An investigation of classical swine fever virus seroprevalence and risk factors in pigs in Timor-Leste.
Classical swine fever virus (CSFV) is a highly infectious pathogen of pigs and believed to be a major constraint to pig production in Timor-Leste. The Ministry of Agriculture and Fisheries conducts vaccination campaigns in an attempt to control clinical disease, however, there is no empirical data available concerning the seroprevalence and distribution of CSFV in Timor-Leste. To help address this knowledge deficit, a cross-sectional study to determine seroprevalence was conducted in the three districts that border Indonesia. Data on farmer- and pig-level factors were also collected to look at their impact on CSFV serological status. Overall, true CSFV seroprevalence was estimated at 34.4%. Seroprevalence estimates varied widely between and within districts, subdistricts, and villages. Older pigs and pigs that had been vaccinated for CSFV were more likely to test positive for CSFV antibody. Pigs owned by farmers that experienced the sudden death of pigs in the 12 months prior to the survey were more likely to test positive for CSFV antibody, while pigs that had been sick in the previous three months were less likely to test positive for CSFV antibody. The final multivariable model accounted for a large amount of variation in the data, however, much of this variation was explained by the random effects with less than one percent of the variation explained by the fixed effects. This work further supports the need for a collaborative approach to whole-island CSFV control between West Timor, Indonesia and Timor-Leste. Further work is needed to better understand the risk factors for CSFV serological status in order to allocate resources for control. As CSFV is now endemic in Timor-Leste research involving a combination of serology, antigen detection and in-depth investigation of suspect cases over a period of time may be required.


Pyruvate production in Candida glabrata: manipulation and optimization of physiological function.
Candida glabrata, a multi-vitamin auxotrophic yeast, can accumulate a large amount of pyruvate extracellularly using glucose as the carbon source, a characteristic that has facilitated the cost-effective biotechnological production of pyruvate on an industrial scale. In this review, we describe the current advances in further improving the performance of C. glabrata for efficient pyruvate production, which includes: optimization of the vitamin and dissolved oxygen concentrations, regulation of intracellular cofactor levels and improvement of the environmental robustness of C. glabrata. We also discuss the current efforts using systems biology to understand the metabolism of C. glabrata. Finally, perspectives on engineering and exploiting C. glabrata as a cell factory for efficiently producing various chemicals and materials are discussed.


Geoacoustic inversion with generalized additive models.
Geoacoustic parameter estimation is presented as a non-linear regression problem where prediction is performed using generalized additive models applied to features extracted from broadband acoustic time-series in a machine learning framework. Qualitatively, it can be seen that signals that have propagated in different environments have distinct structures: in some cases, a single mode is identified, in others, multiple modes can be seen; signals can also be distinguished by different energy levels. Features that are employed here comprise relative amplitudes of distinct peaks in the signals, signal kurtosis, signal strength, decay of the time-series with time, and time difference between distinct peaks of the received signals. Functions are sought that relate sediment sound speed and attenuation to these features. A multivariate generalized additive model is proposed using smoothing splines for the nonlinear regression problem of predicting geoacoustic properties using the features. The spline functions are estimated using noise-free training patterns from known environments. After this training step, the geoacoustic properties are predicted in an efficient manner using noisy testing patterns from a variety of different areas.


Raspail, racism, and migration: Implications for radicalization in a polarizing world.
Jean Raspail's controversial 1973 novel The camp of the saints predicts mass migration to Europe that will destroy European civilization. Decades later, the book has accurately predicted the hundreds of thousands of refugees arriving in Europe annually, prompting a continent-wide crisis. From Lesbos and Lampedusa to the Canary Islands and Calais, no one seems to know how to stem the flow of humanity. Borders are being resurrected, despite Schengen and European Union (EU) agreements, in an effort to control the movement of populations. European governments disagree on how to proceed and some are suggesting that the EU could be torn apart by differing approaches to the problem. But does this have to be the response to the migration crisis? This paper compares the predictions of The camp of the saints to events in Europe today and critiques the book's conclusions with regard to what is an ancient phenomenon: movements of migrants from surplus to deficit labor settings. The paper will also evaluate the response to migrants in the United States under its populist president, Donald Trump, and will review related issues in other parts of the world: Turkey, Russia, and Canada. Contrary to Raspail's predictions, world leaders will need to accept what has already become a de facto reality: large scale admission of migrants and refugees to the EU and North America, as full citizens, will be the only realistic way to preserve prosperity in the years to come.


A systematic review of preclinical studies on therapeutic potential of stem cells or stem cells products in peritoneal fibrosis.
Peritoneal fibrosis remains a serious complication of long-term peritoneal dialysis. Stem cell therapy is an innovative field of scientific investigation with potential for clinical application. Here, we systematically reviewed the studies to determine whether stem cell based therapy could improve the peritoneal fibrosis in experimental models of peritoneal fibrosis. Our systematic search of PubMed, Scopus, Web of Science, and Cochrane Library yield 5219 article. After screening for eligibility, in vivo, experimental, interventional studies using stem cells in animal models of peritoneal fibrosis; 11 articles were included. The studies underwent comprehensive review, quality assessment, and data extraction. Mesenchymal stem cells were the most used type (90.9%) originated either from bone marrow (70%), adipose tissue (20%), or umbilical cord (10%). In 90.9% of studies, stem cells were injected after peritoneal insult and 63.6% of studies used the intraperitoneal injection route. Eight studies met the ≥50% of criteria indicated by ARRIVE recommendation. Information regarding the nature of ethical review permissions, species, strain and gender, dose, route and duration of treatment, was stated by all studies; 81.8% of the studies reported the number of animals in each group. Adverse events were reported in one study. Improvement in histological parameters including attenuation of submesothelial thickness (100%), inflammation (62.5%), angiogenesis (60%), and fibrosis (85.7%) was reported after stem cell therapy. Peritoneal permeability function by assessing the ultrafiltration, glucose transport and solute permeability was improved in all studies. Stem cell treatment resulted in mesothelial recovery in 100% of studies. In preclinical studies, the use of stem cells is associated with improved peritoneal fibrosis. This may provide an important foundation to support future translational clinical research using stem cell therapy to repair the injured peritoneum and modulate immune responses in PD patients.


Painful piezogenic pedal papules: response to local electro-acupuncture.
We report the case of a woman who had pain in both heels which was exacerbated by long periods of exercise. On examination, there were small flesh-coloured papules which appeared over the medial and lateral aspects of the heels only on weight bearing. Coincidentally, she was noted to have larger flesh-coloured papules over the anterior surface of the shins. The diagnoses of painful piezogenic pedal papules and bilateral tibialis anterior muscle herniation, respectively, were made. After many attempts to control the pain, a course of electro-acupuncture was commenced. A good subjective clinical response was achieved which has been maintained by fortnightly treatments. We discuss the prevalence, pathogenesis and treatment of painful piezogenic pedal papules. We believe that our patient is the first to have 'herniations' at both heel and shin sites and the first to have successful sustained pain relief for painful piezogenic pedal papules.


Residua of thoracic trauma.
While most residua of thoracic trauma are obvious, tracheal stenosis, aneurysm of the aortic arch and diaphragmatic hernia are easily overlooked. They may be asymptomatic and may go undetected until the occurrence of life-threatening consequences. Therefore, these three conditions must be thought of and ruled out during the management and follow-up observation of all patients who have trauma to the chest. Surgeons participating in the management of thoracic trauma must anticipate, prevent when possible, diagnose early and treat any of the residua that can, and often do, result.


Oxidation chemistry of acid-volatile sulfide during analysis.
The susceptibility of some components of sediment acid-volatile sulfide (AVS) to chemical oxidation is a critical factor impacting accurate measurement of AVS in sediment samples. This well-documented susceptibility to oxidation led to the requirement for oxygen-free conditions in the analytical method developed for AVS. In light of this acute potential to oxidize, the serendipitous finding that air can be used in the analysis of sediment AVS is counterintuitive and unexpected. To demonstrate and investigate this interesting observation, extraction experiments were performed using aqueous and solid-phase sulfide species. Experiments using air as the carrier gas showed a mean percentage recovery of sulfide matching that of traditional (nitrogen gas) analysis (i.e., >91%) and a time to completion of less than 30 min for aqueous sulfide and less than 60 min for sediment samples. These results are consistent with those of sulfide oxidation studies reported in the literature. Using air as the analytical carrier gas can provide an interesting alternative for developing an analytical method to determine AVS parameters in the field.


An Intensive Multidisciplinary Approach in Management of Extensive Nonuremic Calciphylaxis of the Bilateral Lower Extremities with Angioinvasive Fungus and Mold.
Management of infected wounds related to calciphylaxis poses a significant clinical challenge with high morbidity and mortality. Given no definitive management guidelines exist specific to nonuremic calciphylaxis, multiple modalities including sodium thiosulfate, antibiotics, hyperbaric oxygen therapy, and surgical debridement with wound care must be considered. When occurring over a large surface area, standard daily dressing changes are especially labor intensive, inefficient, and ineffective. Negative pressure wound therapy with instillation and dwell time offers broad wound coverage with ongoing therapeutic benefit. We present the case of a previously healthy 19-year-old woman who was transferred for tertiary level care of extensive nonuremic calciphylaxis wounds of the bilateral lower extremities complicated by angioinvasive coinfection with fungus and mold that was managed with a multidisciplinary approach of intensive medical management, aggressive surgical debridement, and negative pressure wound therapy with instillation of hypochlorous acid solution. Ultimately, she achieved full granulation and wound coverage with skin grafting. Large area, infected wounds related to nonuremic calciphylaxis can be successfully managed with multidisciplinary medical management, aggressive surgical debridement, and negative pressure wound therapy that can instill and dwell hypochlorous acid solution.


Factors influencing transfection efficiency of pIDUA/nanoemulsion complexes in a mucopolysaccharidosis type I murine model.
Mucopolysaccharidosis type I (MPS I) is an autosomal disease caused by alpha-l-iduronidase (IDUA) deficiency. This study used IDUA knockout mice as a model to evaluate whether parameters such as dose of plasmid and time of treatment could influence the transfection efficiency of complexes formed with PEGylated cationic nanoemulsions and plasmid (pIDUA), which contains the gene that encodes for IDUA. Formulations were composed of medium chain triglycerides, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(amino[polyethylene glycol]-2000), 1,2-dioleoyl-sn-glycero-3-trimethylammonium propane (DOTAP), glycerol, and water and were prepared by the adsorption or encapsulation of preformed pIDUA-DOTAP complexes by high-pressure homogenization. A progressive increase in IDUA expression was observed with an increase in the dose and time of transfection for mice treated with both complexes (adsorbed and encapsulated), especially in the liver. Regardless of the complex administered, a significant increase in IDUA activity was detected in lungs and liver compared with nontreated MPS I when a dose of 60 μg was administered and IDUA activity was measured 7 days postadministration. Tissue sections of major organs showed no presence of cell necrosis, inflammatory infiltrate, or an increase in apoptosis. Furthermore, immunohistochemistry for CD68 showed no difference in the number of macrophage cells in treated and nontreated animals, indicating the absence of inflammatory reaction caused by the treatment. The data set obtained in this study allowed establishing that factors such as dose and time can influence transfection efficiency in different degrees and that these complexes did not lead to any lethal effect in the MPS I murine model used.


A robust microfluidic device for the synthesis and crystal growth of organometallic polymers with highly organized structures.
A simple and robust microfluidic device was developed to synthesize organometallic polymers with highly organized structures. The device is compatible with organic solvents. Reactants are loaded into pairs of reservoirs connected by a 15 cm long microchannel prefilled with solvents, thus allowing long-term counter diffusion for self-assembly of organometallic polymers. The process can be monitored, and the resulting crystalline polymers are harvested without damage. The device was used to synthesize three insoluble silver acetylides as single crystals of X-ray diffraction quality. Importantly, for the first time, the single-crystal structure of silver phenylacetylide was determined. The reported approach may have wide applications, such as crystallization of membrane proteins, synthesis and crystal growth of organic, inorganic, and polymeric coordination compounds, whose single crystals cannot be obtained using traditional methods.


Quantification of Protein-Lipid Selectivity using FRET: Application to the M13 Major Coat Protein.
Quantification of lipid selectivity by membrane proteins has been previously addressed mainly from electron spin resonance studies. We present here a new methodology for quantification of protein-lipid selectivity based on fluorescence resonance energy transfer. A mutant of M13 major coat protein was labeled with 7-diethylamino-3((4'iodoacetyl)amino)phenyl-4-methylcoumarin to be used as the donor in energy transfer studies. Phospholipids labeled with N-(7-nitro-2-1,3-benzoxadiazol-4-yl) were selected as the acceptors. The dependence of protein-lipid selectivity on both hydrophobic mismatch and headgroup family was determined. M13 major coat protein exhibited larger selectivity toward phospholipids which allow for a better hydrophobic matching. Increased selectivity was also observed for anionic phospholipids and the relative association constants agreed with the ones already presented in the literature and obtained through electron spin resonance studies. This result led us to conclude that fluorescence resonance energy transfer is a promising methodology in protein-lipid selectivity studies.


Neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of prospective studies.
There is a strong rationale and many theoretical advantages for neoadjuvant therapy in pancreatic cancer (PC). However, study results have varied significantly. In this study, a systematic review and meta-analysis of prospective studies were performed in order to evaluate safety and effectiveness of neoadjuvant therapy in PC. Thirty-nine studies were selected (n = 1458 patients), with 14 studies focusing on patients with resectable disease (group 1), and 19 studies focusing on patients with borderline resectable and locally advanced disease (group 2). Neoadjuvant chemotherapy was administered in 97.4% of the studies, in which 76.9% was given radiotherapy and 74.4% administered with chemoradiation. The complete and partial response rate was 3.8% and 20.9%. The incidence of grade 3/4 toxicity was 11.3%. The overall resection rate after neoadjuvant therapy was 57.7% (group 1: 73.0%, group 2: 40.2%). The R0 resection rate was 84.2% (group 1: 88.2%, group 2: 79.4%). The overall survival for all patients was 16.79 months (resected 24.24, unresected 9.81; group 1: 17.76, group 2: 16.20). Our results demonstrate that neoadjuvant therapy has not been proven to be beneficial and should be considered with caution in patients with resectable PC. Patients with borderline resectable or locally advanced disease may benefit from neoadjuvant therapy, but further research is needed.


Understanding the caregiving experiences of Asian Indian, Chinese, Korean, and Vietnamese American family care partners of persons living with dementia.
Disparities impacting dementia health care exist in racial/ethnic minority groups, including Asian Americans, an understudied population in Alzheimer's disease and related dementias. The qualitative study explored caregiving experiences and potential cultural influences among Asian Indian, Chinese, Korean, and Vietnamese family care partners of persons living with dementia. We conducted focus groups and individual interviews with 32 care partners from these four Asian subgroups using Zoom, WeChat, or telephone. Four themes emerged from the data: (1) Family obligations influencing caregiving decisions; (2) Evolving challenges related to dementia caregiving; (3) Caregiving burdens/negative impacts from caregiving (relationship burdens and emotional distress); and (4) Coping with their situation in their own ways (cognitive, behavioral, and social strategies).Conclusion: Cultural values (e.g. familism or filial piety) played a significant role in caregiving decisions and experiences. There was a need to raise public awareness of dementia and create culturally and linguistically appropriate training programs for this population.


Management of hepatitis B reactivation in lymphoma patients on rituximab with past hepatitis B exposure: An observational study.
Currently, a standardized approach to prevent and manage hepatitis B reactivation in lymphoma patients with past hepatitis exposure receiving rituximab in Singapore is lacking. This study is designed to report the current management approach and outcomes associated with hepatitis B reactivation. The primary objective was to report 6-, 12-, 24-month cumulative hepatitis B reactivation-related outcomes. Secondary objectives were to report monitoring frequencies of hepatitis B DNA and liver function tests performed in lymphoma patients with resolved hepatitis B receiving rituximab, and anti-viral prophylaxis use. This was a single centre, retrospective observational study. Patients with resolved hepatitis B initiated on rituximab from January 2011 to December 2015 were identified and reviewed over a two-year period starting from the date of rituximab initiation. Relevant parameters were obtained from electronic medical records. Hepatitis B reactivation was defined by hepatitis B DNA levels 20 IU/ml (1.30 log/ml) and above. Data were analysed using descriptive statistics. Seventy-five patients were retrospectively reviewed over a two-year period. Hepatitis B reactivation was defined as hepatitis B DNA levels ≥20 IU/ml (1.30 log/ml). The 24-month cumulative hepatitis B reactivation rate was 4.0%. The median (interquartile range) number of hepatitis B DNA tests performed during treatment, initial six-month follow-up, and subsequent follow-up were 1.0 (0.0-2.6), 1.0 (0.0-2.0), and 1.0 (0.0-3.1), respectively. Large variations in hepatitis B reactivation monitoring and management strategies were observed. Further studies are required to develop and determine a standardised protocol that could contribute to safer and more cost-effective care for lymphoma patients with resolved hepatitis B on rituximab.


[Urethral duplication in a male child. Accessory urethra with a normotopic opening in a penopubic epispadias with dorsal penis deviation].
Urethral duplication is a rare deformity which can present in various forms, commonly together with other congenital malformations. The embryological genesis is unknown. The isolated deformity is most often found in young males, while for young females it is very rare. We report the case of a 1.5 year old male child having a duplicate urethra with penopubic epispadias and dorsal penis deviation. The child, with known penopubic epispadias grade II and dorsal penis deviation, presented for pediatric urological consultation involving additional diagnostics and therapy. Examination revealed a penopubic epispadias with an external urethral exit at the base of the penis. A preoperative micturating cystogram led to the diagnosis of an accessory central as well as an epispadic urethra. We then carried out urethral reconstruction with the surgical combination of both urethras into a single functioning unit. The penis deviation was corrected after Ransley in the same operation. The postoperative course and aftercare showed normal micturition with a normotopic urethral entry as well as a good urine stream without evidence of a stricture or residual urine. An duplicate urethra is an uncommon malformation which is, however, found more often in male patients. Surgery is based on the individual and must be planned dependent on the morphology present. In all cases, both functional and cosmetic aspects must be taken into account.


Anti-Neuroinflammatory Effects of Vanillin Through the Regulation of Inflammatory Factors and NF-κB Signaling in LPS-Stimulated Microglia.
Microglia, resident macrophages of the central nervous system (CNS), is responsible for immune responses and homeostasis of the CNS. Microglia plays a complex role in neuroinflammation, which has been implicated in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Therefore, therapeutic agents that suppress the microglia-mediated inflammatory response could potentially be used in the prevention or treatment of neurodegenerative diseases. Vanillin, a primary component of vanilla bean extract, has anti-inflammatory, anticancer, and antitumor properties. However, the effects of vanillin on the anti-neuroinflammatory responses of microglial cells are still poorly understood. In this study, we investigated the mechanism by which vanillin induces anti-neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We found that vanillin significantly decreased the production of nitric oxide and pro-inflammatory cytokines, including interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Vanillin also reduced the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the mRNA expression levels of IL-1β, TNF-α, and IL-6. Moreover, vanillin inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB. Collectively, these results suggest that vanillin has anti-neuroinflammatory properties and may act as a natural therapeutic agent for neuroinflammatory diseases.


What impact do students have on clinical educators and the way they practise?
The clinical education setting plays an important part in teaching students about the real world of clinical practice. Traditionally the educational relationship between student and clinical educator has been considered one-way, with students being the ones that benefit. This review focuses on the areas of clinician practice and behaviour that students are reported to influence through clinical placements and as such, determine the overall impact students can have on supervising clinicians. Electronic searches were conducted across MEDLINE, EMBASE, PsychINFO and CINAHL in July 2016. Retrieved articles were filtered to find those which presented data relating to students in the clinical setting. Data was extracted and analysed independently by two authors through thematic analysis. Twenty-eight studies met the inclusion criteria. Results showed that practitioners enjoy the act of teaching. Clinical student presence encourages clinicians to solidify their knowledge base, stimulates learning and causes them to re-evaluate their practice. Practitioner skills were further developed as a results of students. Clinical educator workload and time spent at work increased when a student was present with time management being the predominant challenge practitioners faced. Studies demonstrated that clinicians feel they benefit by students periodically becoming the teacher. Student placements in clinical practice cause an increase in practitioner workload and lengthen their work day. These perceived limitations are outweighed by the many benefits described by supervising clinicians. Providing clinical education can enrich both the practice, and the practitioner, and the aforementioned advantages should be highlighted when offering or considering the expansion of clinical placements.


Factors associated with HIV testing among male motorbike taxi drivers in urban Vietnam.
Using the Attitude-Skills-Knowledge (ASK) model, this study examined the prevalence of, and factors associated with, human immunodeficiency virus (HIV) testing among male motorbike taxi drivers (MMTDs). In a cross-sectional design, using quantitative approaches, 291 MMTDs were recruited from 135 sites across 13 districts in Hanoi, Vietnam, for a face-to-face interview. Applying the ASK model modified as a central theory, logistic regression was used to identify determinants of HIV testing. Although many MMTDs engaged in multiple risk behaviours for HIV, only 20.6% had been tested for HIV during the past 12 months. The tested model included one factor of the ASK model, HIV prevention knowledge (adjusted odds ratio [AOR] = 4.76; 95% confidence interval [CI] = 2.12-10.7) and five additional factors: being married (AOR = 3.13; 95% CI = 1.25-4.78), preferring sex with men or with both men and women (AOR = 8.72; 95% CI = 1.48-51.5), having lower number of lifetime sex partners (AOR = 0.66; 95% CI = 0.49-0.88), higher number of past year sex partners (AOR = 2.97: 95% CI = 1.21-7.31) and discussing condom use when having sex with partners (AOR = 0.08; 95% CI = 0.01-7.31). This modified ASK model provided better fit than the ASK model, as it explained more variance in HIV testing (47 vs. 29.8%). Recognising factors associated with HIV testing among MMTDs enables us to create suitable public health intervention strategies.


Methylmercury analyses in biological materials by heating vaporization atomic absorption spectrometry.
To develop an analytical method for methylmercury (MeHg) compounds in biological samples (hair, blood, fish) with reproducibly high recovery of MeHg using heating vaporization atomic absorption spectrometry, we examined the pretreatment process of biological samples such as solubilization, degreasing and solvent extraction of MeHg using the Magos method. Samples were solubilized with NaOH at 70 degrees C and degreased of fat components by chloroform and hexane. Hydrobromic acid (HBr) was used to acidify the solubilized solution to form MeHgBr with high solvent transferability. The fraction containing MeHg-L-cysteine complexes in aqueous solution, which had been reverse-extracted from the toluene layer, were determined as MeHg. Recoveries of MeHgBr were approximately equal 95% with little variation. Analytical values for standards materials for hair and fish using the present method agreed well with certified values.


Uptake of D-xylose and D-glucose by Spirochaeta aurantia.
Uptake of D-[14C]glucose and D-[14C]xylose by Spirochaeta aurantia was demonstrated to be osmotic shock sensitive and to require a high-energy phosphorylated compound rather than a proton motive force. These features are similar to those of binding protein-mediated transport systems in other gram-negative bacteria.


Non-core region modulates interleukin-11 signaling activity: generation of agonist and antagonist variants.
Human interleukin-11 (hIL-11) is a pleiotropic cytokine administered to patients with low platelet counts. From a structural point of view hIL-11 belongs to the long-helix cytokine superfamily, which is characterized by a conserved core motif consisting of four α-helices. We have investigated the region of hIL-11 that does not belong to the α-helical bundle motif, and that for the purpose of brevity we have termed "non-core region." The primary sequence of the interleukin was altered at various locations within the non-core region by introducing glycosylation sites. Functional consequences of these modifications were examined in cell-based as well as biophysical assays. Overall, the data indicated that the non-core region modulates the function of hIL-11 in two ways. First, the majority of muteins displayed enhanced cell-stimulatory properties (superagonist behavior) in a glycosylation-dependent manner, suggesting that the non-core region is biologically designed to limit the full potential of hIL-11. Second, specific modification of a predicted mini α-helix led to cytokine inactivation, demonstrating that this putative structural element belongs to site III engaging a second copy of cell-receptor gp130. These findings have unveiled new and unexpected elements modulating the biological activity of hIL-11, which may be exploited to develop more versatile medications based on this important cytokine.


Breast cancer and cancer stem cells: a mini-review.
Breast cancer is the most common type of malignant disease in women worldwide. In developing countries the past few years have sustained an increasing incidence of this type of cancer. Currently, breast cancer is the second leading cause of death due to cancer in women. In 2008 alone it was diagnosed in more than 1 million patients and each year the number of breast cancer-related deaths is estimated to be ~450,000. The mortality rate in breast cancer patients has been decreasing over the years thanks to the development of early diagnostic methods and more effective treatments. But despite the new advances in cancer diagnosis and treatment, the risk of recurrence and metastasis is ever present. It has been theorized that cancer stem cells are involved in the process of tumor growth and metastases. Due to their self-renewing and differentiation capabilities, they are now considered the underlying factor in tumor recurrence and the main reason for therapy resistance. Therefore, the characterization of cancer stem cells may contribute to the development of more effective treatment strategies that should make it possible to eliminate cancer stem cells in order to prevent tumor relapse and metastasis in diagnosed patients.


Genetic Structure of the Endemic Fiddler Crab Uca (Xeruca) formosensis on the West Coast of Taiwan.
Xeruca formosensis is the only endemic species of fiddler crab on the west coast of Taiwan. However, its natural habitats and populations have been compromised by excessive anthropogenic activities and improper land use over the past four decades. In light of these changes, we sought to evaluate the genetic diversity and gene flow of the species by examining the genetic variation of X. formosensis at different sampling locations. To this end, we performed molecular analyses of three endonuclease-amplified fragment length polymorphisms (TE-AFLP) and the cytochrome oxidase subunit I (COI) marker from leg muscle samples. We found that the genetic variation within sampling locations was higher than that among sampling locations, and the expected heterozygosity of genetic diversity (Hj) was 0.152 for TE-AFLP data. Meanwhile, the COI marker showed high haplotype diversity (h = 0.976 ± 0.008) and a low genetic differentiation level (FST = 0.021) in X. formosensis populations. Importantly, the genetic connectivity of X. formosensis may be influenced by larval-stage crabs drifting between coastal and marine habitats. As such, crab gene flow is promoted among populations by larval exchange via nearshore currents. Although X. formosensis has high gene flow, the species could undergo an extinction crisis if the population sizes continue to decline, as with most endangered species. In order to maintain the natural habitats and population size of X. formosensis, long-term monitoring and investigation will be necessary.


Dispersion and loss limitations on the performance of optical delay lines based on coupled resonant structures.
The relative importance of group-velocity dispersion and loss-induced distortion in limiting the performance of optical delay lines based on coupled resonator structures is investigated. It is shown that for the current state of the quality of fabrication both factors play roughly comparable roles for bit rates of 2.5-40 Gbits/s and that as the storage capacity grows, the relative weight of loss-imposed limitation increases.


Safety and efficacy of braided stents as stent monotherapy for the treatment of small intracranial aneurysms.
The safety and efficacy of low-profile braided stent as stent monotherapy require further investigation. To analyze patient outcomes after treatment with braided stents used as "light" flow diverters. Retrospective study to evaluate the occlusion rate of aneurysms treated with braided stent and remodeling of covered side branches and perforators. Several factors potentially influencing aneurysm occlusion were analyzed. Thirty-five aneurysms in 31 patients were included. Six aneurysms (17.1%) had an acute subarachnoid hemorrhage. Braided stent was used as retreatment among 9 previously coiled aneurysms (25.7%). A total occlusion was achieved in 18 aneurysms (51.4%), entry remnant in 3 aneurysms (8.6%), incomplete filling in 6 aneurysms (17.1%) and complete filling in 8 aneurysms (22.9%). None of the aneurysms ruptured during the follow-up period. Of 32 stents deployed, we observed 3 cases (9.4%) of asymptomatic mild stenosis and 3 cases (10.7%) of narrowing of covered branches among 28 covered arteries. There were no cases of perforator infarction and no mortality or permanent morbidity associated with the treatment. Moreover, aneurysms <2.5 mm, aneurysms with a neck <1.8 mm, those with a mean aspect-ratio of 1.4, and lateral wall aneurysms had a higher frequency of adequate occlusion. Braided stents used as stent monotherapy appear to be sufficiently effective in the treatment of very small intracranial aneurysms, despite a lower overall occlusion rate compared to a standard flow diversion strategy. However, given the low morbidity rate, this strategy may be an alternative to flow-diverter stents for small and distally located lesions.


Structure and function in rhodopsin. Measurement of the rate of metarhodopsin II decay by fluorescence spectroscopy.
An increase in fluorescence is observed upon light activation of bovine rhodopsin. The rate of increase is monoexponential (t1/2 = 15.5 min) at 20 degrees C in 0.1% lauryl maltoside, pH 6.0, and parallels the rate of decay of metarhodopsin II. We show that the increase in fluorescence is due to the release of free retinal, which no longer quenches the tryptophan fluorescence. An extrinsic fluorescence reporter group, pyrene maleimide, attached to bovine rhodopsin also shows an increase in pyrene fluorescence on illumination. The rate of increase in pyrene fluorescence matches the rate of increase in tryptophan fluorescence. This result has been used to develop a micromethod, requiring on the order of 1 microgram of rhodopsin, for measurement of metarhodopsin II decay. An Arrhenius plot derived from the fluorescence assay shows the energy of activation barrier for retinal release from rhodopsin to be 20.2 kcal/mol in 0.1% dodecyl maltoside at pH 6.0.


US legal principles and confidentiality of the peer review process.
When drawn into other parties' litigation or investigations, journals often receive requests or subpoenas for confidential peer review documents. We describe reasons for such requests and reasons that journals resist producing confidential documents, ways that journals respond, and steps that journals can take to minimize third-party breaches of journals' confidential processes. We discuss legal principles on which resistance may be based in the United States, including the journalist's privilege, the scholar's privilege, the burdensomeness of response, and the Federal Rules of Civil Procedure, which protect against attempts to obtain expert opinion testimony without compensation. Illustrative cases are described in which courts affirmed the confidentiality of peer review conducted by journals.


Understanding and optimizing the addition of phytohormones in the culture of microalgae for lipid production.
Some studies have described the use of phytohormones in microalgal culture for the production of biodiesel or selected fatty acids. However, no study has determined the amount of phytohormones that maximizes lipid yield. We determined the optimal concentration of auxins and gibberellins (which is between 40 and 60 μM) in two strains (Scenedemus abundans and Chlorella ellipsoidea) suitable for biodiesel production. More than 3-fold increment was reached with S. abundans and near 7-fold increment with C. ellipsoidea. Furthermore, this work suggests that the improved growth of the microalgae in the presence of the phytohormones was due to a reduction in the level of reactive oxygen species (ROS) in the cells. An economic analysis showed that, due to its low cost, auxin offers a positive cost-benefit balance and therefore could be used at large scale. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1203-1211, 2016.


Isolation and characterization of hepatic cancer cells with stem-like properties from hepatocellular carcinoma.
Major burdens in the treatment of hepatocellular carcinoma (HCC) are the high percentage of recurrence and resistance to chemotherapy. Hepatic cancer stem cells provide a reservoir of cells that can self-renew, maintain the tumor by generating differentiated non-stem cells which make up the bulk of the tumor and are responsible for recurrence after ablative surgery and chemoradiotherapy. The objective of this study was to identify and characterize a self-renewing subpopulation of human liver tumor cells with a distinctive genetic profile that adds the capacity to proliferate despite chemotherapy and promotes cancer recurrence. Stemness properties of tumor cells isolated from a HCC biopsy were established by their capacity to form spheroids and by cell proliferation assays. The cells also showed enhanced chemoresistance to cancer drugs. The up-regulation of stem cell markers is proven by immunocytochemistry stainings and reverse transcription-PCR. Cells had a high proliferative potential, even when cultured in medium supplemented with doxorubicin and carboplatin, eliminated Rhodamine 123 immediately in culture and also formed spheroids in suspension. Molecular diagnosis techniques showed that cells expressed the stem cell markers Oct 3/4 and CXCR4. Cells were also positive for CD133 and CD90 cancer stem cell specific markers, with monoclonal antibody staining. The unique characteristics identified in cancer stem cells explain self-renewal and could drive metastasis in patients that have received treatment for cancer. The identification and cloning of such cells can aid in developing of better therapeutic approaches for patients with HCC, as chemosensitive pretherapeutic assays or targeted therapies.


Teachers' quality of work life and attitudes toward implementing a psychosocial intervention for children affected by parental HIV/AIDS: roles of self-efficacy and burnout.
ABSTRACT Several studies have highlighted that facilitators' attitudes toward interventions are crucial for implementing innovative psychosocial interventions. However, in the emerging implementation science field, little research has examined how organizational and individual factors may influence teachers' positive attitudes and readiness toward evidence-based interventions. The current study investigated the association between teachers' quality of work life and their attitudes toward an innovative psychosocial intervention for children affected by parental HIV/AIDS; the study also probed the potential indirect roles of self-efficacy and burnout. A total of 157 teachers with different levels of involvement in the intervention study were recruited from 47 schools. Our results revealed that teachers' quality of work life was positively associated with their attitudes toward the intervention directly and indirectly through enhanced self-efficacy and reduced burnout. The findings highlight the importance of organizational and individual factors in successfully implementing innovative psychosocial interventions for vulnerable children in organizations such as schools. Researchers should work with organizations to provide the necessary quality of work life and sufficient training to semi-professionals in order to boost their self-efficacy, reduce their burnout, and improve their attitudes toward innovative intervention programs to achieve the expected effectiveness of the interventions, particularly in resource-limited regions.


New insights into the genetic basis of infertility.
Infertility is a disease of the reproductive system characterized by inability to achieve pregnancy after 12 or more months of regular unprotected sexual intercourse. A variety of factors, including ovulation defects, spermatogenic failure, parental age, obesity, and infections have been linked with infertility, in addition to specific karyotypes and genotypes. The study of genes associated with infertility in rodent models has expanded the field of translational genetics in identifying the underlying cause of human infertility problems. Many intriguing aspects of the molecular basis of infertility in humans remain poorly understood; however, application of genetic knowledge in this field looks promising. The growing literature on the genetics of human infertility disorders deserves attention and a critical concise summary is required. This paper provides information obtained from a systematic analysis of the literature related to current research into the genetics of infertility affecting both sexes.


[Physiological respiratory changes and venous thromboembolic disease during pregnancy].
During physiological pregnancy, changes in lung functions, ventilatory patterns and gas exchanges happen. Therefore, the dyspnea experienced by a majority of women is usually due to pregnancy itself and is very difficult to differentiate from a pathophysiological state. Anamnesis and clinical examination alone do not rule out dyspnea of thromboembolic origin. Therefore, a structured approach, based on a thromboembolic risk assessment, the application of a specific management algorithm and the use of imaging exams is required for emergency management of dyspnea occurring during the pregnancy and in the postpartum.


Progress in targeting tumor cells by using drug-magnetic nanoparticles conjugate.
To limit cytotoxicity of anticancer drugs against healthy cells, an appropriate carrier should be synthesized to deliver the drug to the tumor tissue only. A good solution is to anchor a magnetic nanoparticle to the molecule of the drug and to use a properly directed external magnetic field. The synthesis of the conjugate of doxorubicin with magnetic nanoparticles (iron oxide) modified by us resulted in a substantial depression of the aggregation process of the nanoparticles and therefore allowed the correct examination of cytotoxicity of the modified drug. It has been shown, by performing the electrochemical microbalance measurements, that the use of magnetic field guaranteed the efficient delivery of the drug to the desired place. The change in the synthesis procedure led to an increase in the number of DOX molecules attached to one magnetic nanoparticle. The release of the drug took place at pH 5.8 (and below it), which pH characterizes the cancer cells. It has also been found that while the iron oxide magnetic nanoparticles were not cytotoxic toward human urinary bladder carcinoma cells UM-UC-3, the tumor cell sensitivity of the DOX-Np complex was slightly higher in comparison to the identical concentration of doxorubicin alone.


Host Nectin-1 Promotes Chlamydial Infection in the Female Mouse Genital Tract, but Is Not Required for Infection in a Novel Male Murine Rectal Infection Model.
Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen, but more than 70% of patients fail to seek treatment due to the asymptomatic nature of these infections. Women suffer from numerous complications from chronic chlamydial infections, which include pelvic inflammatory disease and infertility. We previously demonstrated in culture that host cell nectin-1 knockdown significantly reduced chlamydial titers and inclusion size. Here, we sought to determine whether nectin-1 was required for chlamydial development in vivo by intravaginally infecting nectin-1-/- mice with Chlamydia muridarum and monitoring chlamydial shedding by chlamydial titer assay. We observed a significant reduction in chlamydial shedding in female nectin-1-/- mice compared to nectin-1+/+ control mice, an observation that was confirmed by PCR. Immunohistochemical staining in mouse cervical tissue confirmed that there are fewer chlamydial inclusions in Chlamydia-infected nectin-1-/- mice. Notably, anorectal chlamydial infections are becoming a substantial health burden, though little is known regarding the pathogenesis of these infections. We therefore established a novel male murine model of rectal chlamydial infection, which we used to determine whether nectin-1 is required for anorectal chlamydial infection in male mice. In contrast to the data from vaginal infection, no difference in rectal chlamydial shedding was observed when male nectin-1+/+ and nectin-1-/- mice were compared. Through the use of these two models, we have demonstrated that nectin-1 promotes chlamydial infection in the female genital tract but does not appear to contribute to rectal infection in male mice. These models could be used to further characterize tissue and sex related differences in chlamydial infection.


RNAi based simultaneous silencing of all forms of light-dependent NADPH:protochlorophyllide oxidoreductase genes result in the accumulation of protochlorophyllide in tobacco (Nicotiana tabacum).
Conversion of protochlorophyllide (Pchlide) into chlorophyllide (Chlide), a key step in chlorophyll biosynthesis, is mediated by a light-dependent NADPH:protochlorophyllide oxidoreductase (POR). POR exists in multiple isoforms that share high degree of homology. RNAi-mediated gene silencing approach was used to suppress the expression of POR genes in order to study its role in the Chls biosynthesis in tobacco (Nicotiana tabacum L.). The transgenic plants were devoid of chlorophyll pigments and resembled albino plants. Northern blot analysis confirmed the degradation of POR transcripts into 21-23 bp fragments. Pigment analysis showed the accumulation of various intermediate compounds of Chl biosynthesis pathway including Pchlide. However, no trace of chlorophyll was observed. As compared to wild type, POR-silenced plants accumulated larger (60%) amounts of Pchlide from its endogenous substrate. When leaf discs of WT and POR-silenced plants were treated with exogenous ALA both WT and POR-silenced plants accumulated large amounts of tetrapyrrolic intermediates demonstrating that Pchlide biosynthesis potential was not suppressed in POR-silenced plants. Upon illumination, WT plants photo-transformed large amounts of Pchlide to Chlide. However, POR-silenced plants almost completely failed to do so. Results demonstrate that the antisense approaches to drop expression of individual POR isoforms have provided valuable insights into the role of distinct PORs during greening. Moreover, data illustrate that the POR is the only enzyme that can convert the Pchlide to Chlide and there is no alternate enzyme that can substitute the POR in higher plants. Thus, this investigation describes ideal mechanism for the silencing of POR isozymes in tobacco.


Showercap Mindmap: a spatial activity for learning physiology terminology and location.
Students struggle with the volume and complexity of physiology terminology. We compared first-year undergraduate psychology students' learning of physiological terms using two teaching methods: one verbal (control group; n = 16) and one spatial and multisensory (experimental group; n = 19). The experimental group used clear plastic shower caps to mark brain regions and affix labels to another participant's head. The control group learned the material verbally through a game. When tested verbally, both the control and experimental groups recalled more of the 10 terms immediately after the activity (+106% and +83%, respectively) and 2 wk later (+53% and +31%, respectively) than at the pretest (P < 0.0005). When participants' knowledge was tested spatially (labeling a brain diagram), the experimental group recalled more terms at the posttest (+76%) and followup (+73%) than at the pretest (P < 0.0005), but the control group who showed no improvement at either time point (+12% and +14%, respectively). These findings support the notion that spatial and multisensory learning produces improved spatial recall over time while also supporting the notion of transfer-appropriate processing.


The relationship of trigger finger and flexor tendon volar migration after carpal tunnel release.
It has been suggested that the increased frequency of trigger finger (TF) after carpal tunnel release (CTR) may be caused by the volar migration of the flexor tendons at the wrist altering the tendon biomechanics at the A1 pulley. This hypothesis has not been validated. We performed pre- and post-operative ultrasonography (USG) on the affected wrists of 92 patients who underwent CTR. Pre-operative USG was performed in neutral with no tendon loading; post-operative USG was performed in neutral unloaded and in various positions of wrist flexion whilst loading the flexor tendons with gripping. The mean volar migration of the flexor tendons after CTR was 2.2 (SD 0.4) mm in the unloaded neutral position. It was 1.8 (SD 0.4) mm in patients who did not develop TF and 2.5 (SD 0.5) mm in those who did (p = 0.0067). In loaded wrist flexion, the mean volar migration of flexor tendons after CTR in patients who did not develop TF and those who did was 2.1 and 3.0 mm in 0° flexion; 3.2 and 3.9 mm in 15° flexion; 4.3 and 5.1 mm in 30° flexion; and 4.9 and 5.8 mm in 45° flexion, respectively. There were significant differences between patients with and without TF at each flexion angle. Our data indicate that patients with greater volar migration of the flexor tendons after CTR are more likely to develop TF. This conclusion supports the hypothesis that the occurrence of TF after CTR may be caused by the bowstringing effects of the flexor tendons.


Adjusting the structure and luminescence properties of Sr2-x Bax MgAl22 O36 :Eu2+ phosphors by Sr:Ba ratio.
Europium ion (Eu2+ )-doped phosphors exhibit adjustable photoluminescence due to the sensitivity of their luminescence to the local environment. It is of great significance to adjust the luminescence of Eu2+ by changing their local environment in the host. In this work, we investigated the effect of strontium/barium (Sr:Ba) ratio on the structure and luminescence properties of Sr2-x Bax MgAl22 O36 :Eu2+ phosphors. Our investigation indicates that with the decrease of Sr:Ba ratio, the matrix lattice gradually expands and the peak wavelength for the luminescence of Eu2+ presents an obvious blue shift. The occupancy of Eu2+ was analyzed and the reason for the blue shift was explained. Thermal stability for the luminescence of Eu2+ can also be adjusted by changing the Sr:Ba ratio. This work has a positive effect on the regulation of the emission of phosphors and the improvement of thermal stability, which will promote the application of Sr2-x Bax MgAl22 O36 :Eu2+ phosphors in the field of white light emitting diodes.


Contiguous gene syndrome of holoprosencephaly and hypotrichosis simplex: association with an 18p11.3 deletion.
We report a patient with a unique combination of features, including microcephaly; mental retardation; poorly developed frontal lobes; hypoplastic pituitary gland; hypothyroidism; alopecia universalis; single maxillary central incisor; taurodontism; median palatal ridge; longitudinally grooved nails; and scoliosis. His unbalanced karyotype was found to be 45,XY,der(15;18)(q10;q10). The constellation of anomalies appears to represent a contiguous gene syndrome caused, at least in part, by deletion of TGIF and the gene responsible for hereditary hypotrichosis simplex. The phenotype of our patient differs other reported patients with del(18p). Possible explanations include (1) the effects of a different deleted region, (2) a positional effect caused by a gene close by, or (3) by interruption of a different gene resulting from chromosomal translocation.


Surface Glass Transition Temperature Region of Diarylethene Films Determined by Nano-Marangoni Effect.
For the last two decades, research has addressed whether the glass transition temperature and the molecular motions on the surface of organic films are significantly different from those inside the bulk glasses. It is reported that the surface of the photochromic diarylethene film prepared by vacuum deposition has fluidity and the vacuum deposition of small amount of rubrene molecules induces surface tension fluctuations, generating dents due to the Marangoni flow in nanoscale. The depth of the dents increases in proportion to these radii for the colorless diarylethene film with a bulk glass transition temperature (Tg) close to room temperature. On the other hand, in the colored diarylethene obtained by UV irradiation to the colorless film, the depth becomes constant at a certain level. The Tg distribution in the depth direction is clarified based on an analysis of the dent depth. By approximating the obtained Tg depth distribution with an exponential function, the outermost surface Tg is about 100 K lower than the bulk Tg in the case of photoisomerized diarylethene.


Effective molecular targeting of CDK4/6 and IGF-1R in a rare FUS-ERG fusion CDKN2A-deletion doxorubicin-resistant Ewing's sarcoma patient-derived orthotopic xenograft (PDOX) nude-mouse model.
Ewing's sarcoma is a rare and aggressive malignancy. In the present study, tumor from a patient with a Ewing's sarcoma with cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) loss and FUS-ERG fusion was implanted in the right chest wall of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. The aim of the present study was to determine efficacy of cyclin-dependent kinase 4/6 (CDK4/6) and insulin-like growth factor-1 receptor (IGF-1R) inhibitors on the Ewing's sarcoma PDOX. The PDOX models were randomized into the following groups when tumor volume reached 50 mm3: G1, untreated control; G2, doxorubicin (DOX) (intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, CDK4/6 inhibitor (palbociclib, PD0332991, per oral (p.o.), daily, for 14 days); G4, IGF-1R inhibitor (linsitinib, OSI-906, p.o., daily, for 14 days). Tumor growth was significantly suppressed both in G3 (palbociclib) and in G4 (linsitinib) compared to G1 (untreated control) at all measured time points. In contrast, DOX did not inhibit tumor growth at any time point, which is consistent with the failure of DOX to control tumor growth in the patient. The results of the present study demonstrate the power of the PDOX model to identify effective targeted molecular therapy of a recalcitrant DOX-resistant Ewing's sarcoma with specific genetic alterations. The results of this study suggest the potential of PDOX models for individually-tailored, effective targeted therapy for recalcitrant cancer.


Genome sizes and repeatome evolution in zoantharians (Cnidaria: Hexacorallia: Zoantharia).
Across eukaryotes, large variations of genome sizes have been observed even between closely related species. Transposable elements as part of the repeated DNA have been proposed and confirmed as one of the most important contributors to genome size variation. However, the evolutionary implications of genome size variation and transposable element dynamics are not well understood. Together with phenotypic traits, they are commonly referred to as the "C-value enigma". The order Zoantharia are benthic cnidarians found from intertidal zones to the deep sea, and some species are particularly abundant in coral reefs. Despite their high ecological relevance, zoantharians have yet to be largely studied from the genomic point of view. This study aims at investigating the role of the repeatome (total content of repeated elements) in genome size variations across the order Zoantharia. To this end, whole-genomes of 32 zoantharian species representing five families were sequenced. Genome sizes were estimated and the abundances of different repeat classes were assessed. In addition, the repeat overlap between species was assessed by a sequence clustering method. The genome sizes in the dataset varied up to 2.4 fold magnitude. Significant correlations between genome size, repeated DNA content and transposable elements, respectively (Pearson's correlation test R2 = 0.47, p = 0.0016; R2 = 0.22, p = 0.05) were found, suggesting their involvement in the dynamics of genome expansion and reduction. In all species, long interspersed nuclear elements and DNA transposons were the most abundant identified elements. These transposable elements also appeared to have had a recent expansion event. This was in contrast to the comparative clustering analysis which revealed species-specific patterns of satellite elements' amplification. In summary, the genome sizes of zoantharians likely result from the complex dynamics of repeated elements. Finally, the majority of repeated elements (up to 70%) could not be annotated to a known repeat class, highlighting the need to further investigate non-model cnidarian genomes. More research is needed to understand how repeated DNA dynamics relate to zoantharian evolution and their biology.


Efficacy of early treatment with infliximab in pediatric Crohn's disease.
To investigate the effectiveness of early infliximab use for induction and maintenance therapy in pediatric Crohn's disease. We performed a retrospective chart review of 36 patients with Crohn's disease. Ten patients (group A) were treated with mesalamine after induction therapy with oral prednisolone, and 13 patients (group B) were treated with azathioprine after induction therapy with oral prednisolone. Thirteen patients (group C) received infliximab and azathioprine for induction and maintenance therapy for the first year, and were treated with azathioprine after 1 year. All patients were followed for at least 24 mo. Efficacy was determined by the relapse rate using the pediatric Crohn's disease activity index score in each group at 12 and 24 mo. At the 1 year follow-up, the relapse rate (23.1%, 3 of 13 patients) in group C was lower than that (61.5%, 8 of 13 patients) in group B (P = 0.047). At the 2 years follow-up, the relapse rate (38.5%, 5 of 13 patients) in group C was lower than that (76.9%, 10 of 13 patients) in group B (P = 0.047). Adverse events in group C were fewer than in groups A and B. Early induction with infliximab at diagnosis, known as "top-down" therapy, was effective for reducing the relapse rate compared to conventional therapies for at least 2 years.


Effects of nicotine on the uterine epithelium studied by X-ray microanalysis.
The composition of the uterine fluid is of importance for the development of the embryo. The ionic composition of the uterine fluid is determined by transport processes in the uterine epithelium. The aim of the present study was to investigate whether nicotine can affect the ion transport processes and ultrastructure of the uterine epithelium in mouse and rat. The effects of nicotine on the uterine epithelium were compared with those on kidney and liver. Nicotine was administered to mice as an intraperitoneal injection of a 1 microgram/l nicotine solution twice daily for 8 days, or in the drinking water (108 microM nicotine) for 15 days, whereas rats received nicotine in their drinking water for 10 days (54 or 108 microM nicotine). In addition, primary cultures of endometrial cells were exposed to nicotine in vitro. Changes in morphology were examined by transmission electron microscopy and changes in elemental content by X-ray microanalysis. Nicotine caused a significant decrease in the concentrations of Na, K, and Cl in the uterine fluid and in the endometrial cells in situ. Similar changes in elemental concentrations were observed in endometrial cells in vitro. Ultrastructural changes in endometrial cells included swollen and damaged mitochondria. In liver and kidney much smaller effects of nicotine on the elemental composition of the cells were observed. However, marked ultrastructural effects were seen in the kidney: a reduction in mitochondrial size and an increase in lysosomal volume. It is concluded that nicotine directly interferes with fluid transport across the uterine epithelium.


Caged young pigeons mortality by Coleoptera larvae.
Dermestidae and Tenebrionidae are well known inhabitants of bird's nests and poultry farms, under favourable conditions they can be very abundant under favourable conditions. At times, their larvae shift from a scavenging behaviour to a parasitic/predatory one, entering nestling's plumage and feeding on skin and feathers, and nally provoking skin damages and blood losses. These episodes mainly involve species of the genus Dermestes, but the tenebrionid Alphitobius diaperinus h also been reported to be responsible of similar cases. In June 2014, a mortality of caged young pigeons occurred in a family farm in Central Italy. Post-mortem examination of 1 of the dead nestlings revealed the presence, near the cloacal ori ce, of a triangular shaped hole of about 1 cm side, with rounded edges facing inward and with bleeding from the cavity. Five coleoptera larvae 0.5-2 cm long were collected from the edges of the hole. Bacteriological examination of liver, intestine, and lungs revealed the presence of Escherichia coli in the lung samples. The 5 larvae were morphologically identi ed as Dermestes bicolor (4) and Alphitobius diaperinus (1). This is the rst reported case of pigeon nestling's mortality caused by Dermestidae and Tenebrionidae larvae acting as parasites/predators in Italy.


Synergistic Effect of Erastin Combined with Nutlin-3 on Vestibular Schwannoma Cells as p53 Modulates Erastin-Induced Ferroptosis Response.
Vestibular schwannoma (VS) is a rare neurotology neoplasm that results in partial neurological defects. As we know, a comprehensive understanding of basic mechanisms and targeted therapy is vital for disease management. In VS, p53 has been proved to suppress tumor progression via a cooperative with the key protein, merlin, as well as regulation of the cell cycle. However, there are more potential mechanisms of p53 in VS needed to exploit. First, via genome-wide RNA expression analysis, we identified differentially expressed genes in VS compared with normal nerves, and then, bioinformatics analyses were used to analyze these differential expression data and suggested a high level of enrichment of cysteine and glutathione metabolism pathways in VS. Meanwhile, we observed a downregulation of SLC7A11/xCT, a component of the cystine/glutamate antiporter (also known as system xc -) involved in cystine uptake. Next, for a deeper study, our group extracted tumor cells from vestibular schwannoma tissues and established two immortalized cell lines named JEI-001 and JEI-002. Secondly, in our established cells, we demonstrated that ferroptosis participated in erastin-induced growth inhibition. As a novel cell death process, ferroptosis driven by iron-mediated lipid reactive oxygen species (lipid ROS), as well as cysteine and glutathione metabolism. Furthermore, ferroptosis contributes to the inhibitory effects of tumor suppressor p53. Here, we show that p53 sensitizes schwannoma cells to ferroptosis by repressing expression of SLC7A11/xCT. Finally, erastin combined with Nutlin-3, which s to p53 activation, triggered antitumor effects of ferroptosis on the growth of schwannoma cells in vitro. These findings present potential mechanism of p53 in schwannomas and raise the possibility of treatment strategies directed against this pathogenesis.


Renal dysfunction in acute heart failure: epidemiology, mechanisms and assessment.
Renal dysfunction is often present and/or worsens in patients with heart failure and this is associated with increased costs of care, complications and mortality. The cardiorenal syndrome can be defined as the presence or development of renal dysfunction in patients with heart failure. Its mechanisms are likely related to low cardiac output, increased venous congestion and renal venous pressure, neurohormonal and inflammatory activation and local changes, such as adenosine release. Many drugs, including loop diuretics, may contribute to worsening renal function through the activation of some of these mechanisms. Renal damage is conventionally defined by the increase in creatinine and blood urea nitrogen blood levels. However, these changes may be not related with renal injury or prognosis. New biomarkers of renal injury seem promising but still need to be validated. Thus, despite the epidemiological evidence, we are still lacking of satisfactory tools to assess renal injury and function and its prognostic significance.


Psychiatric Profile of Retinal Detachment Surgery under Regional Block.
The aim of this study was to investigate whether Saudi patients undergoing retinal surgery are more prone to perioperative anxiety and/or depression, to determine the relation between pre and postoperative emotional upset and also, to find the relation between severity of visual impairment and psychological dysfunction. Forty patients with retinal detachment (RD) undergoing Pars Plana Vitrecctomy were enrolled in this descriptive study. Regional block was performed using peribulbar technique in order to avoid confounding psychological effects of general anesthesia. The patients were tested for anxiety and depression using Hamilton Anxiety Rating Scale (HARS) and Beck Depression Inventory (BDI) one day before surgery and before discharge. Psychological disturbance reported only by 17.5 percent of the studied patients. Preoperatively 71 percent of them showed mild to moderate anxiety. After the procedure, 80 percent of anxious patients maintained or experienced decrease level of anxiety. In addition to anxiety, 20 percent of anxious patient developed postoperative mild depression. 14 percent of the psychologically disturbed patients had moderate depression before surgery which became milder after it. Another 14 percent showed severe anxiety and moderate depression only postoperatively. Severe visual impairment was reported by 86 percent of psychological disturbed patients. Saudi patients with RD undergoing retinal procedures infrequently suffered anxiety and/or depression. Preoperative psychological disturbances were a good predictor of postoperative emotional upset. Perioperative psychological disturbances were related positively to the severity of visual impairment.


Patient Protection and Affordable Care Act; Exchange functions: standards for Navigators and non-Navigator assistance personnel; consumer assistance tools and programs of an Exchange and certified application counselors. Final rule.
This final rule addresses various requirements applicable to Navigators and non-Navigator assistance personnel in Federally-facilitated Exchanges, including State Partnership Exchanges, and to non-Navigator assistance personnel in State Exchanges that are funded through federal Exchange Establishment grants. It finalizes the requirement that Exchanges must have a certified application counselor program. It creates conflict-of-interest, training and certification, and meaningful access standards; clarifies that any licensing, certification, or other standards prescribed by a state or Exchange must not prevent application of the provisions of title I of the Affordable Care Act; adds entities with relationships to issuers of stop loss insurance to the list of entities that are ineligible to become Navigators; and clarifies that the same ineligibility criteria that apply to Navigators apply to certain non-Navigator assistance personnel. The final rule also directs that each Exchange designate organizations which will then certify their staff members and volunteers to be application counselors that assist consumers and facilitate enrollment in qualified health plans and insurance affordability programs, and provides standards for that designation.


Methodological Considerations in Scale Refinement with Diverse Populations: A Case Example Using the CES-D with a Community Sample of American Indian Women.
Although many psychometric assessments are used extensively in population-based research to determine psychopathology, these tools have not been thoroughly validated or appropriately adapted for use in diverse populations. Indeed, depression measurement studies among American Indian and female populations are scarce, omitting key opportunities to tailor psychological measurement for this population. To build psychometric evidence of measures in this population, we used a procedural method to examine a standard psychological instrument-the Center for Epidemiological Studies Depression Scale (CES-D)-with a community sample of southeast American Indian women. Our results showed strong psychometric reliability of the 20-item CES-D. The "effort" item presented diminished validity, as demonstrated by a negative counter-intuitive item-to-total correlation (ITC) value. Dropping the "effort" item resulted in a 19-item scale with a better fit in the within-group examination of community-based American Indian women. Compared to the 20-item CES-D scale, the revised 19-item measure ("effort" item removed) resulted in minimal changes to women's depression categories. However, we did detect patterns in shifts such that the 19-item scale generally underestimated (i.e., placed women in a lower category) depressive symptoms compared to the 20-item scale. Depending on their study goals, researchers engaging in population-based research should carefully weigh the use of original scales that allow for consistency in reporting with refined scales that fit psychometrically. We present the outlined method as a tool that expands on current approaches in scale refinement, and aids researchers in making more informed decisions regarding refined scales with diverse populations.


An overview of transducers as platform for the rapid detection of foodborne pathogens.
The driving advent of portable, integrated biosensing ways for pathogen detection methods offers increased sensitivity and specificity over traditional microbiological techniques. The miniaturization and automation of integrated detection systems present a significant advantage for rapid, portable detection of foodborne microbes. In this review, we have highlighted current developments and directions in foodborne pathogen detection systems. Recent progress in the biosensor protocols toward the detection of specific microbes has been elaborated in detail. It also includes strategies and challenges for the implementation of a portable platform toward rapid foodborne sensing systems.


[About the estimation of the possibility of carrying out of several self-inflicted fatal injuries by the victim].
Forensic medical experts are not infrequently faced in their practical work with the question of the possibility of inflicting body injuries by the victim to himself (herself). In such cases, the law-enforcement authorities are in the first place interested not in the possibility of such self-inflicted injuries but rather in the correspondence between the character of the injuries and the circumstances of the event that needs to be objectively established in the course of the forensic medical expertise. The cases of multiple severe self-inflicted injuries in which all the witnesses were one way or another involved in the accident as the participants of the fight with the victim, attract especially close attention and require careful examination. The authors present a case that evolved into a massive public outcry in which a car driver, supposedly under the influence of narcotic drugs, provoked a road traffic accident and the conflict with other road users after which he inflicted severe stab and slash wounds to himself by five knife hits to the left half of the chest.


Pulmonary hypertensive diseases.
Pulmonary hypertension may occur as a primary disorder of the pulmonary vasculature or secondary to a variety of cardiac or pulmonary diseases. The reversibility of pulmonary hypertension is dependent on the relative contribution of reversible vasoconstriction and irreversible structural changes in the pulmonary vessels. Despite recent advances in the understanding of pulmonary vascular physiology, knowledge of the pathogenesis and natural history of pulmonary hypertension has been limited by an inability to measure pulmonary arterial pressure noninvasively. Thus, when patients have symptoms or signs of pulmonary hypertension, the disease is usually at an advanced stage. It is possible that early in the course of hypoxic pulmonary disease, pulmonary hypertension may be protective in optimizing matching of ventilation and perfusion. It is not known at what point pulmonary hypertension per se becomes harmful. Certainly, treatment directed at underlying cardiac or pulmonary disease is indicated. It also seems reasonable to treat severe degrees of pulmonary hypertension complicated by right ventricular dysfunction. With the advent of orally effective pulmonary vasodilators, direct treatment of primary and secondary pulmonary hypertension may now be possible. Hopefully, with careful clinical evaluation of the response to vasodilator therapy, we will learn whether these drugs prolong life and reduce morbidity in primary and secondary pulmonary hypertension. In the meantime, much more information is needed regarding the mechanisms of acute pulmonary vasoconstriction and sustained pulmonary hypertension. In addition, a means of early identification of patients with mild hypertension is needed.(ABSTRACT TRUNCATED AT 250 WORDS)


An infant rat model of bacteremia with Brazilian purpuric fever isolates of Hemophilus influenzae biogroup aegyptius. Brazilian Purpuric Fever Study Group.
Brazilian purpuric fever (BPF) is a newly recognized fulminant pediatric infection caused by bacteremia with Hemophilus influenzae biogroup aegyptius (Hae). Following intraperitoneal inoculation, each of five disease isolates caused bacteremia more frequently than control, conjunctival isolates of Hae in complement-depleted 6-d-old rats. Sustained but self-limited bacteremia was observed in normal infant rats after inoculation with a disease strain. These rats developed meningitis and had depressed hemoglobin concentration and platelet counts. Pathologic examination showed meningitis and contiguous otitis. Pretreatment of infant rats with immune adult rat serum raised against disease isolates protected rats from bacteremia. Normal adult rat serum or immune rat serum against control strains failed to protect infant rats. Thus, strains of Hae isolated from patients with BPF are more virulent than control strains. Antibody against antigens unique to disease isolates protects infant rats from bacteremia.


Bayesian estimation of species richness from quadrat sampling data in the presence of prior information.
We consider the problem of estimating the number of species of an animal community. It is assumed that it is possible to draw up a list of species liable to be present in this community. Data are collected from quadrat sampling. Models considered in this article separate the assumptions related to the experimental protocol and those related to the spatial distribution of species in the quadrats. Our parameterization enables us to incorporate prior information on the presence, detectability, and spatial density of species. Moreover, we elaborate procedures to build the prior distributions on these parameters from information furnished by external data. A simulation study is carried out to examine the influence of different priors on the performances of our estimator. We illustrate our approach by estimating the number of nesting bird species in a forest.


The HIV-derived protein Vpr52-96 has anti-glioma activity in vitro and in vivo.
Patients with actively replicating human immunodeficiency virus (HIV) exhibit adverse reactions even to low irradiation doses. High levels of the virus-encoded viral protein R (Vpr) are believed to be one of the major underlying causes for increased radiosensitivity. As Vpr efficiently crosses the blood-brain barrier and accumulates in astrocytes, we examined its efficacy as a drug for treatment of glioblastoma multiforme (GBM).In vitro, four glioblastoma-derived cell lines with and without methylguanine-DNA methyltransferase (MGMT) overexpression (U251, U87, U251-MGMT, U87-MGMT) were exposed to Vpr, temozolomide (TMZ), conventional photon irradiation (2 to 6 Gy) or to combinations thereof. Vpr showed high rates of acute toxicities with median effective doses of 4.0±1.1 μM and 15.7±7.5 μM for U251 and U87 cells, respectively. Caspase assays revealed Vpr-induced apoptosis in U251, but not in U87 cells. Vpr also efficiently inhibited clonogenic survival in both U251 and U87 cells and acted additively with irradiation. In contrast to TMZ, Vpr acted independently of MGMT expression.Dose escalation in mice (n=12) was feasible and resulted in no evident renal or liver toxicity. Both, irradiation with 3x5 Gy (n=8) and treatment with Vpr (n=5) delayed intracerebral tumor growth and prolonged overall survival compared to untreated animals (n=5; p3x5 Gy<0.001 and pVpr=0.04; log-rank test).Our data show that the HIV-encoded peptide Vpr exhibits all properties of an effective chemotherapeutic drug and may be a useful agent in the treatment of GBM.


Sequence-based polymorphisms in the mitochondrial D-loop and potential SNP predictors for chronic dialysis.
The mitochondrial (mt) displacement loop (D-loop) is known to accumulate structural alterations and mutations. The aim of this study was to investigate the prevalence of single nucleotide polymorphisms (SNPs) within the D-loop among chronic dialysis patients and healthy controls. We enrolled 193 chronic dialysis patients and 704 healthy controls. SNPs were identified by large scale D-loop sequencing and bioinformatic analysis. Chronic dialysis patients had lower body mass index, blood thiols, and cholesterol levels than controls. A total of 77 SNPs matched with the positions in reference of the Revised Cambridge Reference Sequence (CRS) were found in the study population. Chronic dialysis patients had a significantly higher incidence of 9 SNPs compared to controls. These include SNP5 (16108Y), SNP17 (16172Y), SNP21 (16223Y), SNP34 (16274R), SNP35 (16278Y), SNP55 (16463R), SNP56 (16519Y), SNP64 (185R), and SNP65 (189R) in D-loop of CRS. Among these SNPs with genotypes, SNP55-G, SNP56-C, and SNP64-A were 4.78, 1.47, and 5.15 times more frequent in dialysis patients compared to controls (P<0.05), respectively. When adjusting the covariates of demographics and comorbidities, SNP64-A was 5.13 times more frequent in dialysis patients compared to controls (P<0.01). Furthermore, SNP64-A was found to be 35.80, 3.48, 4.69, 5,55, and 4.67 times higher in female patients and in patients without diabetes, coronary artery disease, smoking, and hypertension in an independent significance manner (P<0.05), respectively. In patients older than 50 years or with hypertension, SNP34-A and SNP17-C were found to be 7.97 and 3.71 times more frequent (P<0.05) compared to patients younger than 50 years or those without hypertension, respectively. The results of large-scale sequencing suggest that specific SNPs in the mtDNA D-loop are significantly associated with chronic dialysis. These SNPs can be considered as potential predictors for chronic dialysis.


Site-directed mutagenesis and spectroscopic studies of the iron-binding site of (S)-2-hydroxypropylphosphonic acid epoxidase.
(S)-2-Hydroxylpropanylphosphonic acid epoxidase (HppE) is a novel type of mononuclear non-heme iron-dependent enzyme that catalyzes the O2 coupled, oxidative epoxide ring closure of HPP to form fosfomycin, which is a clinically useful antibiotic. Sequence alignment of the only two known HppE sequences led to the speculation that the conserved residues His138, Glu142, and His180 are the metal binding ligands of the Streptomyces wedmorensis enzyme. Substitution of these residues with alanine resulted in significant reduction of metal binding affinity, as indicated by EPR analysis of the enzyme-Fe(II)-substrate-nitrosyl complex and the spectral properties of the Cu(II)-reconstituted mutant proteins. The catalytic activities for both epoxidation and self-hydroxylation were also either eliminated or diminished in proportion to the iron content in these mutants. The complete loss of enzymatic activity for the E142A and H180A mutants in vivo and in vitro is consistent with the postulated roles of the altered residues in metal binding. The H138A mutant is also inactive in vivo, but in vitro it retains 27% of the active site iron and nearly 20% of the wild-type activity. Thus, it cannot be unequivocally stated whether H138 is an iron ligand or simply facilitates iron binding due to proximity. The results reported herein provide initial evidence implicating an unusual histidine/carboxylate iron ligation in HppE. By analogy with other well-characterized enzymes from the 2-His-1-carboxylate family, this type of iron core is consistent with a mechanism in which both oxygen and HPP bind to the iron as a first step in the in the conversion of HPP to fosfomycin.


Meningioma in congenital adrenal hyperplasia.
A diversity of malignancies have been reported in patients with congenital adrenal hyperplasia. We report a case of multiple meningiomas, tumors which are more common in females and reported to have sex steroid receptors, in a 46,XX male (severe female hermaphrodite raised as a male) with 21-hydroxylase deficiency. The patient has been treated with glucocorticoids since 3 years of age and testosterone since puberty.


Semiparametric Allelic Tests for Mapping Multiple Phenotypes: Binomial Regression and Mahalanobis Distance.
Binary phenotypes commonly arise due to multiple underlying quantitative precursors and genetic variants may impact multiple traits in a pleiotropic manner. Hence, simultaneously analyzing such correlated traits may be more powerful than analyzing individual traits. Various genotype-level methods, e.g., MultiPhen (O'Reilly et al. []), have been developed to identify genetic factors underlying a multivariate phenotype. For univariate phenotypes, the usefulness and applicability of allele-level tests have been investigated. The test of allele frequency difference among cases and controls is commonly used for mapping case-control association. However, allelic methods for multivariate association mapping have not been studied much. In this article, we explore two allelic tests of multivariate association: one using a Binomial regression model based on inverted regression of genotype on phenotype (Binomial regression-based Association of Multivariate Phenotypes [BAMP]), and the other employing the Mahalanobis distance between two sample means of the multivariate phenotype vector for two alleles at a single-nucleotide polymorphism (Distance-based Association of Multivariate Phenotypes [DAMP]). These methods can incorporate both discrete and continuous phenotypes. Some theoretical properties for BAMP are studied. Using simulations, the power of the methods for detecting multivariate association is compared with the genotype-level test MultiPhen's. The allelic tests yield marginally higher power than MultiPhen for multivariate phenotypes. For one/two binary traits under recessive mode of inheritance, allelic tests are found to be substantially more powerful. All three tests are applied to two different real data and the results offer some support for the simulation study. We propose a hybrid approach for testing multivariate association that implements MultiPhen when Hardy-Weinberg Equilibrium (HWE) is violated and BAMP otherwise, because the allelic approaches assume HWE.


Molecular characteristics and efficacy of 16D10 siRNAs in inhibiting root-knot nematode infection in transgenic grape hairy roots.
Root-knot nematodes (RKNs) infect many annual and perennial crops and are the most devastating soil-born pests in vineyards. To develop a biotech-based solution for controlling RKNs in grapes, we evaluated the efficacy of plant-derived RNA interference (RNAi) silencing of a conserved RKN effector gene, 16D10, for nematode resistance in transgenic grape hairy roots. Two hairpin-based silencing constructs, containing a stem sequence of 42 bp (pART27-42) or 271 bp (pART27-271) of the 16D10 gene, were transformed into grape hairy roots and compared for their small interfering RNA (siRNA) production and efficacy on suppression of nematode infection. Transgenic hairy root lines carrying either of the two RNAi constructs showed less susceptibility to nematode infection compared with control. Small RNA libraries from four pART27-42 and two pART27-271 hairy root lines were sequenced using an Illumina sequencing technology. The pART27-42 lines produced hundred times more 16D10-specific siRNAs than the pART27-271 lines. On average the 16D10 siRNA population had higher GC content than the 16D10 stem sequences in the RNAi constructs, supporting previous observation that plant dicer-like enzymes prefer GC-rich sequences as substrates for siRNA production. The stems of the 16D10 RNAi constructs were not equally processed into siRNAs. Several hot spots for siRNA production were found in similar positions of the hairpin stems in pART27-42 and pART27-271. Interestingly, stem sequences at the loop terminus produced more siRNAs than those at the stem base. Furthermore, the relative abundance of guide and passenger single-stranded RNAs from putative siRNA duplexes was largely correlated with their 5' end thermodynamic strength. This study demonstrated the feasibility of using a plant-derived RNAi approach for generation of novel nematode resistance in grapes and revealed several interesting molecular characteristics of transgene siRNAs important for optimizing plant RNAi constructs.


Tuberculosis in living related donor renal transplant recipients.
Ten out of 237 patients who underwent renal transplantation between 1975 and October 1986 developed tuberculosis. Most patients presented with vague symptoms, and typical symptoms commonly associated with tuberculosis were not common. Six had positive urine cultures. One patient had positive sputum and urine cultures and one had positive sputum and cerebrospinal fluid cultures for tuberculosis. In this last patient cryptococcus was also cultured from the sputum and CSF. Nine of the 10 patients responded well to antituberculosis therapy and was cured of the infection. The patient with associated cryptococcal infection died 2 months after presentation. Side effects of antituberculous therapy was minimal and easily resolved on stopping the offending drug.


An industry update: what is new in the field of therapeutic delivery this month?
The present industry update covers the period 1-28 February 2017. Information was sourced primarily from company press releases, regulatory and patent agencies, scientific literature and various news websites. A report issued this month indicated that the recent American election has influenced the rate and volume of pharma acquisitions and mergers (A&M) in the final quarter of 2016 and it remains to be seen what (if any) is the effect on the therapeutic drug delivery sector in the longer term. There was positive approval news this month for Valeant, Intellipharmaceutics and Pfizer for products that offered novel therapeutic delivery. Several companies including Trutag and Novasep announced significant investment in new manufacturing facilities and strategic alliances this month.


The importance of nephron-sparing focal therapy: renal function preservation.
Historically, renal cancer has been treated with radical nephrectomy. Consequently, many patients developed renal insufficiency and the health problems associated with this. With the increasing diagnosis of small renal masses, nephron-sparing treatments have been developed to treat these masses adequately, while maximizing renal function. Focal ablative therapy is a means to treat small renal masses in a minimally invasive manner. Yet, there are few studies that have focused on their ability to preserve renal function. In this article, we review the existing literature on the renal function outcomes of patients treated with either radio frequency ablation or cryoablation.


Coded amino acids in gas phase: the shape of isoleucine.
The solid alpha-amino acid isoleucine has been vaporized by laser ablation and expanded in a supersonic jet, where the molecular conformations of the isolated molecule were probed using Fourier transform microwave spectroscopy. Two conformers of neutral isoleucine have been detected in gas phase, the most stable being stabilized by an intramolecular hydrogen bond N-H...O=C and a cis-COOH arrangement. The higher energy form is stabilized by an intramolecular hydrogen bond N...H-O. The sec-butyl side chain of the amino acid adopts the same configuration in the two observed conformers, with a staggered configuration at Cbeta similar to that observed in valine and a trans arrangement of Calpha and Cdelta. Ab initio calculations at MP2/6-311++G(d,p) level reproduce satisfactorily the experimental results.


The Brazilian Pediatric Myelodysplastic Cooperative Group strategies: are they relevant to improve educational approach and correct diagnosis?
Brazil is a wide country with huge contrasts. Its peculiarities can highlight environmental factors that could influence the frequencies of different cancers. The standard treatment and results achieved from several different areas of the country may not be found in others. The establishment of a national cooperative group has the potential to improve outcomes. The The Brazilian Cooperative Group on Pediatric Patients with Myelodysplastic Syndrome (BCG-MDS-PED) was first organized in January 1997 as a working group of hematologists, pediatric oncologists, pediatric-hematologists, molecular biologists and other professionals in order to study pediatric (age <18 years) MDS. Six distinct subcommittees constituted with members from several universities: cytology, histopathology, clinical, cytogenetics, molecular biology and epidemiology. The goals of the BCG-MDS-PED were: (i) to offer support for diagnosis and orientation for treatment; (ii) educational support for the colleagues all over the country and (iii) research on pathogenesis and new approaches for pediatric MDS patients. There are socio-economical differences among the five regions of the country. The BCG-MDS-PED believes that it is absolutely necessary to study the clinical, cellular, molecular and epidemiological aspects of MDS, taking in account these peculiar differences among populations and regions. Since 1997, 114 pediatric cases were referred to the BCG-MDS-PED from 21 centres. Seven Brazilian states have sent cases to the group, 31 patients were referred from universities, 73 patients from pediatric oncology units (foundations ) and 10 patients came from private clinics. Some of these patients have been followed up and/or treated by the physician who referred them to the BCG-MDS-PED for confirmation of the initial diagnosis. The majority of these physicians have required orientation on diagnostic and treatment issues, as well as to complete cytogenetic and molecular studies. From these 114 patients, 64 patients were confirmed as MDS. We believe that, the more numerous the MDS-studied cases, the more experienced will be the referee group on clinical and laboratory features on childhood MDS in Brazil.


A Rare Phenomenon of Natural Precocious Mummification.
Immediately after death, specific changes occur in the human body, leading to the total dissolution of the soft tissues and internal organs. In some cases, when in suitable conditions, the decomposition process could stop and be displaced by mummification. The last one is time-consuming and needs several weeks to months to set in completely. We present a case of a 34-year-old man found dead 16 days after being last seen alive in a stage of complete mummification. Natural mummification occurring in less than one month is termed precocious mummification and is rarely observed in temperate regions. With only a few cases reported globally, this case is essential for the forensic community. It will help better know the mummification processes and estimate the time since death.


Evaluation of antibacterial activity, phytochemical constituents, and cytotoxicity effects of Thai household ancient remedies.
Household ancient remedies reported here are described in the National List of Essential Medicines and have traditionally been used in Thailand to treat infection-related ailments. However, the safety and effectiveness of these remedies have been poorly evaluated. The aim of this study was to evaluate the antibacterial properties of these remedies against seven gram-positive and gram-negative multidrug-resistant bacteria species. Phytochemical constituents and cytotoxicity of these remedies were also determined. Seven remedies, consisting of Um-Ma-Luk-Ka-Wa-Tee, Chan-Ta-Lee-La, Kheaw-Hom, Learng-Pid-Sa-Mud, Pra-Sa-Chan-Dang, Dhart-Ban-Chob, and Tree-Hom, were prepared by a licensed traditional medical doctor using a mixture of medicinal plants. Antibacterial activity of ethanol extracts of the remedies was determined by using a broth microdilution method. Qualitative phytochemical screening analysis was carried out to identify the presence of major components. Cytotoxicity activities of the extracts against Vero cells were assessed by green fluorescent protein-based assay. With the exception of Dhart-Ban-Chob extract, significant minimum inhibitory concentrations (MICs) of <16 to 32 μg/mL were observed for the remedy extracts depending on the bacterial strains. The Um-Ma-Luk-Ka-Wa-Tee extract was noncytotoxic against Vero cells and possessed the highest activity, with MICs of <16 to 31 μg/mL against all methicillin-resistant Staphylococcus aureus isolates. Remarkable antibacterial activities against multidrug-resistant pathogens, as well as low toxicity on Vero cells, of Um-Ma-Luk-Ka-Wa-Tee support the use of this remedy in traditional medicine. Further investigation on other biological activities related to traditional applications, appropriate biomarkers, and treatment mechanisms of the household remedy are required.


Open surgery in the era of minimally invasive surgery.
The benefits and popularity of minimally invasive surgery are undeniable around the globe. However, open surgery is necessary and learning open surgery skills is still a necessity. Open surgery allows for better exposure to the surgical field and provides tactile sensation to facilitate the stereo visual assessment to precisely remove the lesion. Open surgery is still the key to surgical training, and the skills learned from open surgeries remain crucial for unforeseen circumstances and certain conditions like emergencies, challenge cases, or patients with compromised status.


[Investigation of a carbon monoxide poisoning accident with a hidden source].
In June 2022, a carbon monoxide poisoning accident with hidden source occurred in a bonded gold/silver wire manufacturing enterprise in Guangzhou, causing 10 people to be poisoned, of which 1 was caused by carbon monoxide poisoning and 9 by carbon monoxide contact reaction. The symptoms were dizziness, fatigue and vomiting. After 5 to 7 h, the saturation of carboxyhemoglobin in finger pulse was 4% to 10%, and the saturation of carboxyhemoglobin in blood gas biochemical analysis was 1.9% to 5.8%. The concentration of carbon monoxide detected in the carbon borne purification plant of the enterprise was 34.46-37.26 mg/m(3). It was judged that the accident was carbon monoxide poisoning caused by carbon monoxide gas being transported to the work post along the gas transmission pipeline due to abnormal operation of the carbon borne purification plant. By investigating the source and cause of poison, this paper provides a warning for the similar process to prevent similar events, and provides a new idea for the identification of chemical poisoning risk. At the same time, it is warned that similar enterprises should fully consider the risk of poisoning under specific circumstances, strengthen equipment maintenance and repair, and prevent the occurrence of similar incidents.