARVs in HIV-infected pregnant women show a strong correlation with reduction in cell-free virus levels and protection. ARV treatment in MTCT potentially provides opportunities to better define the infectious form of virus, but these studies will require better tools to measure the infectious cell reservoir.