Mitochondria and Coenzyme Q10 in the Pathogenesis of Preeclampsia.
Hypertensive disorders during pregnancy constitute one of the main causes of maternal and perinatal morbidity and mortality across the world and particularly in developing countries such as Ecuador. However, despite its impact on public health, the primary pathophysiological processes involved are yet to be elucidated. It has been proposed, among other theories, that an abnormal placentation may induce an endothelial dysfunction, which is ultimately responsible for the final clinical manifestations. Mitochondria, particularly from trophoblastic cells, are responsible for the production of energy, which is extremely important for normal placentation. The malfunction in this supply of energy may produce higher levels of free radicals. In both production of energy and free radicals, coenzyme Q10 (CoQ10) plays a crucial role in electron transport. As such, the role of CoQ10 in the genesis and prevention of preeclampsia has become the focus of a number of research groups, including that of the authors. Developing an in-depth understanding of these mechanisms might allow us to design new and feasible strategies with which we can reduce preeclampsia, particularly in the Latin-American countries.


Communication systems for the nonvocal based on frequent phoneme sequences.
A new type of nonvocal communication system has been developed for people unable to produce speech because of neuromotor impairment. It is designed to be as flexible as the alphabet, while requiring significantly fewer acts of selection on the part of the user. The items in this type of system are phoneme sequences which have a high frequency of occurrence in the phoneme sequences included, the fewer the selection gestures required. A system of this type--Par le si la b-- is available for French, and one for English--SPEEC (Sequences of Phonemes for Efficient English Communication)--is being field-tested. Both systems are implemented in lapboard form and on encoded eye-gaze selection (Etran) charts (Eichler, 1975) and are potentially compatible with a variety of electronic communication devices. To the nonvocal individual with good comprehension and the ability to begin learning regular sound-letter correspondences, this approach offers an unrestricted and potentially more rapid communication mode that may allow greater opportunity to develop and exercise language than is currently afforded by the alphabet or by preselected-vocabulary systems.


Comparison of increased expression of wild-type and herbicide-resistant acetolactate synthase genes in transgenic plants, and indication of posttranscriptional limitation on enzyme activity.
Genes encoding wild type acetolactate synthase (ALS) and a sulfonylurea herbicide-resistant form of the enzyme, isolated from Arabidopsis thaliana, were expressed in transgenic Nicotiana tabacum plants under the control of their native promoters or of the highly active cauliflower mosaic virus 35S promoter. Expression of the wild type coding region from the 35S promoter resulted in a small, threefold increase in sulfonylurea tolerance above the levels measured in tissue expressing the native wild type gene. A much larger, 300-fold increase in herbicide tolerance was conferred by the mutant gene encoding a herbicide-resistant ALS. An additional 10-fold increase in tolerance was attained by expressing this coding region from the 35S promoter. The increase in both wild type and mutant gene expression directed by the 35S promoter resulted in over 25-fold higher levels of ALS messenger RNA in some transformants as compared with those expressing the native genes. However, ALS specific activity increased at most twofold, indicating that the amount of functional enzyme and messenger RNA are not correlated.


Effect of Germinated Pigmented Rice "Superjami" on the Glucose Level, Antioxidant Defense System, and Bone Metabolism in Menopausal Rat Model.
Women experience physical, mental, and social changes during menopause. It is important to maintain a healthy diet for effective menopause management. The effect of germinated Superjami, a deep violet colored rice cultivar, on the body weight, glucose level, antioxidant defense system, and bone metabolism in a menopausal rat model was investigated. The animals were randomly divided into three groups and fed with a normal diet (ND), a control diet supplemented with 20% (w/w) non-germinated Superjami flour (NGSF), or germinated Superjami flour (GSF) for eight weeks. The NGSF and GSF groups exhibited significantly lower body weight and fat, glucose and insulin contents, adipokine concentrations, and bone resorption biomarker levels, and higher antioxidant enzyme activities and 17-β-estradiol content than the ND group (p < 0.05). The GSF group showed greater glucose homeostasis, antioxidative, and bone metabolism-improving effects compared with the NGSF group. These findings demonstrate that germination could further improve the health-promoting properties of Superjami and that this germinated pigmented rice cultivar could be useful in the treatment and management of menopause-induced hyperglycemia, oxidative stress, and bone turnover imbalance.


Effect of Increases in Oxygen Concentration during the Argon-Induced Decline in Nitrogenase Activity in Root Nodules of Soybean.
When intact nodulated roots of soybean (Glycine max L. Merr. nodulated with Bradyrhizobium japonicum strain USDA 16) were exposed to an atmosphere lacking N(2) gas (Ar:O(2) 80:20), total nitrogenase activity (measured as H(2) evolution) and respiration (CO(2) evolution) declined with time of exposure. In Ar-inhibited nodules, when the O(2) concentration in the rhizosphere was increased in a linear ;ramp' of 2.7% per minute, 93% of the original H(2) evolution and 99% of the CO(2) evolution could be recovered. The internal nodule O(2) concentration (estimated from leghemoglobin oxygenation) declined to 56% of its initial value after 60 minutes of Ar:O(2) exposure and could be partially recovered by the linear increases in O(2) concentration. Nodule gas permeability, as estimated from the lag in ethylene production following exposure of nodules to acetylene, decreased to 26% of its initial value during the Ar-induced decline. Collectively, the results provide direct evidence that the Ar-induced decline results from decreased nodule gas permeability and indicate that the decline in permeability, rather than being immediate, occurs gradually over the period of Ar:O(2) exposure.


Localization of the intrachain disulfide bonds of the envelope glycoprotein 71 from Friend murine leukemia virus.
Envelope glycoprotein 71 from Friend murine leukemia virus was purified to homogeneity by reversed-phase HPLC. It could be shown that all 20 cysteine residues of the molecule are linked by disulfide bonds. After complete tryptic digestion, peptides containing cystine were identified by comparison of the reversed-phase HPLC profile of the digest with that of a reduced aliquot which had been subjected to affinity chromatography on thiol-Sepharose. The locations of the 10 disulfide bonds were determined by isolation, further digestion and analysis of peptides containing cystine. The first cysteine residue of the sequence (Cys46) was shown to be coupled to the sixth (Cys98), leading to a large loop containing four additional cysteine residues. Computer model building and energy calculations led to the assignment of Cys72 to Cys87 and Cys73 to Cys83. The following four cysteine residues of the sequence also constitute a structural unit, with Cys121 bonded to Cys141 and Cys133 to Cys146, and the last two cysteine residues in the amino-terminal domain of glycoprotein 71 form a small loop (Cys178 to Cys184). The first two cysteine residues of the carboxy-terminal domain produce a very small hydrophobic loop (Cys312-Cys315). Cys361 is bound to Cys373, Cys342 to Cys396 and Cys403 to Cys416. A model for the folding pattern of the viral glycoprotein is proposed.


Translating imaging results into tumor biology: FDG-PET and the response to chemoradiation in human cervical carcinoma.
(18)F-fluoro-deoxyglucose-positron emission tomography (FDG-PET) is a molecular imaging technique that can be used to monitor treatment-related changes in tumor glucose uptake. In cervical cancer, the FDG-PET response is predictive of survival outcome after chemoradiation. In an effort to understand the signaling pathways that regulate the FDG-PET response in cervical cancer, gene expression profiling was performed. Gene set enrichment analysis (GSEA) identified alterations in expression of genes from the PI3K/AKT signaling pathway in tumors with incomplete FDG-PET response after chemoradiation. Pretreatment phosphorylation and activation of AKT is common in cervical cancer, and patients whose tumors have increased pAKT expression prior to treatment have inferior survival outcomes after standard chemoradiation. Recently, activating mutations in the PIK3CA gene have been identified that are associated with poor prognosis after chemoradiation in cervical cancer. These results suggest that targeted inhibition of PI3K/AKT may improve response to chemoradiation in cervical cancer.


Effect of Social Media on Patient's Perception of Dental Aesthetics in Saudi Arabia.
Social media became an influential tool that affects people's way of communication and became a significant source of information for the society. The study aimed to evaluate the impact of SM on patients seeking aesthetic dental treatment. Methodology. The study employed a large-scale online survey of 1940 patients attending and/or seeking dental treatment at KAUFD and Jeddah private clinics. The targeted age of participants ranged from 18 years and above. The study data were collected using a three-part questionnaire. More than half of the patients were females in both groups (52.7%). The majority of patients used SM for communication and entertainment purposes. It was also found that the most popular platform used by patients was Snapchat (71.1%), followed by Instagram (66.9%). A lot of patients did not like their teeth appearance (38.5%). Moreover, patients preferred to have "bleaching" as an aesthetic treatment to improve their smiles (63.8%). The impact of SM on Saudi Arabian citizens and Saudi Arabia residents can be considered as high. Patients are influenced by SM applications and are seeking aesthetic treatment as an outcome. It is the responsibility of dentists to educate patients about the best treatment options.


Ethics In Health Care Settings: Practices Of Healthcare Professionals And Perceptions Of Patients Regarding Informed Consent, Confidentiality And Privacy At Two Tertiary Care Hospitals Of Islamabad, Pakistan.
Medical profession works within thin lines of professionalism and trust. Faith of the patients often breached but less reported among the Low and Middle-Income Countries (LMICs). In Pakistan, though the Pakistan Medical and Dental Council (PMDC) have its own code of medical ethics but there isn't much evidence on regulating ethical misconducts. Apart from the gross violations of the code of conduct, the "insensible" misuse of informed consent, confidentiality and privacy is very common. This study is an effort to explore practices of informed consent, confidentiality and privacy among health care providers along with assessment of perceptions of patients about ethical practices in two tertiary care hospitals of Islamabad, Pakistan. We conducted eight homogenous Focus Group Discussions (FGDs), four each in both the public and private sector hospitals till the saturation was achieved. Informed consent, in clinical practice, was found not being practiced. Confidentiality was not being uniformly applied in practices. Patients perceived the practices being contrary to the ethics. According to patients, ethical measures were found satisfactory in private hospitals. However, patients were not gratified fully with both the systems of healthcare delivery. There is insufficient adherence to the ethical principles in clinical practice, in both public and private sector hospitals in Islamabad, Pakistan. Informed consent, privacy and confidentiality are time and time again unheeded due to lack of robust system of monitoring and penalties by the responsible authorities.


Involvement of flocculin in negative potential-applied ITO electrode adhesion of yeast cells.
The purpose of this study was to develop novel methods for attachment and cultivation of specifically positioned single yeast cells on a microelectrode surface with the application of a weak electrical potential. Saccharomyces cerevisiae diploid strains attached to an indium tin oxide/glass (ITO) electrode to which a negative potential between -0.2 and -0.4 V vs. Ag/AgCl was applied, while they did not adhere to a gallium-doped zinc oxide/glass electrode surface. The yeast cells attached to the negative potential-applied ITO electrodes showed normal cell proliferation. We found that the flocculin FLO10 gene-disrupted diploid BY4743 mutant strain (flo10Δ /flo10Δ) almost completely lost the ability to adhere to the negative potential-applied ITO electrode. Our results indicate that the mechanisms of diploid BY4743 S. cerevisiae adhesion involve interaction between the negative potential-applied ITO electrode and the Flo10 protein on the cell wall surface. A combination of micropatterning techniques of living single yeast cell on the ITO electrode and omics technologies holds potential of novel, highly parallelized, microchip-based single-cell analysis that will contribute to new screening concepts and applications.


Efficacy of negative pressure wound therapy using vacuum-assisted closure combined with photon therapy for management of diabetic foot ulcers.
Diabetes mellitus, one of the most prevalent chronic metabolic diseases, causes many complications. Among the complications, one of the most common chronic complications is diabetic foot ulcers (DFUs). This study was conducted to investigate the efficacy of negative pressure wound therapy using vacuum-assisted closure (VAC) combined with photon therapy for the management of DFUs. The study included a total of 69 patients with DFUs during the period from January 2014 to December 2015. All patients were diagnosed with DFUs with Wagner's stage 2 or 3 and were divided into two groups - the VAC group in which patients received only VAC and the combined group in which patients received both VAC and photon therapy. Data on duration of the treatment, pre- and postoperative wound surface areas, dressing changing times, pain conditions assessed using visual analog scale scores, recurrence rate and amputation rate were collected. Among all patients, 35 patients were divided into the VAC group and 34 patients into the combined group. Areas of foot ulcers for all patients ranged from 5 to 100 cm2. The treatment duration, dressing changing times and the peak value of visual analog scale scores were all significantly lower in the combined group compared with the VAC group (P < 0.05). However, the reduced area for wound surface showed no significant difference between the two groups. Both recurrence and amputation rates showed no significant difference between the two groups of patients. Both VAC and VAC combined with photon therapy were effective and safe in the treatment of DFUs, while the combined therapy might have accelerated wound healing, but did not influence the long-term efficacy.


S-100-protein-positive dendritic cells in nodular vasculitis.
We investigated the distribution of S-100-protein-positive dendritic cells in 20 cases of nodular vasculitis (erythema induratum Bazin). The cells were identified by immunohistochemical demonstration in paraffin sections. S-100-protein-positive dendritic cells were present in all cases and comprised up to 11% of the infiltrating cells in lymphohistiocytic areas (mean 3.7%). Because of the dendritic shape and the association with lymphocytes the cells are considered to represent T-zone histiocytes. Our findings suggest a possible role of delayed-type hypersensitivity in nodular vasculitis.


Demographic, Virological Characteristics and Prognosis of Asymptomatic COVID-19 Patients in South China.
Asymptomatic transmission is a major concern for SARS-CoV-2 community spread; however, little information is available on demographic, virological characteristics and prognosis of asymptomatic cases. All COVID-19 patients hospitalized in Guangdong Province from September 1, 2020 to February 28, 2021, were included and were divided into asymptomatic and symptomaticgroup. The source country of all patients, clinical laboratory test results, the genotype of virus and the time of SARS-CoV-2 RNA turning negative or hospitalization were confirmed. Total 233 patients from 57 different countries or regions were included, with 83 (35.6%) asymptomatic and 150 (64.4%) symptomatic patients. Asymptomatic cases were younger (P = 0.019), lower rate in comorbidities (P = 0.021) such as hypertension (P = 0.083) and chronic liver disease (P = 0.045), lower PCT (P = 0.021), DDI (P < 0.001) and ALT (P = 0.029), but higher WBC count (P = 0.002) and lymphocyte (P = 0.011) than symptomatic patients. As for SARS-CoV-2 subtypes, patients infected with B.1.1 (53.8%), B.1.351 (81.8%) and B.1.524 (60%) are mainly asymptomatic, while infected with B, B.1, B.1.1.63, B.1.1.7, B.1.36, B.1.36.1, B.1.36.16, B.1.5 and B.6 were inclined to be symptomatic. Patients infected with variant B.1.351 and B.1.524 spent longer time in SARS-CoV-2 RNA turn negative (26 days, P = 0.085; 41 days, P = 0.007) and hospitalization (28 days, P = 0.085; 43 days, P = 0.004). The asymptomatic cases are prone to develop in patients with younger age, less comorbidities andinfected with B.1.1 and B.1.524 variants. More attention should be paid for lineage B.1.524 because it can significantly prolong the SARS-CoV-2 RNA negative conversion time and hospitalization in infected cases.


Statistical analysis of influenza vaccine lot consistency studies.
This paper presents an integrated statistical approach to the analysis of influenza vaccine lot consistency studies in which three lots are compared. The approach ensures that the overall Type I error rate (i.e., the probability of wrongly concluding that the lots are similar) is controlled. It is argued that the optimum efficacy measure is the geometric mean titer. The approach is demonstrated using data from a randomized, double-blind lot consistency study in which three consecutive production lots of Solvay Pharmaceuticals' new, virosomal subunit influenza vaccine Invivac were compared.


Pharmacologic management of the arthritic foot and ankle.
The arthritides discussed are presented with many drug therapies because of a not fully understood and accepted cause of the disease process. Similarly, the drug therapies offered are diverse and have mechanisms that are not always fully understood. Because of the destruction and disability the arthritides are capable of and the realization that destruction may be reversible early in the course of the disease, physicians are initiating earlier, aggressive treatment with DMARDs. Long-term outcome studies of the early institution of DMARDs, combination therapies, and newer medications need to be evaluated to produce the most efficient treatment regimens.


Stroke of antiplatelet and anticoagulant therapy in patients with coronary artery disease: a meta-analysis of randomized controlled trials.
We performed a meta-analysis sought to investigate the risk of stroke with antiplatelet and anticoagulant therapies among patients with coronary artery disease (CAD). We searched PubMed, EMBASE, and Cochrane Library for randomized controlled trials from January 1995 to March 2020. Studies were retrieved if they reported data of stroke for patients with CAD and were randomized to receive intensive versus conservative antithrombotic therapies, including antiplatelet and oral anticoagulant (OAC). Analyses were pooled by random-effects modeling. A total of 42 studies with 301,547subjects were enrolled in this analysis. Intensive antithrombotic therapy significantly reduced risk of all stroke (RR 0.86, 95% CI 0.80-0.94) and ischemic stroke (RR 0.80, 95% CI 0.71-0.91), but increased risk of hemorrhagic stroke (RR 1.36, 95% CI 1.00-1.86) and intracranial hemorrhage (RR 1.46, 95% CI 1.17-1.81). Subgroup analyses indicated that OAC yields more benefit to all stroke than antiplatelet therapy (OAC: RR 0.73, 95% CI 0.58-0.92; Antiplatelet: RR 0.90, 95% CI 0.83-0.97; Between-group heterogeneity P value = 0.030). The benefit of antiplatelet therapy on all stroke and ischemic stroke were mainly driven by the studies comparing longer versus shorter duration of dual antiplatelet therapy (All stroke: RR 0.86, 95% CI 0.78-0.95; ischemic stroke: RR 0.84, 95% CI 0.75-0.94). Among CAD patients who have already received antiplatelet therapy, either strengthening antiplatelet or anticoagulant treatments significantly reduced all stroke, mainly due to the reduction of ischemic stroke, although it increased the risk of hemorrhagic stroke and intracranial hemorrhage. OAC yields more benefit to all stroke than antiplatelet therapy.


Highly-expressed p100/p52 (NFKB2) sequesters other NF-kappa B-related proteins in the cytoplasm of human breast cancer cells.
Several observations have suggested that NF-kappa B transcription factors could be involved in carcinogenesis. To investigate the possibility that members of the NF-kappa B family participate in the molecular control of the transformed phenotype, we examined the expression of these proteins in human breast cancer cell lines as well as in primary tumors. Western Immunoblots demonstrated high expression of the p52 precursor p100 (NFKB2) in several breast cancer cell lines while human mammary epithelial cells express this protein only faintly. Eighteen primary breast tumors out of 24 displayed significant expression of the p100/p52 protein. In MDA-MB-435 cells, overexpressed p100 and p52 are predominantly cytoplasmic and coimmunoprecipitation experiments demonstrated that p100 sequesters the heterodimer p50/p65 in the cytoplasm. We demonstrate that most p65 protein is complexed with p100 in these cells while it is complexed predominantly with I kappa B-alpha in cell lines expressing less p100. Our data strengthen the hypothesis that NF-kappa B could be involved in carcinogenesis and suggest that the p100/p52 NF-kappa B subunit could play a role in the development of human breast cancers, possibly by sequestering other NF-kappa B-related proteins in the cytoplasm.


Physical and sexual violence during pregnancy and after delivery: a prospective multistate study of women with or at risk for HIV infection.
We sought to describe and compare prevalence rates of and risk factors for violence against women during pregnancy and postpartum. Physical and sexual violence and violence risk factors were assessed during late pregnancy and 6 months postpartum in a prospective study of pregnant women with (n=336) and without (n=298) HIV in 4 US states. Overall, 10.6% of women reported having experienced violence, 8.9% during pregnancy and 4.9% after delivery. Of these women, 61.7% were abused only during their pregnancy, 21.7% were repeatedly abused, and 16.7% were abused only after their delivery. Sexual violence rarely occurred in the absence of physical violence. The strongest predictor of violence was engaging in bartered sex (adjusted odds ratio [OR]=5.54; 95% confidence interval [CI] =2.0, 15.4). Other predictors included frequent changes in residence (adjusted OR=1.57; 95% CI=1.1, 2.2), financial support from family or partners (adjusted OR=0.42; 95% CI=0.2, 0.8), and HIV diagnosis during current pregnancy (adjusted OR=0.30; 95% CI=0.1, 0.7). Women more commonly experienced violence during than after their pregnancy, but violence was best predicted by socioeconomic and behavioral indicators whose influence did not vary over time.


Transplantation of human menstrual blood stem cells to treat premature ovarian failure in mouse model.
The incidence of premature ovarian failure (POF), also known as ovarian insufficiency, has been increasing in recent years. Although some treatments are currently available, improved treatment strategies are urgently required. Many researchers have reported that human endometrial stem cells (HuMenSCs), which exhibit stem/progenitor cell properties in vitro repaired damaged cells in vivo. Thus, we aimed to determine whether HuMenSCs can serve as cell therapy tools and be used for the treatment of POF. After treating with cyclophosphamide, on the first estrus period (we predicted mouse estrus cycle was generally 5 days), HuMenSCs were injected into a cyclophosphamide-induced mouse model of POF. The results revealed that the HuMenSCs could survive within POF mouse ovaries for at least 14 days in vivo; further, ovaries of the HuMenSCs-transplanted group expressed higher levels of ovarian markers [AMH, inhibin α/β, and follicle-stimulating hormone receptor (FSHR)], and the proliferative marker Ki67. In addition, the ovarian weight, plasma E2 level, and the number of normal follicles increased over time in the HuMenSC group compared with the control group. Further, microarray analysis of cDNA expression patterns revealed that, after HuMenSC transplantation, the gene mRNA expression patterns in the ovarian cells following stimulation of the host ovarian niche became increasingly similar to those observed in human ovarian tissue compared with the pretransplantation mRNA expression pattern in HuMenSCs. Hence, we can safely conclude that the mesenchymal stem cell properties and in vivo survival of HuMenSCs make them ideal seed cells for stem cell transplantation in the treatment of POF.


The Effect of Empathy Training on the Empathic Skills of Nurses.
The profound impact of empathy training on quality nursing care has been recognized. Studies have shown that there has been little improvement in nurses' communication skills, and that they should work to enhance this area. Relevant training will lead to an improvement in nurses' empathic skills, which in turn, will enable them to understand their patients better, establish positive interpersonal relationships with them, and boost their professional satisfaction. To reveal the effect of empathy training on the empathic skills of nurses. This study was conducted as an experimental design. The research sample consisted of 48 nurses working at the pediatric clinics of Farabi hospital of Karadeniz Technical University in Turkey (N = 83). Two groups, an experimental group (group 1) and a control group (group 2) were determined after questionnaires were supplied to all nurses in the study sample. At first, it was intended to select these groups using a random method. However, since this may have meant that the experimental and control groups were formed from nurses working in the same service, the two groups were selected from different services to avoid possible interaction between them. The nurses in the Group 1 were provided with empathy training through group and creative drama techniques. Pre-tests and post-tests were conducted on both groups. Data was collected via a questionnaire designed around the topic "empathic skill scale-ESS", developed by Dokmen. The Kolmogorov Smirnov test was employed to assess whether the measurable data was suitable for normal distribution. Data was presented as numbers and percentage distributions, as mean ± standard deviation and Chi-square, and as student t tests and paired t tests. The level of significance was accepted as P < 0.05. The nurses in the experimental group had a mean score of 146.7 ± 38.8 and 169.5 ± 22.1 in the ESS pre-test and post-test, respectively. Although the nurses in the control group had a pre-test mean score of 133.7 ± 37.1, which increased to 135.1 ± 51.7 after the training, no statistically significant difference was found (P = 0.886). A comparison of the groups indicated that they scored similarly in the pre-test. However, the experimental group scored significantly higher than the control group in the post-test (P = 0.270 and P = 0.015, respectively). In the light of these findings, it is recommended that communication skills should be widely included in in-service training programs; similar studies should be conducted on broader control groups formed through randomization; and a comparison should be made between the findings.


Surveillance colonoscopy in Austria: Are we following the guidelines?
The European guidelines for quality assurance in colorectal cancer screening and diagnosis contain postpolypectomy surveillance recommendations. They recommend follow-up intervals depending on the findings at index colonoscopy, and divide patients into a low-, intermediate- or high-risk group. The aim of this study was to assess the adherence of Austrian endoscopists to the European guidelines and to determine whether sending a reminder letter resulted in better adherence. A single reminder letter containing the guidelines was sent to all endoscopists who participated in the Certificate of Quality for Screening Colonoscopy program in Austria. Adherence was assessed before and after the letter had been sent. Factors associated with adherence were investigated. We found poor baseline adherence to the guidelines. After the reminder letter, the adherence slightly improved in the low-risk group, but did not change in the intermediate-risk or high-risk groups. An adenoma detection rate of at least 20 % was associated with higher adherence rates. Generally, internists and hospitals showed better adherence compared with surgeons and private practices, respectively, both before and after the reminder letter. A single reminder letter was not enough to improve the poor adherence to the European postpolypectomy surveillance guidelines. Thus, future studies are required to identify and eliminate all factors responsible for nonadherence to postpolypectomy guidelines in order to reach the goal of a safe, effective, and cost-effective colorectal cancer prevention tool in the near future.


Evaluation of seatback vibration based on ISO 2631-1 (1997) standard method: The influence of vehicle seat structural resonance.
Although much research has been done in developing the current ISO 2631-1 (1997) standard method for assessment seat vibration comfort, little consideration has been given to the influence of vehicle seat structural dynamics on comfort assessment. Previous research has shown that there are inconsistencies between standard methods and subjective evaluation of comfort at around vehicle seat twisting resonant frequencies. This study reports the frequency-weighted r.m.s. accelerations in [Formula: see text], [Formula: see text] and [Formula: see text] axes and the total vibration (point vibration total value) at five locations on seatback surface at around vehicle seat twisting resonant frequencies. The results show that the vibration measured at the centre of seatback surface, suggested by current ISO 2631-1 (1997), at around twisting resonant frequencies was the least for all tested vehicle seats. The greatest point vibration total value on the seatback surface varies among vehicle seats. The variations in vibration measured at different locations on seatback surface at around twisting resonant frequencies were sufficiently great that might affect the comfort assessment of vehicle seat.Practitioner Summary: The influence of vehicle seat structural dynamics has not been considered in current ISO 2631-1 (1997). The results of this study show that the vibration measures on seatback surface at around vehicle seat twisting resonant frequency depends on vehicle seats and dominate at the top or the bottom of seatback but not at the centre.


Evaluating the Use of Telepractice for Bottle-Feeding Assessments.
There is currently limited evidence supporting the use of telepractice to conduct bottle-feeding assessments. This study aimed to investigate the inter-rater reliability of bottle-feeding assessments conducted via synchronous telepractice (real-time videoconferencing). Secondary aims were to investigate parent and clinician satisfaction. Bottle-feeding skills of 30 children (aged 1 month-2 years) were simultaneously assessed by a telepractice SP (T-SP) at a remote location and an in-person SP (IP-SP) at the family home. A purpose-designed assessment form was used to evaluate: (1) developmental level (screen only), (2) state, color, and respiration, (3) oral motor skills, (4), infant oral reflexes, (5) tongue tie (screen only), (6) non-nutritive suck, (7) bottle-feeding, (8) overall feeding skills and (9) recommendations. Results of the T-SP and IP-SP assessments were compared using agreement statistics. Parents reported perceptions of telepractice pre and post session, and also rated post-session satisfaction. The telepractice SP completed a satisfaction questionnaire post-appointment. The majority of assessment components (45/53, 85%) met the agreement criteria (≥80% exact agreement). Difficulties were noted for the assessment of palate integrity, gagging during non-nutritive suck assessment, and 6 components of the tongue tie screen. Parent and clinician satisfaction was high; SPs reported that they would offer telepractice services to 93% of families again in the future. Overall, the results demonstrated that most components of a bottle-feeding assessment could be reliably completed via synchronous telepractice in family homes. However, further research is required to improve the reliability of some intra-oral assessment components.


Deep Unrolled Low-Rank Tensor Completion for High Dynamic Range Imaging.
The major challenge in high dynamic range (HDR) imaging for dynamic scenes is suppressing ghosting artifacts caused by large object motions or poor exposures. Whereas recent deep learning-based approaches have shown significant synthesis performance, interpretation and analysis of their behaviors are difficult and their performance is affected by the diversity of training data. In contrast, traditional model-based approaches yield inferior synthesis performance to learning-based algorithms despite their theoretical thoroughness. In this paper, we propose an algorithm unrolling approach to ghost-free HDR image synthesis algorithm that unrolls an iterative low-rank tensor completion algorithm into deep neural networks to take advantage of the merits of both learning- and model-based approaches while overcoming their weaknesses. First, we formulate ghost-free HDR image synthesis as a low-rank tensor completion problem by assuming the low-rank structure of the tensor constructed from low dynamic range (LDR) images and linear dependency among LDR images. We also define two regularization functions to compensate for modeling inaccuracy by extracting hidden model information. Then, we solve the problem efficiently using an iterative optimization algorithm by reformulating it into a series of subproblems. Finally, we unroll the iterative algorithm into a series of blocks corresponding to each iteration, in which the optimization variables are updated by rigorous closed-form solutions and the regularizers are updated by learned deep neural networks. Experimental results on different datasets show that the proposed algorithm provides better HDR image synthesis performance with superior robustness compared with state-of-the-art algorithms, while using significantly fewer training samples.


[The effect of different variables in the determination of plasma fibronectin in diabetes mellitus].
Fibronectin is a high molecular weight glycoprotein which forms part of the basal membrane and is found in plasma that has suffered quantitative alterations during the development of various pathological processes. The aim of this paper is to study, in diabetic patients, the quantitative seric changes of this protein in relation to diabetes mellitus and the influence of different variables (type of diabetes, weight, sex, age, treatment involved, period of evolution and control of the disease according to glycemia and HbA1c).


Influence of pressure on quasielastic scattering in glasses: relationship to the boson peak.
We report unexpectedly strong variations in the quasielastic scattering (QES) intensity in glasses under pressure. Analysis of the data reveals strong correlations between pressure-induced changes in the QES intensity and the intensity of the boson peak. This observation emphasizes a direct relationship between these two components of the fast dynamics. In addition, we observe changes of the QES spectral shape that can be interpreted as pressure-induced variations in the underlying energy landscape.


Femur statistical atlas construction based on two-level 3D non-rigid registration.
The statistical atlas is a 3D medical image analysis tool to enable more patient-oriented and efficient diagnosis. The atlas includes information on geometry and its variation across populations. The comparison with information from other patients is very useful for objective quantitative diagnosis. The statistical atlas can also be used to solve other challenging problems such as image segmentation. As a key to the construction of statistical atlases, 3D registration remains an important yet unsolved problem in the medical image field due to the geometrical complexity of anatomical shapes and the computational complexity arising from the enormous size of volume data. In this work we developed a two-level framework to efficiently solve 3D non-rigid registration, and applied the method to the problem of constructing statistical atlases of the femur. In contrast to a general multi-resolution framework, we employed an interpolation to propagate the matching instead of repeating the registration scheme in each resolution. The registration procedure is divided into two levels: a low-resolution solution to the correspondences and mapping of surface models using Chui and Rangarajan's thin-plate spline (TPS)-based algorithm, followed by an interpolation to achieve high-resolution matching. Next, principal component analysis (PCA) is used to build the statistical atlases. Experimental results show the shape variation learned from the atlases, and also demonstrate that our method significantly improves the efficiency of registration without decreasing the accuracy of the atlases.


Infected pancreatic necrosis.
Infected pancreatic necrosis is a late infective complication of acute necrotizing pancreatitis in which infection tends to spread from the pancreas to the peripancreatic tissues, retroperitoneum, and, more rarely, the peritoneal cavity. Severe and rapid deterioration of the clinical condition may lead to septic shock and multiple organ dysfunction syndrome. CAUSATIVE ORGANISMS: The microorganisms most frequently isolated in cases of acute bacterial pancreatitis have been historically gram-negative bacteria of enteric origin. However, gram-positive cocci are isolated with increasing frequency. Enterococci are the single most commonly isolated species. Aggressive multimodal therapy in the early stage of severe necrotizing pancreatitis improves survival; patients with infective complications tend to die later from multiple organ dysfunction syndrome. Initially, the treatment consists of fluids, analgesics, and oxygen supplementation. Surgical debridement should be limited to proved infections and delayed as long as possible to allow necrotic tissue to become demarcated. When surgery is necessary, blunt debridement of necrotic tissues is the procedure largely utilized and usually is not accompanied by excessive bleeding. Pancreatic resection should be reserved for massive necrosis of the gland substance. In many situations, the abdominal incision can be closed primarily. Treatment by the "open abdomen" technique should be reserved for those patients in whom further laparotomies are planned, mainly because of incomplete unsatisfactory debridement or uncontrolled bleeding that necessitates packing of the lesser sac. Modern management techniques have reduced the mortality of infected pancreatic necrosis to 15-20% from historical rates that were twice as high. Aggressive resuscitation and surveillance of infection are crucial for successful outcomes, although fewer patients are undergoing surgical debridement.


Lipids and Lipid Derivatives for RNA Delivery.
RNA-based therapeutics have shown great promise in treating a broad spectrum of diseases through various mechanisms including knockdown of pathological genes, expression of therapeutic proteins, and programmed gene editing. Due to the inherent instability and negative-charges of RNA molecules, RNA-based therapeutics can make the most use of delivery systems to overcome biological barriers and to release the RNA payload into the cytosol. Among different types of delivery systems, lipid-based RNA delivery systems, particularly lipid nanoparticles (LNPs), have been extensively studied due to their unique properties, such as simple chemical synthesis of lipid components, scalable manufacturing processes of LNPs, and wide packaging capability. LNPs represent the most widely used delivery systems for RNA-based therapeutics, as evidenced by the clinical approvals of three LNP-RNA formulations, patisiran, BNT162b2, and mRNA-1273. This review covers recent advances of lipids, lipid derivatives, and lipid-derived macromolecules used in RNA delivery over the past several decades. We focus mainly on their chemical structures, synthetic routes, characterization, formulation methods, and structure-activity relationships. We also briefly describe the current status of representative preclinical studies and clinical trials and highlight future opportunities and challenges.


Single locus affects embryonic segment polarity and multiple aspects of an adult evolutionary novelty.
The characterization of the molecular changes that underlie the origin and diversification of morphological novelties is a key challenge in evolutionary developmental biology. The evolution of such traits is thought to rely largely on co-option of a toolkit of conserved developmental genes that typically perform multiple functions. Mutations that affect both a universal developmental process and the formation of a novelty might shed light onto the genetics of traits not represented in model systems. Here we describe three pleiotropic mutations with large effects on a novel trait, butterfly eyespots, and on a conserved stage of embryogenesis, segment polarity. We show that three mutations affecting eyespot size and/or colour composition in Bicyclus anynana butterflies occurred in the same locus, and that two of them are embryonic recessive lethal. Using surgical manipulations and analysis of gene expression patterns in developing wings, we demonstrate that the effects on eyespot morphology are due to changes in the epidermal response component of eyespot induction. Our analysis of morphology and of gene expression in mutant embryos shows that they have a typical segment polarity phenotype, consistent with the mutant locus encoding a negative regulator of Wingless signalling. This study characterizes the segregation and developmental effects of alleles at a single locus that controls the morphology of a lineage-specific trait (butterfly eyespots) and a conserved process (embryonic segment polarity and, specifically, the regulation of Wingless signalling). Because no gene with such function was found in the orthologous, highly syntenic genomic regions of two other lepidopterans, we hypothesize that our locus is a yet undescribed, possibly lineage-specific, negative regulator of the conserved Wnt/Wg pathway. Moreover, the fact that this locus interferes with multiple aspects of eyespot morphology and maps to a genomic region containing key wing pattern loci in different other butterfly species suggests it might correspond to a 'hotspot' locus in the diversification of this novel trait.


Childhood Obesity, Endothelial Cell Activation, and Critical Illness.
Pediatric obesity is increasing in prevalence and is frequently an antecedent to adult obesity and adult obesity-associated morbidities such as atherosclerosis, type II diabetes, and chronic metabolic syndrome. Endothelial cell activation, one aspect of inflammation, is present in the early stages of atherosclerosis, often prior to the onset of symptoms. Endothelial activation is a pathological condition in which vasoconstricting, pro-thrombotic, and proliferative mediators predominate protective vasodilating, anti-thrombogenic, and anti-mitogenic mediators. Many studies report poor outcomes among obese children with systemic endothelial activation. Likewise, the link between childhood obesity and poor outcomes in critical illness is well-established. However, the link between obesity and severity of endothelial activation specifically in the setting of critical illness is largely unstudied. Although endothelial cell activation is believed to worsen disease in critically ill children, the nature and extent of this response is poorly understood due to the difficulty in measuring endothelial cell dysfunction and destruction. Based on the data available for the obese, asymptomatic population and the obese, critically ill population, the authors posit that obesity, and obesity-associated chronic inflammation, including oxidative stress and insulin resistance, may contribute to endothelial activation and associated worse outcomes among critically ill children. A research agenda to examine this hypothesis is suggested.


Rapidity of fibrosis progression in liver transplant recipients with recurrent hepatitis C is influenced by toll-like receptor 3 polymorphism.
Liver transplantation activates the innate immune system through toll-like receptors (TLRs), potentially leading to allograft rejection and graft failure. We evaluated the association of single-nucleotide polymorphisms in TLR genes with the severity of hepatitis C virus recurrence after liver transplantation (LT). This is a two-center study of 176 adult patients who received a first LT from deceased donors for hepatitis C virus (HCV) cirrhosis. Eleven polymorphisms were evaluated by real-time polymerase chain reaction and melting curves analyses: TLR1 (Asp248Ser and Ser602Ile), TLR2 (Arg753Gln), TLR3 (Leu412Phe), TLR4 (Asp299Gly), TLR5 (Arg392Stop), TLR6 (Ser249Pro), TLR7 (Gln11Leu), TLR8 (Met1Val), and TLR9 (-1237T/C and -1486C/T). The CC genotype of TLR3 Leu412Phe in liver recipients was associated with severe recurrence (odds ratio (OR) = 2.01, 95% confidence interval (95% CI) = 1.02-3.93, p = 0.04). We also analyzed this polymorphism in 72 of their donors but no association was found with severity of HCV recurrence (p = 0.89). Multivariate analysis showed donor age older than 40 yr (OR=2.93; 95% CI = 1.49-5.8, p = 0.002) and the TLR3 Leu412Phe CC genotype (OR=2.02, 95%CI=1.01-4.05, p = 0.046) were independently associated with severe HCV recurrence. Our results show that the TLR3 Leu412Phe CC genotype is independently associated with severity of hepatitis C recurrence after LT.


[Comparison of chiral separations of felodipine by high performance liquid chromatography using two cellulose tris (4-methyl benzoate) stationary phases].
Chiral resolutions of felodipine (FEL) were compared using two cellulose tris (4-methyl benzoate) stationary phases, Chiralcel OJ-R and Chiralcel OJ-H. The effects of the mobile phase and the column temperature on the retention and separation were compared. Using n-hexane/2-propanol (90:10, v/v) as mobile phase, the FEL can be enantioseparated. There are transition temperatures in the van't Hoff plots of the two columns. In the higher temperature region the enantioseparation was enthalpy controlled, and in the lower temperature region it was entropy controlled. The higher temperature was good for the resolution of FEL enantiomers even though the selectivity was change with maximum value at 19 degrees C for OJ-R and 14 degrees C for OJ-H. The two columns showed similar mechanism in the FEL chiral separation.


Names in frames: infants interpret words in sentence frames faster than words in isolation.
In child-directed speech (CDS), adults often use utterances with very few words; many include short, frequently used sentence frames, while others consist of a single word in isolation. Do such features of CDS provide perceptual advantages for the child? Based on descriptive analyses of parental speech, some researchers argue that isolated words should help infants in word recognition by facilitating segmentation, while others predict no advantage. To address this question directly, we used online measures of speech processing in a looking-while-listening procedure. In two experiments, 18-month-olds were presented with familiar object names in isolation and in a sentence frame. Infants were 120 ms slower to interpret target words in isolation than when the same words were preceded by a familiar carrier phrase, suggesting that the sentence frame facilitated word recognition. Familiar frames may enable the infant to 'listen ahead' more efficiently for the focused word at the end of the sentence.


Identification of GINS2 prognostic potential and involvement in immune cell infiltration in hepatocellular carcinoma.
Background: GINS2 has been reported to have prognostic value in several solid tumors other than hepatocellular carcinoma (HCC), and its influence on tumor immunity has not been investigated thus far. Methods: The transcriptome profiles were retrieved from two public databases, GEO and TCGA. The median GINS2 expression was considered as cutoff to define GINS2 high and GINS2 low groups and to obtain differentially expressed genes. These genes were then subjected to KEGG pathway and gene ontology (GO) analysis and to gene set enrichment analysis (GSEA). Survival analyses according to GINS2 level were performed utilizing Kaplan-Meier plotter. TIMER database was adopted to investigate associations between GINS2 level and infiltrating immunocytes, and the correlation between immunocyte-related gene expression and GINS2 level was evaluated via GEPIA database. A 236-patient validation cohort were applied to confirm the bioinformatic results of TCGA and TIMER database. Results: GINS2 is augmented in tumorous tissues of HCC patients compared with nontumor specimens, and GINS2-overexpressed patients have poorer overall survival (OS) and disease-specific survival (DSS) than those with low GINS2 expression in HCC (P = 0.009 and P = 0.002 respectively). Cell cycle and DNA replication were two main processes that enriched in tumor cells overexpressed GINS2 gene (NES = 1.848, P = 0.007; and NES = 1.907, P = 0.005, respectively). Moreover, GINS2 correlates positively with markers of activated CD8+ and CD4+ T cells, as well as exhausted T lymphocytes. Conclusions: HCC patients overexpressed GINS2 have poorer prognoses than those with low GINS2 expression, possibly as a result of the function of GINS2 in cell cycle and DNA replication as well the exhaustion of T lymphocytes.


Creating a balance between breathing and viability: experiences of well-being when living with chronic obstructive pulmonary disease.
To describe experiences of well-being among people with moderate to very severe chronic obstructive pulmonary disease (COPD). Living with COPD is related to a complex life situation, and quality of life (QOL) is shown to decrease because of respiratory symptoms and fatigue. However, studies describing well-being in COPD as a subjective description of QOL are rare. Ten participants with moderate to very severe COPD from the Obstructive Lung Disease in Northern Sweden (OLIN) COPD study were interviewed about their experiences of well-being. A latent qualitative content analysis was used to analyse the data. To achieve well-being despite breathlessness, the participants had to adapt to their limitations and live towards the future. They created a balance between breathing and viability by adjusting to a lifelong limitation, handling variations in illness, relying on self-capacity and accessibility to a trustful care. The participants adjusted to lifelong limitations through acceptance and replacement of former activities. They handled variations in illness by taking advantage of the good days and using emotional adaptation strategies. The participants relied on their own self-capacity, feeling that smoking cessation, physical activity and breathing fresh air increased their well-being. They requested accessibility to a trustful care and highlighted the need for continuous care relationships and access to medications. These findings can enhance health-care professionals' understanding of the possibilities for increased well-being for people living with COPD.


Peripheral blood mononuclear cells from patients with systemic sclerosis spontaneously secrete increased amounts of vascular endothelial growth factor (VEGF) already in the early stage of the disease.
To investigate the capacity of the peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (SSc) to produce vascular endothelial growth factor (VEGF), and to identify clinical associations of altered production of VEGF by PBMC in SSc. In addition, correlation with another pro-angiogenic cytokine, TNF-related weak inducer of apoptosis (TWEAK), was evaluated. PBMC were isolated from 25 patients with SSc and 17 healthy controls (HC). VEGF and TWEAK were measured in the supernatants of cultured PBMC using commercially available ELISA kits. PBMC from SSc patients spontaneously released significantly greater amounts of VEGF as compared with HC. Production of VEGF was comparable between patients with early SSc and those with longer disease duration, and in both SSc groups higher than in HC. Patients without active digital ulcers produced significantly greater amounts of VEGF as compared with HC, while there was no significant difference in the production of VEGF between SSc patients with active digital ulcers and HC. VEGF/TWEAK ratio was significantly higher in PBMC from SSc patients than in HC indicating that high production of VEGF is not paralleled by increased release of TWEAK in SSc. PBMC form SSc patients produce increased amounts of VEGF already in the early stage of disease. There is an imbalance in the profile of pro-angiogenic mediators produced by PBMC in SSc which might contribute to the pathogenesis of SSc. Further studies should address clinical significance of our findings.


A new group-training procedure for habituation demonstrates that presynaptic glutamate release contributes to long-term memory in Caenorhabditis elegans.
In the experiments reported here we have developed a new group-training protocol for assessing long-term memory for habituation in Caenorhabditis elegans. We have replicated all of the major findings of the original single-worm protocol using the new protocol: (1) distributed training produced long-term retention of training, massed training did not; (2) distributed training at long interstimulus intervals (ISIs) produced long-term retention, short ISIs did not; and (3) long-term memory for distributed training is protein synthesis-dependent as it could be blocked by heat shock during the inter-block interval. In addition, we have shown that long-term memory for habituation is graded, depending on the number of blocks of stimuli in training. The inter-block interval must be >40 min for long-term retention of training to occur. Finally, we have tested long-term memory for habituation training in a strain of worms with a mutation in a vesicular glutamate transporter in the sensory neurons that transduce tap (eat-4). The results from these eat-4 worms indicate that glutamate release from the sensory neurons has an important role in the formation of long-term memory for habituation.


Spatiotemporal Dynamics of Ecological Total-Factor Energy Efficiency and Their Drivers in China at the Prefecture Level.
Improvement of ecological total-factor energy efficiency (ETFEE) is crucial for transformation of China's economic growth pattern, energy conservation and emissions abatement. Here we combined the epsilon-based measure (EBM) and the Global Malmquist-Luenberger (GML) productivity index to evaluate ETFEE and ecological total-factor energy productivity (ETFEP) and its decompositions for 283 prefecture-level cities in China between 2003 and 2013. A spatial econometric model is used to investigate factors influencing ETFEE and ETFEP. Results indicated that ETFEE, ETFEP and corresponding trends differ significantly depending on whether environmental constraints are considered. No convergence trend was found in ETFEE between prefecture-level cities. Technical progress plays the largest role in increasing ETFEP growth. Pure efficiency change and scale efficiency change, however, are the main hindering factors. Boosting cumulative technological progress, cumulative scale efficiency growth rate and cumulative pure efficiency growth rate are important means of increasing ETFEP. I also found that areas with high levels of economic development do not completely overlap with areas of high ETFEE. Surprisingly, the fiscal expenditure on scientific undertakings and technological spillover effects from foreign direct investment (FDI) have not substantially increased ETFEE. Whereas increased industrialization hinders the improvement of ETFEE. Furthermore, reducing per capita energy consumption help boost ETFEE. In addition, endowment advantages of factors of production have a positive overall effect on improving ETFEE. Lastly, important policy implications are inferred.


Long-Lived Hot Carriers in III-V Nanowires.
Heat management mechanisms play a pivotal role in driving the design of nanowire (NW)-based devices. In particular, the rate at which charge carriers cool down after an external excitation is crucial for the efficiency of solar cells, lasers, and high-speed transistors. Here, we investigate the thermalization properties of photogenerated carriers by continuous-wave (cw) photoluminescence (PL) in InP and GaAs NWs. A quantitative analysis of the PL spectra recorded up to 310 K shows that carriers can thermalize at a temperature much higher than that of the lattice. We find that the mismatch between carrier and lattice temperature, ΔT, increases exponentially with lattice temperature and depends inversely on the NW diameter. ΔT is instead independent of other NW characteristics, such as crystal structure (wurtzite vs zincblende), chemical composition (InP vs GaAs), shape (tapered vs columnar NWs), and growth method (vapor-liquid-solid vs selective-area growth). Remarkably, carrier temperatures as high as 500 K are reached at the lattice temperature of 310 K in NWs with ∼70 nm diameter. While a population of nonequilibrium carriers, usually referred to as "hot carriers", is routinely generated by high-power laser pulses and detected by ultrafast spectroscopy, it is quite remarkable that it can be observed in cw PL measurements, when a steady-state population of carriers is established. Time-resolved PL measurements show that even in the thinnest NWs carriers have enough time (∼1 ns) after photoexcitation to interact with phonons and thus to release their excess energy. Nevertheless, the inability of carriers to reach a full thermal equilibrium with the lattice points to inhibited phonon emission primarily caused by the large surface-to-volume ratio of small diameter NWs.


Vascular reconstruction using deep vein for limb length discrepancy in a child.
Iatrogenic vascular injuries can result in claudication and limb length discrepancy in growing children. Traditional reconstruction has been performed with great saphenous vein as a conduit. We report the case of a 7-year-old boy with a symptomatic limb length discrepancy and vascular reconstruction using femoropopliteal vein. The use of deep vein as an autogenous conduit may facilitate reconstruction of iliofemoral arteries in preadolescent children, providing an excellent size match and an efficacious means of restoring normal blood flow.


BET 1: Does the use of emollients prevent frostbite to the face?
A short cut review was carried out to establish whether routine use of emollients on the face reduced the incidence of frostbite in cold environments. 126 papers were found using the reported searches, of which three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. It is concluded that the use of emollients on the face is not a good protection against frostbite and may even result in a higher risk.


Glutathione ester delays the onset of scurvy in ascorbate-deficient guinea pigs.
Previous studies showed that administration of ascorbate to glutathione (GSH)-deficient newborn rats and guinea pigs prevented toxicity and mortality and led to increased tissue and mitochondrial GSH levels; ascorbate thus spares GSH. In the present work, we tried to answer the converse question: Does administration of GSH spare ascorbate? Because administered GSH is not well transported into most cells, we gave GSH monoethyl ester (which is readily transported and converted into GSH intracellularly) to guinea pigs fed an ascorbate-deficient diet. We found that treatment with GSH ester significantly delays appearance of the signs of scurvy and that this treatment spares ascorbate; thus, the decrease of tissue levels of ascorbate was delayed. The findings support the conclusions that (i) GSH is essential for the physiological function of ascorbate because it is required in vivo for reduction of dehydroascorbate and (ii) there is metabolic redundancy and overlap of the functions of these antioxidants. The sparing effect of GSH in scurvy may be mediated through an increase in the reduction of dehydroascorbate (which would otherwise be degraded) and to antioxidant effects of GSH that are also produced by ascorbate. Other studies indicate that GSH deficiency in adult mice stimulates ascorbate synthesis in liver. During this work we found that administration of GSH itself is highly toxic to ascorbate-deficient guinea pigs when given in divided i.p. doses totaling 3.75 mmol/kg daily.


Unconstrained 3D-kinematics of prehension in five primates: lemur, capuchin, gorilla, chimpanzee, human.
Primates are known for their use of the hand in many activities including food grasping. Yet, most studies concentrate on the type of grip used. Moreover, kinematic studies remain limited to a few investigations of the distal elements in constrained conditions in humans and macaques. In order to improve our understanding of the prehension movement in primates, we analyse here the behavioural strategies (e.g., types of grip, body postures) as well as the 3D kinematics of the whole forelimb and the trunk during the prehension of small static food items in five primate species in unconstrained conditions. All species preferred the quadrupedal posture except lemurs, which used a typical crouched posture. Grasp type differed among species, with smaller animals (capuchins and lemurs) using a whole-hand grip and larger animals (humans, gorillas, chimpanzees) using predominantly a precision grip. Larger animals had lower relative wrist velocities and spent a larger proportion of the movement decelerating. Humans grasped food items with planar motions involving small joint rotations, more similar to the smaller animals than to gorillas and chimpanzees, which used greater rotations of both the shoulder and forearm. In conclusion, the features characterising human food prehension are present in other primates, yet differences exist in joint motions. These results provide a good basis to suggest hypotheses concerning the factors involved in driving the evolution of grasping abilities in primates.


Physiological and cytotoxic effects of Ca(2+) ionophores on Caco-2 paracellular permeability: relationship of 45Ca(2+) efflux to 51 Cr release.
The human intestinal cell line, Caco-2, and the Ca2+ ionophores, A23187 and ionomycin, were used to determine the interrelationships of 45Ca(2+) efflux, transepithelial electrical resistance (Rt), and [3H]-mannitol flux to changes in 51Cr release and lactate dehydrogenase (LDH) activity. Treatment of Caco-2 monolayers with ionomycin at concentrations of between 0.25 and 2.50 mumol/l showed similar 45Ca(2+) efflux rate constants and coefficients. Analysis of the control and ionomycin-induced 45Ca(2+) efflux values showed the data to best fit a three Ca(2+) compartmental model. All changes in Caco-2 Rt and [3H]-mannitol flux were reversible with no significant increases in 51Cr release with ionomycin concentrations of less than or equal to 2.5 mumols/l. Caco-2 monolayers treated with ionomycin at concentrations of between 5.0 and 50.0 mumols/l showed rapid non-exponential 45Ca(2+) effluxes with irreversible changes in Rt, [3H]-mannitol flux, and significant increases in 51Cr release. There was no changes in media LDH activity using either ionomycin or A23187 at concentrations of up to 50 mumols/l for 60 min. The results of our study show that: (1) disruption of Ca(2+) homeostasis in Caco-2 cells will occur with the addition of Ca(2+) ionophores at concentrations of greater than 2.50 mumols/l; (2) high concentrations (greater than 2.5 mumols/l) of ionomycin will cause non-exponential 45Ca(2+) efflux rates with irreversible changes in intracellular Rt and 14C-mannitol flux, and (3) early signs of Ca(2+) ionophore-induced damage can be detected by 51Cr release from Caco-2 cells into the media and not by changes in LDH media activity.


Targeting the Spleen as an Alternative Site for Hematopoiesis.
Bone marrow is the main site for hematopoiesis in adults. It acts as a niche for hematopoietic stem cells (HSCs) and contains non-hematopoietic cells that contribute to stem cell dormancy, quiescence, self-renewal, and differentiation. HSC also exist in resting spleen of several species, although their contribution to hematopoiesis under steady-state conditions is unknown. The spleen can however undergo extramedullary hematopoiesis (EMH) triggered by physiological stress or disease. With the loss of bone marrow niches in aging and disease, the spleen as an alternative tissue site for hematopoiesis is an important consideration for future therapy, particularly during HSC transplantation. In terms of harnessing the spleen as a site for hematopoiesis, here the remarkable regenerative capacity of the spleen is considered with a view to forming additional or ectopic spleen tissue through cell engraftment. Studies in mice indicate the potential for such grafts to support the influx of hematopoietic cells leading to the development of normal spleen architecture. An important goal will be the formation of functional ectopic spleen tissue as an aid to hematopoietic recovery following clinical treatments that impact bone marrow. For example, expansion or replacement of niches could be considered where myeloablation ahead of HSC transplantation compromises treatment outcomes.


Topological Nernst Effect of the Two-Dimensional Skyrmion Lattice.
The topological Hall effect (THE) and its thermoelectric counterpart, the topological Nernst effect (TNE), are hallmarks of the skyrmion lattice phase (SkL). We observed the giant TNE of the SkL in centrosymmetric Gd_{2}PdSi_{3}, comparable in magnitude to the largest anomalous Nernst signals in ferromagnets. Significant enhancement (suppression) of the THE occurs when doping electrons (holes) to Gd_{2}PdSi_{3}. On the electron-doped side, the topological Hall conductivity approaches the characteristic threshold ∼1000 (Ω cm)^{-1} for the intrinsic regime. We use the filling-controlled samples to confirm Mott's relation between TNE and THE and discuss the importance of Gd-5d orbitals for transport in this compound.


Mechanistic molecular imaging of cardiac cell therapy for ischemic heart disease.
Cell-based myocardial regeneration has emerged as a promising therapeutic option for ischemic heart disease, though not yet at the level of routine clinical utility. Despite the encouraging results from initial preclinical studies that have demonstrated improved function and reduced infarct size of the ischemic myocardium following several candidate cell transplantation, the beneficial effects and molecular mechanisms of cardiac cell therapy are still unclear in clinical applications to date, and much remains to be optimized. To improve engraftment, accurate methods are required for tracking cell fate and quantifying functional outcome. In the present review, we summarized the current status and challenges of cardiac cell therapy for ischemic heart disease and discussed the strengths and limitations of currently available in vivo imaging techniques with special focus on the newly developed multimodality approaches for assessing the efficacy of engrafted donor cells. We also addressed the hurdles these imaging modalities are facing, including issues regarding immunogenicity and tumorigenicity of transplanted stem cells, and provided some the future perspectives on stem cell imaging.


Flow replacement cerebrovascular bypass in the management of skull base meningiomas.
Meningiomas are common skull base lesions that are often in the vicinity of the internal carotid artery and its major branches. Their growth compresses, occludes or invades these vessels. Although most of the lesions can be carefully dissected from the vessels, a vascular bypass and sacrifice of the vessel may be necessary to achieve complete excision or prevent ischaemic complications from vessel manipulation. These procedures require considerable planning and skill and their use is quickly waning in the face of improving modalities for managing small residual meningiomas in inaccessible locations.


Cyclic tetraselenadiynes: rigid cycles with long-range van der Waals forces between chalcogen centers.
The synthesis of cyclic tetraselenadiynes could be achieved by a stepwise approach. Key steps were the reaction of the lithium salt of trimethylsilylacetylene (1) with alpha,omega-diselenocyanatoalkanes 2(m) (m = 2-5). By treating the bis-lithium salt of the resulting alpha,omega-diselenaalkadiynes 4(m) (m = 2-5) again with 2(n) (n = 2-5) the cyclic tetraselenadiynes 5(m.n) resulted, with methylene chains of length m and n between the SeC triple bond CSe units. The structures of seven ring systems could be investigated in the solid state. These investigations reveal that the molecular structures are determined by the rigid SeC triple bond CSe units, which try to adopt torsion angles of the CH(2)-Se sigma-bonds between 60 degrees and 90 degrees. In the solid state, the systems 5(3.3) and 5(5.5) show columnar structures that can be traced back to close contacts between Se atoms of neighboring rings.


Sex specific changes in placental growth and MAPK following short term maternal dexamethasone exposure in the mouse.
Maternal glucocorticoid (GC) exposure during pregnancy can alter fetal development and program the onset of disease in adult offspring. The placenta helps protect the fetus from excess GC exposure but is itself susceptible to maternal insults and may be involved in sex dependant regulation of fetal programming. This study aimed to investigate the effects of maternal GC exposure on the developing placenta. Pregnant mice were treated with dexamethasone (DEX-1 μg/kg/h) or saline (SAL) for 60 h via minipump beginning at E12.5. Placentas were collected at E14.5 and E17.5 and the expression of growth factors and placental transporters examined by real-time PCR and/or Western blot. Histological analysis was performed to assess for morphological changes. At E14.5, DEX exposed male and female fetuses had a lower weight compared to SAL animals but placental weight was lower in females only. Hsd11b2 and Vegfa gene expression was increased and MAPK1 protein expression decreased in the placentas of females only. At E17.5 placental and fetal body weights were similar and differences in MAPK were no longer present although HSD11B2 protein was elevated in placentas of DEX females. Levels of glucose or amino acid transporters were unaffected. Results suggest sex specific responses to maternal GCs within the placenta. Decreased levels of MAPK protein in placentas of female fetuses suggest alterations in the MAPK pathway may contribute to the lower placental weights in this sex. This may contribute towards sex specific fetal programming of adult disease.


Evaluation of ferritin, interleukin-6, interleukin-8 and tumor necrosis factor alpha in the differentiation of exudates and transudates in pleural effusions.
In an attempt to define diagnostic criteria for the differentiation of pleural exudates from transudates, we measured ferritin (FER), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in pleural effusions and blood serum in 84 consecutive patients with pleural effusions of various etiologies. Concentrations of FER, IL-8 and TNF-alpha were significantly higher in serum and pleural effusion in patients with exudates than in patients with transudates. Serum concentrations of IL-6 were not significantly increased in pleural exudate patients (9.78 +/- 17.12 fmol/L) compared to transudate patients (4.05 +/- 2.33 fmol/L), while significant differences were found between pleural exudates and transudates (p < 0.001). Increased levels of FER were found in serum and pleural effusion of cancer patients in comparison to non cancer patients (p < 0.001 and p < 0.001, respectively). Serum concentrations of IL-6, IL-8, and TNF-alpha were not significantly increased in cancer compared to non-cancer patients, while increased concentrations of IL-6 and IL-8 were found in pleural fluid of patients with cancer in comparison to non-cancer patients. Finally/ no statistically significant differences were found in serum and pleural TNF-alpha concentrations among patients with cancer and patients with non-cancer effusion. We conclude that FER, IL-6, IL-8 and TNF-alpha concentrations in pleural effusions are useful markers in differentiating exudates from transudates.


Influence of Penicillin on Biofilm Formation by Streptococcus agalactiae Serotype Ia/CC23.
Streptococcus agalactiae (Group B Streptococcus , GBS) is a major agent of perinatal infections. Biofilms have been associated with GBS colonization and disease, as well as with infection persistence and recurrence. Although GBS remains susceptible to beta-lactams, it is still unknown how sessile cells respond to these antibiotics. Here, we evaluated the effect of different concentrations of penicillin (3-48 mg/L) on in vitro biofilm formation by four GBS strains belonging to serotype Ia/clonal complexes23 that were recovered from the oropharynx or urine of pregnant women and were previously characterized as strong biofilm producers. All four GBS strains were fully susceptible to penicillin (minimum inhibitory concentration = 0.023 mg/L), but penicillin was not able to fully prevent biofilm formation by these GBS strains. Biofilms formed in the presence of penicillin had reduced biomasses and thickness, but they were still classified as strong. Penicillin significantly reduced the density of live cells, but higher penicillin concentrations did not lead to improved prevention of biofilm formation. Biofilms formed in the presence of penicillin had no channels or long cocci chains observed in penicillin-free biofilms. Overall, results highlight the concerning possible impacts of biofilm formation in penicillin-based treatment and preventive strategies of GBS infections, even when the bacterial strain involved is fully antibiotic-susceptible.


Paraganglioma presenting as metastatic lesion in a cervical vertebra: a case report and review of the literature.
Case report. To discuss the spinal presentation and treatment of paraganglioma, a rare tumor of the extra-adrenal paraganglia, derived from neural crest cells in sympathetic ganglions. Malignant paragangliomas are a very rare entity. The diagnosis of malignant paraganglioma is made by local recurrence after total resection of the primary mass, or findings of distant metastases. Roughly half of distant metastases are located in the cervical lymph nodes, and the remainder is evenly distributed among bone, lung, and liver. Vertebral metastases are exceedingly rare, and only isolated case reports have described them. A 71-year-old man reported increasing neck pain and upper extremity weakness. The patient had a previous carotid body tumor resection in the past and a contralateral carotid body tumor left intact. Our imaging workup, including plain radiograph, computerized tomography scan and MRI, revealed an intraosseous lesion at C6 with vertebral body destruction. The patient underwent decompressive surgery through an anterior Smith-Robinson approach for myelopathy, followed by adjuvant external beam radiation. The histologic and immunohistochemical assays revealed a malignant paraganglioma. Paragangliomas are often highly vascular tumors. Intraoperative blood loss was significant and may have been mitigated by preoperative embolization. The patient showed clinical improvement almost immediately after surgery. We report a rare case of malignant paraganglioma and discussed adjuvant treatments to consider for distant metastases, such as I-MIBG, conventional radiotherapy, and chemotherapy.


[Clinico-hemostatic characteristics of serum disease in toxic forms of diphtheria].
Coagulative changes at the height of serum disease were investigated in 28 patients with severe diphtheria. It was found that on day 10 after first injection of diphtheria antitoxin hemocoagulation underwent activation with prevailing thrombogenesis coinciding in time with acute period of serum disease. The severity of serum complications correlated with the degree of coagulation activity. A relationship exists between the amount of the given antitoxin, duration of hormone therapy and occurrence of serum complications. There were specific for serum disease biochemical alterations indicative of destruction of blood cells and vascular-endothelial structures on the disease day 12-14.


Graphene-Based Thermal Interface Materials: An Application-Oriented Perspective on Architecture Design.
With the increasing power density of electrical and electronic devices, there has been an urgent demand for the development of thermal interface materials (TIMs) with high through-plane thermal conductivity for handling the issue of thermal management. Graphene exhibited significant potential for the development of TIMs, due to its ultra-high intrinsic thermal conductivity. In this perspective, we introduce three state-of-the-art graphene-based TIMs, including dispersed graphene/polymers, graphene framework/polymers and inorganic graphene-based monoliths. The advantages and limitations of them were discussed from an application point of view. In addition, possible strategies and future research directions in the development of high-performance graphene-based TIMs are also discussed.


Cytosolic calcium changes in cultured rat aortic smooth-muscle cells induced by oxyhemoglobin.
To clarify the mechanism of contractive effects in arteries caused by oxyhemoglobin, changes in the concentration of cytosolic calcium [( Ca++]i) before and after exposure to oxyhemoglobin were measured in vitro in cultured vascular smooth-muscle cells obtained from rat aorta. This was accomplished by preloading these cells with a fluorescent intracellular Ca++ probe fura-2/AM. Oxyhemoglobin induced a significant elevation of [Ca++]i in vascular smooth-muscle cells which was sustained for 10 minutes. This response was completely abolished by chelating extracellular calcium with ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetra-acetic acid (EGTA). Oxyhemoglobin induced no accumulation of mass content of inositol 1,4,5-trisphosphate (IP3(1,4,5]. The oxyhemoglobin-induced elevation of [Ca++]i was not blocked by verapamil, a calcium antagonist. Serotonin induced a rapid, transient increase of [Ca++]i followed by a sustained elevation above baseline for 5 minutes. Additions of EGTA or verapamil had a small effect on the peak height of serotonin-induced [Ca++]i elevation, but the [Ca++]i level declined more quickly to the basal level in treated compared with control cells. These results indicate that oxyhemoglobin-induced [Ca++]i elevation is caused by the influx of extracellular calcium, which is independent of the verapamil-blocked voltage-gated calcium channel. The long-lasting high elevation of [Ca++]i caused by oxyhemoglobin suggests that oxyhemoglobin may contribute to the production of abnormal contractions and/or irreversible damage in vascular smooth-muscle cells.


Hand Hygiene Practices Among Adults with Diabetes Living in Communities: The 2015 Korea Community Health Survey.
Hand hygiene is the most effective strategy to prevent infectious diseases. This study investigated and compared the hand hygiene practices of adults with diabetes and an age- and gender-matched comparison group. Adults with diabetes (n = 22,920) who participated in the 2015 Korea Community Health Survey and an appropriate comparison group (n = 22,920) were selected. Descriptive analyses, chi-square tests, and multiple logistic regression analyses were used. Greater than 98% of participants with diabetes recognized that hand hygiene helps prevent infectious diseases. Among participants with diabetes, 84.3%, 82.4%, 72.5%, and 64.1% washed their hands frequently before eating, after using the restroom, after returning from the outdoors, and with soap or hand sanitizer, respectively, but these values were significantly lower than those of the comparison group. After performing multiple regression analyses, treatments for diabetes, being educated about diabetes management and handwashing, and awareness of hemoglobin A1c levels were significantly associated with hand hygiene practices in participants with diabetes. Almost all people with diabetes were aware of the efficacy of hand hygiene, but handwashing rates were significantly lower in people with diabetes than in the comparison group. Considering treatments for diabetes, educational campaigns regarding handwashing, and increasing awareness of handwashing efficacy will help improve hand hygiene in people with diabetes.


The role and regulation of COX-2 during viral infection.
Prostaglandins are lipid mediators, generated by cyclooxygenase (COX), that have been shown to participate in the regulation of virus replication and the modulation of inflammatory responses following infection. A number of studies support a role for PGE2 in the modulation of virus replication and virulence in a cell type and virus selective manner. Virus infection also stimulates the expression of a number of proinflammatory gene products, including COX-2, inducible nitric oxide synthase (iNOS) as well as proinflammatory cytokines. This review will focus on the mechanisms by which proinflammatory prostaglandin production regulates virus replication and virulence. In addition, the signaling pathways that are activated during a virus infection, and that regulate proinflammatory gene expression in macrophages will be reviewed. Specific attention will be placed on the ability of virus infection to activate multiple signaling cascades (such as PKR, MAPK, iPLA2, NF-kappaB) and how these pathways are integrated in the regulation of individual target gene expression.


Ruxolitinib Cream in the Treatment of Cutaneous Lichen Planus: A Prospective, Open-Label Study.
Ruxolitinib is a Janus kinase 1/2 inhibitor that blocks signal transduction of interferon-gamma, a critical cytokine involved in the pathogenesis of cutaneous lichen planus (LP). In this prospective phase II study, we investigated the efficacy of topical ruxolitinib in cutaneous LP and performed transcriptomic analysis before and after therapy. Twelve patients with cutaneous LP applied topical ruxolitinib twice daily for 8 weeks. Primary endpoints were changes in total lesion count and changes in modified Composite Assessment of Index Lesion Severity score in index treated and untreated index control lesions at week 4. Total lesion count decreased by a median of 50 lesions (interquartile range 25, 723; P < 0.001). modified Composite Assessment of Index Lesion Severity scores decreased by a mean difference of 7.6 (standard deviation 8.8, P = 0.016) between index treated and control lesions. Type I and II interferon pathways were enriched in LP, and responsive disease displayed downregulation of interferon-stimulated genes. In this small pilot study, topical ruxolitinib was highly effective in the treatment of cutaneous LP. Transcriptomic analysis confirmed LP as an interferon-driven disease and downregulation of interferon-stimulated genes correlated with disease response.


Characterizing protein motions from structure.
To clarify the extent structure plays in determining protein dynamics, a comparative study is made using three models that characterize native state dynamics of single domain proteins starting from known structures taken from four distinct SCOP classifications. A geometrical simulation using the framework rigidity optimized dynamics algorithm (FRODA) based on rigid cluster decomposition is compared to the commonly employed elastic network model (specifically the Anisotropic Network Model ANM) and molecular dynamics (MD) simulation. The essential dynamics are quantified by a mode subspace constructed from ANM and a principal component analysis (PCA) on FRODA and MD trajectories. Aggregate conformational ensembles are constructed to provide a basis for quantitative comparisons between FRODA runs using different parameter settings to critically assess how the predictions of essential dynamics depend on a priori arbitrary user-defined distance constraint rules. We established a range of physicality for these parameters. Surprisingly, FRODA maintains greater intra-consistent results than obtained from MD trajectories, comparable to ANM. Additionally, a mode subspace is constructed from PCA on an exemplar set of myoglobin structures from the Protein Data Bank. Significant overlap across the three model subspaces and the experimentally derived subspace is found. While FRODA provides the most robust sampling and characterization of the native basin, all three models give similar dynamical information of a native state, further demonstrating that structure is the key determinant of dynamics.


[Predisposition to thyroid autoimmune diseases].
Genetic predisposition is required for the expression of thyroid autoimmune disorder addition to the immune dysfunction and the environmental factors. In order to evaluate the role of this genetic factor, we reported the results of immunological and hormonal investigations of 62 members (TD), belonging to a large Akr family, who are related to 40 patients with Graves' disease or Hashimoto's thyroiditis. The hormonal analyses showed that 19 subjects exhibited an infraclinical hypothyroidism, subdivided into 7 members with pathological rates of TSH evocative of thyroid insufficiency and 12 others with compensative thyroid insufficiency. Seventeen subjects of the Akr family who had solely antithyroid autoantibodies were considered as potential candidates to develop thyroid autoimmune diseases. The clinical follow-up, during two years, confirmed the diagnosis of Hashimoto's thyroiditis in 3 members among 19 subjects with infraclinical hypothyroidism (TD05, TD28 and TD54) and in only 1 member out of the 17 potential candidates (TD03). Our results showed that a serological study of hormones and/or autoantibodies directed against thyroid antigens, could allow the detection of predisposed subjects to develop a thyroid autoimmune pathology. The Akr family seems to be suitable for the study of the localization of susceptibility genes to TAID.


The need for regulation in the practice of human assisted reproduction in Mexico. An overview of the regulations in the rest of the world.
The emergence of assisted reproductive technology (ART) in humans has been an important tool for the treatment of infertility. The number of treatments performed in Latin America has been increasing, and Mexico is the third country with the most assisted reproduction cycles performed in the region. However, Mexico lacks a national regulation for assisted reproduction. Therefore, it is necessary to implement regulations that allow for a safe clinical practice based on ethics which can be available to any social group. The aim of this review was to examine the existing legislation that regulates human assisted reproduction practices in Mexico, but also to examine the legal analysis of the policies, laws, and regulations in effect in some countries in Latin America, North America, and Europe. For this, seven databases were consulted, and 34 articles from 2004 to 2021 referring to the practice of ART within the legal framework and the anthropological analysis that this entails were analyzed. Eight documents were also consulted such as the Mexican General Health Law of the Official Journal of the Federation (February 7, 1984) with its last published reform (DOF 01-06-2021). And three official agency websites were also consulted. No specific legislation was found for human assisted reproduction practices in Mexico; however, assisted reproduction clinics are ruled under some agreements implemented by national organizations such as the Mexican Association of Reproductive Medicine and, at the Latin America level, the Latin America Network of Assisted Reproduction (abbreviated REDLARA in Spanish); in addition, the practice of ART is considered, although not explicitly, in the General Health Law. In Mexico, there is no legal regulation in charge of assisted reproduction practices, which is why there is an urgent need to establish human assisted reproduction laws without incurring discriminatory and unconstitutional acts, and at the same time, be in accordance with scientific advances. This will allow a considerable reduction in the violation of human rights.


Two Oxygen-Coordinated Metastable Ru-ON States for Ruthenium Mononitrosyl Complex.
The properties of Ru-ON states were studied in cis-[RuNO(NH3)2(NO2)2OH] under illumination. The structure contains two nonequivalent complexes, and the metastable state was generated for both molecules with 19(1) and 31(1)% populations. The MS1 thermal decay occurs as a one-step process at about 240 K according to differential scanning calorimetry (DSC). For the first-order reaction, the frequency factor and activation energy for the decay process were determined as 2.0(2) × 10(13) s(-1) and 68.3(4) kJ mol(-1), respectively. Also, the simultaneous metastable state decay observed via DSC was in agreement with IR spectroscopy.


Influence of poly(I:C) variability on thermoregulation, immune responses and pregnancy outcomes in mouse models of maternal immune activation.
Maternal immune activation (MIA) models that are based on administration of the viral mimetic, poly(I:C), are widely used as experimental tools to study neuronal and behavioral dysfunctions in relation to immune-mediated neurodevelopmental disorders and mental illnesses. Evidence from investigations in non-pregnant rodents suggests that different poly(I:C) products can vary in terms of their immunogenicity, even if they are obtained from the same vendor. The present study aimed at extending these findings to pregnant mice, while also controlling various poly(I:C) products for potential contamination with lipopolysaccharide (LPS). We found significant variability between different batches of poly(I:C) potassium salt obtained from the same vendor (Sigma-Aldrich) in terms of the relative amount of dsRNA fragments in the high molecular weight range (1000-6000 nucleotides long) and with regards to their effects on maternal thermoregulation and immune responses in maternal plasma, placenta and fetal brain. Batches of poly(I:C) potassium salt containing larger amounts of high molecular weight fragments induced more extensive effects on thermoregulation and immune responses compared to batches with minimal amounts of high molecular weight fragments. Consistent with these findings, poly(I:C) enriched for high molecular weight dsRNA (HMW) caused larger maternal and placental immune responses compared to low molecular weight (LMW) poly(I:C). These variable effects were unrelated to possible LPS contamination. Finally, we found marked variability between different batches of the poly(I:C) potassium salt in terms of their effects on spontaneous abortion rates. This batch-to-batch variability was confirmed by three independent research groups using distinct poly(I:C) administration protocols in mice. Taken together, the present data confirm that different poly(I:C) products can induce varying immune responses and can differentially affect maternal physiology and pregnancy outcomes. It is therefore pivotal that researchers working with poly(I:C)-based MIA models ascertain and consider the precise molecular composition and immunogenicity of the product in use. We recommend the establishment of reference databases that combine phenotype data with empirically acquired quality information, which can aid the design, implementation and interpretation of poly(I:C)-based MIA models.


Endothelin-1 production during the acute chest syndrome in sickle cell disease.
To investigate the role of the endothelial-derived vasoactive mediator endothelin (ET-1) in the acute chest syndrome (ACS), we incubated bovine pulmonary artery endothelial cells (BPAEC) with red blood cells (equivalent to a hematocrit of 20%) and/or autologous plasma (1:10 dilution) from two patients during ACS and during routine clinic visits. Cellular RNA was analyzed for ET-1 transcripts by Northern analysis and ET-1 protein levels in BPAEC supernatants and in plasma measured by radioimmunoassay. ET-1 mRNA expression and protein levels increased in BPAEC exposed to plasma obtained during ACS; in contrast, exposure to plasma obtained during routine clinic visits did not alter BPAEC ET-1 mRNA expression or protein levels. Plasma ET-1 level was elevated during ACS, decreased during resolution, and remained slightly elevated during routine clinic visits. Plasma obtained from one patient 4 d prior to hospitalization for vasoocclusive crisis contained the highest ET-1 level and markedly increased BPAEC ET-1 mRNA expression and protein levels. In both patients, BPAEC ET-1 mRNA and protein expression in vitro and plasma ET-1 levels in vivo correlated with stage of disease and occurred in the absence of direct erythrocyte contact in vitro. These observations suggest that ET-1 production contributes to development of ACS.


Two year experience with transrectal prostate ultrasound.
During the last two and a half years, transrectal prostate ultrasound has been used extensively at our institution. Three hundred and twenty patients have been evaluated in a double blind fashion as part of a study comparing digital rectal examination and transrectal prostatic ultrasound. Prostate cancer was detected in twenty three patients (7.2%); 13 had palpable nodules (4.1%) and 10 had non-palpable nodules (3.1%). Of the 23 patients, 19 had clinically localized (Stage B) prostate cancer. Clinical and pathologic staging correlated in 15 patients (79%). This compares favorably to clinical staging accuracy of 55% in patients prior to utilization of transrectal prostatic ultrasound.


Pigmented nevi. Induced changes in the junctional component.
The pigmented nevus represents a potentially more dynamic lesion than has been indicated by most published studies. New nevus cell clusters frequently appear in the epidermis over the residual portion of a nevus that remains after partial surgical excision. Even in relatively inactive nevi in adults, new junctional nevus cells may be induced by surgical trauma. This stimulated growth usually regresses by the time one year or more has elapsed. The growth of nevus cells is probably comparable to that induced in other cells by traumatic injury. There is no evidence to suggest that it is related to the development of melanoma in pigmented nevi.


Meibomian gland dysfunction: the past, present, and future.
To recount the historic evaluation of meibomian gland dysfunction (MGD) and describe new techniques to monitor disease and therapy. A review of the literature regarding the description of MGD and the role of abnormalities of meibomian gland secretion in health and disease. Meibomian gland dysfunction is a common clinical condition and is a major cause of evaporative dry eye with associated discomfort, visual disturbance, and contact lens intolerance. Despite the early description of the anatomy and physiology of the meibomian gland, recognition of the importance of the MGD and particularly therapeutic options to treat it has been limited. Improved methods of spectroscopic and chemical analysis of the meibomian gland secretion in health and disease are providing a better understanding of the physical and chemical abnormalities of the meibomian gland secretions and are allowing better evaluation of medical therapies.


Prenatal Exposure to High Cortisol Induces ADHD-like Behaviors with Delay in Spatial Cognitive Functions during the Post-weaning Period in Rats.
High levels of cortisol in blood are frequently observed in patients with major depressive disorders and increased cortisol level induces depressivelike symptoms in animal models. However, it is still unclear whether maternal cortisol level during pregnancy is a critical factor resulting in neuropsychiatric disorders in offspring. In this study, we increased cortisol level in rats by repetitively injecting corticosterone subcutaneously (Corti. Mom, 20 mg/kg/day) during pregnancy and evaluated the behavioral patterns of their pups (Corti.Pups) via forced swimming (FS), open field (OF), elevated plus maze (EPM) and Morris water maze (MWM) tests during the immediate post-weaning period (postnatal day 21 to 25). In results, corticosterone significantly increased plasma cortisol levels in both Corti.Moms and Corti.Pups. Unlike depressive animal models, Corti.Pups showed higher hyperactive behaviors in the FS and OF tests than normal pups (Nor.Pups) born from rats (Nor.Moms) treated with saline. Furthermore, Corti.Pups spent more time and traveled longer distance in the open arms of EPM test, exhibiting higher extremity. These patterns were consistent with behavioral symptoms observed in animal models of attention deficit hyperactivity disorder (ADHD), which is characterized by hyperactivity, impulsivity, and inattention. Additionally, Corti.Pups swam longer and farther to escape in MWM test, showing cognitive declines associated with attention deficit. Our findings provide evidence that maternal cortisol level during pregnancy may affect the neuroendocrine regulation and the brain development of offspring, resulting in heterogeneous developmental brain disorders such as ADHD.