Insights into the morphology of human serum albumin and sodium dodecyl sulfate complex: A spectroscopic and microscopic approach.
Exploring and understanding the fundamental interaction between protein and surfactant is utmost important for various pharmaceutical and biomedical applications. However, very less is known about the arrangement of individual negatively charged sodium dodecyl sulfate (SDS) molecules on the human serum albumin (HSA). Here, we have investigated the morphology and mechanistic insights of complexation between HSA and SDS by means of photoluminescence (PL) spectroscopy, circular dichroism (CD) and PL microscopy using amine-functionalized silicon quantum dot (Si QD) as an external luminescent marker. The present study is based on a unique and dynamic SDS-Si QD system. The synthesized allylamine-functionalized Si QDs show a distinct PL band centered at 455nm upon excitation at 375nm. At neutral pH, these Si QDs form ordered aggregates in the presence of 1mM SDS due to the hydrogen bonding interaction with the sulfate head groups of surfactants, which is manifested in the appearance of a large Stokes shifted luminescence band centered at 610nm. It has been observed that the PL intensity of SDS-Si QD aggregates at 610nm decreases gradually with concomitant increase in the PL intensity of monomeric Si QDs at 455nm upon increasing the concentration of HSA from 1 to 10μM. These observations combined with PL lifetime, PL microscopy and CD results reveal that SDS forms micelle-like aggregates on the partially unfolded HSA mainly via electrostatic interaction between negatively charged sulfate head groups and positively charged residues of partially unfolded HSA. For the present HSA-SDS system, our results fit a model with type I "necklace and bead"-like structures, where micelle-like SDS aggregates wrap around by the partially unfolded HSA backbone.


The proto-oncogene BCL-6 is expressed in olfactory sensory neurons.
Mammalian olfactory sensory neurons harbor a large repertoire of odorant receptors. Yet, each cell chooses a single odorant receptor gene to express, which may then serve as the molecular identification of that cell. This process of differentiation or receptor gene regulation of olfactory sensory neurons has largely been enigmatic. Here, we showed that the important proto-oncogene in B lymphocyte terminal differentiation, B-Cell Leukemia/Lymphoma 6 (BCL-6), which codes for a sequence-specific transcription repressor, is expressed in olfactory sensory neurons in the mouse. We detected BCL-6 mRNA in most, if not all, mature olfactory sensory neurons by in situ hybridization histochemistry. Western blot analysis also revealed the presence of BCL-6 protein in the olfactory epithelium, but immunohistochemical analysis using anti-BCL-6 antibodies showed that only a subset of olfactory sensory neurons highly expressed BCL-6 protein. BCL-6 mRNA was detected as early as embryonic day 14 (E14) in most olfactory sensory neurons as in adults, and at E15, BCL-6 protein was detected in most cells that were likely to be differentiating into mature olfactory sensory neurons. Artificial induction of apoptosis of olfactory sensory neurons resulted in the decrease of BCL-6 mRNA, but during the subsequent phase of regeneration and differentiation, it markedly increased. Taken together, our results suggest the possibility that BCL-6 plays an important role in terminal differentiation not only in B lymphocytes but also in olfactory sensory neurons.


Preventing weight gain through exercise and physical activity in the elderly: a systematic review.
This review examines the role of exercise and physical activity for preventing weight gain in older people. A structured search using MeSH-vocabulary and Title/Abstract-searches was conducted in PubMed for January 2000 to June 2011, identifying weight gain and exercise or physical activity as study topics, and aged adults as target group. In study selection, all types of exercise and physical activity and any measure of weight change in aged adults (≥65 years) or postmenopausal women were considered. N=9 primary studies were identified. All were conducted in the US, with one study additionally including samples from Canada and the UK. Three studies focused on aged adults, while six concentrated specifically on postmenopausal women. Forms of exercise or physical activity comprised self-reported exercise history in four studies and low, moderate or high intensity exercise interventions in five studies. Four studies combined exercise with a hypocaloric diet and included comparison groups receiving either diet only, health education, stretching or a delayed intervention (one study each). Exercise was associated with weight loss (1.1-6 kg) in all intervention studies, all of which studied an overweight sample, and with weight maintenance in most observational studies, all of which studied a general population or otherwise overweight-unspecific sample. In sum, exercise and physical activity can effectively prevent weight gain in older adults and postmenopausal women either in terms of weight loss or maintenance. They can preserve lean body mass and thus are important for the balance between potentially positive and negative effects of weight reduction in later life. In addition, since all intervention studies were conducted with an overweight sample, it seems that primordial prevention (in terms of preventing the development of risk factors such as excess weight in the first place) might be a neglected issue in geriatric and postmenopausal prevention.


Pityrosporum species associated with dacryoliths in obstructive dacryocystitis.
Two dacryoliths removed from the obstructed and enlarged lacrimal sac of a 54-year-old woman during dacryocystorhinostomy were found to contain filamentous forms consistent with Pityrosporum orbiculare. To my knowledge, this fungus has not been observed before in a dacryolith or in dacryocystitis.


Assessment of patients' perceptions towards embryo disposition after donation of embryos to a research biobank.
To explore perceptions towards embryo disposition among patients donating excess embryos to a research biobank. Cross-sectional study of survey responses collected as part of enrollment in a research biobank. Patients are asked questions regarding the difficulty of their disposition decision, their alternative disposition choice if donation to research was not available, quality of the counseling they received, and if additional counseling throughout their treatment would have been beneficial. Survey responses use 5-point Likert scales, with "1" being lowest/least and "5" being highest/most. A total of 157 men and 163 women enrolled in the biobank. Median scores for difficulty of disposition decision were 3 for females and 2 for males, and for quality of counseling, the median scores were 4 for females and 3 for males. Seventy percent of patients would have chosen to discard their excess embryos had donation to research not been an option. Statistical analyses showed no significant difference in responses based on variations in race, religion, sexual orientation, and infertility diagnoses. Concordance of responses within heterosexual couples was tested and found to be poor to moderate. Assessing patients' perceptions towards embryo disposition after donation of their excess embryos to a research biobank affords a unique perspective. The difficulty of the disposition decision, the tendency to discard embryos in the absence of a means for donation to research, and the poor agreement between heterosexual partners highlight the importance of donation to research as an accessible disposition option and the need for a personalized approach to counseling and consenting for embryo disposition.


Integrin αvβ3-targeted radionuclide therapy combined with immune checkpoint blockade immunotherapy synergistically enhances anti-tumor efficacy.
Radiotherapy combined with immunotherapy has revealed promising outcomes in both preclinical studies and ongoing clinical trials. Targeted radionuclide therapy (TRT) is a branch of radiotherapy concerned with the use of radioisotopes, radiolabeled molecules or nanoparticles that deliver particulate radiation to cancer cells. TRT is a promising approach in cases of metastatic disease where conventional treatments are no longer effective. The increasing use of TRT raises the question of how to best integrate TRT with immunotherapy. In this study, we proposed a novel therapeutic regimen that combined programmed death ligand 1 (PD-L1)-based immunotherapy with peptide-based TRT (177Lu as the radionuclide) in the murine colon cancer model. To explore the most appropriate timing of immunotherapy after radionuclide therapy, the anti-PD-L1 antibody (αPD-L1 mAb) was delivered in a concurrent or sequential manner when 177Lu TRT was given. The results demonstrated that TRT led to an acute increase in PD-L1 expression on T cells, and TRT in combination with αPD-L1 mAb stimulated the infiltration of CD8+ T cells, which improved local tumor control, overall survival and protection against tumor rechallenge. Moreover, our data revealed that the time window for this combination therapy may be critical to outcome. This therapeutic combination may be a promising approach to treating metastatic tumors in which TRT can be used. Clinical translation of the result would suggest that concurrent rather than sequential blockade of the PD-1/PD-L1 axis combined with TRT improves overall survival and long-term tumor control.


Improving the prevention, diagnosis and treatment of TB among people living with HIV: the role of operational research.
Operational research is necessary to improve the access to and delivery of tuberculosis prevention, diagnosis and treatment interventions for people living with HIV. We conducted an extensive review of the literature and reports from recent expert consultations and research-related meetings organized by the World Health Organization and the Stop TB Partnership to identify a TB/HIV operational research agenda. We present critical operational research questions in a series of key areas: optimizing TB prevention by enhancing the uptake of isoniazid preventive therapy and the implementation of infection control measures; assessing the effectiveness of existing diagnostic tools and scaling up new technologies; improving service delivery models; and reducing risk factors for mortality among TB patients living with HIV. We discuss the potential impact that addressing the operational research questions may have on improving programmes' performance, assessing new strategies or interventions for TB control, or informing global or national policy formulation. Financial resources to implement these operational research questions should be mobilized from existing and new funding mechanisms. National TB and HIV/AIDS programmes should develop their operational research agendas based on these questions, and conduct the research that they consider crucial for improving TB and HIV control in their settings in collaboration with research stakeholders.


Exploration of a novel and efficient source for production of bacterial nanocellulose, bioprocess optimization and characterization.
The demand for bacterial nanocellulose is expected to rise in the coming years due to its wide usability in many applications. Hence, there is a continuing need to screen soil samples from various sources to isolate a strain with a high capacity for bacterial nanocellulose production. Bacillus sp. strain SEE-12, which was isolated from a soil sample collected from Barhiem, Menoufia governorate, Egypt, displayed high BNC production under submerged fermentation. Bacillus sp. strain SEE-12 was identified as Bacillus tequilensis strain SEE-12. In static cultures, BNC was obtained as a layer grown in the air liquid interface of the fermentation medium. The response surface methodology was used to optimise the process parameters. The highest BNC production (22.8 g/L) was obtained using 5 g/L peptone, 5 g/L yeast extract, 50%, v/v Cantaloupe juice, 5 g/L Na2HPO4, 1.5 g/L citric acid, pH 5, medium volume of 100 mL/250 mL conical flask, inoculum size 5%, v/v, temperature 37 °C and incubation time 6 days. The BNC was purified and characterized by scanning electron microscopy (SEM), Energy-dispersive X-ray (EDX) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and transmission electron microscopy (TEM).


Monoclonal antibodies against respiratory syncytial virus and their use for rapid detection of virus in nasopharyngeal secretions.
We developed five monoclonal antibodies against respiratory syncytial virus. Three of these (23A3, 12A4, and 18B2) were used in an indirect fluorescent antibody test, and the results were compared with those of a similar indirect fluorescent test with commercial anti-respiratory syncytial virus serum. The results obtained with antibody 18B2 and commercial anti-respiratory syncytial virus serum were identical, whereas with antibodies 23A3 and 12A4 the incidence of positive identifications was around 50%.


Evaluation of an interprofessional care coordination model: Benefits to health professions students and the community served.
An innovative care coordination program was developed to enhance wellness among low-income older adults living in subsidized apartment buildings and to provide rich interprofessional education experiences for health professions students. Program effectiveness for the residents was measured through an evaluation of participation, services used, and healthcare utilization. Educational effectiveness was measured through a change in health concepts and perceptions of interprofessional practice. Health care utilization among participating residents showed an 8.6% reduction in emergency department visits and 9.8% reduction in hospital admissions. Students demonstrated improved knowledge in motivational interviewing (p = .02); diabetes (p = .02); hypertension (p≤.01); and frailty (p≤.01). Changes in students perception of interprofessional practice were significant in two areas; Teamwork and Collaboration (p≥.00); and Person Centeredness (p = .00). This care coordination model may be an effective approach to reduce care resource utilization among medically complex lower income older adults and provides a rich interprofessional learning experience for students.


Breast metastasis and lung large-cell neuroendocrine carcinoma: first clinical observation.
The lung large-cell neuroendocrine carcinoma (LCNEC) is a very rare aggressive neuroendocrine tumor with a high propensity to metastasize and very poor prognosis. We report an atypical presentation of lung LCNEC was diagnosed from a metastatic nodule on the breast. Our patient is a 59-years-old woman that presented in March 2014 nonproductive cough. A CT scan showed multiple brain, lung, adrenal gland and liver secondary lesions; moreover, it revealed a breast right nodule near the chest measuring 1.8 cm. The breast nodule and lung lesions were biopsied and their histology and molecular diagnosis were LCNEC of the lung. To our knowledge, this is the first documented case of breast metastasis from LCNEC of the lung. Furthermore, breast metastasis from extramammary malignancy is uncommon and its diagnosis is difficult but important for proper management and prediction of prognosis. Therefore, a careful clinical history with a thorough clinical examination is needed to make the correct diagnosis. Moreover, metastasis to the breast should be considered in any patient with a known primary malignant tumor history who presents with a breast lump. Anyhow, pathological examination should be performed to differentiate the primary breast cancer from metastatic tumor. Therefore, an accurate diagnosis of breast metastases may not only avoid unnecessary breast resection, more importantly it is crucial to determine an appropriate and systemic treatment.


Tumor expression of Nectin-1-4 and its clinical implication in muscle invasive bladder cancer: An intra-patient variability of Nectin-4 expression.
There is limited evidence regarding the tumor expression of nectins and their clinical implications in muscle invasive bladder cancer. Herein, we evaluated expression of Nectins 1-4 in 64 patients with muscle invasive bladder cancer who underwent radical cystectomy using a histochemical scoring method (H-score; immunohistochemical staining intensity multiplied by the percentage of positive-staining cells). The cutoff values were defined based on the median H-scores. Of the 64 patients, 45 (70%) had residual tumors in radical cystectomy specimens, while 13 (20%) had lymph node metastasis. The median (interquartile range) H-scores of Nectin-1, - 2, - 3, and - 4 expression were 0 (0-10), 80 (30-180), 5 (0-30), and 100 (33-160), respectively. The Nectin-4 H-score of the neuroendocrine variant was significantly lower than that of pure urothelial carcinoma (P = 0.015). Post-neoadjuvant chemotherapy pathological response (<ypT2N0 residual disease and pN-negative) was achieved in 18 (49%) of the 37 patients who received neoadjuvant chemotherapy. Clinical stage II, not Nectin expression, was an independent factor associated with pathological response (P = 0.019, adjusted odds ratio 6.9, vs stage III/IV). There was no correlation in Nectin-4 tumor expression between transurethral resection and matched radical cystectomy specimens and between radical cystectomy specimens and matched lymph node metastatic lesions. However, there was a significant decrease in Nectin-4 expression in post-neoadjuvant chemotherapy radical cystectomy specimens compared to pre-neoadjuvant chemotherapy transurethral resection specimens (P = 0.008). Given the downregulation of Nectin-4 by chemotherapy and the significant discrepancy between radical cystectomy and matched lymph node metastasis specimens, baseline primary tumors may not be a suitable material for evaluating Nectin-4 expression and its potential as a predictive biomarker for enfortumab vedotin treatment.


Water, a powerful tool in surgery.
Inflammation of the gallbladder, also known as acute cholecystitis, may be caused by infection and inflammation of the gallbladder wall due to bile stasis, with or without gallstones. It is one of the most common surgical procedures that are performed laparoscopically. Gangrenous gallbladders are one of the most difficult conditions to treat clinically and surgically, being the cause of many medical malpractice litigations. Gangrenous gallbladders constitute 15% of all laparoscopic surgeries, with the cost of these surgeries being approximately $48,000, compared to other laparoscopic gallbladder surgeries being around $7,000. Dr. Dinesh Vyas and his team have worked together to develop the novel HydroLap, which is a tool that utilizes hydrodissection technology during laparoscopic cholecystectomies to remove the delicate, dead tissue while preserving the healthy tissue of surrounding structures. This decade-long journey began in the operating room and resulted in an innovation that is awaiting Food and Drug Administration (FDA) approval for use in 2023.


Population genomics and morphological features underlying the adaptive evolution of the eastern honey bee (Apis cerana).
The adaptation of organisms to changing environments is self-evident, with the adaptive evolution of organisms to environmental changes being a fundamental problem in evolutionary biology. Bees can pollinate in various environments and climates and play important roles in maintaining the ecological balance of the earth. We performed an analysis of 462 Apis cerana (A. cerana) specimens from 31 populations in 11 regions and obtained 39 representative morphological features. We selected 8 A. cerana samples from each population and performed 2b-RAD simplified genome sequencing. A total of 11,506 high-quality single nucleotide polymorphism (SNP) loci were obtained. For these SNPs, the minor allele frequency (MAF) was > 1%, the average number of unique labels for each sample was 49,055, and the average depth was 72.61x. The ratios of the unique labels of all samples were 64.27-86.33%. Using 39 morphological characteristics as the data set, we proposed a method for the rapid classification of A. cerana. Using genomics to assess population structure and genetic diversity, we found that A. cerana has a large genetic difference at the ecotype level. A comparison of A. cerana in North China revealed that some physical obstacles, especially the overurbanization of the plains, have isolated the populations of this species. We identified several migration events in North China and Central China. By comparing the differences in the environmental changes in different regions, we found that A. cerana has strong potential for climate change and provides a theoretical basis for investigating and protecting A. cerana.


Two-component blocking kinetics of open NMDA channels by organic cations.
NMDA receptor channel responses were recorded from acutely isolated rat hippocampal neurons, using whole-cell patch-clamp techniques. In the continuous presence of aspartate, tetraethylammonium, tetrabutylammonium, 1-amino-3-propyl-adamantane and 9-aminoacridine caused changes in the current through NMDA channels, which were described by two-exponential functions. It was established that depending on the behavior of the amplitude of the fast component for the recovery kinetics, the blocker action can be assigned to one of five types described by the simplest models. The effects of tetraethylammonium, tetrabutylammonium and 1-amino-3-propyl-adamantane were well described by these models. Using 9-aminoacridine as an example, it was shown that the simplest models cannot describe all possible types of the blocker-channel interaction. In such cases, the method of the simplest models combination can be used. The application of the simplest kinetic models analysis allowed to make the following conclusions: at least two molecules of 1-amino-3-propyl-adamantane or 9-aminoacridine can simultaneously bind to the open channel and block it; the occupation of 9-aminoacridine blocking sites in the channel can proceed in at least two different ways; the binding of tetrabutylammonium and 9-aminoacridine prevented the closure of the activation and/or desensitization gates of the channel, while that of tetraethylammonium did not.


The Natriuretic Peptides for Hypertension Treatment.
Hypertension is a common pathological condition predisposing to a higher occurrence of cardiovascular diseases and events. Unfortunately, treatment of hypertension is still suboptimal worldwide. More efforts are needed to implement the availability of anti-hypertensive drugs. The family of natriuretic peptides, including atrial and brain natriuretic peptides (ANP and BNP), play a key role on blood pressure regulation through the natriuretic, diuretic and vasorelaxant effects. A large number of experimental and human studies, ranging from pathophysiological to genetic investigations, supported ANP as the most relevant component of the family able to modulate blood pressure and to contribute to hypertension development. On this background, it is expected that ANP-based therapeutic approaches may give a significant contribution to the development of efficacious therapies against hypertension. Since native ANP cannot be administered due to its short half-life, several approaches were attempted over the years to overcome the difficulties inherent to the ANP instability. These approaches included ANP recombinant and fusion peptides, gene therapy, inhibition of ANP degradation by neprilysin inhibition, and designer peptides. The most relevant achievements in the field are discussed in this article. Based on the available evidence, therapies targeting ANP represent efficacious and clinically applicable anti-hypertensive agents.


Effect of streptozotocin diabetes and insulin replacement on growth hormone in rats.
The effects of insulin deprivation on the growth rate, plasma and pituitary growth hormone (GH) and GH synthesis were investigated in male Wistar rats. Diabetes was induced by administration of streptozotocin (STZ), 7 mg/100 g bw, and plasma and pituitary GH levels were measured by means of a specific radioimmunoassay. GH synthesis was determined in pituitaries by the in vitro incorporation of [3H] leucine into specific immunoprecipitates. The body weight and the pituitary GH content of normally developing rats showed an almost linear increase throughout the observation period, whereas diabetic rats stopped growing immediately after receiving STZ, and remained smaller than age-paired controls. Pituitary GH content remained within the control range through the 5 days following STZ administration and thereafter decreased reaching 10% of control values by the 30th day. Furthermore, pituitaries from diabetic rats incorporated [3H] leucine into r-GH at a greatly reduced rate, which could explain the diminished r-GH storage in pituitaries of diabetic rats. Plasma GH concentrations remained within the normal range for 10 days after STZ, thereafter plasma GH were markedly reduced. Insulin treatment prevented the metabolic changes, and restored normal levels of plasma and pituitary GH in diabetic rats. These findings indicate that diabetes, in rat, is characterized by an inhibitory effect on GH secretion, probably via a diminished GH synthesis by the pituitary gland.


Color-naming evidence for tritan vision in the fovea.
A color-naming task was used to assess color vision in the fovea and parafovea. Like traditional psychophysical procedures, color naming showed that short-wavelength vision is suppressed centrally. The anatomical and physiological mechanisms underlying tritan foveal vision are discussed.


Immunological role of TAM receptors in the cancer microenvironment.
TAM receptors belong to the family of receptor tyrosine kinases, comprising of Tyro3, Axl and Mertk receptors (TAMs) and are important homeostatic regulators of inflammation in higher eukaryotes. Along with their ligands, Gas6 and ProteinS, TAMs acts as receptors to phosphatidylserine (PtdSer), an anionic phospholipid that becomes externalized on the surface of apoptotic and stressed cells. TAM receptors, specially Mertk, have been well established to play a role in the process of efferocytosis, the engulfment of dying cells. Besides being efferocytic receptors, TAMs are pleiotropic immune modulators as the lack of TAM receptors in various mouse models lead to chronic inflammation and autoimmunity. Owing to their immune modulatory role, the PtdSer-TAM receptor signaling axis has been well characterized as a global immune-suppressive signal, and in cancers, and emerging literature implicates TAM receptors in cancer immunology and anti-tumor therapeutics. In the tumor microenvironment, immune-suppressive signals, such as ones that originate from TAM receptor signaling can be detrimental to anti-tumor therapy. In this chapter, we discuss immune modulatory functions of TAM receptors in the tumor microenvironment as well role of differentially expressed TAM receptors and their interactions with immune and tumor cells. Finally, we describe current strategies being utilized for targeting TAMs in several cancers and their implications in immunotherapy.


Effects of high-protein milk powder, linseed paste, and grape molasses levels on physiochemical, rheological, and sensory attributes of linseed spread.
Separate levels of roasted linseed paste (RLP) (15, 22.5, and 30 g), Persian grape molasses (PGM) (40, 50, and 60 g), and high-protein milk powder (HPMP) (3.75, 6.5, and 9.25 g) were ground and mixed in a ball mill (3 h at 45°C) to make samples of linseed spread (LS). After applying response surface methodology and central composite design, the optimized LS was obtained with 22.5 g RLP, 50 g PGM, 6.5 g HPMP, fine particle sizes (<30 μm), and 92% of the highest acceptable sensory scores (ASS). The mathematical model of ASS had good fitness (R 2 > 95%) with the ingredient's levels of LS samples. While the PV, aw, and acidity of optimized LS did not change even after 90-day storage at 4°C, it showed viscoelastic properties and very low stickiness (0.2-0.4 mJ). Additionally, the hardness, adhesiveness, cohesiveness, springiness, gumminess, and chewiness of optimized LS, respectively, decreased by 50, 25, 3, 8, 55, and 63% when its temperature increased from 4 to 25°C.


A mouse embryonic stem cell line showing pluripotency of differentiation in early embryos and ubiquitous beta-galactosidase expression.
For analysis of chimeric mice made by injecting embryonic stem (ES) cells into host blastocysts, it is very desirable if the ES cells have a good cell marker that can distinguish them from host cells. It is ideal if the marker can be easily visualized in every type of cell and tissue throughout the embryogenesis. We tried to produce such ES cell lines by introducing an E. coli beta-galactosidase (beta-gal) gene construct by electroporation. One of the transformant lines (MS1-EL4) showed beta-gal activity in every undifferentiated stem cell. After being induced to differentiate in vitro, cells with various morphologies showed beta-gal activity. We also detected beta-gal activity in a wide variety of tissue elements in solid tumors made by injecting the MS1-EL4 cells into syngeneic mice. Then we produced chimeric embryos by injecting the MS1-EL4 cells into blastocysts and recovering the embryos at various developmental stages. We found that the MS1-EL4 cells contributed to various tissues and expressed beta-gal activity, including not only descendants of the inner cell mass but also the trophectoderm-derived extraembryonic ectoderm.


Ruthenium red attenuated cardiomyocyte and mitochondrial damage during the early stage after severe burn.
To investigate the effects of ruthenium red on cardiomyocyte and mitochondrial damage during the early stage after severe burn. Adult Wistar rats were randomized into normal control group (control), burn group (burns) and ruthenium red-treated group (RR) (n=8). Rats in the burn and RR groups were scalded to 30% TBSA III degree, and 30 min later, resuscitated with Ringer's solution. Ruthenium red was injected into rats of RR group at a dose of 2mg kg(-1), and again 3h later. Rats were sacrificed at the 6th hour post-scald, myocardial mitochondrial respiratory function and Ca(2+) concentration ([Ca(2+)](m)), serum creatine kinase (CK) and lactate dehydrogenase (LDH), myocardial ATP, ADP, AMP and lactate contents were determined. [Ca(2+)](m) in the RR group was significantly lower than that of the burn group. Mitochondrial respiratory control rate (RCR) and ST(3) were higher than those of burns, but ST(4) was high compared to the control group. Serum CK and LDH of the RR group decreased significantly, and were 65.0 and 45.5% of the burn group, myocardial ATP content in the ruthenium red-treated group increased by 100.4% and lactate level was decreased by 53.5% compared to the burn group. Ruthenium red attenuated myocyte and mitochondrial damage during the early stage after severe burns.


Preparing BSN students for a new workplace: Experiences in a COVID-19 designated unit as an RN extender.
Academic nursing programs were impacted by the onset of the pandemic with the challenges of social distancing, detecting, and controlling the spread of the virus. Many traditionally campus-based, face-to-face programs transitioned quickly to include virtual activities for classes, laboratories, and clinical experiences for students. Initially direct patient care clinical activities came to a halt due to concerns for student safety and overwhelming numbers of COVID-19 cases stressing health system resources. However, as COVID-19 cases began to rise and hospitals struggled with staffing shortages, it became necessary to explore how nursing students could contribute to relieving the staffing burden while obtaining critical education as RN Extenders. Students that participated in the RN Extender program were seniors entering the nursing workforce within the next two months. Significant student screening and preparation was provided to support students serving as RN Extenders in COVID-19 units. The prior working relationships and personal contact between academic and practice leaders, a sense of equal participation, clear and realistic expectations of the benefits and responsibilities of each group were crucial. Building ongoing and frequent opportunities for formal and informal communication among all stakeholders was vital and the major contributor to the success of this program.


The Efficacy of Bulbar Urethral Mobilization for Anastomotic Anterior Urethroplasty in a Case With Recurrent Anterior Urethral Stricture.
A 2-month-old boy was diagnosed with febrile urinary tract infection. Voiding cystourethrography showed bulbar and anterior urethral strictures, and endoscopic internal urethrotomy was performed. He developed febrile urinary tract infection again and revealed the recurrence of the anterior urethral stricture. Consequently, endoscopic internal urethrotomy was performed 4 times. Because the anterior urethral stricture had not improved, he was referred to us. Anterior urethroplasty was performed when he was 5 years. After excision of the scarred portions of the urethra, the defect of the urethra was 20 mm. Transperineal bulbar urethral mobilization was performed, and a single-stage end-to-end anterior urethroplasty without tension could be performed simultaneously.


ASPP2 inhibits tumor growth by repressing the mevalonate pathway in hepatocellular carcinoma.
Cancer is, fundamentally, a disorder of cell growth and proliferation, which requires adequate supplies of energy and nutrients. In this study, we report that the haplo-insufficient tumor suppressor ASPP2, a p53 activator, negatively regulates the mevalonate pathway to mediate its inhibitory effect on tumor growth in hepatocellular carcinoma (HCC). Gene expression profile analysis revealed that the expression of key enzymes in the mevalonate pathway were increased when ASPP2 was downregulated. HCC cells gained higher cholesterol levels and enhanced tumor-initiating capability in response to the depletion of ASPP2. Simvastatin, a mevalonate pathway inhibitor, efficiently abrogated ASPP2 depletion-induced anchorage-independent cell proliferation, resistance to chemotherapy drugs in vitro, and tumor growth in xenografted nude mice. Mechanistically, ASPP2 interacts with SREBP-2 in the nucleus and restricts the transcriptional activity of SREBP-2 on its target genes, which include key enzymes involved in the mevalonate pathway. Moreover, clinical data revealed better prognosis in patients with high levels of ASPP2 and low levels of the mevalonate pathway enzyme HMGCR. Our findings provide functional and mechanistic insights into the critical role of ASPP2 in the regulation of the mevalonate pathway and the importance of this pathway in tumor initiation and tumor growth, which may provide a new therapeutic opportunity for HCC.


Comparison Between Early-Onset and Common Gout: A Systematic Literature Review.
Gout is an inflammatory, metabolic disease associated with a high comorbidity burden including cardiovascular disease, hypertension, type 2 diabetes, hyperlipidemia, renal disease, and metabolic syndrome. Approximately 9.2 million Americans have gout, making prognosis and treatment outcome predictors highly important. About 600,000 Americans have early-onset gout (EOG), generally defined as first gout attack at ≤ 40 years of age. However, data on EOG clinical features, comorbidity profile, and treatment response are sparse; this systematic literature review provides insight. PubMed and American College of Rheumatology (ACR)/European Alliance of the Associations for Rheumatology (EULAR) abstract archives were searched for early-onset gout, "early onset gout," and ("gout" AND "age of onset"). Duplicate, foreign language, single case report, older (before 2016), and irrelevant/data insufficient publications were excluded. The age of diagnosis categorized patients as having common gout (CG, generally > 40 years) or EOG (generally ≤ 40 years). Applicable publications were extensively reviewed/discussed among authors for inclusion/exclusion consensus. A total of 283 publications were identified, with 46 (35 articles, 10 abstracts) reviewed and 17 (12 articles, 5 abstracts) ultimately included. Eleven reported clinical characteristics, with 6 EOG-CG retrospective/cross-sectional comparisons. Gout diagnosis preceded cardiometabolic comorbidity and renal comorbidities were less prevalent in EOG than CG patients. EOG patients had more severe disease (more gout flares, polyarticular disease), higher pre-therapy serum urate (SU), and worse oral urate-lowering therapy response. Genetics-focused publications reported higher incidences of dysfunctional urate transporter mutations in EOG patients. This review suggests that EOG is more recalcitrant to urate-lowering therapy, is associated with urate transporter defects, and carries heavy disease burden. Therefore, early rheumatology referral and urate-lowering in a treat-to-target fashion may benefit EOG patients. Interestingly, EOG patients had fewer cardiometabolic comorbidities at diagnosis than CG patients, presenting a potential "window of opportunity" to attenuate cardiometabolic comorbidity development with SU control. Preventing gout-related suffering and health burden is particularly important in these young EOG patients who will live with gout and its sequelae for decades.


A pneumatic phantom for mimicking respiration-induced artifacts in spinal MRI.
To design a phantom capable of mimicking human respiration to serve as a testing platform for correction of the static and time-evolving magnetic field distortions typically encountered in MRI of the spinal cord. An inflation system to mimic the air variation of the human lungs was constructed. The inflation system was linked to a phantom containing synthetic lungs and an ex vivo human spine. The relationship between air pressure and phantom lung volume was evaluated via imaging experiment. The geometric distortion (pseudo-displacement) caused by the B0 inhomogeneities was measured on echo planar imaging slices for different air volumes. Linear and quadratic relations linking air pressure to phantom lung volume were observed with a Pearson correlation coefficient of 0.99. Air distribution was uneven across the synthetic lungs, exhibiting a left-to-right lung volume ratio of up to 5/4. The pseudo-displacement artifact of the spine caused by the air-filled lungs was observed. The proposed phantom can reproduce the lung volume variation of human respiration and thus can serve as a reliable testing platform for the correction of the associated time-varying B0 field distortions. Details of the construction and code for the inflation system microcontroller are available for download as open source. Magn Reson Med 79:600-605, 2017. © 2017 International Society for Magnetic Resonance in Medicine.


A simple serum galactosyltransferase assay method suitable for routine use.
UDP-Galactose: N-acetylglucosaminyl glycoprotein beta 1-4 galactosyltransferase (GT) catalyzes the transfer of galactose to N-acetylglucosamine from UDP-[3H]Gal. The uncharged reaction product (tritiated N-acetyllactosamine) is separated from the unreacted UDP-[3H]Gal by ion-exchange chromatography. The major advantage of this method is its rapidity compared to other isotopic techniques.


Four-year follow-up of psychological reactions to false positive screening tests for congenital hypothyroidism.
Thirty-two families were investigated four years after a false alarm in the neonatal screening of their newborns. Sixteen of the families showed signs of persistent anxiety 6-12 months after the screening. Thirteen of them still show anxiety after 4 years. Of the 16 without anxiety at 6-12 months, 6 show signs of anxiety now. This persistent anxiety may be related to the initial psychological trauma of the false positive screening result. Thus, 19 of the 32 families have not completely integrated their experience. Twenty-four children were psychologically evaluated. Eight families refused to have their children examined. Twelve of the children showed disturbed behavior, 10 of these have parents who show unsatisfactory integration. Medical measures have psychological side-effects, which may be interpreted as iatrogenic. However, the effects of an external stress depend on the individual's susceptibility to it and abilities to cope with it and use external support available.


Tumor-induced rickets: usefulness of MR gradient echo recall imaging for tumor localization.
An 11-year-old boy presented with a femur fracture, bone hypomineralization, and hypophosphatemia, suggesting tumor-induced rickets. Conventional radiologic techniques including magnetic resonance skeletal survey did not identify a tumor. Magnetic resonance gradient echo recall imaging demonstrated a 3-cm iliac tumor, the resection of which rapidly reversed metabolic abnormalities. This technique may be useful in identifying elusive tumors associated with tumor-induced rickets.


Prediction of plan adaptation in head and neck cancer proton therapy using clinical, radiographic, and dosimetric features.
Because proton head and neck (HN) treatments are sensitive to anatomical changes, plan adaptation (re-plan) during the treatment course is needed for a significant portion of patients. We aim to predict re-plan at plan review stage for HN proton therapy with a neural network (NN) model trained with patients' dosimetric and clinical features. The model can serve as a valuable tool for planners to assess the probability of needing to revise the current plan. Mean beam dose heterogeneity index (BHI), defined as the ratio of the maximum beam dose to the prescription dose, plan robustness features (clinical target volume (CTV), V100 changes, and V100 > 95% passing rates in 21 robust evaluation scenarios), as well as clinical features (e.g., age, tumor site, and surgery/chemotherapy status) were gathered from 171 patients treated at our proton center in 2020, with a median age of 64 and stages from I-IVc across 13 HN sites. Statistical analyses of dosimetric parameters and clinical features were conducted between re-plan and no-replan groups. A NN was trained and tested using these features. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performance of the prediction model. A sensitivity analysis was done to determine feature importance. Mean BHI in the re-plan group was significantly higher than the no-replan group (p < .01). Tumor site (p < .01), chemotherapy status (p < .01), and surgery status (p < .01) were significantly correlated to re-plan. The model had sensitivities/specificities of 75.0%/77.4%, respectively, and an area under the ROC curve of .855. There are several dosimetric and clinical features that correlate to re-plans, and NNs trained with these features can be used to predict HN re-plans, which can be used to reduce re-plan rate by improving plan quality.


Fabrication and Characterization of Electrospun Chitosan/Polylactic Acid (CH/PLA) Nanofiber Scaffolds for Biomedical Application.
The present study demonstrates a strategy for preparing porous composite fibrous materials with superior biocompatibility and antibacterial performance. The findings reveal that the incorporation of PEG into the spinning solutions significantly influences the fiber diameters, morphology, and porous area fraction. The addition of a hydrophilic homopolymer, PEG, into the Ch/PLA spinning solution enhances the hydrophilicity of the resulting materials. The hybrid fibrous materials, comprising Ch modified with PLA and PEG as a co-solvent, along with post-treatment to improve water stability, exhibit a slower rate of degradation (stable, moderate weight loss over 16 weeks) and reduced hydrophobicity (lower contact angle, reaching 21.95 ± 2.17°), rendering them promising for biomedical applications. The antibacterial activity of the membranes is evaluated against Staphylococcus aureus and Escherichia coli, with PEG-containing samples showing a twofold increase in bacterial reduction rate. In vitro cell culture studies demonstrated that PEG-containing materials promote uniform cell attachment, comparable to PEG-free nanofibers. The comprehensive evaluation of these novel materials, which exhibit improved physical, chemical, and biological properties, highlights their potential for biomedical applications in tissue engineering and regenerative medicine.


An ab initio study of S(N)2 reactivity at C6 in hexopyranose derivatives. I. Influence of dipole-dipole interactions in the transition structure.
It is widely accepted that dipole-dipole interactions in the S(N)2 transition structure can play a dominant role in determining reaction rates. A model of this type was proposed some years ago to explain the remarkably low reactivity of galactopyranose-6-O-sulfonates toward S(N)2 displacement, and similar arguments have recently been restated in the context of gas-phase reactions. In this paper, we present ab initio calculations (B3LYP/6-31+G(d,p)) on model structures and an analysis of charge densities using the theory of atoms in molecules. We find that the maximum possible impact of local dipole-dipole interactions is insufficient to account for the observed reactivity differences.


Relative thermodynamic stability of DNA, RNA, and DNA:RNA hybrid duplexes: relationship with base composition and structure.
Fourteen oligonucleotides 8-21 nucleotides in length and their complements were synthesized as DNA and RNA. For each sequence, four kinds of duplexes, DNA:DNA, RNA:RNA, DNA:RNA, and RNA:DNA, were prepared. Twelve sequences had A.T/U content varying from 25 to 80% and dPy content in the DNA strands varying from 0 to 100%. Thermodynamic stabilities of four duplexes for each sequence were determined in solution containing 100 mM Na+, 10 mM phosphate, and 0.1 mM EDTA, pH 7.1. CD spectra and electrophoretic mobility on native polyacrylamide gel were measured for most duplexes. Quantitative correlations of hybrid stability both with deoxypyrimidine content and, at fixed dPy content, with the fraction of A.T/U in duplexes were found. We also demonstrated that hybrids with 70-80% deoxypyrimidine DNA strand and a high or moderate A.T/U fraction displayed the highest relative stability compared to their RNA counterparts. Relationships of relative intensities of CD bands at 210 nm and relative electrophoretic mobilities of hybrids with relative hybrid stability suggested that hybrid conformation varies continuously between A- and B-form and is the decisive factor in relative hybrid stability.


Bony exostoses developed subsequent to free gingival grafts: case series.
Bony exostosis (BE) is described as a benign localised overgrowth of bone of unknown aetiology. Buccal bony exostosis (BBE) development secondary to soft tissue graft procedures has been reported in a small number of cases. The dental literature describes BBE development also at sites where free gingival grafts (FGG) have been used to increase the amount of gingiva. The following case series describes BBE development at nine sites (five cases) at which FGG was performed to increase the width of the attached gingiva. The presence of exostoses has been recognised during postoperative visits. Histological examination revealed osseous enlargements compatible with the diagnosis of exostoses at two re-entry procedures. In conclusion, based on previous reports, periosteal trauma, eg fenestration, seems to be the main aetiologic agent associated with the development of BBE in areas where FGG were placed.


Immunohistological reaction patterns of cervical lymph nodes in patients with laryngeal carcinomas.
An attempt was made to assess the immunological importance of regional lymph node histology in relation to the survival of 107 patients with carcinoma of the larynx, operated on from 1973 to 1982 at the ENT-Clinic in Marburg. A total of 2765 sections of lymph nodes removed during neck dissections were examined microscopically to evaluate the morphological patterns of response. Microscopically, four distinct patterns were defined. Patients whose lymph nodes demonstrated immunological responses according to patterns I and II in the form of either expanded inner cortices or increased numbers of germinal centers had a greater 5-year survival rate than those patients whose lymph nodes showed an unstimulated pattern. Eight patients whose lymph nodes showed a depleted pattern, IV, did not survive more than 3 years. Morphological assessment of immunological activity in lymph nodes draining malignant tumors seems to be of value in predicting survival. The evaluation of the reaction pattern and difficulties in methodology, however, set definite limitations to our study.


Epidural clonidine does not decrease blood pressure or spinal cord blood flow in awake sheep.
Preliminary data in animals and humans suggest that epidurally administered clonidine produces antinociception and is not neurotoxic. However, clonidine can produce vasoconstriction, and epidurally administered clonidine decreases spinal cord blood flow in anesthetized pigs. To examine the effect of epidurally administered clonidine on spinal cord blood flow in awake animals, the authors inserted lumbar epidural, femoral arterial and venous, pulmonary arterial, and left ventricular catheters in 13 adult sheep. Following a 24-h recovery, the authors injected saline (N = 6) or clonidine, 750 micrograms (17-25 micrograms/kg; N = 7) epidurally, and measured arterial blood gas tensions; temperature; heart rate; systemic and pulmonary arterial, right atrial, and pulmonary capillary wedge pressures; and spinal cord and renal blood flows (by radioactive microsphere injection) before and at 45 min and 4 h following injection. Epidural saline injection did not affect measured variables. Heart rate decreased from 112 +/- 9 to 86 +/- 4 beats/min (mean +/- SE; P = .003) and arterial PO2 decreased from 99 +/- 3 to 78 +/- 6 mmHg (P = .04) 45 min following clonidine injection. Temperature increased from 39.1 +/- .2 to 40.6 +/- 1 degree C (P = .0001) 4 h following clonidine injection. Epidural clonidine administration did not affect cardiac output, pulmonary and systemic pressures, or renal or spinal cord blood flows, except for an increase in mid-thoracic spinal cord blood flow 45 min following injection. The authors conclude that, in sheep, epidural clonidine does not produce dangerous cardiovascular depression or global spinal cord ischemia.


Economies of scale and scope in the Danish hospital sector prior to radical restructuring plans.
The Danish hospital sector faces a significant rebuilding program driven by recent regional reform and guidelines for acute admission hospitals. Within the next 5-10 years, the number of public hospitals offering acute admission will be reduced from 35 to approximately 20 larger hospitals. As the administrative data may be biased during the middle of a restructuring process our objective was to analyze whether the configuration of Danish public hospitals was subject to economies of scale and scope prior to the restructuring plans. We estimated a quadratic cost function using panel data on the total costs for somatic treatment, casemix adjusted DRG-production values, and other cost drivers for the three years before the 2007 reforms. A short-run cost function was used to derive estimates of a long-run cost function by applying the envelope condition. Next, we estimated economies of scale and scope. We identified moderate-to-significant economies of scale and scope. This indicates that the Danish hospital sector was characterized by unexploited gains from consolidation. Our results suggest that the proposed plans have the potential to result in hospitals that are more efficient. However, post-restructuring studies elsewhere show that the strategy of horizontal integration has failed.


Changes in GI hormones and their effect on gastric emptying and transit times after Roux-en-Y gastric bypass in rat model.
We determined whether Roux-en-Y gastric bypass (RYGB)-induced protracted weight loss is associated with an increase in anorectic peptide YY (PYY) and decreased gastrointestinal (GI) motility. RYGB and control sham-operated GI intact obese (SO Obese) and sham-operated GI intact pair-fed (PF) rats were studied. Postoperatively, body weight (BW) and food intake were measured for 90 days. Rats were killed to measure PYY, ghrelin, cholecystokinin (CCK), and glucagonlike peptide-1 (GLP-1). Ninety-day food intake trends were examined by quadratic trend analysis. On the basis of a 28-day weight loss rate, PYY also was measured at 14 and 28 days. Peak 28-day PYY results corresponded with peak BW loss rate; thus, gastric emptying (GE) and intestinal transit time were measured. Data were analyzed by analysis of variance and Tukey's pairwise multiple comparison. At 90 days, BW in SO Obese versus PF versus RYGB rats was 801 +/- 15 g versus 661 +/- 24 g versus 538 +/- 32 g respectively (P < .05). Concentrations of plasma PYY were increased, while plasma ghrelin was decreased in RYGB versus SO Obese and PF (P < .05). CCK and GLP-1 were unchanged. In RYGB versus controls, PYY was increased at 14 and 28 days but was most elevated at 28 days. In RYGB versus controls, GE was delayed (P < .05) and intestinal transit time was longer (P < .05). After RYGB, an increase in PYY and a decrease in ghrelin occurred, probably explaining the decrease in food intake, the slower GE and transit time, which contributed to weight loss. Longitudinal studies can be performed with the use of our RYGB model, providing insight into weight loss mechanisms by generating long-term follow-up data currently not available in human studies.


Adenine nucleotides of the stria vascularis.
The levels of the adenine nucleotides ATP, ADP, and AMP in the stria vascularis were measured under normal conditions, and following various durations of ischemia. The concentrations of these compounds were used for the calculation of the adenylate energy charge, the energy status and the phosphorylation state of the stria. Following 10 min of ischemia the adenylate energy charge had decreased three fold, the energy status seven fold and the phosphorylation state 14 fold. To study the potential for recovery of strial function following various brief and prolonged ischemic intervals, a method for the perfusion of the ear via the anterior inferior cerebellar artery was developed. For various reasons it was found advantageous to use "artifical blood" as perfusate, relying upon fluorocarbons as oxygen carriers. The endolymphatic potential was used as electrical indicator of strial function. Recovery of the endolymphatic potential following brief periods of ischemia was paralleled by a corresponding increase of the ATP levels and a drastic decrease of the AMP levels of the stria vascularis. Preliminary results on the effects of substrate-free perfusion are presented.


Late-onset cytomegalovirus reactivation in critically ill renal transplant patients.
Cytomegalovirus (CMV) reactivation occurs frequently in the first months after renal transplantation. However, reports concerning long-term kidney transplant recipients are rare and have always pertained to symptomatic CMV disease. We report four cases of late-onset asymptomatic CMV reactivation in critically ill renal transplant patients who suffered from severe bacterial infections and in whom CMV antigenemia was observed. CMV reactivation in these patients might indicate an additional disturbance in the patients' immune defenses at the time of critical illness, possibly even necessitating a temporary reduction in immunosuppressive therapy. Prospective, controlled trials are needed to define the role of CMV antigenemia in critically ill patients, including the role of antiviral therapy for asymptomatic reactivations.


Acute Hyperammonemia Induces NMDA-Mediated Hypophosphorylation of Intermediate Filaments Through PP1 and PP2B in Cerebral Cortex of Young Rats.
In the present work, we studied the effects of toxic ammonia levels on the cytoskeleton of neural cells, with emphasis in the homeostasis of the phosphorylating system associated with the intermediate filaments (IFs). We used in vivo and in vitro models of acute hyperammonemia in 10- and 21-day-old rats. In the in vivo model, animals were intraperitoneally injected with ammonium acetate (7 mmol/Kg), and the phosphorylation level of the cytoskeletal proteins was analyzed in the cerebral cortex and hippocampus 30 and 60 min after injection. The injected ammonia altered the IF phosphorylation of astrocytes (GFAP and vimentin) and neurons (neurofilament subunits of low, middle, and high molecular weight, respectively: NFL, NFM, and NFH) from cerebral cortex of 21-day-old rats. This was a transitory effect observed 30 min after injection, recovering 30 min afterward. Phosphorylation was not altered in the cerebral cortex of 10-day-old pups. The homeostasis of hippocampal IFs was preserved at the studied ages and times. In the in vitro model, cortical slices of 10- and 21-day-old rats were incubated with 0.5, 1, or 5 mM NH4Cl, and the phosphorylation level of the IF proteins was analyzed after 30 min. The IF phosphorylation was not altered in cortical slices of 10-day-old rats; however, in cortical slices of 21-day-old pups, 5 mM NH4Cl induced hypophosphorylation of GFAP and vimentin, preserving neurofilament phosphorylation levels. Hypophosphorylation was mediated by the protein phosphatases 1 (PP1) and 2B (PP2B), and this event was associated with Ca(2+) influx via N-methyl-D-aspartate (NMDA) glutamate receptors. The aim of this study is to show that acute ammonia toxicity targets the phosphorylating system of IFs in the cerebral cortex of rats in a developmentally regulated manner, and NMDA-mediated Ca(2+) signaling plays a central role in this mechanism. We propose that the disruption of cytoskeletal homeostasis could be an endpoint of the acute hyperammonemia in the developing brain. We believe that these results contribute for better understanding the molecular basis of the ammonia toxicity in brain.


Environmental filtering and spillover explain multi-species edge responses across agricultural boundaries in a biosphere reserve.
To ensure integrity of protected areas we need to understand how species respond to anthropogenic borders. We investigate, from a metacommunity perspective, the direct and indirect mechanisms by which transformed areas affect distribution patterns of ground-living arthropod assemblages inhabiting an extensive protected area adjacent to fruit orchards in an important biosphere reserve. Arthropods and environmental variables were sampled along transects perpendicular to natural-orchard edges. Influence of distance from orchard boundary, degree of impermeability of the boundary, orchard habitat quality (local scale land-use intensity), and edge-induced changes in local environmental variables on arthropod species richness and composition in non-crop habitats were assessed. Arthropod groups were assessed in terms of habitat fidelity: species associated with natural habitat (stenotopic species), those within crop habitat (cultural species), and those showing no preference for either habitat (ubiquitous species). Spillover resulted in higher cultural species richness near edges, but not higher overall species richness. Environmental filtering was important for stenotopic species composition, which was influenced by edge-induced changes in environmental variables. Ubiquitous species composition was determined by orchard impermeability. Increased orchard habitat quality was associated with higher cultural and ubiquitous species richness. The effects of orchards on assemblages in natural habitats can be variable, but predictable when using species habitat specificity in conjunction with a metacommunity framework. High intensity orchards may act as sink habitats, especially for species that readily disperse between crop and natural habitats. Here we recommend that local buffer strips are > 85 m wide, which will reduce the influence of cultural species spillover on sensitive natural ecosystems.


Bicarbonate ion-ATPase in rat liver cell fractions.
The distribution of HCO3MINUS-ATPase activity was studied in cell fractions prepared from homogenates of rat liver. The level of mitochondrial contamination in the microsomal fraction depended on the fractionation procedure and on the method of homogenization. With proper care, microsomes with undetectable mitochondrial contamination could be prepared. These microsomes had no detectable HCO3MINUS-ATPase activity. Approximately 85% of the total HCO3minus-ATPase activity of the post 6000 times g-min supernatant was recovered in the mitochondrial fraction. The properties of this mitochondrial HCO3minus-ATPase were not distinguishable from those of the various microsomal HCO3minus-ATPases previously described by other investigators.


The role of lactate in brain metabolism.
According to the astrocyte-neurone-lactate shuttle (ANLS) hypothesis, activated neurones use lactate released by astrocytes as their energy substrate. The hypothesis, based largely on in vitro experiments, postulates that lactate is derived from the uptake by astrocytes of synaptically released glutamate. The time course of changes in lactate, derived from in vivo experiments, is incompatible with the ANLS model. Neuronal activation leads to a delayed rise in lactate followed by a slow decay, which greatly outlasts the period of neuronal activation. The present review proposes that the uptake of stimulated glutamate release from astrocytes, rather than synaptically released glutamate, is the source of lactate released following neuronal activation. This rise in lactate occurs too late to provide energy for neuronal activity. Furthermore, there is no evidence that lactate undergoes local oxidative phosphorylation. In conclusion, under physiological conditions, there is no evidence that lactate is a significant source of energy for activated neurones.


Cohnella plantaginis sp. nov., a novel nitrogen-fixing species isolated from plantain rhizosphere soil.
A novel bacterium capable of fixing nitrogen was isolated from plantain rhizosphere soil in China. The isolate, designated YN-83(T), is Gram-positive, aerobic, motile and rod-shaped (0.4-0.6 μm × 1.9-2.6 μm). Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain YN-83(T) was a member of the genus Cohnella. High similarity of 16S rRNA gene sequence was found between YN-83(T) and Cohnella ginsengisoli DSM18997(T) (97.99%), whereas the similarity was below 96.0% between YN-83(T) and the other Cohnella species. DNA-DNA relatedness between strain YN-83(T) and C. ginsengisoli DSM18997(T) was 27.4 ± 6.2%. The DNA G+C content of strain YN-83(T) was 59.3 mol%. The predominant isoprenoid quinone was MK-7 and the major fatty acids were anteiso-C(15:0) (44.3%), iso-C(15:0) (11.3%), iso-C(16:0) (18.6%) and C(16:0) (7.7%). The polar lipids of strain YN-83(T) consist of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, lyso- phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides. On the basis of phenotypic and chemotaxonomic properties, 16S rRNA gene sequence, G+C content and DNA-DNA hybridization, strain YN-83(T) represents a novel species of the genus Cohnella, for which the name Cohnella plantaginis sp. nov. (type strain YN-83(T) = DSM 25424(T) = CGMCC 1.12047(T)) is proposed.


New Zr-25Ti-xMo alloys for dental implant application: Properties characterization and surface analysis.
A series of Zr-25Ti-xMo (x = 0, 2.5, 5, 7.5, 10 and 12.5 wt %) as-cast alloys were designed to advance a new-brand Zr-based alloy with low Young's elastic, moderate compression strength, superior corrosion resistance and good wear behavior for the application of dental implant materials. In the present study, the microstructures of the alloys were evaluated by X-ray diffraction, scanning electron microscopy and X-ray photoelectron spectroscopy. The microhardness and uniaxial compression measurement were performed to evaluate the mechanical properties of the alloys. The electrochemical behaviors of the alloys was investigated in artificial saliva solution. The friction and wear performances of the Zr-25Ti-xMo alloys were examined by pin-on-disk under the load of 15 N. The results shows that the crystalline structure transforms from hexagonal close-pack (α phase, x = 0 wt %) to body-centered cubic structure (β phase, 5 ≤ x ≤ 12.5 wt %) through a α + β dual-phase region (x = 2.5 wt %). They exhibits excellent mechanical properties with low elastic modulus (from 17.7 to 24.4 GPa) and moderate compression strength (from 1154.4 to 1310.8 MPa). The Zr-25Ti-xMo alloys possess good corrosion resistance due to the formation of a protective passive film consisting mainly of ZrO2, TiO2 and minor MoO3. Especially, the polarization curves demonstrates that the Zr-25Ti-7.5Mo alloy has a wider passive region than the other five alloys and it possesses the lower corrosion current density and corrosion rate. Furthermore, this alloy exhibits good abrasion resistance with the lowest coefficients of friction and volume wear loss. Thus, the Zr-25Ti-7.5Mo alloy has a combination of excellent mechanical properties such as low elastic modulus, moderate yield strength and the compression strength, good electrochemical stability and well wear resistance, it is considered a promising candidate for orthopedic materials as dental implant.


A 12-year follow-up study of all-cause and cardiovascular mortality among 10,532 people newly diagnosed with Type 2 diabetes in Tayside, Scotland.
To determine absolute and relative risks of all-cause and cardiovascular mortality among patients newly diagnosed with Type 2 diabetes. In an observational cohort study using record-linkage databases, based in Tayside, Scotland, UK, we identified newly diagnosed patients with Type 2 diabetes in 1993-2004. We also identified a set of non-diabetic comparators from lists of patients registered with a general practice, individually matched to the diabetic patients by sex, age and deprivation. We followed up patients for mortality and cardiovascular mortality over a 12-year period and calculated hazard ratios using Cox regression. There were 10,532 patients with Type 2 diabetes and 21,056 non-diabetic comparators. Diabetic patients in every age/sex group had higher absolute mortality rates. Even taking deprivation into account, the hazard ratio for mortality was 1.32 (95% CI 1.25-1.40), decreasing to 1.15 (1.09-1.22) after adjusting for pre-existing cardiovascular disease. The hazard ratios for cardiovascular mortality were higher, decreasing from 1.51 (1.37-1.67) to 1.23 (1.11-1.36) after adjusting for pre-existing cardiovascular disease. The hazard ratios decreased with increasing age at diagnosis, although the difference in absolute rate of mortality increased slightly with age. Increased mortality risks were only evident 2 years after diagnosis and increased thereafter. Patients with Type 2 diabetes have an increased risk of all-cause and cardiovascular mortality compared with non-diabetic comparators, although this is not observable immediately after diagnosis. Age at diagnosis and duration of the disease independently affect absolute and relative mortality risk.


Low palaeoelevation of the northern Lhasa terrane during late Eocene: Fossil foraminifera and stable isotope evidence from the Gerze Basin.
The Lhasa terrane is a key region for understanding the paleoelevation of the southern Tibetan Plateau after India-Asia collision. The Gerze Basin, located in the northern part of the Lhasa terrane, is a shortening-related basin. We discovered Lagena laevis (Bandy) fossils in upper Eocene strata of the Gerze Basin. This type of foraminifera is associated with lagoon and estuarine environments, indicating that the northern part of the Lhasa terrane was near sea level during the late Eocene. We speculate that these foraminifera were transported inland by storm surges to low elevation freshwater lakes during times of marine transgressions. This inference is consistent with the relatively positive δ(18)O values in carbonate from the same deposits that indicate low palaeoelevations close to sea level. Considering the palaeoelevation results from the nearby Oligocene basins at a similar latitude and the volcanic history of the Lhasa terrane, we infer that large-magnitude surface uplift of the northern Lhasa terrane occurred between late Eocene and late Oligocene time.


[The Phlebotomine sandflies (Diptera) from the Mayombe area in the Popular Republic of Congo (author's transl)].
Fifteen species and subspecies of Phlebotomine sandflies have been inventorized in the Mayombe forest in the People's Republic of the Congo. Nine of them are confined strictly to the rain forest; the others belong to secondary forest, clearing or savannah. We have drawn a comparison between the Phlebotomine fauna in the Mayombe and those existing in several other dense Congolense forests.


Two new mouse models of Gjb1-associated Charcot-Marie-Tooth disease type 1X.
Charcot-Marie-Tooth disease type 1X is caused by mutations in GJB1, which is the second most common gene associated with inherited peripheral neuropathy. The GJB1 gene encodes connexin 32 (CX32), a gap junction protein expressed in myelinating glial cells. The gene is X-linked, and the mutations cause a loss of function. A large number of disease-associated variants have been identified, and many result in mistrafficking and mislocalization of the protein. An existing knockout mouse lacking Gjb1 expression provides a valid animal model of CMT1X, but the complete lack of protein may not fully recapitulate the disease mechanisms caused by aberrant CX32 proteins. To better represent the spectrum of human CMT1X-associated mutations, we have generated a new Gjb1 knockin mouse model. CRISPR/Cas9 genome editing was used to produce mice carrying the R15Q mutation in Gjb1. In addition, we identified a second allele with an early frame shift mutation in codon 7 (del2). Mice were analyzed using clinically relevant molecular, histological, neurophysiological, and behavioral assays. Both alleles produce protein detectable by immunofluorescence in Schwann cells, with some protein properly localizing to nodes of Ranvier. However, both alleles also result in peripheral neuropathy with thinly myelinated and demyelinated axons, as well as degenerating and regenerating axons, predominantly in distal motor nerves. Nerve conduction velocities were only mildly reduced at later ages and compound muscle action potential amplitudes were not reduced. Levels of neurofilament light chain in plasma were elevated in both alleles. The del2 mice have an onset at ~3 months of age, whereas the R15Q mice had a later onset at 5-6 months of age, suggesting a milder loss of function. Both alleles performed comparably to wild type littermates in accelerating rotarod and grip strength tests of neuromuscular performance. We have generated and characterized two new mouse models of CMT1X that will be useful for future mechanistic and preclinical studies.


S-to-αC radical migration in the radical cations of Gly-Cys and Cys-Gly.
The radical cations of Cys-Gly and Gly-Cys were studied using ion-molecule reactions (IMR), infrared multiple-photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations. Homolytic cleavage of the S-NO bond of nitrosylated precursors generated radical cations with the radical site initially located on the sulfur atom. Time-resolved ion-molecule reactions showed that radical site migration via hydrogen atom transfer (HAT) occurred much more quickly in Gly-Cys(•+) than in Cys-Gly(•+). IRMPD and DFT calculations indicated that for Gly-Cys, the radical migrated from the sulfur atom to the α-carbon of glycine, which is lower in energy than the sulfur radical (-53.5 kJ/mol). This migration does not occur for Cys-Gly because the glycine α-carbon is higher in energy than the sulfur radical (10.3 kJ/mol). DFT calculations showed that the highest energy barriers for rearrangement are 68.2 kJ/mol for Gly-Cys and 133.8 kJ/mol for Cys-Gly, which is in agreement with both the IMR and IRMPD data and explains the HAT in Gly-Cys.


Identifying the Chinese Herbal Medicine Network and Core Formula for Allergic Rhinitis on a Real-World Database.
Patients with a primary diagnosis of AR (ICD-9-CM code: 477.9) in 2010 were included, and the National Health Insurance Research Database in Taiwan was used as the data source. Association rule mining and social network analysis were used to establish and explore the CHM network. Possible molecular pathways of the CHM network were summarized and compared with commonly used western medicine (WM) by conducting overrepresentation analysis in the Reactome pathway database. The potential proteins acted by CHMs were obtained from the CHM ingredient-protein databases, including STITCH, TCMSP, TCMID, and TCM@Taiwan. There were 89,148 AR subjects found in 2010, and a total of 33,507 patients ever used CHM. On an average, 5.6 types of CHMs were utilized per prescription. Xin-Yi-Qing-Fei-Tang was used most frequently (25.5% of 222,279 prescriptions), while Xiao-Qing-Long-Tang with Xin-Yi-San was the most commonly prescribed CHM-CHM combination. Up to six distinctive clusters could be found among the CHM network, and core CHMs could be found for AR, such as Xiao-Qing-Long-Tang and Xin-Yi-Qing-Fei-Tang. A total of 140 molecular pathways were covered by the CHM network (2,432 ingredients from 31 kinds of CHMs), while 39 WMs covered 55 pathways. Among pathways responding to the immune system, WM mainly acted on cytokine signaling-related pathways, while CHM mostly acted on neutrophil/macrophage-related innate pathways and dendritic cell-related adaptive immunity pathways. Our study demonstrated and analyzed the CHM network for AR. Core CHM for AR and possible molecular pathways were presented as well, and this information is crucial for researchers to select candidates for CHM-related studies.


Public sector physiotherapists believe that staff supervision should be broad ranging, individualised, structured, and based on needs and goals: a qualitative study.
What do physiotherapists consider to be the structure and content of an effective clinical supervision program for public sector staff? Qualitative study using emergent-systematic focus group design. 46 physiotherapists and six physiotherapy assistants from a large, regional, Australian health service participated in one of seven focus groups. Data were represented by three major categories: the content of supervision; the structure of supervision; and participants' roles and attributes. The content of supervision should encompass all issues affecting workplace experience and performance; supervision should be individualised and needs based. For the structure of supervision, a variety of methods and formats should be available, including: scheduled and unscheduled supervision (unscheduled supervision addresses needs as they arise but its usefulness can be restricted by supervisor availability); the environment should be organised to facilitate supervision; supervision should be integrated into existing practices; and supervision should be adequately prioritised and resourced to enable sustainability. In relation to participants' roles and attributes, respondents recommended: clearly defined supervisor and supervisee roles, responsibilities, skills and attributes are required to facilitate a constructive relationship on which successful supervision depends; the supervisee should take primary responsibility for leading and organising their supervision; the supervisor provides support and accountability and assists with goal setting and attainment; and successful supervision requires considerable knowledge and skills from the supervisee and supervisor (supervision education and training might be necessary). The physiotherapists' perspectives that were identified in this study are important to consider when assessing current clinical supervision models, as well as when designing and implementing effective physiotherapy supervision programs.


Expression of the energy substrate transporters in uterine fibroids.
Proliferating cells exhibit accelerated rates of substrate utilization, favoring glucose over fatty acids (FA's) oxidation. Protein-mediated transport is thought to play a predominant role in facilitating either glucose or FA routing into the cells. In the present study, we examined the expression of glucose transporters (GLUT-1, GLUT-4) and fatty acids transporters (FAT/CD36, FATP-1, FATP-4) at transcript and protein levels as well as cytosolic fatty acid binding proteins (H-FABP, ACBP) in human fibroids (n=74, size up to 3cm diameter) and compared with pair-matched healthy myometrium. Additionally lipid content (diacylglycerols, triacylglycerols and ceramide) was estimated by gas liquid chromatography (GLC). Uterine fibroids displayed decreased expression of both FAT/CD36 and FATP-1 proteins along with lower diacylglycerol (DAG) and triacylglycerol (TAG) content as compared to healthy pair-matched myometrium. The expression of glucose transport proteins (GLUT-4 and GLUT-1) remained relatively constant, although the higher expression of GLUT-1 in uterine fibroids did not reach the minimum significance threshold (p=0.056). However, no change in either cytochrome c oxidase (COX IV) or hydroxyacyl-CoA dehydrogenase (HADHSC) was observed and these data confirm a possible metabolic shift favoring glucose utilization over fatty acid oxidation in human uterine fibroids.


Expanding and engineering the genetic code in a single expression experiment.
Expanding and engineering the code simultaneously: This concept was experimentally realized in a single in vivo expression experiment whereby residue-specific, sense codon reassignments Met→Nle/Pro→(4S-F)Pro (code engineering) were combined with position-specific STOP→Bpa read-through by an amber suppressor tRNA (code expansion).


Effects of leaf age, nitrogen nutrition and photon flux density on the distribution of nitrogen among leaves of a vine (Ipomoea tricolor Cav.) grown horizontally to avoid mutual shading of leaves.
Effects of leaf age, nitrogen nutrition and photon flux density (PFD) on the distribution of nitrogen among leaves were investigated in a vine, Ipomoea tricolor Cav., which had been grown horizontally so as to avoid mutual shading of leaves. The nitrogen content was highest in newly developed young leaves and decreased with age of leaves in plants grown at low nitrate concentrations and with all leaves exposed to full sunlight. Thus, a distinct gradient of leaf nitrogen content was formed along the gradient of leaf age. However, no gradient of leaf nitrogen content was formed in plants grown at a high nitrate concentration. Effects of PFD on the distribution of nitrogen were examined by shading leaves in a manner that simulated changes in the light gradient of an erect herbaceous canopy (i.e., where old leaves were placed under increasingly darker conditions with growth of the canopy). This canopy-type shading steepened the gradient of leaf nitrogen content in plants grown at a low nitrogen supply, and created a gradient in plants grown at high concentrations of nitrate. The steeper the gradient of PFD, the larger the gradient of leaf nitrogen that was formed. When the gradient of shading was inverted, that is, younger leaves were subjected to increasingly heavier shade, while keeping the oldest leaves exposed to full sunlight, an inverted gradient of leaf nitrogen content was formed at high nitrate concentrations. The gradient of leaf nitrogen content generated either by advance of leaf age at low nitrogen availability, or by canopy-type shading, was comparable to those reported for the canopies of erect herbaceous plants. It is concluded that both leaf age and PFD have potential to cause the non-uniform distribution of leaf nitrogen. It is also shown that the contribution of leaf age increases with the decrease in nitrogen nutrition level.


Multiple Bowen's disease on the finger associated with human papillomavirus type 34.
Human papillomavirus (HPV) infection has been suggested as a potential risk factor for Bowen's disease. Here, we report a case of a 40-year-old man with Bowen's disease on the finger showing a discontinuous skip lesion, in which HPV-34 was detected. Our case is a reminder that the possibility of multiple lesions must be considered when Bowen's disease occurs on the finger.


Fear and overprotection in Australian residential aged-care facilities: The inadvertent impact of regulation on quality continence care.
Most residents in residential aged-care facilities are incontinent. This study explored how continence care was provided in residential aged-care facilities, and describes a subset of data about staffs' beliefs and experiences of the quality framework and the funding model on residents' continence care. Using grounded theory methodology, 18 residential aged-care staff members were interviewed and 88 hours of field observations conducted in two facilities. Data were analysed using a combination of inductive and deductive analytic procedures. Staffs' beliefs and experiences about the requirements of the quality framework and the funding model fostered a climate of fear and risk adversity that had multiple unintended effects on residents' continence care, incentivising dependence on continence management, and equating effective continence care with effective pad use. There is a need to rethink the quality of continence care and its measurement in Australian residential aged-care facilities.


Three-dimensional dentoskeletal effects of the Angelalign A6 clear aligners in a skeletal Class II growing patient: A case report.
This case report illustrates the successful nonsurgical and nonextraction treatment of a 12-year-old boy with skeletal Class II deep bite malocclusion undergoing two-phase clear aligner treatment. During A6 mandibular advancement phase, Class II buccal segment relationship was corrected by differential forward growth of the mandible, unplanned distalization of maxillary posterior teeth, and unplanned mesialization of mandibular posterior teeth. The maxillary sagittal curve of occlusion was deepened, the mandibular curve of Spee was not fully levelled, and the maxillary arch experienced downward-backward rotation resulting in premature contact on anterior and posterior open bite. Buccal crown tipping of maxillary posterior teeth was observed after arch expansion. The forward growth of the mandible improved the skeletal relationship, and the advancement of the chin position and sagittal movements of the incisors altered the nose-lip-chin relationship, resulting in an improved profile of the patient. During refinement phase, the posterior open bite was corrected. The mandibular plane angle did not increase throughout the treatment. The patient was satisfied with the aesthetic and functional outcome.


Correction: The Cotton WRKY Gene GhWRKY41 Positively Regulates Salt and Drought Stress Tolerance in Transgenic Nicotiana benthamiana.
[This corrects the article DOI: 10.1371/journal.pone.0143022.].


Clinical teaching and clinical outcomes: teaching capability and its association with patient outcomes.
There is little research on the impact of medical education on patient outcome. We studied whether teaching capability is associated with altered short-term patient outcomes. We performed a multicentre retrospective cross-sectional study involving 40 clinician teachers who had attended on the general internal medicine services in hospitals affiliated with the University of Toronto along with the clinical outcomes of consecutive patients treated for community-acquired pneumonia, congestive heart failure, chronic obstructive pulmonary disease and gastrointestinal bleeding (n = 4377) between 1999 and 2001. Doctors were characterised by teaching effectiveness scores (n = 677) as high-rated or low-rated according to house staff ratings. There was no correlation between the teaching effectiveness scores and the mean length of stay for those patients treated for community-acquired pneumonia (high-rated = 10.3 versus low-rated = 8.1 days, P = 0.058), congestive heart failure (high-rated = 10.1 versus low-rated = 9.9 days, P = 0.978), chronic obstructive pulmonary disease (high-rated = 9.4 versus low-rated = 9.9 days, P = 0.419) and gastrointestinal bleeding (high-rated = 6.3 versus low-rated = 6.8 days, P = 0.741). In addition, we observed no significant correlation between teaching effectiveness scores and 7-day, 28-day and 1-year readmission rates for all pre-specified diagnoses. There is no large correlation between teaching effectiveness scores and short-term patient outcomes, suggesting that doctor teaching capabilities, as perceived by house staff, does not generally impact clinical care.


Conjunctival melanocytic lesions in children.
Seventy-one conjunctival melanocytic proliferations in patients 20 years of age or younger were examined. Sixty-five (91.5%) were nevi; there were three cases (4.2%) of racial or acquired melanosis, and three patients were identified who had malignant melanoma of the conjunctiva. The melanoma patients are presented in detail, and additional cases of conjunctival melanoma in children and adolescents reported in the literature are reviewed to determine factors that might influence prognosis. The number of cases is so small, however, that factors cannot be identified with confidence. Follow-up data are presented. Conjunctival nevi are relatively common in children, and appear to carry no risk for the development of melanoma during childhood. However, -conjunctival melanomas do occur rarely in children and have a variable prognosis.


Evidence regarding the hypothesis that the histidine-histidine contact pairs may affect protein stability.
It has been lately proposed that the interaction between like-charged residues stabilizes the native state of proteins. To explore this, we created a histidine-histidine pair in the Ca-III binding site of the Bacillus amyloliquefaciens α-amylase (BAA) and then examined the impact of this pairing on the BAA. For this purpose, we used site-directed mutagenesis (SDM) to substitute Pro407 with His, Ala, Gln, Arg, and Glu in the BAA. Subsequently, thermostability, kinetic parameters and structural properties of these variants were measured. Moreover, His-His pairing effect on the BAA thermostability was examined by simultaneous mutation of two residues (P407H/H406A and P407H/H406N). The data exhibited a significant improve in thermostability and structural features of enzyme by His replacement instead of Pro407. Other substitutions in this site did not have a significant effect on the enzyme properties, except for P407R, which yielded a partial improvement. The results also showed that the thermostabilities of double mutants significantly decreased compared with that of the P407H mutant. Moreover, the thermostability of P407H remarkably increased compared with that of other variants even in the absence of Ca(2+). Our data clearly demonstrated that His406-His407 pairing was the major cause for improved thermal stability.


Pemphigoid in children.
Pemphigoid is an autoimmune blistering disease that is rare in childhood. A review of the English, German, and French literature published prior to 1989 revealed 31 cases of juvenile bullous pemphigoid and 12 of other forms (10 cases of juvenile cicatricial and 2 of juvenile localized bullous pemphigoid). Childhood pemphigoid, although less frequent, seems no different than its adult counterpart. While oral lesions are more common in the juvenile bullous form, there is no association with malignancy, which is a controversial and presumably incorrectly assumed association in the adult disease. The prognosis for children is good in most cases, and the disease is self-limiting. The mainstay of therapy has been oral corticosteroids, but dapsone also often produces a good response. A relatively new approach is to give a combination of erythromycin and niacinamide with dapsone for a steroid-sparing effect. In some patients the response to erythromycin plus niacinamide alone has been satisfactory; however, controlled therapeutic trials are lacking. It has been stated that high doses of steroids and immunosuppressive drugs are indicated for the cicatricial, as opposed to juvenile, bullous pemphigoid. From this review of the few cases of childhood cicatricial disease, it seems that the therapeutic approach might be the same for both forms.


Analyzing the sources and nature of influence: how the Avahan program used evidence to influence HIV/AIDS prevention policy in India.
Major investments by development partners in low- and middle-income countries (LMICs) often seek to develop a supportive policy environment. There is limited knowledge about the mechanisms that development partners use to influence government policy, or which mechanisms are effective. This study assessed the influence of Avahan, a large HIV/AIDS prevention program in India supported by the Bill and Melinda Gates Foundation, on the development of HIV/AIDS policies in India, particularly the National AIDS Control Program III (NACP III). A retrospective assessment of the contributions of Avahan to the development of NACP III was conducted based upon document review and in-depth interviews with key informants, including Avahan staff and staff of implementing partners. This assessment was carried out within a framework centered on three domains: evidence considered by policy and decision-makers; the channel through which influence is exerted; and the target audience for influence. Respondents identified a number of respects in which Avahan influenced NACP III policy, notably, Avahan influenced perception of the feasibility of scaling up services (through a demonstration effect) and Avahan, along with others, helped ensure a strong focus on targeted interventions. Overall Avahan's influence was greatest during policy implementation. While the extent to which research evidence generated by Avahan influenced NACP III was limited, best practice evidence generated by Avahan, including the lessons learned from routine implementation and management, contributed significantly to NACP III. This was largely due to the credibility Avahan had established and strategic 'inside track' communications. While studies of knowledge translation typically focus primarily on scientific evidence, this study suggests that other forms of evidence, notably best practice evidence derived from program experience, and disseminated through personal communication, were particularly influential. The framework developed for the paper provides a useful tool to analyze how evidence-based influence is exerted.


Biochemical activity of soil contaminated with BPS, bioaugmented with a mould fungi consortium and a bacteria consortium.
This study analysed the scale of bisphenol S (BPS) toxicity to the soil biochemical activity and is part of a wider effort to find solutions to restore the global soil environment balance, including elimination of the effects of ecosystem pollution with BPA, of which BPS is a significant analogue. However, since there has been no research on the effect of BPS on soil health, the objective of the study was pursued based on increasing the levels of soil contamination with the bisphenol 0, 5, 50 and 500 mg BPS kg-1 DM of soil and by observing the response of seven soil enzymes: dehydrogenases, catalase, urease, acid phosphatase, alkaline phosphatase, arylsulphatase and β-glucosidase to the growing BPS pressure. The potential negative effect of bisphenol S was offset by bioaugmentation with a bacteria consortium-Pseudomonas umsongensis, Bacillus mycoides, Bacillus weihenstephanensis and Bacillus subtilis-and a fungi consortium Mucor circinelloides, Penicillium daleae, Penicillium chrysogenum and Aspergillus niger. BPS was found to be a significant inhibitor of the soil enzymatic activity and, in consequence, its fertility. Dehydrogenases and acid phosphatase proved to be the most susceptible to BPS pressure. Bioaugmentation with a bacteria consortium offset the negative effect of 500 mg BPS kg-1 DM of soil by inducing an increase in the activity of acid phosphatase and alkaline phosphatase, whereas the fungi consortium stimulated the activity of β-glucosidase and acid phosphatase. A spectacular dimension of bisphenol S inhibition corresponded with both the spring rape above-ground parts and root development disorders and the content of Ca and K in them. The BPS level in soil on day 5 of the experiment decreased by 61% and by another 19% on day 60.


Formation of extracellular matrix in normal rat liver: lipocytes as a major source of proteoglycan.
Proteoglycans are a major component of the normal hepatic extracellular matrix and undergo quantitative and qualitative changes in hepatic fibrosis. The cellular sources of proteoglycans are as yet incompletely defined. We examined this question using primary cultures of hepatocytes and lipocytes isolated from normal rat liver. Proteoglycan synthesis was assessed by measuring production of sulfated glycosaminoglycan, the polysaccharide moiety of proteoglycans. The findings indicate that lipocytes produce sixfold more glycosaminoglycan, per cell, than do hepatocytes. Two-thirds of the newly synthesized material is cell- or matrix-associated. Of the individual glycosaminoglycan species produced by lipocytes, dermatan sulfate represents 60% of the total; heparan sulfate and chondroitin sulfate are measurable but relatively minor. In hepatocyte cultures, heparan sulfate accounted for essentially all of the glycosaminoglycan detected. We conclude that lipocytes are an important source of proteoglycan in normal liver and may be the principal source of dermatan sulfate associated with hepatic fibrosis.


Renal replantation (orthotopic autotransplantation) for echinococcosis of the kidney.
Ex vivo surgery with replantation of the kidney into the renal fossa was used to treat a centrally located renal hydatid cyst in a 44-year-old patient. The replanted kidney showed good urographic function 2 months postoperatively. Orthotopic replantation of the kidney into its original location is preferred to heterotopic autotransplantation into the groin.


Droplet motion driven by surface freezing or melting: a mesoscopic hydrodynamic approach.
A fluid droplet may exhibit self-propelled motion by modifying the wetting properties of the substrate. We propose a model for droplet propagation upon a terraced landscape of ordered layers formed as a result of surface freezing driven by the contact angle dependence on the terrace thickness. Simultaneous melting or freezing of the terrace edge results in a joint droplet-terrace motion. The model is tested numerically and compared to experimental observations on long-chain alkane systems in the vicinity of the surface melting point.


Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 2.
Modification of the C-2 position of a benzofuran derivative 6 (RO-09-4609), an N-myristoyltransferase (Nmt) inhibitor, has led us to discover antifungal agents that are active in a murine systemic candidiasis model. The drug design is based on the analysis of a crystal structure of a Candida Nmt complex with 2. The optimization has been guided by various biological evaluations including a quasi in vivo assay and pharmacokinetic analysis.


Triiodothyronine-dietary interrelationships in the modulation of brown adipose tissue and liver lipogenesis in the rat.
The influence of diet and triiodothyronine on "in vivo" lipogenesis has been compared in liver and brown adipose tissue of the rat at weaning and in adult life. At both ages studied, hyperthyroidism increases lipogenesis only in the liver. However brown adipose tissue accumulates lipid (probably derived from white adipose tissue) thus helping to explain previous observations of low rates of lipogenesis in this tissue during the late suckling period when thermogenesis is high and plasma triiodothyronine levels rise. Suppression of lipogenesis by dietary polyunsaturated fat in both tissues at both ages studied confirms previous studies on adult animals. Malic enzyme and glucose-6-phosphate dehydrogenase activities correlate well with changes in lipogenesis in brown adipose tissue but not in liver and the hepatic enzymes exhibit a diminished response to dietary and hormonal factors with age.


Quality and standardization in blood component preparation with an automated blood processing technique.
The use of automated blood processors in combination with bottom and top blood containers has been found to improve the standardization and quality of blood components. A study was performed to validate a new type of processor (Optipress II) and compare its performance with a first generation processor (Optipress I). Primary separation on the Optipress II was investigated on 570 mL (+/- 10%) of anticoagulated blood in a nonpaired study. In addition, the quality of the products in routine production was compared between the results of the Optipress I and Optipress II. The whole blood units were kept overnight at room temperature (20 +/- 2 degrees C). Separation was performed under conditions to obtain 55 mL buffy coats with a 50% haematocrit (ht). Platelet concentrate preparation was investigated in a paired study and compared to the routine manual method using PAS II additive solution. Parameters studied were volume, red cell, white cell and platelet counts, ht, haemoglobin (hb, total and free). Primary separation was more efficient in the Optipress II because the platelet count was lower in the erythrocyte concentrates (P < 0.0001), platelets were lower in plasma (P < 0.0001) and platelet counts were higher in buffy coats (P < 0.0001). Buffy coat volume showed less variation (Optipress II VC = 4%, Optipress I VC = 7.4%). Secondary separation did not show differences between the Optipress II and manual method but was advantageous because of the automatic termination of the procedure. Further improvement of standardization in blood component preparation is possible with an automated blood processor, leading to improvement of the quality of blood products for patient care.