Predictors of Clostridium difficile infection after stoma reversal following TaTME surgery.
The aim of this study was to determine the incidence of Clostridium Difficile infection (CDI) after stoma reversal in patients who underwent transanal Total Mesorectal Excision (TaTME) and to evaluate variables correlated with this post-operative infection. Patients who underwent stoma reversal surgery following TaTME for rectal cancer between 2015 and 2023 at a high-volume Institution, were retrospectively reviewed for the post-operative occurrence of diarrhea and in-hospital CDI (positive toxin in the stools). Patients were divided into the following subgroups according to the post-operative course: Group A-no clinical symptoms; Group B-mild diarrhea (< 10 evacuations/day); Group C-severe watery diarrhea (> 10 evacuations/day) with CDI negative; and Group D-severe watery diarrhea (> 10 evacuations/day) CDI positive. Clinical and laboratory data were analyzed for their correlation with CDI. A machine learning approach was used to determine predictors of diarrhea following stoma reversal. A total of 126 patients were selected, of whom 79 were assessed as Group A, 16 Group B, 25 Group C and 6 (4.8%) Group D. Univariable analysis documented that delayed stoma reversal correlated with CDI (Group A mean interval 44.6 weeks vs. Group D 68.4 weeks, p 0.01). The machine learning analysis confirmed the delay in stoma closure as a probability factor of presenting diarrhea; also, diarrhea probability was 80.5% in males, 77.8% in patients who underwent neoadjuvant therapy, and 63.9% in patients who underwent adjuvant therapy. Stoma reversal surgery can result in moderate rate of in-hospital CDI. Time-to stoma reversal is a crucial variable significantly related with this adverse outcome.


[Creation of reaction-less pseudoarthrosis on the ulna of the dog (author's transl)].
The model situation of so called "avital, avascular" pseudoarthrosis was surgiclly induced in 25 beagle dogs using defectosteotomy and heat-necrotization of both ulna bones. The clinical evolution was examined weekly using roentgengraphy and each 4th week by scintigraphy. According to roentgen pictures three stages can be identified: 1. Reaction of the bone on surgical trauma (until 4th week). 2. Sequestration or asepticosteolysis (until 18th week). 3. Consolidation of the pseudoarthrosis model-situation (after 18th week). Scintigraphy revealed by the continuing so called "avital" pseudoarthrosis an enhanced metabolism activity at the tips of both bone fragments. The cause for these active metabolic processes evoking enhanced activity on both fragment ends during scintigraphy wich is not demonstrable with roentgen device are the pulling, pushing and tensile strengths originating from a connective-tissue-cord existing between them. The results of scintigraphy lead us to use the term "reaction-less pseudoarthrosis" instead of "avascular" or "avital" for this model of pseudoarthrosis.


Characterization of yeast isolates originating from Hungarian dairy products using traditional and molecular identification techniques.
Yeast isolates collected from various Hungarian dairy products were identified using simplified identification system (SIM) and restriction fragment analysis of PCR-amplified 18S rDNA with the neighbouring ITS1 region (ITS-PCR; ribotyping). The isolates were grouped into 26 species; Geotrichum candidum, Debaryomyces hansenii, Yarrowia lipolytica, Kluyveromyces lactis and Candida catenulata were found as the predominant species. SIM and ITS-PCR proved to be useful and convenient taxonomic tools for rapid identification at species level. Two most frequent species, G. candidum and D. hansenii, were further characterized by randomly amplified polymorphic DNA (RAPD-PCR) analysis. RAPD-PCR using M13 primer resulted in discrimination between most strains of the same species and allowed a certain degree of intraspecific typing.


A predictive multi-linear regression model for organic micropollutants, based on a laboratory-scale column study simulating the river bank filtration process.
This study investigated relationships between OMP biodegradation rates and the functional groups present in the chemical structure of a mixture of 31 OMPs. OMP biodegradation rates were determined from lab-scale columns filled with soil from RBF site Engelse Werk of the drinking water company Vitens in The Netherlands. A statistically significant relationship was found between OMP biodegradation rates and the functional groups of the molecular structures of OMPs in the mixture. The OMP biodegradation rate increased in the presence of carboxylic acids, hydroxyl groups, and carbonyl groups, but decreased in the presence of ethers, halogens, aliphatic ethers, methyl groups and ring structures in the chemical structure of the OMPs. The predictive model obtained from the lab-scale soil column experiment gave an accurate qualitative prediction of biodegradability for approximately 70% of the OMPs monitored in the field (80% excluding the glymes). The model was found to be less reliable for the more persistent OMPs (OMPs with predicted biodegradation rates lower or around the standard error=0.77d(-1)) and OMPs containing amide or amine groups. These OMPs should be carefully monitored in the field to determine their removal during RBF.


Osteochondral lesions of the talus: defining the surgical approach.
It has become clear that contrary to the previously held belief that osteochondral lesions of the talus occurred anterolaterally and posteromedially, there is a much wider spread across the talus. Lesions can now be mapped by their biology and geography, and from this the ideal procedure and the ideal surgical approach can be selected. Familiarization with a range of skills, such as posterior ankle arthroscopy and malleolar osteotomies, are required to be able to perform this surgical plan.


Exploring intrusions without awareness: A preliminary study of the characteristics and influences of meta-awareness failures.
Research shows that people can lack meta-awareness (i.e., being explicitly aware) of their trauma-related thoughts, which impacts our understanding of re-experiencing symptoms, a key symptom type in posttraumatic stress disorder (PTSD), assessed through self-report. This preliminarily study explored differences between (meta-)aware and unaware intrusion characteristics to understand why some intrusions are not immediately apparent to individuals. Trauma-exposed participants (N = 78) were recruited from online crowd-sourcing platforms to complete an online meta-awareness task. During a reading task, participants were intermittently probed to index the occurrence of unreported (i.e., unaware) trauma-related intrusions. Once participants indicated trauma-related intrusions were present, they then completed a questionnaire that indexed intrusion characteristics. Although unaware intrusions did occur in a subset of the sample, there were no fundamental differences between aware and unaware intrusions in terms of modality of experience (imagery vs. non-imagery), meaningfulness, accessibility, or other characteristics (e.g., vividness). There was potential for lower participant engagement and attention due to the online delivery of the meta-awareness task, which may have minimized meta-awareness failure. Future research could consider using a continuous measure to index levels of meta-awareness. In addition, recruiting clinical samples (e.g., individuals with PTSD) who typically experience multiple daily intrusions would allow generalizability of the current findings to be tested. Our findings from this preliminary study suggest that unaware and aware intrusions show more commonality than not in their characteristics, with further research required to improve our understanding of the mechanisms leading to meta-awareness or lack of in PTSD.


Primary retroperitoneal mucinous cystoadenocarcinomas: an immunohistochemical and molecular study.
Special immunohistochemical stains for the identification of gastroenteropancreatic antigens in two cases of primary retroperitoneal mucinous cystoadenocarcinomas (PRMC) show that these tumours have patterns similar to ovarian mucinous tumours. Markers of pyloric type gastric mucosa differentiation (M1, cathepsin E, concavavalin A, pepsinogen II) are mostly positive in benign and borderline areas with endocervical type differentiation, while immunoreactivity for intestinal cell markers (M3SI and CAR-5) and for DU-PAN-2 is present mainly in frankly malignant areas, regardless of differentiation type. DNA analysis shows a point mutation of K-ras oncogene at codon 12 (GGT to CGT) in one case. The immunohistochemical and genotypic similarity of PRMC and ovarian mucinous tumours may indicate similar mechanisms in their histogenesis.


Sequence and spacing requirements of a retrovirus integration site.
Following infection, retroviruses insert a DNA copy of their RNA genome into the host cell genome. This integrative recombination reaction occurs at specific sites on the viral DNA: inverted repeat sequences near the termini of the linear DNA form of the viral genome. We have described elsewhere the generation and analysis of deletion mutations at one of the inverted repeat sequences in Moloney murine leukemia virus. We describe here the effects of insertion mutations made at this locus. Our results show that substantial sequence changes at the site of recombination can be tolerated, and that the spacing between the cleavage sites on the viral DNA can be expanded as well as contracted while still allowing efficient viral integration. After several rounds of virus replication, each of the insertion mutants gave rise to pseudorevertants with new alterations at the integration site.


[Risc factors for assisted suicide for cancer patients - mental burden of bereaved].
Chronic and progressive disease represents a significant risk factor for suicidal behavior. Cancer patients have almost twice the rate of suicides compared to the general population. Based on a case report, the suicidal risk factors for cancer patients are presented. It is further investigated to what extent professional support by a mobile palliative care team can affect the wish for assisted suicide or the suicidal behavior generally among patients receiving palliative care. In addition, the mental impact on individuals, who were witnesses of assisted suicide of relatives or close friends are presented. The occurrence of posttraumatic stress disorder (PTSD), depressions, anxiety disorders and complicated grief (CG) in close family members is shown. However, further research will be necessary to develop adequate support for patients (and their relatives), who plan an assisted suicide.


Heat shock protein expression and injury optimization for laser therapy design.
Hyperthermia can induce heat shock protein (HSP) expression in tumor regions where non-lethal temperature elevation occurs, enhancing cell viability and resistance to chemotherapy and radiation treatments typically employed in conjunction with thermal therapy. However, HSP expression control has not been incorporated into current thermal therapy design. Treatment planning models based on achieving the desired post-therapy HSP expression and injury distribution in the tumor and healthy surrounding tissue can enable design of more effective thermal therapies that maximize tumor destruction and minimize healthy tissue injury. An optimization algorithm for prostate cancer laser therapy design was integrated into a previously developed treatment planning model, permitting prediction and optimization of the spatial and temporal temperature, HSP expression, and injury distributions in the prostate. This optimization method is based on dosimetry guidelines developed from measured HSP expression kinetics and injury data for normal and cancerous prostate cells and tumors exposed to hyperthermia. The optimization model determines laser parameters (wavelength, power, pulse duration, fiber position, and number of fibers) necessary to satisfy prescribed HSP expression and injury distributions in tumor and healthy tissue. Optimization based on achieving desired injury and HSP expression distributions within the tumor and normal tissue permits more effective tumor destruction and diminished injury to healthy tissue compared to temperature driven optimization strategies. Utilization of the treatment planning optimization model can permit more effective tumor destruction by mitigating tumor recurrence and resistance to chemotherapy and radiation arising from HSP expression and insufficient injury.


Race-associated molecular changes in gynecologic malignancies.
The difference in cancer morbidity and mortality between individuals of different racial groups is complex. Health disparities provide a framework to explore potential connections between poor outcomes and individuals of different racial backgrounds. This study identifies genomic changes in African-American patients with gynecologic malignancies, a population with well-established disparities in outcomes. Our data explore whether social health disparities might mediate interactions between the environment and tumor epigenomes and genomes that can be identified. Using The Cancer Genetic Ancestry Atlas, which encodes data from The Cancer Genome Atlas by ancestry and allows for systematic analyses of sequencing data by racial group, we performed large-scale, comparative analyses to identify novel targets with alterations in methylation, transcript, and microRNA expression between tumors from women of European American or African American racial groups across all gynecologic malignancies. We identify novel discrete genomic changes in these complex malignancies and suggest a framework for identifying novel therapeutic targets for future investigation.


Expressions of Holocaust experience and their relationship to mental symptoms and physical morbidity among Holocaust survivor patients.
This study explores current expressions of past trauma among Holocaust survivors. Medical records and extensive interviews were analyzed for 38 Holocaust survivors who were hospitalized and/or under ambulatory care. The sample consisted of 55% women and 45% men whose mean age was 72 (SD = 9.2). Expressions of Holocaust experience yielded two factors: Holocaust-as-Present (e.g., feeling the Holocaust experience as continuing, Holocaust-related somatization) and Holocaust-as-Past (e.g., avoiding preoccupation with traumatic memories, feeling unduly stigmatized as a survivor). The results indicate that mental symptoms and the number of medical diagnoses are positively correlated with Holocaust-as-Present but negatively correlated with Holocaust-as-Past. However, scoring high on Holocaust-as-Past relates to a higher danger to life as a result of significant morbidity. The findings suggest two differential modes of either remaining enmeshed in the traumatic experience or attempting to contain the sequelae of the trauma. These modes differ in their implications for mental and physical health.


Comparative study of umbilical cord cross-sectional area in foetuses with isolated single umbilical artery and normal umbilical artery.
Single umbilical artery (SUA) is one of the most common prenatal diagnoses in cases of foetal abnormality. This prospective study evaluated 77 foetuses with isolated SUAs and 77 healthy foetuses, both at 22-39 gestational weeks. We categorised gestational age into the second and third trimesters, measured the umbilical arterial blood flow parameters and calculated the umbilical vein (UV) area, umbilical artery (UA) area and UV area/UA area ratio. In the second and third trimesters, a higher UA area was obtained in the isolated SUA group than in the control group (p < .01). Furthermore, the isolated SUA group had a lower UV area/UA area ratio than the control group (p < .01), and a positive linear correlation was found between gestational age and UV area in both groups (p < .01). The presence of isolated SUAs was associated with low birth weight and a high prevalence of small for gestational age.IMPACT STATEMENTWhat is already known on this subject? Single umbilical artery (SUA) is one of the most common prenatally diagnosed foetal abnormalities and approximately 80% foetuses with SUA have isolated SUA, which is a soft indicator of chromosome abnormalities, congenital malformations and premature birth. Umbilical cord cross-sectional area can be evaluated prenatally by ultrasound imaging. Normal values increase with gestational age and foetal size in single pregnancies. Changes in umbilical cord thickness have been associated with complications during pregnancy.What do the results of this study add? The correlation between gestational age and umbilical vein area in the isolated single umbilical artery (SUA) group and control group was better than that between gestational age and umbilical artery area. UA area increased significantly in both groups before 28 weeks but not after 28 weeks, particularly in the isolated SUA group.What are the implications of these findings for clinical practice and/or further research? The study provides a reliable basis for maternal foetal monitoring during pregnancy in the isolated SUA and control groups. Objective assessment of the occurrence and development of foetuses with isolated single umbilical artery was performed.


Spiritual Well-being Among Palliative Care Patients With Different Religious Affiliations: A Multicenter Korean Study.
Spiritual well-being (SWB) is very important in palliative care patients. The aim of this study was to investigate the SWB among palliative care patients in Korea with different religious affiliations and to identify the correlates of SWB. This study is a cross-sectional, multicenter study involving hospitalized patients seen by palliative care teams. We collected data on basic clinicodemographic characteristics, factors related to religion (meaningful religious events, religious activities such as attending worship, individual spiritual activities such as prayer), overall quality of life, and SWB. SWB was measured using Functional Assessment of Chronic Illness Therapy-Spirituality 12. We examined the differences in SWB among patients who reported themselves as Protestants, Catholics, Buddhists, and having no religious affiliations. Among the 202 patients enrolled, 69 (34.2%), 48 (23.8%), 43 (21.3%), and 42 (20.8%) persons were Protestants, were Catholics, were Buddhists, and had no religious affiliation, respectively. The Functional Assessment of Chronic Illness Therapy-Spirituality 12 was highest among Protestants, followed by Catholics, Buddhists, and those without religious affiliation (29.8 vs. 27.0 vs. 23.2 vs. 16.3, P < 0.001). The faith subscale (12.4 vs. 10.4 vs. 7.7 vs. 2.5, P < 0.001) showed similar distributions. Christians reported higher SWB in the meaning and the peace subscale than patients without a religious affiliation. In the multivariate analysis, religious affiliation (P < 0.001), individual spiritual activities (P < 0.001), and quality of life (P < 0.001) were significantly related to a greater SWB. Age was inversely associated with the meaning subscale (P = 0.002). Although faith practices may be particularly helpful to improve spiritual well-being among Christians, further research is needed to determine what individual spiritual activities can support non-Christians.


Achieving door-to-balloon times that meet quality guidelines: how do successful hospitals do it?
We sought to recommend an approach for minimizing preventable delays in door-to-balloon time on the basis of experiences in top-performing hospitals nationally. Prompt percutaneous coronary intervention (PCI) for patients with ST-segment elevation myocardial infarction (STEMI) significantly reduces mortality and morbidity; however, door-to-balloon times often exceed the 90-min guideline set forth by the American College of Cardiology (ACC) and the American Heart Association (AHA). We conducted a qualitative study using in-depth interviews (n = 122) of hospital staff at hospitals (n = 11) selected as top performers based on data from the National Registry of Myocardial Infarction from January 2001 to December 2002. We used the constant comparative method of qualitative data analysis to synthesize best practices across the hospitals. Top performers were those with median door-to-balloon times of < or =90 min for their most recent 50 PCI cases through December 2002 and the greatest improvement in median door-to-balloon times during the preceding four-year period 1999 to 2002. Several critical innovations are described, including use of pre-hospital electrocardiograms (ECGs) to activate the catheterization laboratory, allowing emergency physicians to activate the catheterization laboratory, and substantial interdisciplinary collaboration throughout the process. In the ideal approach, door-to-balloon time is 60 min for patients transported by paramedics with a pre-hospital ECG and 80 min for patients who arrive without paramedic transport and a pre-hospital ECG. Hospitals can achieve the recommended ACC/AHA guidelines for door-to-balloon time with specific process design efforts. However, the recommended best practices involve extensive interdisciplinary collaboration and will likely require explicit strategies for overcoming barriers to organizational change.


Toward the Identification of Novel Antimicrobial Agents: One-Pot Synthesis of Lipophilic Conjugates of N-Alkyl d- and l-Iminosugars.
In the effort to improve the antimicrobial activity of iminosugars, we report the synthesis of lipophilic iminosugars 10a-b and 11a-b based on the one-pot conjugation of both enantiomeric forms of N-butyldeoxynojirimycin (NBDNJ) and N-nonyloxypentyldeoxynojirimycin (NPDNJ) with cholesterol and a succinic acid model linker. The conjugation reaction was tuned using the established PS-TPP/I2/ImH activating system, which provided the desired compounds in high yields (94-96%) by a one-pot procedure. The substantial increase in the lipophilicity of 10a-b and 11a-b is supposed to improve internalization within the bacterial cell, thereby potentially leading to enhanced antimicrobial properties. However, assays are currently hampered by solubility problems; therefore, alternative administration strategies will need to be devised.


Optimal H∞ tracking control of nonlinear systems with zero-equilibrium-free via novel adaptive critic designs.
In this paper, a novel adaptive critic control method is designed to solve an optimal H∞ tracking control problem for continuous nonlinear systems with nonzero equilibrium based on adaptive dynamic programming (ADP). To guarantee the finiteness of a cost function, traditional methods generally assume that the controlled system has a zero equilibrium point, which is not true in practical systems. In order to overcome such obstacle and realize H∞ optimal tracking control, this paper proposes a novel cost function design with respect to disturbance, tracking error and the derivative of tracking error. Based on the designed cost function, the H∞ control problem is formulated as two-player zero-sum differential games, and then a policy iteration (PI) algorithm is proposed to solve the corresponding Hamilton-Jacobi-Isaacs (HJI) equation. In order to obtain the online solution to the HJI equation, a single-critic neural network structure based on PI algorithm is established to learn the optimal control policy and the worst-case disturbance law. It is worth mentioning that the proposed adaptive critic control method can simplify the controller design process when the equilibrium of the systems is not zero. Finally, simulations are conducted to evaluate the tracking performance of the proposed control methods.


Calcium current variation between acutely isolated adult rat dorsal root ganglion neurons of different size.
1. The distribution of pharmacologically and/or biophysically unique Ca2+ current subtypes was studied in different diameter rat dorsal root ganglion (DRG) neuron cell bodies. DRG cells which fell into three diameter ranges, small (20-27 microns), medium (33-38 microns) and large (45-51 microns), were studied. T-type Ca2+ current was defined as low-threshold, rapidly inactivating current evoked by a weak test depolarization (-50 mV) from negative holding potentials (-80 to -100 mV), and which was sensitive to changes in holding potential. L-type Ca2+ current was defined as peak high-threshold Ca2+ current evoked from a holding potential of -60 mV and sensitive to blockade by 2 microM-nimodipine. N-type Ca2+ current was defined as peak high-threshold Ca2+ current evoked from a holding potential of -60 mV and sensitive to blockade by 0.9 microM-omega-conotoxin GVIA. 2. T-type Ca2+ currents were observed in small and medium diameter, but not in large diameter, DRG cell bodies. Large diameter DRG cell bodies had a small amount of low-threshold Ca2+ current but this current did not inactivate and was insensitive to a change in holding potential from -80 to -90 mV, and thus did not appear to be conducted through T-type Ca2+ channels. The T-type Ca2+ currents observed in medium diameter DRG cell bodies were considerably larger in amplitude (1-6 nA) than those observed in small diameter DRG cell bodies (100 pA-1 nA). This difference could not be accounted for by the difference in membrane surface area of small versus medium diameter DRG cell bodies. 3. The T-type Ca2+ currents observed in medium diameter DRG cells were sensitive to blockade by amiloride. Amiloride (500 microM) blocked 79.4 +/- 0.9% (mean +/- S.E.M.) of T-type Ca2+ current amplitude in six medium diameter DRG cell bodies which were held at -80 mV and depolarized to -50 or -40 mV. Amiloride (500 microM) failed to block high-threshold current in five medium diameter DRG cell bodies, indicating that it was specific for T-type Ca2+ current in these cells. 4. The percentage of peak whole-cell L-type Ca2+ current was significantly larger in small diameter DRG cell bodies (52.9 +/- 4.7% of total whole-cell Ca2+ current) than in medium diameter DRG cell bodies (6.6 +/- 3.9% of total whole-cell Ca2+ current) or large diameter DRG cell bodies (19.4 +/- 5.7% of total whole-cell Ca2+ current).(ABSTRACT TRUNCATED AT 400 WORDS)


Reengineering biopharmaceuticals for targeted delivery across the blood-brain barrier.
Recombinant protein therapeutics cannot enter brain drug development because these large molecule drugs do not cross the blood-brain barrier (BBB). However, recombinant proteins can be reengineered as BBB-penetrating IgG fusion proteins, where the IgG part is a genetically engineered monoclonal antibody (MAb) against an endogenous BBB receptor, such as the human insulin receptor (HIR) or the transferrin receptor (TfR). The IgG binds the endogenous insulin receptor or TfR to trigger transport across the BBB and acts as a molecular Trojan horse (MTH) to ferry into brain the fused protein therapeutic. The most potent MTH to date is a MAb against the HIR, designated the HIRMAb, which is active in humans and Old World primates, such as the Rhesus monkey. There is no known MAb against the mouse insulin receptor. For drug delivery in the mouse, protein therapeutics are fused to a chimeric MAb against the mouse TfR, designated the cTfRMAb. The HIRMAb or cTfRMAb Trojan horses have been engineered and expressed as fusion proteins with multiple classes of protein therapeutics, including lysosomal enzymes, neurotrophins, decoy receptors, single chain Fv therapeutic antibodies, and avidin. The pharmacokinetic (PK) properties of the IgG fusion proteins differ from that of typical MAb drugs and resemble the PK profiles of small molecules due to rapid uptake by peripheral tissues, as well as brain. The brain uptake of the IgG fusion proteins, 2-3% of injected dose/brain, is comparable to the brain uptake of small molecules. The IgG fusion proteins have been administered chronically in mouse models, and the immune response is low titer and has no effect on the fusion protein clearance from blood or brain uptake in vivo. The BBB MTH technology enables the reengineering of a wide spectrum of recombinant protein therapeutics for targeted drug delivery to the brain.


Review of the Gargara genistae (Fabricius, 1775) species group (Hemiptera: Membracidae) from Russia and adjacent territories.
In Russia, Kazakhstan, and Central Asia the Gargara genistae species group includes three species differing from each other in the male calling signal patterns, but almost indistinguishable in external appearance and the male genitalia shape. Illustrated descriptions of morphology and the male calling signals, and data on host plants and distribution for all species are given. Considerations concerning possible modes of species divergence in this group are provided.


Important mammalian veterinary viral immunodiseases and their control.
This paper offers an overview of important veterinary viral diseases of mammals stemming from aberrant immune response. Diseases reviewed comprise those due to lentiviruses of equine infectious anaemia, visna/maedi and caprine arthritis encephalitis and feline immunodeficiency. Diseases caused by viruses of feline infectious peritonitis, feline leukaemia, canine distemper and aquatic counterparts, Aleutian disease and malignant catarrhal fever. We also consider prospects of immunoprophylaxis for the diseases and briefly other control measures. It should be realised that the outlook for effective vaccines for many of the diseases is remote. This paper describes the current status of vaccine research and the difficulties encountered during their development.


EAT-4, a homolog of a mammalian sodium-dependent inorganic phosphate cotransporter, is necessary for glutamatergic neurotransmission in caenorhabditis elegans.
The Caenorhabditis elegans gene eat-4 affects multiple glutamatergic neurotransmission pathways. We find that eat-4 encodes a protein similar in sequence to a mammalian brain-specific sodium-dependent inorganic phosphate cotransporter I (BNPI). Like BNPI in the rat CNS, eat-4 is expressed predominantly in a specific subset of neurons, including several proposed to be glutamatergic. Loss-of-function mutations in eat-4 cause defective glutamatergic chemical transmission but appear to have little effect on other functions of neurons. Our data suggest that phosphate ions imported into glutamatergic neurons through transporters such as EAT-4 and BNPI are required specifically for glutamatergic neurotransmission.


Early infant feeding and risk of type 1 diabetes mellitus-a nationwide population-based case-control study in pre-school children.
The evidence on the role of environmental factors in the development of type 1 diabetes is conflicting. Reducing potential bias and the variety of exposures, we investigated the association between type 1 diabetes risk and nutritional and environmental exposures in pre-school children. This nationwide population-based case-control study included 760 cases under 5 years of age newly diagnosed with type 1 diabetes during 1992-1995. From the general population, 1,871 controls were randomly selected and individually matched on age ( +/- 1 year), sex, and residence. Information on infant diet, foetal, perinatal and socio-economic factors, and familial diabetes was obtained by a parent-administered questionnaire. Data were analysed by multiple conditional logistic regression. Duration of breastfeeding and age at introduction of bottle-feeding were inversely associated with type 1 diabetes risk according to a dose-response relationship (trend test p < 0.05). Adjusted odd ratios (95% CI) for a long breastfeeding period and a late introduction of bottle-feeding (>or=5 month versus < 2 weeks) were 0.71 (0.54-0.93) and 0.80 (0.62-1.04), respectively. Familial type 1 diabetes, maternal age > 40 years, and low birth weight were found more frequently among diabetic than among control children. Current cow's milk consumption, higher social status, and a larger family were associated with a reduced diabetes risk. Up to one half of the diabetic cases in the population could be attributed to modifiable exposures. Our findings indicate that infant feeding is associated with type 1 diabetes risk and that a considerable part of new type 1 diabetic cases is potentially preventable.


Test-retest variability in glaucomatous visual fields.
We measured test-retest variations in computerized visual fields from glaucomatous eyes. Fifty-one patients were tested four times within a four-week period; the severity of disease varied from incipient to advanced. We determined the dependence of threshold variability on defect depth and test point location. In areas of the visual field initially found to have moderate loss of sensitivity, variation in follow-up measurements ranged from normal sensitivity to absolute defect, with little dependence on distance from fixation. Conversely, large changes were considerably more unusual in locations initially showing normal or near-normal sensitivities, and variability was lowest in the most central portion of the field. Our findings suggest that differentiation between true progression and random variation will be facilitated if these factors are taken into account, as well as if comparisons are based on more than two tests. The complex nature of interest variation in glaucoma makes it natural to approach this problem with the help of computer-assisted analyses.


Investigating interactions between chloroquine/hydroxychloroquine and their single enantiomers and angiotensin-converting enzyme 2 by a cell membrane chromatography method.
Chloroquine and hydroxychloroquine have been studied since the early clinical treatment of SARS-CoV-2 outbreak. Considering these two chiral drugs are currently in use as the racemate, high-expression angiotensin-converting enzyme 2 cell membrane chromatography was established for investigating the differences of two paired enantiomers binding to angiotensin-converting enzyme 2 receptor. Molecular docking assay and detection of SARS-CoV-2 spike pseudotyped virus entry into angiotensin-converting enzyme 2-HEK293T cells were also conducted for further investigation. Results showed that each single enantiomer could bind well to angiotensin-converting enzyme 2, but there were differences between the paired enantiomers and corresponding racemate in frontal analysis. R-Chloroquine showed better angiotensin-converting enzyme 2 receptor binding ability compared to S-chloroquine/chloroquine (racemate). S-Hydroxychloroquine showed better angiotensin-converting enzyme 2 receptor binding ability than R-hydroxychloroquine/hydroxychloroquine. Moreover, each single enantiomer was proved effective compared with the control group; compared with S-chloroquine or the racemate, R-chloroquine showed better inhibitory effects at the same concentration. As for hydroxychloroquine, R-hydroxychloroquine showed better inhibitory effects than S-hydroxychloroquine, but it slightly worse than the racemate. In conclusion, R-chloroquine showed better angiotensin-converting enzyme 2 receptor binding ability and inhibitory effects compared to S-chloroquine/chloroquine (racemate). S-Hydroxychloroquine showed better angiotensin-converting enzyme 2 receptor binding ability than R-hydroxychloroquine/hydroxychloroquine (racemate), while the effect of preventing SARS-CoV-2 pseudovirus from entering cells was weaker than R-hydroxychloroquine/hydroxychloroquine (racemate).


Lipid oxidation in fragrant rapeseed oil: Impact of seed roasting on the generation of key volatile compounds.
This work sought to identify the influence of roasting on lipid oxidation-derived volatile compounds in fragrant rapeseed oils (FROs) via gas chromatography-mass spectrometry and gas chromatography-ion mobility spectrometry. Seven volatiles could be regard as aroma-active compounds by application of odor activity value (OAV ≥ 1) calculation, and caused fatty-like, nutty-like, and green-like notes. After 60 min of roasting, the OAVs of hexanal, octanal, (E,E)-2,4-heptadienal, and nonanal in FROs were greater than 3. The same compounds, including hexanal, (E,E)-2,4-heptadienal, nonanal, 1-octanol, and nonanoic acid were also detected in the model systems of lipid oxidation. Notably, the values of p-anisidine, conjugated dienes, and conjugated trienes increased significantly (p < 0.05). Furthermore, correlation analysis showed that hexanal, (E,E)-2,4-heptadienal, and nonanal have a significant positive correlation with the oxidative degree of FROs (R = 0.70-0.94, p < 0.05). Thus, the three above-mentioned aldehydes could serve as important markers for FRO quality during roasting.


Anorexia nervosa in Glasgow.
A case note review of referrals to psychiatrists in Glasgow for 1979-1983 yielded 122 patients. Demographic and clinical data are described and compared to findings in earlier British series. Social class distribution for the Glasgow patients was no different from that of the local general population. This finding contrasted with the upper social class bias found in earlier studies and possible reasons for this difference are discussed.


Central serous chorioretinopathy and heart rate variability analysis with a smartphone application.
The purpose of this study was to quantitatively analyze heart rate variability (HRV) in patients with central serous chorioretinopathy (CSC) by using a smartphone-based application (ANBAI: DUMSCO Inc.) for measurement, and to clarify its relationships with CSC. The subjects were 64 CSC patients (mean age 48.7 ± 7.6 years, 57 males and 7 females). After providing consent, the patients downloaded ANBAI apps to their smartphones. HRV was measured by photoelectric volume pulse wave measurement with a smartphone camera each morning for a minimum of 1 week. The primary outcome was to analyze HRV by calculating log LF/HF (Low Frequency/High Frequency components), an index of autonomic tone, which was then compared with a control group of 35,226 individuals from the application. Secondary outcome measures included disease duration, body mass index, exercise habits, smoking history, steroid use, occupation, lifestyle regularity, psychological fatigue, physical fatigue, and average sleep time. The log LF/HF was significantly higher in the patient group than in the control group (P < 0.001). Log LF/HF was significantly lower in patients with exercise habits as a factor contributing to log LF/HF in the patient group (P = 0.019). Analysis of HRV in CSC patients showed an impairment of the autonomic nervous system. Exercise habits may also be associated with CSC.


ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility.
We describe two signaling events downstream of ERK-MAP kinase contributing to cell motility in colon carcinoma cells. The Fos family member Fra-1 is expressed in an ERK-dependent manner. Silencing of Fra-1 expression with short interfering RNAs leads to losses of cell polarization, motility, and invasiveness in vitro. These effects of ablating Fra-1 are a consequence of activation of a RhoA-ROCK pathway by beta1-integrin, leading to an increase in the amount of stress fibers and stabilization of focal adhesions. We propose that Fra-1 promotes cell motility by inactivating beta1-integrin and keeping RhoA activity low. This depression of RhoA activity is necessary to permit a second ERK-dependent signaling event via uPAR, the receptor for urokinase-type plasminogen activator, to activate Rac and to drive motility through polarized lamellipodia extension.


The use of monocyte to HDL ratio to predict postoperative atrial fibrillation after aortocoronary bypass graft surgery.
Postoperative atrial fibrillation (POAF) is a frequent and serious complication after aortocoronary bypass graft (ACBG) surgery and one that, unfortunately, increases morbidity and mortality. Postoperative stroke, hemodynamic instability, renal failure, infection, need for inotropic agent and coronary unit are complications caused by POAF. Inflammation and oxidative stress are among several mechanisms that contribute to pathogenesis of POAF. Monocyte to HDL (M/H) ratio is a newly defined parameter of both inflammation and oxidative stress. In this study, M/H ratio was investigated as predictor of POAF after ACBG surgery. Total of 311 patients who underwent ACBG surgery were included in the study. Blood samples for analysis of routine biochemistry and lipid panel were obtained from the patients on the morning of ACBG surgery after 12 hours of fasting. Patients were continuously monitored for occurrence of POAF throughout hospitalization. POAF was observed in 71 patients following ACBG operation. M/H ratio was significantly higher in POAF(+) group compared with POAF(-) group (p<0.001). Median age of POAF(+) patients was 62.0±10.1 years, which was significantly higher than mean age of POAF(-) patients. Other atrial fibrillation (AF) risk factors, such as hypertension, diabetes mellitus, smoking, and alcohol consumption, were similar between groups. Potassium level was statistically lower in POAF(+) group compared with POAF(-) group (p=0.01). M/H ratio is an indicator of inflammation and oxidative stress, both of which play important role in pathogenesis of AF. M/H ratio was found be statistically significantly higher in POAF(+) patients than in POAF(-) patients.


Deletion 9p22-pter and loss of Y as primary chromosome abnormalities in a squamous cell carcinoma of the vocal cord.
Loss of distal 9p is a common genetic alteration in squamous cell carcinoma of the head and neck. A vocal cord lesion incorporating a carcinoma-in-situ and a focus of invasive carcinoma revealed loss of the Y chromosome and a 9p22 rearrangement with loss of 9p22-pter. Loss of 9p22-pter appears to be a primary autosomal abnormality in this squamous cell carcinoma.


Submaximal force production during perceptually guided isometric exercise.
The aim of this study was to examine submaximal isometric force production guided by perceptual feelings of exertion. Thirty young adults performed isometric knee extensions on an isokinetic dynamometer. Subjects performed five different tests; the first test was the same for all subjects (standard naïve test). During the standard naïve test, subjects were asked to randomly produce force at perceived contraction intensities (25%, 50% and 75% of their maximum voluntary contraction (MVC)), with 100% MVC performed as the final intensity. All intensities, including the 100% MVC, were randomly performed in the other four tests (control tests 1 and 2, post 20% MVC and post 100% MVC tests). Post 20% MVC and post 100% MVC tests included fatiguing isometric exercise at 20% and 100% MVC respectively, which were performed prior to the test protocol. Results show that absolute peak force increased with increasing intensity (P<0.001) during all tests. During the standard naïve test, absolute peak force at 25% and 50% MVC was significantly lower (P=0.009) compared to control test 2, post 20% MVC and 100% MVC tests, and relative peak force was lower at all intensities compared to all other tests (P<0.001). Absolute and relative peak force was most accurate at 50% MVC (-12.06 N and -2.42%, respectively). Prior fatiguing isometric exercise did not affect the subsequent perceptual response range. In conclusion, isometric force was most accurate at 25% MVC but under-produced (perceptually overestimated) during higher contraction intensities preceding a maximal voluntary contraction (100% MVC). The ability to match absolute force with target contraction intensities was most accurate at 50% MVC during all five experimental conditions and poor at opposite ends of the force domain. Furthermore, prior fatiguing isometric exercise did not have an effect on the subsequent perceptual response range.


Discovery of novel benzimidazole derivatives as potent potassium-competitive acid blockers for the treatment of acid-related diseases.
H+, K+-ATPase, as the most critical enzyme in gastric acid secretion, has long been an attractive target for the treatment of acid-related diseases. In this study, a series of benzimidazole derivatives were designed and synthesized through conformational restriction and skeleton hopping strategies by using vonoprazan as the lead compound. Among them, compounds A12 (IC50 = 9.32 μM) and A18 (IC50 = 5.83 μM) showed better inhibition at the enzyme level. In addition, gastric acid secretion inhibition was assessed in vivo, and the results showed that A12 and A18 significantly inhibited basal gastric acid secretion, 2-deoxy-d-glucose (2DG) stimulated gastric acid secretion and histamine-stimulated gastric acid secretion. In further in vitro metabolic experiments, A12 and A18 demonstrated excellent stability and low toxicity. Pharmacokinetic studies showed that the p.o. and i.v. half-lives of A18 were 3.21 h and 8.67 ± 1.15 h, respectively. In summary, A18 might be a novel and effective potassium-competitive acid blocker, and this study provides strong support for it use in the treatment of acid-related diseases.


Interactions of the excision proteins of CTnDOT in the attR intasome.
Excision of the conjugative transposon CTnDOT from the chromosome of Bacteroides spp. involves four CTnDOT-encoded proteins: IntDOT, Xis2c, Xis2d, and Exc along with a host factor. These proteins form excisive intasomes on the attR and attL sites which undergo synapsis and recombination to form the attDOT and attB sites. We recently developed an in vitro intramolecular excision reaction where the attL and attR sites are on the same plasmid. This reaction requires IntDOT, Xis2c, Xis2d, and is stimulated by Exc. We used this reaction to identify the binding sites of the IntDOT, Xis2c, and Xis2d. In this paper, we show that three of the six arm-type sites are absolutely required for excision. Furthermore, we also identified two binding sites for Xis2d and two possible binding sites for Xis2c on the attR site. We also showed that IntDOT interacts cooperatively with the Xis2c and Xis2d proteins on the attR site.


The effect of the use of Limosilactobacillus fermentum S8 isolated from organic acid whey on nitrosyl pigment concentration and the colour formation of uncured cooked meat products.
This paper studies the application of Limosilactobacillus fermentum S8 from organic whey in meat processing and investigation the effect of bacteria on the concentration of nitrosyl pigments, colour formation, physicochemical characteristics and microbiological quality of uncured cooked meat products. 3 canned meat batters' were produced: control with salt and sodium nitrite (100 mg/ kg), treatment with salt, treatment with salt and L. fermentum S8 (107 cfu/g), then the cans were stored and cooked. The tests were carried out after production, 32 and 56 days of cold storage. It was shown that the use of L. fermentum in the processing of uncured meat caused the increase concentration of nitrosyl pigments and redness (a*) in the products after cooking. The addition of bacteria had a significant impact on the lowering pH value and the redox potential of the cooked products. The product from L. fermentum was characterized by a similar microbiological quality as compared to the traditionally cured and non-cured products (P < 0.05).


Inhabited or Uninhabited? Pitfalls in the Interpretation of Possible Chemical Signatures of Extraterrestrial Life.
The "Rare Earth" hypothesis-put forward by Ward and Brownlee in their 2000 book of the same title-states that prokaryote-type organisms may be common in the universe but animals and higher plants are exceedingly rare. If this idea is correct, the search for extraterrestrial life is essentially the search for microorganisms. Various indicators may be used to detect extant or extinct microbial life beyond Earth. Among them are chemical biosignatures, such as biomolecules and stable isotope ratios. The present minireview focuses on the major problems associated with the identification of chemical biosignatures. Two main types of misinterpretation are distinguished, namely false positive and false negative results. The former can be caused by terrestrial biogenic contaminants or by abiotic products. Terrestrial contamination is a common problem in space missions that search for biosignatures on other planets and moons. Abiotic organics can lead to false positive results if erroneously interpreted as biomolecules, but also to false negatives, for example when an abiotic source obscures a less productive biological one. In principle, all types of putative chemical biosignatures are prone to misinterpretation. Some, however, are more reliable ("stronger") than others. These include: (i) homochiral polymers of defined length and sequence, comparable to proteins and polynucleotides; (ii) enantiopure compounds; (iii) the existence of only a subset of molecules when abiotic syntheses would produce a continuous range of molecules; the proteinogenic amino acids constitute such a subset. These considerations are particularly important for life detection missions to solar system bodies such as Mars, Europa, and Enceladus.


Members of the tomato FRUITFULL MADS-box family regulate style abscission and fruit ripening.
The tomato (Solanum lycopersicum) protein MADS-RIN plays important roles in fruit ripening. In this study, the functions of two homologous tomato proteins, FUL1 and FUL2, which contain conserved MIKC domains that typify plant MADS-box proteins, and which interact with MADS-RIN, were analysed. Transgenic functional analysis showed that FUL1 and FUL2 function redundantly in fruit ripening regulation, but exhibit distinct roles in the regulation of cellular differentiation and expansion. Over-expression of FUL2 in tomato resulted in a pointed tip at the blossom end of the fruit, together with a thinner pericarp, reduced stem diameter, and smaller leaves, but no obvious phenotypes resulted from FUL1 over-expression. Dual suppression of FUL1 and FUL2 substantially inhibited fruit ripening by blocking ethylene biosynthesis and decreasing carotenoid accumulation. In addition, the levels of transcript corresponding to ACC SYNTHASE2 (ACS2), which plays a key role in ethylene biosynthesis, were significantly decreased in the FUL1/FUL2 knock-down tomato fruits. Overall, our results suggest that FUL proteins can regulate tomato fruit ripening through fine-tuning ethylene biosynthesis and the expression of ripening-related genes.


Mononuclear phagocyte maturation: a cytotoxic monoclonal antibody reactive with postmonoblast stages.
The rat IgM monoclonal antibody B23.1 was found to bind to mononuclear phagocytes that had matured beyond the monoblast stage. Macrophages from several anatomical sites, elicited by different means, as well as those cultured from bone marrow precursors, bound B23.1 antibody. The increase, with time, of B23.1-positive cells in the nonadherent fraction of cultured bone marrow paralleled that of immature mononuclear phagocytes as detected by esterase staining. Treatment of freshly explanted bone marrow cells with B23.1 and complement did not reduce the number of macrophage colony-forming cells (monoblasts) in that population. Treatment with B23.1 antibody alone did not alter the activation of macrophages for tumor cell killing; however, with added complement, B23.1 reduced activated macrophage-mediated cytotoxicity to background levels. In similar studies B23.1 and complement did not affect antibody production by B cells, the cytotoxic capacity of T cells, or NK cell-mediated lysis. These data indicate that antibody B23.1 is useful for either the detection or elimination of mouse mononuclear phagocytes from the promonocyte stage to that of the mature macrophage.


[The investigation with contrast sensitivity after implantation with UV and UVCY types of intraocular lens].
To research the difference in vision after UV and UVCY two types of intraocular lens implantation (The light 380-790 nm may transmit through the UV lens, and the UVCY lens may partly filter the light < 640 nm including part of the light < 460 nm.). MCT 8000 contrast tester was used in the postoperative two months. The contrast sensitivity of the patients with UVCY lenses was superior to that with UV lenses obviously (P < 0.05) under the condition of glare and 3 c/d, 6 c/d space frequency. The UVCY lens is more advantageous to improve visual function.


Phylogeny of the Asparagales based on three plastid and two mitochondrial genes.
The Asparagales, with ca. 40% of all monocotyledons, include a host of commercially important ornamentals in families such as Orchidaceae, Alliaceae, and Iridaceae, and several important crop species in genera such as Allium, Aloe, Asparagus, Crocus, and Vanilla. Though the order is well defined, the number of recognized families, their circumscription, and relationships are somewhat controversial. Phylogenetic analyses of Asparagales were based on parsimony and maximum likelihood using nucleotide sequence variation in three plastid genes (matK, ndhF, and rbcL) and two mitochondrial genes (atp1 and cob). Branch support was assessed using both jackknife analysis implementing strict-consensus (SC) and bootstrap analysis implementing frequency-within-replicates (FWR). The contribution of edited sites in the mitochondrial genes to topology and branch support was investigated. The topologies recovered largely agree with previous results, though some clades remain poorly resolved (e.g., Ruscaceae). When the edited sites were included in the analysis, the plastid and mitochondrial genes were highly incongruent. However, when the edited sites were removed, the two partitions became congruent. Some deeper nodes in the Asparagales tree remain poorly resolved or unresolved as do the relationships of certain monogeneric families (e.g., Aphyllanthaceae, Ixioliriaceae, Doryanthaceae), whereas support for many families increases. However, the increased support is dominated by plastid data, and the potential influence of mitochondrial and biparentially inherited single or low-copy nuclear genes should be investigated.


Time-dependent effects of isolation on lymphocyte and adrenocortical activity.
Individual housing of previously group-housed animals was found to result in time-dependent changes in mitogen-induced lymphocyte proliferation and plasma corticosterone concentrations. During the first week of isolation, both B and T lymphocyte responses were depressed. However, within 2 weeks at least a 2-fold enhancement was observed. The increased lymphocyte response was still present after 35 days of isolation. Within the first day of isolation and continuing for 2 weeks, plasma corticosterone levels were found to be significantly decreased in isolated animals compared to those of continuously housed animals. No significant differences in steroid levels were observed by 35 days. These data demonstrate that isolation is accompanied by a depressed adrenocortical activity and suggest that the immunosuppression associated with short-term exposure is mediated by factors other than corticosterone.


Genome-scale reconstruction of Salinispora tropica CNB-440 metabolism to study strain-specific adaptation.
The first manually curated genome-scale metabolic model for Salinispora tropica strain CNB-440 was constructed. The reconstruction enables characterization of the metabolic capabilities for understanding and modeling the cellular physiology of this actinobacterium. The iCC908 model was based on physiological and biochemical information of primary and specialised metabolism pathways. The reconstructed stoichiometric matrix consists of 1169 biochemical conversions, 204 transport reactions and 1317 metabolites. A total of 908 structural open reading frames (ORFs) were included in the reconstructed network. The number of gene functions included in the reconstructed network corresponds to 20% of all characterized ORFs in the S. tropica genome. The genome-scale metabolic model was used to study strain-specific capabilities in defined minimal media. iCC908 was used to analyze growth capabilities in 41 different minimal growth-supporting environments. These nutrient sources were evaluated experimentally to assess the accuracy of in silico growth simulations. The model predicted no auxotrophies for essential amino acids, which was corroborated experimentally. The strain is able to use 21 different carbon sources, 8 nitrogen sources and 4 sulfur sources from the nutrient sources tested. Experimental observation suggests that the cells may be able to store sulfur. False predictions provided opportunities to gain new insights into the physiology of this species, and to gap fill the missing knowledge. The incorporation of modifications led to increased accuracy in predicting the outcome of growth/no growth experiments from 76 to 93%. iCC908 can thus be used to define the metabolic capabilities of S. tropica and guide and enhance the production of specialised metabolites.


The inhibitory effect of tumor necrosis factor and interleukin-1 on Ia induction by interferon-gamma on endothelial cells from murine central nervous system microvessels.
The effect of both tumor necrosis factor-alpha (TNF) and interleukin-1 (IL-1) on interferon-gamma (IFN)-induced Ia expression was studied using cultured endothelial cells (EC) isolated from cerebral microvessels of SJL mice. TNF inhibited Ia induction by IFN in a dose-dependent manner. The degree of inhibition by TNF was related to the IFN concentration: 200 U/ml TNF inhibited Ia expression induced by 20 U/ml IFN by 80% and Ia induced by 100 U/ml IFN by 45%. FACS analysis revealed the induction of Ia antigen on 30-40% of EC after 3 days' culture with IFN; TNF significantly reduced the percent of EC expressing Ia antigens. Identical treatment of SJL astrocytes showed TNF augmented Ia expression induced by IFN. IL-1 also inhibited Ia induction by IFN in a manner similar to that observed with TNF. The percent reduction of Ia-positive EC by Il-1 (2.0 U/ml) was 30% and 50% during incubations with 100 and 20 U/ml IFN, respectively. When combined at suboptimal concentrations IL-1 and TNF synergistically inhibited Ia expression induced by IFN. These results demonstrate that TNF acts on EC and astrocytes in a disparate manner and indicate that TNF and IL-1 can synergistically down-regulate immune responses involving central nervous system EC.


[Jejuno-ileal bypass in the treatment of severe obesity: transverse or vertical approach?].
The criteria applicable to the selection of the approach route in the surgical management of essential gross obesity by means of a jejunal-ileal by-pass are discussed. Median vertical and transverse incision are compared in the light of early and late hypoxaemia in the immediate postoperative period; postoperative acidosis and alkalosis; rapidity; exposure; extendibility; tightness; postoperative pain; cosmetic results. A preference for the vertical approach is both stated and justified.


Ulcer healing time and antibiotic treatment before and after the introduction of the Registry of Ulcer Treatment: an improvement project in a national quality registry in Sweden.
To investigate changes in ulcer healing time and antibiotic treatment in Sweden following the introduction of the Registry of Ulcer Treatment (RUT), a national quality registry, in 2009. A statistical analysis of RUT data concerning the healing time and antibiotic treatment for patients with hard-to-heal ulcers in Sweden between 2009 and 2012. RUT is a national web-based quality registry used to capture areas of improvement in ulcer care and to structure wound management by registering patients with hard-to-heal leg, foot and pressure ulcers. Registration includes variables such as gender, age, diagnosis, healing time, antibiotic treatment, and ulcer duration and size. Every patient with a hard-to-heal ulcer registered with RUT between 2009 and 2012 (n=1417) was included. Statistical analyses were performed using Stata V.12.1. Healing time was assessed with the Kaplan-Meier analysis and adjustment was made for ulcer size. A log-rank test was used for equality of survivor functions. According to the adjusted registry in December 2012, patients' median age was 80 years (mean 77.5 years, range 11-103 years). The median healing time for all ulcers, adjusted for ulcer size, was 146 days (21 weeks) in 2009 and 63 days (9 weeks) in 2012 (p=0.001). Considering all years between 2009 and 2012, antibiotic treatment for patients with hard-to-heal ulcers was reduced from 71% before registration to 29% after registration of ulcer healing (p=0.001). Healing time and antibiotic treatment decreased significantly during 3 years after launch of RUT.


Cognitive-Behavioral Therapy to Alleviate Treatment-Induced Menopausal Symptoms in Women With Breast Cancer: A Systematic Review.
Numerous women with breast cancer (BC) exhibit early menopausal symptoms after undergoing cancer treatments. Medications that control menopausal symptoms can cause severe side effects and are contraindicated for patients with BC. Therefore, complementary and alternative medicines should be used. This study investigates the use of cognitive-behavioral therapy (CBT) for patients with menopausal symptoms after BC treatment. A systematic review was conducted to determine the efficacy and availability of CBT interventions in reducing treatment-induced menopausal symptoms in female patients with BC. Keywords were searched in Medical Subject Headings and 5 databases. The search criteria included randomized controlled trials (RCTs), non-RCTs, and single-group pre- and post-studies. Because of the risk of bias in non-RCTs using Joanna Briggs Institute's critical appraisal tools and single-group studies, the Critical Appraisal Skills Programme checklist for qualitative studies and RCTs was appraised using the Jadad scale. After the review, 9 suitable studies were identified. Standard CBT programs lasted for 6 consecutive weeks, with 1 session of 1.5 hours weekly. The follow-up time was approximately 9 to 26 weeks. Women receiving CBT exhibited improvement in physical function and psychological state. This review supported the use of CBT to effectively improve the mental health of and reduce treatment-induced menopausal symptoms in BC survivors. Cognitive-behavioral therapy interventions yielded positive outcomes in patients with BC, particularly in those experiencing menopausal symptoms. Cancer treatment generated severe menopausal symptoms in patients with BC. However, health professionals may use CBT to alleviate patients' menopausal symptoms.


HSV-1 amplicon vector-mediated expression of ATM cDNA and correction of the ataxia-telangiectasia cellular phenotype.
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by neurodegeneration, immunodeficiency, cancer predisposition, genome instability, and radiation sensitivity. Previous research has shown that it is possible to correct the hereditary deficiency A-T by DNA transfection in cell culture, but the large size of the ATM cDNA (9 kb) limits the use of many vector types for gene replacement. HSV-1 amplicon vectors provide a means to deliver large genes to cells efficiently and without toxicity. In this study, the FLAG-tagged cDNA for human ATM was inserted into an HSV-1 amplicon under control of the CMV promoter (designated as HGC-ATM). FLAG-ATM expression was confirmed in 293T/17 cells and human A-T fibroblasts (GM9607) after transduction, by immunoprecipitation, Western analysis, and immunocytochemistry. Functional recovery was assessed by two independent assays. First, in vitro kinase assay showed that vector-derived ATM in GM9607 cells could successfully phosphorylate wt p53 using recombinant GST-p53(1-101). Second, in A-T cells infected with the HGC-ATM vector, the extent of accumulation in G2/M phase at 24 h postirradiation was similar to that observed in cells with wild-type endogenous ATM and lower than that observed in A-T cells infected with a control vector. Thus, these vectors provide a tool to test the feasibility of HSV-amplicons as gene therapy vectors for A-T.


Enzymatic Generation of Highly Anticoagulant Bovine Intestinal Heparin.
Unlike USP porcine heparin, bovine intestinal heparin (BIH) has a low anticoagulant activity. Treatment with 6-OST-1, -3, and/or 3-OST-1 afforded two remodeled heparins that met USP heparin activity and Mw specifications. We explored the pharmacodynamics and pharmacokinetics in a rabbit model. We conclude that a modest increase in the content of 3-O-sulfo groups in BIH increases the number of antithrombin III binding sites, making remodeled BIH behave similarly to pharmaceutical heparin.


[Addisonian crisis provoked by levothyroxine substitution therapy].
A women aged 36 with a positive family anamnesis for autoimmune endocrine diseases and a history of thyroid diseases, developed major complaints of general malaise, orthostatic hypotension and loss of appetite after the start of a treatment with levothyroxin because of (sub)clinical hypothyroidism. She was found to suffer from primary adrenocortical insufficiency masked by excessive use of liquorice and a lowered metabolism, but which via the suppletion with thyroid hormone had led to an addisonian crisis.


[Characteristics of a gynecology clinic in the inland region of Ceará (Brazil)].
To identify the strategies (interactive and educational) used by physicians and nurses in gynecology consultations and the length of consultations. We performed an exploratory descriptive study. A questionnaire was used to interview 5 health professionals working in a gynecology clinic (3 physicians and 2 nurses). A total of 141 women who attended the clinic between July and August 2004 in a health district of the inland region of the State of Ceará in Brazil were also interviewed. Of the 141 women, 130 (92.2%) had sufficient education to understand the information given during the consultation. Eighty patients (56.7%) attended the service for gynecological disorders, the most frequent of which were pelvic pain (45%), followed by pruritus and discharge (33.8%). A total of 14.2% attended for cervical and breast cancer prevention. All 5 health professionals performed the Pap test and one health professional provided an educational leaflet during the consultation. The health professionals believed that the women understood half of the explanations given during the consultation and attributed this lack of understanding to their low educational level. The mean length of the consultation ranged from 2 to 7.5 minutes. Few women attended the clinic for cervical and breast cancer prevention. This finding could be related to the way in which the health professionals carried out the consultation and its length.


Revealing and IgG4 analysis to factor VIII in haemophilia-A patients with and without inhibitors.
The acquisition of factor VIII inhibitors poses major management challenges for haemophilia A (HA) patients. Most (Factor VIII) inhibitors are immunoglobulin G4 (IgG4) and G1 (IgG1) subclasses, with IgG4 being the most prevalent. The Nijmegen Bethesda Assay (NBA) was used to quantify inhibitors. However, the requirement for a large sample volume, accompanying costs, and required technical expertise complicate NBA, particularly in developing countries. ELISA-based screening proved to be more viable in a resource-constrained scenario. This study aimed to standardise and evaluate an in-house IgG4 ELISA for the detection of haemophilia A inhibitors. This study enrolled thirty HA patients with inhibitors, thirty three HA without inhibitors, and 33 healthy controls. Standardisation of in-house IgG4 ELISA was performed. The checkerboard method was employed to optimise plasma-derived Factor VIII concentrations (HEMOFIL M Baxalta US Inc.), sample dilutions, and anti-human IgG4-HRP conjugate (Southern Biotechnology, USA). The samples were evaluated three times, and the mean optical density (OD) was used to determine the cutoff. Using a cutoff OD (mean±2SD) of 0.502 in our in-house ELISA, we could differentiate healthy controls and HA without inhibitors from HA with inhibitors with 93.3 % sensitivity, 97.0 % specificity, 97 % NPV, and 93.3 % PPV, respectively. However, the accuracy was 95.83 %. The two-way mixed-effects model, interclass correlation (ICC) derived by Cronbach's Alpha was 0.912 (p = 0.001) and close to perfect agreement. IgG4 ELISA is an effective method for detecting neutralising or functionally significant FVIII inhibitors, particularly in resource-constrained settings, following which patients may be referred to referral laboratories for quantification of inhibitors.


Reconsideration of the ECG in pericarditis; have we been led astray all these years?
Recently, new criteria for the diagnosis of pericarditis have been published. This paper has been thought to point out the limits in the new criteria specificity as well in the application of the new criteria for the diagnosis of pericarditis as recently demonstrated by studies based on cardiac magnetic resonance imaging. We report the case of A 18y old male with no significant past medical history who presented with complaints of chest pain typical for pericarditis, initially labeled as pericarditis; the patient was evaluated by electrocardiography, trans-thoracic echocardiography and cardiac magnetic resonance imaging; the condition, based on electrocardiogram and trans-thoracic echocardiography findings, was labeled as pericarditis in keeping with current diagnostic criteria. Cardiac magnetic resonance imaging demonstrated myocardial edema with no T2-defined pericardial inflammation on TIR/T2 imaging; late gadolinium enhancement imaging demonstrated multiple irregular, punctate, epicardial zones. The constellation of findings was consistent with acute myocarditis without pericardial involvement. In conclusion, limits in specificity of the newly published criteria for diagnosis of pericarditis, which add to the already demonstrated limits in sensitivity, subsist. Cardiac magnetic resonance imaging plays a unique role in the initial assessment of pericarditis; this is particularly important in the Covid-19 era in light of the increasing incidence of myocarditis and pericarditis; also, the case suggests that the combination of information between advanced echocardiography and cardiac magnetic resonance imaging may have an important diagnostic role in this setting. Additionally, we suggest that despite recent enthusiasm for colchicine, its role may be best defined in those with myocarditis, not pericarditis.


Malignant fibrous histiocytoma of the retroperitoneum and genitourinary tract: a clinicopathological correlation and review of the literature.
Malignant fibrous histiocytoma is an uncommon pleomorphic tumor of the soft tissues possibly arising from the histiocyte. A case of malignant fibrous histiocytoma in the retroperitoneal space is reported. Pathologic and clinical features of this lesion as they relate to the retroperitoneum and genitourinary tract are discussed and suggestions for therapy are presented.


Effects of the Israel doctors' strike on hypertension control in Ashdod.
We examined hypertension control during the Israel doctors' strike in a defined insured population of known hypertensives enrolled in a nurse-based hypertension control program. The strike was associated with a measurable increase in the prevalence of uncontrolled hypertension which was limited to males of relatively higher social class. No strike-related changes in hypertension control were seen for women or lower social class males. We infer from this finding that the presence of a physician is a necessary component of good hypertension control in the sub-group of males of higher socioeconomic status. The incidence of hypertension-related complications in this relatively non-compliant subpopulation needs further investigation.


Effect of facet-joint degeneration on the in vivo motion of the lower lumbar spine.
This research studied the in vivo motion characteristics of the L3-S1 lumbar spine with facet-joint degeneration during functional activities. Thirteen male and 21 female patients with facet-joint degeneration at the L3-S1 spinal region were included in the study. The L3-S1 lumbar segments of all the patients were divided into 3 groups according to the degree of facet-joints degeneration (mild, moderate, or severe). The ranges of motion (ROM) of the vertebrae were analyzed using a combination of computed tomography and dual fluoroscopic imaging techniques. During functional postures, the ROMs were compared between the 3 groups at each spinal level (L3-L4, L4-L5, and L5-S1). At L3-L4 level, the primary rotations between the mild and moderate groups during left-right twisting activity were significantly different. At L4-L5 level, the primary rotation of the moderate group was significantly higher than the other groups during flexion-extension. During left-right bending activities, a significant difference was observed only between the moderate and severe groups. At L5-S1 level, the rotation of the moderate group was significantly higher than the mild group during left-right bending activity. Degeneration of the facet joint alters the ROMs of the lumbar spine. As the degree of facet-joint degeneration increased, the ROMs of the lumbar vertebra that had initially increased declined. However, when there was severe facet-joint degeneration, the ROMs of the lumbar spine declined to levels comparative to the moderate group. The relationship between the stability of the lumbar vertebra and the degree of facet-joint degeneration requires further study.


Intravitreal administration of adalimumab delays retinal degeneration in rd10 mice.
Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by the progressive and irreversible loss of vision. We previously found that intraperitoneal administration of Adalimumab, a monoclonal anti-TNFα antibody, slowed down retinal degeneration in the murine model of RP, the rd10 mice. The aims of this study were to improve its neuroprotective effect and to deepen understanding of the molecular mechanisms involved in this effect. We analyzed (i) the in vitro effect of Adalimumab on the TNFα-mediated cell death in retinal cells; (ii) the effect of a single intravitreal injection of Adalimumab on retinal degeneration in rd10 mice at postnatal day (P) 23. In vitro studies showed that TNFα induced caspase and poly ADP ribose polymerase (PARP) activation, downregulation of (kinase receptor-interacting protein 1) RIPK1 and upregulation of RIPK3 in retinal cells. Adalimumab reduced cell death probably through the inhibition of caspase 3 activation. In vivo studies suggested that PARP and NLRP3 inflammasome are mainly activated and to a lesser extent caspase-dependent mechanisms in rd10 retinas at P23. Necroptosis seems to be inhibited by the downregulation of RIPK1. Adalimumab prevented from retinal degeneration without affecting caspase -dependent mechanisms but decreasing PARP activation, microglia activation as well as NLRP3 inflammasome.


A 116-kDa phytoglycoprotein inhibits aberrant crypt foci formation through modulation of manganese superoxide dismutase, inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-kappa B, activator protein-1, and proliferating cell nuclear antigen in 1,2-dimethylhydrazine/dextran sodium sulfate-treated ICR mice.
The 116-kDa Ulmus davidiana Nakai (UDN) glycoprotein is a naturally occurring phytoglycoprotein found in the stem of UDN. In this study, we investigated the chemopreventive effect of UDN glycoprotein on inflammation-mediated colorectal carcinogenesis induced by 10 mg/kg 1,2-dimethylhydrazine and 2% dextran sodium sulfate in ICR mice. Consumption of UDN glycoprotein (0.01 and 0.02%) significantly reduced the frequency of colonic aberrant crypt foci, the expression of colonic proliferating cell nuclear antigen, and the release of plasma lactate dehydrogenase without any cytotoxic activity at the initiation stage of colorectal carcinogenesis in 1,2-dimethylhydrazine/dextran sodium sulfate-treated mice. In addition, UDN glycoprotein has antioxidative effects on the formation of plasma thiobarbituric acid reactive substances and on the production of plasma inducible nitric oxide, accompanying the normalizing effects on the activity of colonic antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) in the mice. UDN glycoprotein intake also remarkably attenuated the expression of inflammation-related factors (inducible nitric oxide synthase and cyclooxygenase-2) and the DNA-binding activity of redox-sensitive transcription factors (nuclear factor-kappa B and activator protein-1) in the mice. Collectively, the results suggest that UDN glycoprotein has chemopreventive potential at the initiation stage of colorectal cancer by reducing the factors responsible for oxidative stress, inflammation, and carcinogenesis.


Immunoelectron microscopic localization of thyrotropin-releasing hormone (TRH) precursor in the rat raphe nuclei.
Using antisera to two pro-thyrotropin-releasing hormone (pro-TRH)-derived cryptic peptides, we have studies by immunocytochemistry the ultrastructural localization of pro-TRH in the rat raphe nuclei. The same results were obtained with both antisera. Immunostaining was found in cell bodies, dendrites and endings. In cell bodies, the reaction product was restricted to Golgi saccules and dense core vesicles which were very few in number. In dendrites, the staining was rather diffuse without any association with specific organelles. These results suggest that the Golgi apparatus might be involved in pro-TRH processing.


[Phospholipid composition of lymphocytes from normal and leukemic blood, lymph, lymph nodes and spleen of cattle].
The phospholipid composition and cholesterol content of lymphocytes from bovine blood, lymph, lymph-nodes and spleen were studied. The cholesterol/phospholipid molar ratio in the normal lymphocytes of blood and spleen was found to be about two times higher than that in the normal lymphocytes from lymph and lymph-nodes. On lymphocytic leukemia the cholesterol/phospholipid molar ratio of the blood lymphocytes decreased sharply, whereas that in lymph and lymph-nodes lymphocytes was unaffected.


Feasibility of force myography for the direct control of an assistive robotic hand orthosis in non-impaired individuals.
Assistive robotic hand orthoses can support people with sensorimotor hand impairment in many activities of daily living and therefore help to regain independence. However, in order for the users to fully benefit from the functionalities of such devices, a safe and reliable way to detect their movement intention for device control is crucial. Gesture recognition based on force myography measuring volumetric changes in the muscles during contraction has been previously shown to be a viable and easy to implement strategy to control hand prostheses. Whether this approach could be efficiently applied to intuitively control an assistive robotic hand orthosis remains to be investigated. In this work, we assessed the feasibility of using force myography measured from the forearm to control a robotic hand orthosis worn on the hand ipsilateral to the measurement site. In ten neurologically-intact participants wearing a robotic hand orthosis, we collected data for four gestures trained in nine arm configurations, i.e., seven static positions and two dynamic movements, corresponding to typical activities of daily living conditions. In an offline analysis, we determined classification accuracies for two binary classifiers (one for opening and one for closing) and further assessed the impact of individual training arm configurations on the overall performance. We achieved an overall classification accuracy of 92.9% (averaged over two binary classifiers, individual accuracies 95.5% and 90.3%, respectively) but found a large variation in performance between participants, ranging from 75.4 up to 100%. Averaged inference times per sample were measured below 0.15 ms. Further, we found that the number of training arm configurations could be reduced from nine to six without notably decreasing classification performance. The results of this work support the general feasibility of using force myography as an intuitive intention detection strategy for a robotic hand orthosis. Further, the findings also generated valuable insights into challenges and potential ways to overcome them in view of applying such technologies for assisting people with sensorimotor hand impairment during activities of daily living.


Teachers' Experiences With LGBTQ+ Issues in Secondary Schools: A Mixed Methods Study.
This study investigated teachers' experiences with LGBTQ+ instruction as well as other school environment changes related to LGBTQ+ issues. It looked at teachers' attitudes towards LGBTQ+ individuals, comfort levels with the topics and administrative support, self-perceived knowledge and teacher preparation, and supports and barriers to instruction. Lastly, the study investigated teachers' in-service and pre-service training experiences. Using a sequential mixed methods approach, research began with qualitative inquiry, followed by quantitative assessment via self-administered paper surveys. There were 11 in-depth participant interviews, and 94 surveys assessing teachers' attitudes, comfort levels, self-perceived knowledge and preparation, and supports and barriers to LGBTQ+ topics. Data analysis revealed teachers' school location and pre-service and in-service training experiences impacted comfort levels and self-perceived knowledge and preparation levels to teach these issues. Data also indicated that new teachers were the least comfortable with LGBTQ+ topics in the classroom and school environment. Data demonstrated lack of LGBTQ+ teacher training, indicated need to support new Health Education professionals, and inadequate pre-service teacher training.


Extraocular proprioceptive projections to the visual cortex.
Electrical stimulation of the intraorbital part of the motor branches of extraocular muscles, where proprioceptive fibers run, evokes responses in 25% of the units of the striate cortex of the cat. The latency ranges between 25 and 40 msec. Mechanical stretch of extraocular muscles evokes multiunit responses in the striate cortex. The response is abolished by injection of xylocaine into the stretched muscle. The suppression of the response is reversible.


N-Terminal chemical derivatization of peptides with 4-formyl-benzenesulfonic acid and electrospray positive and negative tandem mass spectrometry with high abundance of b-ion series.
Selective derivatization of peptide N-terminus with 4-formyl-benzenesulfonic acid (FBSA) enables chemically activated fragmentation in positive and negative ion modes (ESI+/-) under charge reduction conditions. Overlapped positive and negative tandem mass spectra show b-ions making the assignment of b-ion series fragments easy and accurate. We developed an FBSA-peptide microwave-assisted derivatization procedure. Derivatized and nonderivatized bovine serum albumin tryptic peptides and insulin non-tryptic peptide were compared after tandem mass spectrometry (MS/MS) analysis in positive and negative ion modes. A high-quality data set of sulfonated b-ions obtained in negative tandem mass spectra of singly charged FBSA-peptides were matched to detected b-ions in positive MS/MS spectra. Moreover, negative spectra signals were converted and matched against y-ions in positive tandem mass spectra to identify complete peptide sequences. The FBSA derivatization procedure produced a significantly improved MS/MS data set (populated by high-intensity signals of b- and y-ions) compared to commonly used N-terminal sulfonation reagents. Undesired side reactions almost do not occur, and the procedure reduces the derivatization time. It was found that b-ion intensities comprise 15% and 13% compared to combined ion intensities generated in positive- and negative ion modes, respectively. High visibility of b-ion series in negative ion mode can be attributed to N-terminal sulfonation that had no negative effect on the production of b- and y-ion series in positive ion mode. The FBSA derivatization and de novo sequencing approach outlined here is a reliable method for accurate peptide sequence assignment. Increased production of b-ions in positive- and negative ion modes greatly improves peak assignment and thus enables accurate sequence reconstruction. Implementation of the named methodology would improve the quality of de novo sequencing data and reduce the number of misinterpreted spectra.


Acute pancreatitis as a complication of anaphylactoid (Henoch-Schönlein) purpura.
A case of acute pancreatitis complicating anaphylactoid purpura (Henoch-Schönlein syndrome) is reported. In cases of this syndrome with abdominal pain, serum amylase levels should be estimated.


Genome-wide analysis of MdPLATZ genes and their expression during axillary bud outgrowth in apple (Malus domestica Borkh.).
Branching is a plastic character that affects plant architecture and spatial structure. The trait is controlled by a variety of plant hormones through coordination with environmental signals. Plant AT-rich sequence and zinc-binding protein (PLATZ) is a transcription factor that plays an important role in plant growth and development. However, systematic research on the role of the PLATZ family in apple branching has not been conducted previously. In this study, a total of 17 PLATZ genes were identified and characterized from the apple genome. The 83 PLATZ proteins from apple, tomato, Arabidopsis, rice, and maize were classified into three groups based on the topological structure of the phylogenetic tree. The phylogenetic relationships, conserved motifs, gene structure, regulatory cis-acting elements, and microRNAs of the MdPLATZ family members were predicted. Expression analysis revealed that MdPLATZ genes exhibited distinct expression patterns in different tissues. The expression patterns of the MdPLATZ genes were systematically investigated in response to treatments that impact apple branching [thidazuron (TDZ) and decapitation]. The expression of MdPLATZ1, 6, 7, 8, 9, 15, and 16 was regulated during axillary bud outgrowth based on RNA-sequencing data obtained from apple axillary buds treated by decapitation or exogenous TDZ application. Quantitative real-time PCR analysis showed that MdPLATZ6 was strongly downregulated in response to the TDZ and decapitation treatments, however, MdPLATZ15 was significantly upregulated in response to TDZ, but exhibited little response to decapitation. Furthermore, the co-expression network showed that PLATZ might be involved in shoot branching by regulating branching-related genes or mediating cytokinin or auxin pathway. The results provide valuable information for further functional investigation of MdPLATZ genes in the control of axillary bud outgrowth in apple.


Molecular differentiation between NS1 gene of a field strain Bluetongue virus serotype 2 (BTV-2) and NS1 gene of an attenuated BTV-2 vaccine.
At the end of September 2000, clinical symptoms of Bluetongue appeared in sheep flocks of the Balearic Islands (Spain). The presence of the BTV serotype 2 in tissue and blood samples of affected animals was confirmed by laboratory techniques. A systematic vaccination were carried out in affected areas using a live monovalent serotype 2 vaccine available from Onderstepoort laboratory (South Africa). In order to perform epidemiological studies, a new method to differentiate between the NS1 genes of BTV-2 affecting the Balearic islands and that of the Onderstepoort commercial live virus vaccine (monovalent, serotype 2) has been developed. This procedure is based on the use of an RT-PCR, followed by restriction endonuclease analysis. Epidemiological data of a study carried out in the period January-October 2001 using this procedure are included.


Retracted: Application of Mathematical Models in Economic Variable Input and Output Models under the Scientific Visualization.
[This retracts the article DOI: 10.1155/2022/6269358.].


Freedom of choice and health services' performance: Evidence from a national health system.
Public policies fostering the freedom of choice of provider in the healthcare sector are increasingly common in many countries and regions, where policymakers wish to empower patients and improve health service performance. However, in the literature there is not clear consensus about the impact of expanded patient choice on healthcare quality yet. This study investigates whether increasing patients' freedom of choice influences health system outcomes in terms of various non-clinical aspects of care, a dimension often overlooked by researchers in this field. Our study considers a "natural experiment" that took place within the Spanish National Health System in 2009 under which citizens of the Community (region) of Madrid were allowed to freely choose among any GP and/or specialist in their region. The empirical analysis was conducted by using Spanish microdata for the period 2002-2016 and used synthetic control estimation techniques. The key findings show the reform had a strong and long-lasting impact, reducing average waiting times and increasing patients' satisfaction with the specialist attention received. We did not detect any statistically significant impact of the reform on the other responsiveness domains analysed. Our analysis shows that freedom of choice policies could improve health system performance if they are combined with appropriate economic incentives for health providers.


Migrant farmworker housing regulation violations in North Carolina.
The quality of housing provided to migrant farmworkers is often criticized, but few studies have investigated these housing conditions. This analysis examines housing regulation violations experienced by migrant farmworkers in North Carolina, and the associations of camp characteristics with the presence of housing violations. Data were collected in183 eastern North Carolina migrant farmworker camps in 2010. Housing regulation violations for the domains of camp, sleeping room, bathroom, kitchen, laundry room, and general housing, as well as total violations were assessed using North Carolina Department of Labor standards. Violations of housing regulations were common, ranging from 4 to 22 per camp. Housing regulation violations were common in all domains; the mean number of camp violations was 1.6, of sleeping room violations was 3.8, of bathroom violations was 4.5, of kitchen violations was 2.3, of laundry room violations was 1.2, and of general housing violations was 3.1. The mean number of total housing violations was 11.4. Several camp characteristics were consistently associated with the number of violations; camps with workers having H-2A visas, with North Carolina Department of Labor Certificates of Inspection posted, and assessed early in the season had fewer violations. These results argue for regulatory changes to improve the quality of housing provided to migrant farmworkers, including stronger regulations and the more vigorous enforcement of existing regulations.


Emodin upregulates urokinase plasminogen activator, plasminogen activator inhibitor-1 and promotes wound healing in human fibroblasts.
Urokinase plasminogen activator (uPA) system is important for several biological processes that call for extracellular proteolysis, fibrinolysis, cell migration, proliferation and angiogenesis. The current study highlights the fibrinolytic and wound healing potential of emodin, an anthraquinone, with relevance to the uPA system. Emodin increased the fibrinolytic activity of fibroblast cells in a dose-dependent manner. Zymography linked the activity to increased uPA activity. Subsequent RT-PCR and western analyses demonstrated uPA gene upregulation. Interestingly, PAI-1, the inhibitor of uPA was also upregulated. EMSA showed the upregulation occurred independent of emodin's effect on nuclear factor kappa B (NFkappaB). The effect on uPA system is supposedly via generation of reactive oxygen species (ROS) since cotreatment with ascorbic acid, an anti-oxidant, attenuated the activity. In addition to profibrinolytic potential, emodin also demonstrated wound healing activity in in vitro wound models. Presence of emodin in the medium enhanced the rate of migration of fibroblasts into the wounded region. These in vitro experiments reveal that emodin is a potent profibrinolytic and wound healing agent.


[Analysis on the genetics of Hantavirus S85-46 isolated from Sichuan province].
To understand the molecular and epidemic characteristics of Hantavirus S85-46 isolated from Sichuan province. RT-PCR products were amplified from S85-46 virus infected cells, cloned into T vector, sequenced and analyzed using DNASTAR software. The homology of M segment of S85-46 strain and HTN type strain varied from 84.1%-99.7%, compared to 70.4%-70.9% with SEO strains. This result indicated that S85-46 strain belonged to hantavirus. The nucleotide sequence analyses indicated that S85-46 strain, LR1 strain and 76-118 strain were highly homologous. The two latter strains were isolated from Shaanxi province of China and South Korea respectively, which were far from Sichuan province of China. The nucleotide sequence analyses of S segment was similar to M segment. The epidemic strains isolated from different regions may have been highly homologous.


DBFOX-Ph/metal complexes: evaluation as catalysts for enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones.
We examined the catalytic enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones 1 with N-fluorobenzenesulfonimide (NFSI) by DBFOX-Ph/metal complexes under a variety of conditions. After optimization of the metal salts, solvents and additives, we found that the fluoro-2-thiazolidinones 2 were obtained in good to high yields with moderate to good enantioselectivities (up to 78% ee) when the reaction was carried out in the presence of DBFOX-Ph (11 mol%), Ni(ClO(4))(2).6H(2)O (10 mol%) and 2,6-lutidine (0 or 1.0 equiv) in CH(2)Cl(2).


The Touching Tail of a Mechanotransduction Channel.
In mechanotransduction, sensory receptors convert force into electrical signals to mediate such diverse functions as touch, pain, and hearing. In this issue of Cell, Zhang et al. present evidence that the fly NompC channel senses mechanical stimuli using its N-terminal tail as a tether between the cell membrane and microtubules.


A B3LYP and MP2(full) theoretical investigation into the cooperativity effect between dihydrogen-bonding and H-M∙∙∙π (M = Li, Na, K) interactions among HF, MH with the π-electron donor C2H2, C2H4 or C6H6.
The DFT-B3LYP/6-311++G(3df,2p) and MP2(full)/6-311++G(3df,2p) calculations were carried out on the binary complex formed by HM (M = Li, Na, K) and HF or the π-electron donor (C2H2, C2H4, C6H6), as well as the ternary system FH∙∙∙HM∙∙∙C2H2/C2H4/C6H6. The cooperativity effect between the dihydrogen-bonding and H-M∙∙∙π interactions was investigated. The result shows that the equilibrium distances R(H∙∙∙H) and R(M∙∙∙π) in the ternary complex decrease and both the H∙∙∙H and H-M∙∙∙π interactions are strengthened when compared to the corresponding binary complex. The cooperativity effect of the dihydrogen bond on the H-M∙∙∙π interaction is more pronounced than that of the M∙∙∙π bond on the H∙∙∙H interaction. Furthermore, the values of cooperativity effect follow the order of FH∙∙∙HNa∙∙∙π > FH∙∙∙HLi∙∙∙π > FH∙∙∙HK∙∙∙π and FH∙∙∙HM∙∙∙C6H6 > FH∙∙∙HM∙∙∙C2H4 > FH∙∙∙HM∙∙∙C2H2. The nature of the cooperativity effect was revealed by the analyses of the charge of the hydrogen atoms in H∙∙∙H moiety, atom in molecule (AIM) and electron density shifts methods.


The novel human SHOX allelic variant database.
Short stature due to SHOX deficiency represents the most commonly known form of growth failure, with a frequency greater than 1:1,000 in the Caucasian population. As many different mutations can cause SHOX haploinsufficiency, a comprehensive collection of gene variants represents an essential tool to distinguish between functional variants and polymorphisms. We have created a novel and widely extended SHOX database using the "LOVD in a box-solution." This database contains not only a larger amount of mutation data (140 novel mutations were added), but also reports on phenotypic consequences, mode of inheritance, and ethnic origin, as well as on functional consequences of mutations investigated. In addition, the database now includes non-disease-related polymorphisms to enable researchers to evaluate their diagnostic findings. The database (Available at: http://hyg-serv-01.hyg.uni-heidelberg.de/lovd/index.php?select_db=SHOX; Last accessed: 12 April 2007) contains all presently known 199 intragenic mutations (SNPs as well as small deletions and insertions), 126 of which are unique. The remote user is able to search the data and to submit new mutations into the database. Furthermore, it includes general information about the SHOX gene via links to other resources such as MIM, GDB, HGMD, and HAPMAP, as well as websites of Short Stature Associations.


Population structure and antimicrobial profile of Staphylococcus aureus strains associated with bovine mastitis in China.
Staphylococcus aureus is a significant bacterial pathogen associated with bovine mastitis. The aim of the present study was to investigate and characterize of S. aureus strains isolated from the milk of cows suffering from mastitis in the mid-east of China. Among the 200 milk samples analyzed, 58 were positive for S. aureus, of these isolates, 11 isolates were methicillin-resistant Staphylococcus aureus (MRSA). All of the 58 S. aureus strains were classified in agr group I, while seven different sequence type (ST) patterns were identified and among them the most common was ST630 followed by ST188. All of the S. aureus isolates belonging to ST630 were resistant to more than four antimicrobials, and 22.2% of isolates belonging to ST188 were resistant to eight antimicrobials. Interestingly, while strong biofilm producers demonstrated higher resistance to multiple antimicrobials, they exhibited lower intracellular survival rates. The results of this study illustrated the distribution, antimicrobial susceptibility profiles, genotype, and the ability of biofilm production and mammary epithelial cells invasion of these S. aureus isolates. This study can provide the basis for the development of a disease prevention program in dairy farms to reduce the potential risk in both animal and human health.