Genetic toxicology: can we design predictive in vivo assays?
The present analysis examines the assumptions in, the perceptions and predictivity of and the need for short-term tests (STTs) for genotoxicity in light of recent findings that most noncarcinogens from the National Toxicology Program are genotoxic (i.e., positive in one or more in vitro STTs). Reasonable assumptions about the prevalence for carcinogens (1-10% of all chemicals), the sensitivity of these STTs (ca. 90% of all carcinogens are genotoxic) and their estimated "false positive" incidence (60-75%) imply that the majority of chemicals elicit genotoxic responses and, consequently, that most in vitro genotoxins are likely to be noncarcinogenic. Thus, either the usual treatment conditions used in these in vitro STTS are producing a large proportion of artifactual and meaningless positive results or else in vitro mutagenicity is too common a property of chemicals to serve as a useful predictor of carcinogenicity or other human risk. In contrast, the limited data base on in vivo STTs suggests that the current versions of these assays may have low sensitivity which appears unlikely to improve without dropping either their 'short-term' aspect or the rodent carcinogenicity benchmark. It is suggested that in vivo genotoxicity protocols be modified to take into consideration both the fundamentals of toxicology as well as the lessons learned from in vitro genetic toxicology. In the meantime, while in vivo assays are undergoing rigorous validation, genetic toxicology, as currently practiced, should not be a formal aspect of chemical or drug development on the grounds that it is incapable of providing realistic and reliable information on human risk. It is urged that data generated in new, unvalidated in vivo genotoxicity assays be exempted from the normal regulatory reporting requirements in order to encourage industry to participate in the laborious and expensive development of this next phase of genetic toxicology.


Appraisal of recommended respiratory infection control practices in primary care and emergency department settings.
The severe acute respiratory syndrome (SARS) epidemic and concern about pandemic influenza prompted the Centers for Disease Control and Prevention (CDC) to develop guidelines to prevent the transmission of all respiratory infections in health care settings during first contact with a potentially infected person. The extent to which health care workers and institutions use these CDC recommended practices is uncertain. The study examined health care worker adherence to CDC recommended respiratory infection control practices in primary care clinics and emergency departments of 5 medical centers in King County, Washington, using a self-administered questionnaire. All clinical, allied, and administrative health care workers in study settings were invited to participate: 653 (53%) responded, and 630 were included. The survey revealed important shortcomings in overall personal and institutional use of CDC recommended practices, including deficiencies in posted alerts, patient masking and separation, hand hygiene, personal protective equipment, staff training, and written procedures. Use of recommended measures was generally higher among nursing staff than medical practitioners. This study found significant gaps in adherence to CDC recommendations for the control of respiratory infections in ambulatory care clinical settings. Practical strategies are needed to identify and reduce barriers to implementation of recommended practices for control of respiratory infections.


The localization of the divergent beta 2-tubulin isotype in the microtubular arrays of Physarum polycephalum.
The beta 2-tubulin isotype of Physarum polycephalum is only 83% identical in amino acid sequence with the constitutively expressed beta 1B-tubulin and the myxamoeba-specific beta 1A-tubulin isotypes. A polyclonal antibody specific for beta 2-tubulin was used to monitor the subcellular distribution of the beta 2-tubulin antigen in the mitotic spindle of the mature plasmodium - the sole microtubular array in that stage of Physarum. By immunofluorescence, the beta 2-tubulin antigen was detected throughout this anastral mitotic spindle, at all stages of mitosis. Physarum myxamoebae contain astral mitotic spindles and cytoskeletal microtubules. No beta 2-tubulin antigen was detected in the myxamoebal stage. However, as cultures of myxamoebae developed into plasmodia, the beta 2-tubulin antigen was found in the astral mitotic spindles and cytoskeletons in developing cells. Thus, the presence of the plasmodial beta 2-tubulin isotype in a mitotic spindle does not determine a closed, anastral mitosis.


Complex of lac repressor headpiece with a 14 base-pair lac operator fragment studied by two-dimensional nuclear magnetic resonance.
Two-dimensional nuclear Overhauser enhancement spectra are presented of the complex of lac repressor headpiece with a 14 base-pair lac operator fragment. Analysis of nuclear Overhauser enhancements observed between protein and DNA shows that the second helix of the headpiece ("the recognition helix") binds in the major groove of DNA as has been suggested, but that the orientation of this helix is approximately 180 degrees different from the proposed models.


Computational design of membrane proteins.
Membrane proteins are involved in a wide variety of cellular processes, and are typically part of the first interaction a cell has with extracellular molecules. As a result, these proteins comprise a majority of known drug targets. Membrane proteins are among the most difficult proteins to obtain and characterize, and a structure-based understanding of their properties can be difficult to elucidate. Notwithstanding, the design of membrane proteins can provide stringent tests of our understanding of these crucial biological systems, as well as introduce novel or targeted functionalities. Computational design methods have been particularly helpful in addressing these issues, and this review discusses recent studies that tailor membrane proteins to display specific structures or functions and examines how redesigned membrane proteins are being used to facilitate structural and functional studies.


Hypothalamic hamartoma, precocious puberty and gelastic seizures: a special model of "epileptic" developmental disorder.
Based on a review of the literature and a detailed longitudinal single case study of a child with early onset gelastic seizures and hypothalamic hamartoma, the authors review the arguments suggesting that the acquired cognitive and behavioral symptoms seen in the majority of cases of this special epileptic syndrome result from a direct effect of the seizures. The early neurobehavioral profile of the case presented in this paper and that of a previous study is particular and combines features of a pervasive developmental and an attention deficit disorder which are probably closely related to the particular location of the epilepsy and its spread from the hypothalamus.


Is helodermin produced by medullary thyroid carcinoma cells and normal C-cells? Immunocytochemical evidence.
Helodermin is a VIP/secretin-like 35-amino acid peptide originally isolated from the venom of the lizard Gila monster. Recently, helodermin-immunoreactive material was demonstrated in mammalian salivary glands, brain and gut. In the present study 8 human medullary thyroid carcinomas as well as 4 normal thyroid glands were examined immunocytochemically for the presence of helodermin using an antiserum raised against helodermin-(5-35) that does not cross-react with VIP or secretin. Cells displaying helodermin-like immunoreactivity were found in all tumours examined except one. On the whole the helodermin-immunoreactive cells had the same distribution as those storing calcitonin, suggesting coexistence of the two peptides in most of the tumour cells. Also normal human C-cells displayed helodermin immunoreactivity. The results suggest that a peptide chemically related to helodermin is a constituent of human medullary thyroid carcinoma cells as well as of normal C-cells.


Supportive therapies in patients with advanced adrenocortical carcinoma submitted to standard EDP-M regimen.
The management of patients with advanced/metastatic adrenocortical carcinoma (ACC) is challenging, EDP-M (etoposide, doxorubicin, cisplatin combined with mitotane) is the standard regimen. However, it is quite toxic, so an adequate supportive therapy is crucial to reduce as much as possible the side effects and maintain the dose intensity of cytotoxic agents. We describe the main side effects of the EDP-M scheme and the best way to manage them based on the experience of the Medical Oncology Unit of the Spedali Civili of Brescia. We also deal with the administration of EDP-M in specific frail patients, such as those with huge disease extent and poor performance status (PS) and those with mild renal insufficiency. In patients with hormone secreting ACC the rapid control of Cushing syndrome using adrenal steroidogenesis inhibitors such as metyrapone or osilodrostat is mandatory before starting EDP-M. Primary prophylaxis of neutropenia with Granulocyte-Colony Stimulating Factors is crucial and should be introduced at the first chemotherapy cycle. Possible mitotane induced hypoadrenalism should be always considered in case of persistent nausea and vomiting and asthenia in the interval between one cycle to another. In case of poor PS. A 24 h continuous infusion schedule of cisplatin could be an initial option in patients with poor PS as well as to reduce the risk of nefrotoxocity in patients with mild renal impairment. A careful and accurate supportive care is essential to mitigate EDP-M side effects as much as possible and avoid that, due to toxicity, patients have to reduce doses and or postpone cytotoxic treatment with a negative impact on efficacy of this chemotherapy regimen.


Photochemical processes involving the UV absorber benzophenone-4 (2-hydroxy-4-methoxybenzophenone-5-sulphonic acid) in aqueous solution: reaction pathways and implications for surface waters.
The sunlight filter benzophenone-4 (BP-4) is present in surface waters as two prevailing forms, the singly deprotonated (HA-) and the doubly deprotonated one (A(2-)), with pKa2 = 7.30 ± 0.14 (μ ± σ, by dissociation of the phenolic group). In freshwater environments, BP-4 would mainly undergo degradation by reaction with ·OH and direct photolysis. The form HA(-) has a second-order reaction rate constant with ·OH (k(·OH)) of (1.87 ± 0.31)·10(10) M(-1) s(-1) and direct photolysis quantum yield Φ equal to (3.2 ± 0.6)·10(-5). The form A(2-) has (8.46 ± 0.24)·10(9) M(-1) s(-1) as the reaction rate constant with ·OH and (7.0 ± 1.3)·10(-5) as the photolysis quantum yield. The direct photolysis of HA(-) likely proceeds via homolytic breaking of the O-H bond of the phenolic group to give the corresponding phenoxy radical, as suggested by laser flash photolysis experiments. Photochemical modelling shows that because of more efficient direct photolysis (due to both higher sunlight absorption and higher photolysis quantum yield), the A(2-) form can be degraded up to 3 times faster than HA(-) in surface waters. An exception is represented by low-DOC (dissolved organic carbon) conditions, where the ·OH reaction dominates degradation and the transformation kinetics of HA(-) is faster compared to A(2-). The half-life time of BP-4 in mid-latitude summertime would be in the range of days to weeks, depending on the environmental conditions. BP-4 also reacts with Br2(·-), and a rate constant k(Br2(·-),BP-4) = (8.05 ± 1.33)·10(8) M(-1) s(-1) was measured at pH 7.5. Model results show that reaction with Br2(·-) could be a potentially important transformation pathway of BP-4 in bromide-rich (e.g. seawater) and DOM-rich environments.


Prevalence of metabolic syndrome and association with burden of atherosclerotic disease in patients with stable coronary artery disease.
We aimed to estimate the prevalence of metabolic syndrome (Met.S.) and to explore the association of Met.S. with the number of diseased vessels in patients with stable coronary artery disease (C.A.D.). This cross-sectional study enrolled stable C.A.D. patients who attended the outpatient cardiology departments of four hospitals between 2006 and 2008. Met.S. was defined according to the National Cholesterol Education Program Adult Treatment Panel III (N.C.E.P./A.T.P. III). In the study 742 patients (mean age: 62 ± 9 years, male: n = 631, 85.0%) with stable C.A.D. were recruited. The prevalence of Met.S. was 47.3% (95% C.I. = 43.6-50.9%). Among women, a high percentage of the patients had Met.S. (n = 68, 61.3%), whereas in male patients the prevalence of Met.S. was 44.8% (n = 283). Multivariable analysis showed that C.A.D. patients with Met.S. had 84% higher odds of double or triple vessel disease, whereas those with four or five Met.S. components had two times higher odds of double or triple vessel disease after adjustment for potential confounders (O.R. = 1.84 with 95% C.I. = 1.26-2.68, p = 0.001 and O.R. = 2.08 with 95% C.I. = 1.17-3.69, p = 0.012, respectively). Met.S. as well as the accumulation of four or five Met.S. components had a positive association with the likelihood of double or triple vessel disease and this was independent of the presence of diabetes. Almost one out of two patients with stable C.A.D. was found to fulfill the criteria of Met.S. Met.S. as well as four or five Met.S. components increased the odds of double or triple vessel disease in patients with stable C.A.D. The study suggests that cardiologists and health care practitioners should be aware that Met.S. is highly prevalent when established C.A.D. is present and that Met.S. and accumulation of four or five Met.S. components seem to be associated more often with double or triple vessel C.A.D.


Diazepam actions and plasma concentrations following ethanol ingestion.
In eight normal volunteers, the combination of ethanol (0.5 g/kg) and diazepam (10 mg) administered orally produced a greater decrease in motor performance on a pursuit rotor than diazepam alone. The pharmacologic effect of diazepam was enhanced by 73% and this potentiation was associated with significantly greater diazepam concentrations (p less than 0.01) than after diazepam alone. The failure to observe any increase in the concentrations of the principal metabolite, N-desmethyl diazepam, during the period of enhanced pharmacologic effect precludes any change in the demethylating metabolic process as being responsible. The data suggest (0.10 greater than p greater than 0.05) a trend to a smaller volume of distribution of diazepam when ethanol is administered prior to diazepam ingestion. The subjects showed acute tolerance to the effects of diazepam. Lower plasma concentrations on the ascending side of the plasma diazepam concentration versus time profile were linked with the same pharmacologic responses associated with a greater drug concentration on the descending portion, of the same curve.


Multimodal analgesic protocol for cervical disc replacement in the ambulatory setting: Clinical case series.
Effective pain management is paramount for outpatient surgical success. This study aims to report a case series of patients undergoing cervical disc replacement (CDR) in an ambulatory surgery center (ASC) with the use of an enhanced multimodal analgesic (MMA) protocol. Primary, single-/2-level CDR procedures at an ASC with an enhanced MMA protocol were included. ASC patients were discharged day of surgery. Patient-reported outcome measures (PROMs) were administered at preoperative/6-week/12-week/6-month/1-year/2-year timepoints and included Visual Analogue Scale (VAS) neck, VAS arm, Neck Disability Index (NDI), Patient-Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF), and 12-Item Short-Form Physical and Mental Composite Score (SF-12 PCS/SF-12 MCS). A t-test assessed postoperative PROM improvement from baseline. MCID achievement was determined by comparing ΔPROM scores to previously established thresholds. 106 patients were included, 76 single-level and 30 2-level. Most single-levels occurred at C5-C6, most 2-levels at C5-C7. One 2-level patient developed a hematoma 5 days postoperatively and underwent revision for evacuation. Five patients reported postoperative dysphagia; all were quickly resolved. One patient had an episode of seizure secondary to serotonin syndrome from concealed drug use. Patient was reintubated, transferred, and treated for serotonin syndrome. Two patients experienced postoperative nausea/vomiting. Cohort significantly improved from baseline for all PROMS at all timepoints except SF-12 MCS at 1-year/2-years and SF-12 PCS at 2 years (p < 0.047, all). Overall MCID achievement rates were: VAS arm (48.7%), VAS neck (69.1%), NDI (98.9%), SF-12 MCS (50.0%), SF-12 PCS (54.6%), and PROMIS-PF (73.4%). Outpatient CDR, incorporating an enhanced MMA protocol, can be safely and effectively performed with proper patient selection and surgical technique. Patients saw timely discharge, well-controlled postoperative pain, and favorable long-term outcomes.


Occlusion of renal arterial tumor supply with absolute ethanol. Experience with 20 cases.
Absolute ethanol was used for renal ablation in 20 patients with carcinoma of the kidney. The procedure was followed by nephrectomy in 6 patients without metastases, all of whom are alive without evidence of recurrence 4 to 20 months after treatment. Fourteen patients with metastatic or locally advanced disease were embolized to palliate pain or hematuria without subsequent nephrectomy. Of these only 2 are alive, 4 and 18 months following the procedure. The technique for ethanol embolization is described and the use of occluding balloon catheters is recommended. No complications were encountered and the 'postembolization syndrome' was less marked as compared with a previous material of equal size where other methods of renal artery occlusion were employed. Microscopic examination in 10 of the infarcted kidneys showed extensive tumor necroses, sometimes with no evidence of viable tumor cells at all. Natural killer cell activity was determined before and 48 hours after renal artery occlusion in 7 patients, showing somewhat increased activity in 4. It is concluded that absolute ethanol is a safe, effective and easily administered agent for the infarction of renal tumors.


The Role of Anabolic Androgenic Steroids in Disruption of the Physiological Function in Discrete Areas of the Central Nervous System.
Anabolic-androgenic steroids (AAS) abuse is often associated with a wide spectrum of adverse effects. These drugs are frequently abused by adolescents and athletes for esthetic purposes, as well as for improvement of their endurance and performances. In this literature review, we evaluated the correlation between AAS and anxiety or aggression. Two pathways are thought to be involved in AAS-induced behavioral disorders. Direct pathway via the amygdalo-fugal pathway, which connects the central nucleus of the amygdala to the brainstem, is involved in cognitive-emotive and homeostatic processes. The latter is modified by chronic AAS use, which subsequently leads to increased anxiety. Indirect pathways via the serotonergic, dopaminergic, and glutamatergic signals which are modified by AAS abuse in latero-anterior hypothalamus and can mediate the aggressive behavior. In conclusion, the molecular mechanisms underlying the behavioral alterations following AAS abuse is unclear and remains ambiguous as additional long-term studies aimed to understand the precise mechanisms are required.


Data on degradome sequencing and analysis from mock-inoculated and Fusarium oxysporum treated leaves samples in Persicaria minor.
Degradome sequencing referred as parallel analysis of RNA ends (PARE) by modifying 5'-rapid amplification of cDNA ends (RACE) with deep sequencing method. Deep sequencing of 5' products allow the determination of cleavage sites through the mapping of degradome fragments against small RNAs (miRNA or siRNA) on a large scale. Here, we carried out degradome sequencing in medicinal plant, Persicaria minor, to identify cleavage sites in small RNA libraries in control (mock-inoculated) and Fusarium oxysporum treated plants. The degradome library consisted of both control and treated samples which were pooled together during library preparation and named as D4. The D4 dataset have been deposited at GenBank under accession number SRX3921398, https://www.ncbi.nlm.nih.gov/sra/SRX3921398.


circSKA3 acts as a sponge of miR-6796-5p to be associated with outcomes of ischemic stroke by regulating matrix metalloproteinase 9 expression.
This study was undertaken to screen the circular RNAs (circRNAs) influencing matrix metalloproteinase 9 (MMP9) through the competing endogenous RNA (ceRNA) network and evaluate the prognostic value of these circRNAs for acute ischemic stroke. A total of 220 ischemic stroke patients and 62 healthy subjects were included in this study. RNA was isolated from blood collected in PAXgene tubes. Illumina sequencing, quantitative real-time polymerase chain reaction (qRT-PCR) validation, and luciferase reporter assay were explored to construct and verify the existence of a circRNA-microRNA (miRNA)-matrix metalloproteinase-9 (MMP9) network. The 215 ischemic stroke patients were recruited in a prognostic cohort. They were prospectively followed up for 3 months after stroke onset, and a poor functional outcome was defined as a major disability or death. After Illumina sequencing, six circRNAs were predicted to bind miRNAs and then regulate MMP9 messenger RNA (mRNA). qRT-PCR showed that only circSKA3 was significantly increased in ischemic stroke patients compared to healthy controls and positively associated with MMP9 mRNA expression. Luciferase reporter assay further verified a direct interaction between circSKA3, MMP9, and hsa-miR-6796-5p. Patients in the top tertile of circSKA3 had a 2.672-fold (p < 0.05) risk of poor functional outcome, compared with those in the bottom tertile (p for trend = 0.016). The outcome was predicted by circSKA3 with area under the receiver operating characteristic curve at 0.614 (p = 0.004). circSKA3 functioned as a ceRNA for hsa-miR-6796-5p to aggravate the progression of ischemic stroke via targeting MMP9. Baseline circSKA3 was positively associated with poor outcomes of ischemic stroke. circSKA3 may be a potential biomarker or therapeutic target in ischemic stroke.


INTRAOCULAR INFLAMMATION INCIDENCE AFTER INTRAVITREAL BROLUCIZUMAB INJECTION FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.
We evaluated the clinical outcomes of intraocular inflammation (IOI) of eyes with neovascular age-related macular degeneration (AMD) injected with brolucizumab in our tertiary referral center. A retrospective case series for which clinical records of all eyes that received intravitreal brolucizumab at Bascom Palmer Eye Institute between December 1, 2019, and April 1, 2021, were reviewed. There were 345 eyes of 278 patients who received 801 brolucizumab injections. IOI was detected in 16 eyes of 13 patients (4.6%). In those patients, baseline Logarithm of Minimu Angle of Resolution (logMAR) best-corrected visual acuity was 0.32 0.2 (20/42), while it was 0.58 0.3 (20/76) at IOI presentation. The mean number of injections among eyes experiencing IOI was 2.4, and the interval between the last brolucizumab injection and IOI presentation was 20 days. There was no known case of retinal vasculitis. Management of IOI included topical steroids in seven eyes (54%), topical and systemic steroids in five eyes (38%), and observation in one eye (8%). Best-corrected visual acuity returned to baseline and inflammation resolved in all eyes by the last follow-up examination. Intraocular inflammation after brolucizumab injection for neovascular AMD was not uncommon. Inflammation resolved in all eyes by the last follow-up visit.


Selenium status is independently related to bone mineral density, FRAX score, and bone fracture history: NHANES, 2013 to 2014.
Selenium is an essential trace mineral element for humans. Although previous in vitro and animal studies have reported the vital role of selenium in bone, the results of the relationship between the selenium status and bone health were inconsistent in epidemiological studies. The risk of selenium deficiency is negligible for U.S. general population, however, the relationship between selenium status and bone health has never been surveyed in a nationally representative sample. In this study, we analyzed the data of 2983 adults (aged ≥40 years) in the National Health and Nutrition Examination Survey (NHANES) 2013-2014 to investigate the association among three markers of the selenium status (measured from whole blood, serum, and dietary intake), total spine and femur bone mineral density (BMD), and FRAX scores, and history of bone fractures. We found a one-unit increase in the ln-whole-blood selenium level was correlated with an increase in the total femur BMD of 0.064 g/cm2 (S.E. = 0.025; P = 0.022) in all participants and 0.086 g/cm2 (S.E. = 0.031; P = 0.013) in menopausal women. Additionally, a one-unit increase in the ln-selenium intake amount was associated with an increase in the total femur BMD of 0.014 g/cm2 (S.E. = 0.007; P = 0.043) in all participants. We also found that the dietary and whole-blood selenium statuses were negatively associated with the FRAX score, while levels of all the three selenium biomarkers were negatively associated with a history of bone fractures. In conclusion, increased selenium status is correlated with an increased total femur BMD, decreased FRAX scores, and a reduced incidence of previous bone fractures in the U.S. representative survey of adults. Further study is warranted to clarify the causal inference.


Purification, recovery, and characterization of chick pea (Cicer arietinum) β-galactosidase in single step by three phase partitioning as a rapid and easy technique.
In this study chick pea β-galactosidase was first time purified and recovered in single step by three phase partitioning (TPP). Optimal purification parameters for TPP were 60% ammonium sulfate saturation (w/v) with 1:0.5 (v/v) ratio of crude extract:t-butanol at pH 6.8, which gave 10.1 purification fold with 133% recovery of β-galactosidase. SDS-PAGE analysis showed that protein has two subunits with molecular masses of 48 and 38kDa, respectively. Characterization of enzyme showed that optimal pH of purified enzyme was 2.8 and optimal temperature was 50°C. Enzyme was further characterized by the Arrhenius activation energy and Michael-Menten kinetic constants. Activation energy (Ea) was calculated by using Arrhenius equation and determined to be 15.52kcalmol(-1). Km value of purified enzyme was estimated for the o-nitrophenyl β-d galactopyranoside (ONPG) substrate as 1.09mM, while its maximum velocity, Vm was 0.90U/mL/min at 37°C. TPP improved substrate affinity of enzyme by the increased flexibility during the partitioning. TPP is simple, easy and economic technique for purification and recovery of β-galactosidase from chick pea, and has a big potential use for industrial applications.


Meconium peritonitis: prenatal diagnosis, postnatal management and outcome.
Prenatal ultrasonography (USS) is a routine screening test for fetal abnormalities. Its accuracy for detecting meconium peritonitis (MP), which may carry high mortality, is important for prenatal counseling. The aim of this study was to assess the accuracy of prenatal USS for diagnosing MP and predicting patient outcomes. The prenatal and postnatal medical records of all patients referred to our institutions with confirmed MP were reviewed, with emphasis on prenatal USS findings, results of postnatal investigations, operative findings, outcomes, and possible causes of MP. From January 2000 to November 2004, seven fetuses were confirmed to have MP at birth. Three MP patients (3/7, 43%) were diagnosed prenatally because of USS showing ascites and calcification/dilated or hyperechoic bowel loops. One (1/7, 14.3%) suspected cystic MP was confirmed by prenatal MRI. In the other three cases, USS showed only ascites. All patients had postnatal contrast CT scans. Two patients' CT scans showed persistent intestinal perforation not visible with prenatal USS, and required emergency operations. All patients survived and prospered, and were sweat test negative. Prenatal USS allows suspected MP babies to be transferred to a tertiary centre for delivery and appropriate management. In this way, the chances of survival of these babies can be excellent if they are not associated with cystic fibrosis (CF). Prenatal MRI can improve the low diagnostic yield of prenatal USS for MP. Postnatal contrast CT scan is required to define persistent intestinal perforation invisible with prenatal USS.


[Cutaneous leishmaniasis due to Leishmania major involving the bone marrow in an AIDS patient in Burkina Faso].
Leishmaniasis covers three well-individualized clinical variants, each due to individual species found in different geographic areas. Herein we report the first case of cutaneous leishmaniasis due to Leishmania major involving bone marrow in an AIDS patient in Burkina Faso. A 38-year-old HIV-positive man presented with generalized, copper-coloured, painless, infiltrated, itching, papulonodular lesions present over the previous 10 months. Skin biopsy confirmed the diagnosis of diffuse cutaneous leishmaniasis. The bone-marrow smear showed numerous leishmania. The culture was positive and L. major was identified. The patient was being treated with antiretroviral medication and a pentavalent antimonial compound. The disease progression consisted of attacks and remissions separated by an average of three weeks. L. major is the Leishmania species identified in Burkina Faso. It is responsible for typical cutaneous leishmaniasis but particular clinical forms have been described in immunodeficient patients, especially with diffuse cutaneous involvement. The spread of L. major infection to bone marrow could represent a public health problem in our country, where the HIV epidemic is still not under control, and particular vigilance is thus called for.


Portal vein tumor thrombosis in hepatocellular carcinoma: molecular mechanism and therapy.
Portal vein tumor thrombosis (PVTT), a common complication of advanced hepatocellular carcinoma (HCC), remains the bottleneck of the treatments. Liver cancer cells potentially experienced multi-steps during PVTT process, including cancer cells leave from cancer nest, migrate in extracellular matrix, invade the vascular barrier, and colonize in the portal vein. Accumulated evidences have revealed numerous of molecular mechanisms including genetic and epigenetic regulation, cancer stem cells, immunosuppressive microenvironment, hypoxia, et al. contributed to the PVTT formation. In this review, we discuss state-of-the-art PVTT research on the potential molecular mechanisms and experimental models. In addition, we summarize PVTT-associated clinical trials and current treatments for PVTT and suppose perspectives exploring the molecular mechanisms and improving PVTT-related treatment for the future.


Interventions to support the mental health and well-being of front-line healthcare workers in hospitals during pandemics: an evidence review and synthesis.
Pandemics negatively impact healthcare workers' (HCW's) mental health and well-being causing additional feelings of anxiety, depression, moral distress and post-traumatic stress. A comprehensive review and evidence synthesis of HCW's mental health and well-being interventions through pandemics reporting mental health outcomes was conducted addressing two questions: (1) What mental health support interventions have been reported in recent pandemics, and have they been effective in improving the mental health and well-being of HCWs? (2) Have any mobile apps been designed and implemented to support HCWs' mental health and well-being during pandemics? A narrative evidence synthesis was conducted using Cochrane criteria for synthesising and presenting findings when systematic review and pooling data for statistical analysis are not suitable due to the heterogeneity of the studies. Evidence summary resources, bibliographic databases, grey literature sources, clinical trial registries and protocol registries were searched. Subject heading terms and keywords covering three key concepts were searched: SARS-CoV-2 coronavirus (or similar infectious diseases) epidemics, health workforce and mental health support interventions. Searches were limited to English-language items published from 1 January 2000 to 14 June 2022. No publication-type limit was used. Two authors determined eligibility and extracted data from identified manuscripts. Data was synthesised into tables and refined by coauthors. 2694 studies were identified and 27 papers were included. Interventions were directed at individuals and/or organisations and most were COVID-19 focused. Interventions had some positive impacts on HCW's mental health and well-being, but variable study quality, low sample sizes and lack of control conditions were limitations. Two mobile apps were identified with mixed outcomes. HCW interventions were rapidly designed and implemented with few comprehensively described or evaluated. Tailored interventions that respond to HCWs' needs using experience co-design for mental health and well-being are required with process and outcome evaluation.


Differential inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine release.
The effects of a potent and specific antagonist of 5-HT3 receptors, ICS 205-930, on the dopamine (DA)-releasing properties of morphine (1.0 mg/kg s.c.), nicotine (0.6 mg/kg s.c.), ethanol (1.0 g/kg i.p.) and amphetamine (0.25 and 1.0 mg/kg s.c.) were studied in rats. DA release was estimated by trans-cerebral dialysis in the nucleus accumbens of freely moving rats. ICS 205-930 (15-30 micrograms/kg s.c.) failed to modify the basal output of DA and its metabolites, however, ICS 205-930 dose dependently reduced the stimulation of DA release by morphine, nicotine and ethanol. Thus, at doses of 30 micrograms/kg s.c., ICS 205-930 completely prevented the morphine-, nicotine- and ethanol-induced stimulation of DA release in the nucleus accumbens; doses of 15 micrograms/kg s.c. partially prevented the morphine-, nicotine- and ethanol-induced stimulation of DA release while doses of 7.5 micrograms/kg s.c. were ineffective. In contrast, ICS 205-930 (up to 30 micrograms/kg s.c.) failed to affect the amphetamine-induced stimulation of DA release in the nucleus accumbens. The inhibitory effects of ICS 205-930 (15 and 30 micrograms/kg s.c.) on the drug-induced stimulation of DA release could also be extended to the neuroleptic haloperidol (0.1 mg/kg s.c.). The results indicate that blockade of 5-HT3 receptors selectively prevents the stimulation of DA release induced by drugs known to stimulate the firing activity of DA neurons.


CircRNA_15430 reduced by Helicobacter pylori infection and suppressed gastric cancer progression via miR-382-5p/ZCCHC14 axis.
Helicobacter pylori (H.pylori, HP) is one of the main causes of gastric cancer (GC). CircRNAs have been reported to play a crucial role in developing many types of cancer. However, the role of circRNAs in the development and progression of HP infected-GC has not been studied. The location of circRNA_15430 in GC cells were detected by nuclear and cytoplasmic RNA fractionation and RNA fluorescence in situ hybridization analysis (FISH) assays, and circRNA_15430, miR-382-5p and ZCCHC14 expression in GC cell lines and tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The function of circRNA_15430 in GC cells were examined by using colony formation, cell counting kit-8 (CCK-8) and Transwell assays, flow cytometry and laser scanning confocal microscopy. The protein levels were detected by Western blotting. Whether circRNA_15430 sponges miR-382-5p was monitored with a dual-luciferase reporter assay. Furthermore, circRNA_15430 was analyzed in vivo in tumor growth with nude mice. CircRNA_15430 is primarily localized in the cytoplasm of GC cells, and downregulated in the GC cell lines and tissues, and is negatively correlated with the tumor size. Downregulation of circRNA_15430 promotes proliferation, migration and suppresses cell apoptosis and autophagy in GC cells. Mechanically, circRNA_15430 acts as a miR-382-5p sponge, alleviating the inhibitory effect of miR-382-5p on its target ZCCHC14. Knockdown circRNA_15430 enhances tumor growth in vivo. In addition, circRNA_15430 was reduced in HP + gastritis tissues and HP-infected MGC-803 cells, reversing the pro-HP effect on autophagy. Additionally, miR-382-5p was increased in HP + gastritis tissue and HP-infected MGC-803 cells while ZCCHC14 decreased in HP-infected MGC-803 cells. MiR-382-5p reverses the effect of si-ZCCHC14 on autophagosome numbers in MGC-803 cells. Therefore, circRNA_15430 plays an inhibitory role in GC and regulates the progression of HP infection-related GC, providing a novel molecular marker for GC therapy.


Intracortical Microstimulation Parameters Dictate the Amplitude and Latency of Evoked Responses.
Microstimulation of brain tissue plays a key role in a variety of sensory prosthetics, clinical therapies and research applications. However, the effects of stimulation parameters on the responses they evoke remain widely unknown. We aimed to investigate the contribution of each stimulation parameter to the response and identify interactions existing between parameters. Parameters of the constant-current, biphasic square waveform were examined in acute terminal experiments under ketamine anaesthesia. The motor cortex of 7 Sprague-Dawley rats was stimulated while recording motor evoked potentials (MEP) from the forelimb. Intracortical microstimulation (ICMS) parameters were systematically tested in a pair-wise fashion to observe the influence of each parameter on the amplitude and latency of the MEP. The amplitude of the MEP increased continually with stimulus amplitude (p < 0.001) and pulse duration (p = 0.001) throughout the range tested. Increases were also observed when stimuli were raised from low to moderate values of frequency (p = 0.022) and train duration (p = 0.045), after which no further excitation occurs. The latency of MEP initiation decreased when stimulus amplitude (p = 0.037) and frequency (p = 0.001) were raised from low to moderate values, after which the responses plateaued. MEP latencies were further reduced by increasing the pulse duration (p = 0.011), but train duration had no effect. Our data indicate that MEP amplitude and onset latency can be modulated by alterations to a number of stimulus parameters, even in restrictive paradigms, and suggest that the parameters of the standard ICMS signal used for evoking movements from the motor cortex can be further optimized.


Hijacking of hippocampal-cortical oscillatory coupling during sleep in temporal lobe epilepsy.
Memory impairment is the most common cognitive deficit in patients with temporal lobe epilepsy (TLE). This type of epilepsy is currently regarded as a network disease because of its brain-wide alterations in functional connectivity between temporal and extra-temporal regions. In patients with TLE, network dysfunctions can be observed during ictal states, but are also described interictally during rest or sleep. Here, we examined the available literature supporting the hypothesis that hippocampal-cortical coupling during sleep is hijacked in TLE. First, we look at studies showing that the coordination between hippocampal sharp-wave ripples (100-200 Hz), corticothalamic spindles (9-16 Hz), and cortical delta waves (1-4 Hz) during nonrapid eye movement (NREM) sleep is critical for spatial memory consolidation. Then, we reviewed studies showing that animal models of TLE display precise coordination between hippocampal interictal epileptiform discharges (IEDs) and spindle oscillations in the prefrontal cortex. This aberrant oscillatory coupling seems to surpass the physiological ripple-delta-spindle coordination, which could underlie memory consolidation impairments. We also discuss the role of rapid eye movement (REM) sleep for local synaptic plasticity and memory. Sleep episodes of REM provide windows of opportunity for reactivation of expression of immediate early genes (i.e., zif-268 and Arc). Besides, hippocampal theta oscillations during REM sleep seem to be critical for memory consolidation of novel object place recognition task. However, it is still unclear which extend this particular phase of sleep is affected in TLE. In this context, we show some preliminary results from our group, suggesting that hippocampal theta-gamma phase-amplitude coupling is exacerbated during REM in a model of basolateral amygdala fast kindling. In conclusion, there is an increasing body of evidence suggesting that circuits responsible for memory consolidation during sleep seem to be gradually coopted and degraded in TLE. This article is part of the Special Issue "NEWroscience 2018".


Knowledge of chronic intestinal failure among US gastroenterologists: Cause for concern and learning opportunity.
Chronic intestinal failure (CIF) is an ultrarare disease, with an estimated national prevalence of ∼25,000 cases. There is a suspicion of widespread lack of expertise in CIF care, but no formal assessment tool or data exist. We developed and validated a knowledge test in CIF and now report our preliminary results from testing CIF knowledge in a cohort of US gastroenterologists. We developed a 20-question knowledge test in CIF, covering four key components of IF. After internal testing, refinement, and revision, we administered the test to a convenience sample of experts and nonexperts in IF. We then deployed the validated test to a cohort of 100 US gastroenterologists. The test had a Cronbach alpha of 0.74, suggesting a reliable test, with a threshold score to discriminate experts and nonexperts of 13.4 (maximum 20) and with a sensitivity of 81.3% and specificity of 86.4%. The overall mean score of 8.2 for the 100 US gastroenterologists was at the level of nonexperts in our convenience sample. The preliminary results of our validated knowledge test in IF among a broad group of US gastroenterologists demonstrate lack of knowledge in IF.


Plasma glucocorticoid and adrenocorticotropin concentrations measured serially in growth-retarded fetal lambs.
We studied the fetal pituitrary-adrenal axis in 9 growth retarded fetal lambs by serially measuring plasma glucocorticoids and ACTH concentrations from 115 to 140 days of gestation and adrenal blood flow at 138 days of gestation. At each gestational age period studied, plasma glucocorticoid and ACTH concentrations were similar in both growth retarded and control fetuses (Figs. 1, 2). However, ACTH concentration tended to be higher in the last 20 days of gestation in the growth retarded fetuses. This resulted in a significantly lower glucocorticoid/ACTH ratio between 121 to 130 days of gestation in the growth retarded fetal lambs as compared to the control fetuses (212 +/- 111 vs. 1042 +/- 257). The glucocorticoid/ACTH ratio in the growth retarded fetuses became similar to the ratio of the control fetuses at 131 to 140 days (445 +/- 145 vs. 554 +/- 182). Adrenal blood flow was significantly increased at term in the the growth retarded fetuses (535 +/- 87 vs. 302 +/- 40 ml/min/100g). These data indicate that the pattern of maturation of the fetal adrenal gland in the growth retarded fetal lamb is similar to that of the normal sized fetus. Because of the increased adrenal blood flow observed at 138 days of gestation, there is a suggestion of a decreased sensitivity to ACTH in these animals.


Catestatin in defense of oxidative-stress-induced apoptosis: A novel mechanism by activating the beta2 adrenergic receptor and PKB/Akt pathway in ischemic-reperfused myocardium.
Apoptosis induced by oxidative stress is one of the most important cardiomyocytes losses during ischemia-reperfusion (I/R). Catestatin (CST) has been demonstrated to have the anti-oxidative capacity in vitro. We hypothesized that CST intervention could reduce apoptosis of cardiomyocytes induced by oxidative stress in I/R. In Langendorff-perfused rat heart global I/R model, CST was introduced at the reperfusion stage. In comparison to the control group, CST led to preservation on activities of superoxide dismutase and glutathione peroxidase, improvement of hemodynamics, and reduced infarction area in reperfused myocardium. The protection of CST was also shown by less apoptotic cardiomyocytes in TUNEL staining, less caspase-3 activation, and increased phosphorylation of protein kinase B (PKB/Akt) in Western blot. To further demonstrate the benefits of CST and explore the possible underlying mechanism, H2O2-challenged primary-cultured neonatal rat cardiomyocytes were used to simulate the oxidative-stressed scenario. CST incubation with the H2O2-challenged cardiomyocytes led to reduction of apoptosis, which was demonstrated by less Hoechst 33342 positive staining of nuclei, less caspase-3 activation, and DNA fragmentation. The effect of CST was abrogated by pretreatment of the cardiomyocytes with the PI3K inhibitor LY294002. Furthermore, Akt activation and the anti-apoptosis effect of CST were abolished by pretreatment of the cardiomyocytes with β2 receptor inhibitor ICI118551. Thus, the salvage of oxidative-stress-induced apoptotic cardiomyocytes in I/R by CST might involve activation β2 receptor and regulation of PI3K/Akt signaling in reperfusion injury salvage kinase (RISK) pathway.


Pure red cell aplasia in B-cell lymphoproliferative disorder treated with rituximab: report of two cases and review of the literature.
Pure red cell aplasia (PRCA) is an unusual cause of anemia in patients with chronic lymphoproliferative disorders. Here, we present two cases of PRCA, one associated with chronic lymphocytic leukemia (CLL) and the other with splenic marginal zone lymphoma, in which the PRCA responded dramatically to treatment with rituximab. We then review the literature on PRCA in lymphoma and response to rituximab. PRCA associated with CLL or lymphoma may be another indication for rituximab therapy.


Clinical Molecular Imaging of Pulmonary CXCR4 Expression to Predict Outcome of Pirfenidone Treatment in Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a progressive disease for which two antifibrotic drugs recently were approved. However, an unmet need exists to predict responses to antifibrotic treatment, such as pirfenidone. Recent data suggest that upregulated expression of CXCR4 is indicative of outcomes in IPF. Can quantitative, molecular imaging of pulmonary CXCR4 expression as a biomarker for disease activity predict response to the targeted treatment pirfenidone and prognosis in patients with IPF? CXCR4 expression was analyzed by immunohistochemistry examination of lung tissues and reverse-transcriptase polymerase chain reaction analysis of BAL. PET-CT scanning with the specific CXCR4 ligand 68Ga-pentixafor was performed in 28 IPF patients and compared with baseline clinical characteristics. In 16 patients, a follow-up scan was obtained 6 to 12 weeks after initiation of treatment with pirfenidone. Patients were followed up in our outpatient clinic for ≥ 12 months. Immunohistochemistry analysis showed high CXCR4 staining of epithelial cells and macrophages in areas with vast fibrotic remodeling. Targeted PET scanning revealed CXCR4 upregulation in fibrotic areas of the lungs, particularly in zones with subpleural honeycombing. Baseline CXCR4 signal demonstrated a significant correlation with Gender Age Physiology stage (r = 0.44; P = .02) and with high-resolution CT scan score (r = 0.38; P = .04). Early changes in CXCR4 signal after initiation of pirfenidone treatment correlated with the long-term course of FVC after 12 months (r = -0.75; P = .0008). Moreover, patients with a high pulmonary CXCR4 signal on follow-up PET scan after 6 weeks into treatment demonstrated a statistically significant worse outcome at 12 months (P = .002). In multiple regression analysis, pulmonary CXCR4 signal on follow-up PET scan emerged as the only independent predictor of long-term outcome (P = .0226). CXCR4-targeted PET imaging identified disease activity and predicted outcome of IPF patients treated with pirfenidone. It may serve as a future biomarker for personalized guidance of antifibrotic treatment.


Arginine and lysine product inhibition of bovine adrenomedullary carboxypeptidase H, a prohormone processing enzyme.
Carboxypeptidase H (CPH) is one of the later enzymes in the cascade of proteolytic steps required for the posttranslational processing of peptide hormone precursors, including processing of proenkephalin. In this study, CPH activity in the soluble and membrane fractions of enkephalin-containing bovine chromaffin granules was competitively inhibited by its products arginine and lysine. Ki values for arginine and lysine were 4.6 +/- 1.3 and 7.6 +/- 1.9 mM, respectively, indicating that arginine was a more effective inhibitor than lysine. Other amino acids (at 10 mM) had no effect. The in vivo intragranular concentrations of lysine and arginine are similar to the measured Ki values, indicating that product inhibition of CPH by basic amino acids may occur in vivo.


A Bayesian generative neural network framework for epidemic inference problems.
The reconstruction of missing information in epidemic spreading on contact networks can be essential in the prevention and containment strategies. The identification and warning of infectious but asymptomatic individuals (i.e., contact tracing), the well-known patient-zero problem, or the inference of the infectivity values in structured populations are examples of significant epidemic inference problems. As the number of possible epidemic cascades grows exponentially with the number of individuals involved and only an almost negligible subset of them is compatible with the observations (e.g., medical tests), epidemic inference in contact networks poses incredible computational challenges. We present a new generative neural networks framework that learns to generate the most probable infection cascades compatible with observations. The proposed method achieves better (in some cases, significantly better) or comparable results with existing methods in all problems considered both in synthetic and real contact networks. Given its generality, clear Bayesian and variational nature, the presented framework paves the way to solve fundamental inference epidemic problems with high precision in small and medium-sized real case scenarios such as the spread of infections in workplaces and hospitals.


Moyamoya syndrome as a manifestation of varicella-associated cerebral vasculopathy-case report and review of literature.
Varicella-associated cerebral vasculopathy (VACV) is a serious complication of Varicella zoster virus (VZV) infection. VACV has protean manifestations, with varying clinical, radiological features and prognosis. Moyamoya syndrome (MMS) with VACV is reported in few cases in the past. All the patients were in paediatric age group, presenting with multiple episodes of transient ischemic attacks (TIAs) and infarct. Our case was a 10-year-old Indian girl with ischemic stroke due to VACV who was treated with intravenous acyclovir. She presented 11 months later with multiple episodes of TIAs. Her angiogram showed bilateral moyamoya vasculature. Acetazolamide challenge study revealed areas of hypoperfusion. Previously reported such cases had been treated medically with steroids and antiplatelets. Most of these patients had resolution of motor symptoms after long follow-up; however, this period was marred by recurrent symptoms. Our patient underwent cerebral revascularisation procedure, following which her TIAs resolved, there was improvement in her limb power and, according to her parents, her performance in school has improved at 2-year follow-up. MMS can be a manifestation of VACV and should be suspected in paediatric patient of non-east Asian population. These patients require treatment with intravenous acyclovir to inactivate the virus. Those with TIAs should undergo cerebral revascularisation procedures. Medical management should be reserved for patients with adequate collaterals.


Chemical characterization of inks in skin reactions to tattoo.
Skin reactions are well described complications of tattooing, usually provoked by red inks. Chemical characterizations of these inks are usually based on limited subjects and techniques. This study aimed to determine the organic and inorganic composition of inks using X-ray fluorescence spectroscopy (XRF), X-ray absorption spectroscopy (XANES) and Raman spectroscopy, in a cohort of patients with cutaneous hypersensitivity reactions to tattoo. A retrospective multicenter study was performed, including 15 patients diagnosed with skin reactions to tattoos. Almost half of these patients developed skin reactions on black inks. XRF identified known allergenic metals - titanium, chromium, manganese, nickel and copper - in almost all cases. XANES spectroscopy distinguished zinc and iron present in ink from these elements in endogenous biomolecules. Raman spectroscopy showed the presence of both reported (azo pigments, quinacridone) and unreported (carbon black, phtalocyanine) putative organic sensitizer compounds, and also defined the phase in which Ti was engaged. To the best of the authors' knowledge, this paper reports the largest cohort of skin hypersensitivity reactions analyzed by multiple complementary techniques. With almost half the patients presenting skin reaction on black tattoo, the study suggests that black modern inks should also be considered to provoke skin reactions, probably because of the common association of carbon black with potential allergenic metals within these inks. Analysis of more skin reactions to tattoos is needed to identify the relevant chemical compounds and help render tattoo ink composition safer.


Precision manufacture of phase-change perfluorocarbon droplets using microfluidics.
Liquid perfluorocarbon droplets have been of interest in the medical acoustics community for use as acoustically activated particles for tissue occlusion, imaging and therapeutics. To date, methods to produce liquid perfluorocarbon droplets typically result in a polydisperse size distribution. Because the threshold of acoustic activation is a function of diameter, there would be benefit from a monodisperse population to preserve uniformity in acoustic activation parameters. Through use of a microfluidic device with flow-focusing technology, the production of droplets of perfluoropentane with a uniform size distribution is demonstrated. Stability studies indicate that these droplets are stable in storage for at least two weeks. Acoustic studies illustrate the thresholds of vaporization as a function of droplet diameter, and a logarithmic relationship is observed between acoustic pressure and vaporization threshold within the size ranges studied. Droplets of uniform size have very little variability in acoustic vaporization threshold. Results indicate that microfluidic technology can enable greater manufacturing control of phase-change perfluorocarbons for acoustic droplet vaporization applications.


Aerobic performance capacity in athletes.
Maximal oxygen uptake (max VO2) in leg and arm work, succinate dehydrogenase activity (SDH) and percentage of slow twitch fibers (%ST fibers) in M. vastus lateralis (VL), M. gastrocnemius c.l. (GL) and M. deltoideus (D) were studied in 89 athletes practising 11 different sport events. It was found that maximal oxygen uptake correlated positively with %ST fibers and SDH activity in M. VL. The SDH activity and %ST fibers in M. VL correlated also with one another. The results suggest that oxidative capacity of the muscles is not the limiting factor for maximal oxygen uptake. The role of the oxidative capacity of the muscles might be important during submaximal work of long duration and when a relatively small muscle mass is activated (long-distance running). MaxVO2 might be the most important determinant of performance when large muscle mass is activated during maximal work of a duration from several minutes up to 1 h (cross-country skiing).


Comparison of four commercial SARS-CoV-2 IgG immuno-assays in RT-PCR negative patients with suspect CT findings.
A subset of patients with Covid-19 presents with negative RT-PCR screening but suspect CT findings. Using four commercially available anti-SARS-CoV-2 IgG immuno-assays, we found this subset constituted 9.2% of all consecutively admitted outpatients with Covid-19 in our hospital. Clinical specificity for Covid-19 of some N protein-based immuno-assays was suboptimal, as positive results were observed in control patients with recent common human coronavirus, influenza B and adenovirus infections.


Application of open-tubular gas-liquid chromatography in an investigation of the stability of pristanic and phytanic acids towards alkaline treatment of their methyl or [-] menthyl esters.
Comparison between GLC separation of the (--) menthyl and methyl esters of two diastereoisomeric isoprenoid acids of geological interest showed that a 46 m x 0.25 mm ID butanediol succinate column gives effective separation of 2S,6R,10R- and 2R,LR,10R-isomers of (--) menthyl pristanate (2,6,10,14-tetramethylpentadecanoate), but inferior separation of the corresponding methyl ester mixture. With the latter, a small proportion (2%) of 2S,6R,10R-isomer is well resolved from the major 2R,6R,10R-component on a 92 m column. Use of the methyl esters in such analyses thus avoids the cumbersome preparation of the menthyl esters. No epimerization at the 2-methyl carbon of pristanic acid and its methyl or (--) menthyl esters was detected after treatment in 1N aqueous or methanolic NaOH under reflux for 1 hr or at 120 degrees (sealed tube) for 24 hr. Similarly no 3-methyl carbon epimerization was observed inphytanic (3R,7R,11R,15-tetramethylhexadecanoic) acid and its methyl ester after the same treatments.


Structures of genomic and complementary DNAs coding for Pleurotus ostreatus manganese (II) peroxidase.
To study the mechanism of regulation and structure/function relationship of the Pleurotus ostreatus manganese (II) peroxidase (MnP), we amplified the full-length genomic and complementary DNAs for the major isozyme of the MnP mainly by the cassette-primer PCR technique and then sequenced them. The cDNA contained an open reading frame of 1083 bp encoding for a polypeptide of 361 amino-acid residues, including the suggested signal peptide of 29 amino-acid residues with a prepro structure. The predicted amino-acid sequence of the protein shared several common characteristics with those of fungal lignin and manganese (II) peroxidases. We could find a suggested metal response element and two heat-shock element-like sequences in the 5'-flanking region of the structural gene. The structural gene contained 15 introns, many of which lie identical to those in lignin peroxidase genes rather than to those in the known MnP genes.


Effect of B-value in revealing postinfarct myocardial microstructural remodeling using MR diffusion tensor imaging.
Nonmonoexponential diffusion behavior has been previously reported to exist in some biological tissues, making quantification of diffusion tensor imaging (DTI) indices dependent on diffusion sensitivity of b-value. This study aims to investigate the effect of b-value in revealing postinfarct myocardial microstructural remodeling in ex vivo hearts. DTI scans were performed on heart samples 1, 3, 5, and 7 days after infarction induction as well as intact controls with b-values of 500 to 2500s/mm(2). DTI indices, including fractional anisotropy (FA), and mean and directional diffusivities, were measured in infarct, adjacent and remote regions with zero and each non-zero b-values respectively using conventional DTI analysis. Experimental results showed that these DTI indices decreased gradually with b-values in all regions and groups. Optimal b-values were found to vary with targeted DTI indices, and could strengthen DTI ability in revealing myocardium degradation with using conventional DTI approach. Specifically, FA showed the most sensitive detection of fiber integrity degradation at moderate b-values (≈1500 to 2000s/mm(2)), and the greatest ability of mean and directional diffusivities in monitoring diffusivity alteration occurred at relatively small b-values (≤1500s/mm(2)) during the necrotic and fibrotic phases. These findings may provide useful information for DTI protocol parameter optimization in assessing heart microstructures at other pathological or in vivo states in the future.


Differential miRNA expression analysis during late stage terminal hindgut development in fetal rats.
Terminal hindgut deformity is the leading digestive tract malformation, however, the etiology and pathogenesis remained unknown. To date, gene expression abnormalities were considered the primary cause of these diseases. miRNAs have been found to play an important role in regulating the expression of genes. A total of 24 pregnant rats were randomly divided into two groups. The experimental group (n=12) received 1% ethylenethiourea (125mg/kg) by gavage on gestational day 11, while the control group (n=12) received the same volume of distilled water. From each group, fetal rats were obtained by cesarean section on gestational day 16. For the extraction of total RNA, 1 cm rectum samples were obtained from four fetal rats that had similar weights. Chip hybridization was conducted after poly(A) and biotin were added to the RNA samples, and this was followed by washing, dyeing, and scanning of the chip. Differences identified in the miRNA expression profiles and the target gene analysis results were further analyzed to identify potential regulators of terminal hindgut development. Compared with the control group, 111 miRNAs expressed in the terminal hindgut of the experimental group were up-regulated on gestational day 16, while 117 miRNAs were down-regulated. The ten miRNAs with the greatest differential expression profiles between the experimental and control samples were selected for target gene prediction, pathway analysis, and gene ontology analysis. A subset of these miRNAs was found to be closely related to rat fetus terminal hindgut growth and development. In addition, target gene analysis showed that miR-193 may have an important role in regulating a key gene in anorectal development, Hoxd13. This role was confirmed in a dual luciferase reporter assay when miR-193 was able to inhibit expression of a reporter gene under the control of the 3' untranslated region of the Hoxd13 gene in the human embryonic kidney cell line, 293T. Real-time PCR and Western blotting experiments further showed that the expression of Hoxd13 was significantly lower when miR-193 was highly expressed in rat intestinal epithelial cells. The differences in both sets of experiments were statistically significant compared with the negative control group (P<0.05). These data support an important regulatory role for miRNAs in the expression of target genes during terminal hindgut development in fetal rats. In particular, miR-193-mediated inhibition of Hoxd13 was found to be significant in rat intestinal epithelial cells.


A research model for relating job characteristics to job satisfaction of university foodservice employees.
The purpose of this study was to determine the relationship between job characteristics and job satisfaction and between demographic variables and job satisfaction for university foodservice employees. A three-part survey was developed which included the 30-item Job Characteristics Inventory, 6 items related to job satisfaction, and 7 demographic items. Separate written questionnaires were administered to 32 managerial and 147 non-managerial employees of a large state university foodservice department. The response rate was 98% (32 managers and 143 non-managers). The reliability for the instrument, as determined by Cronbach's alpha, was 0.88 for employees and 0.91 for supervisors. Multiple linear regression analyses were used to test research hypotheses at a significance level of p less than or equal to .05. There was a positive relationship between job characteristics (autonomy, task identity, feedback, variety, dealing with others, and friendship opportunities) and job satisfaction for both employees and supervisors. Feedback and dealing with others were the individual job characteristics that were significant. Only one job characteristic, dealing with others, was rated higher by managerial than by non-managerial employees. There was no difference in job satisfaction by role (managerial vs. non-managerial) or demographic variables, except age for non-managerial employees. Older, non-managerial employees tended to be more satisfied with their jobs than did younger employees. Dietitians and foodservice managers can use the findings for implementing job design strategies, such as job enrichment and job rotation, to improve employee satisfaction.


Catastrophic paradoxical embolus after hemodialysis access thrombectomy in a patient with a patent foramen ovale.
We present the first case of documented clot in-transit through a patent foramen ovale (PFO), caused by mechanical thrombectomy of a clotted AV fistula. Embolus after access thrombectomy is a rare, but known complication of the procedure. Paradoxical embolus is likewise a rare consequence of a right-sided clot, embolising to the left-sided circulation in a patient with a PFO. Suspected embolus through a PFO after dialysis access thrombectomy has been reported, but no case has ever documented the clot in-transit through the PFO.


(+)- and (-)-Corydecumbenines A and B, two pairs of novel quaternary protoberberine alkaloid cycloadduct enantiomers with anti-neuroinflammatory and neuroprotective activities from the rhizomes of Corydalis decumbens.
Two novel Diels-Alder [4 + 2] cycloadducts of quaternary protoberberine alkaloids and fumaric acid monoanion, corydecumbenines A and B (1 and 2), and six known isoquinoline analogues (3-8) were isolated from the rhizomes of Corydalis decumbens. The planar structures of 1 and 2 were elucidated by extensive spectroscopic analysis including UV, IR, HRESIMS, 1D and 2D NMR. Chiral chromatography of 1 and 2 afforded two pairs of enantiomers (+)-corydecumbenine A (1a), (-)-corydecumbenine A (1b), (+)-corydecumbenine B (2a), and (-)-corydecumbenine B (2b), respectively, and their absolute configurations were determined by single-crystal X-ray crystallography and comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1b and 2b exhibited significant nitric oxide (NO) inhibitory activities in lipopolysaccharide (LPS)-stimulated BV-2 cells with IC50 values of 11.6 and 16.2 μM, respectively, comparable to the positive control indomethacin (IC50 = 10.3 μM), and they could also decrease the level of interleukin (IL)-1β in BV-2 cells in a dose-dependent manner. Most of the isolates showed neuroprotective effects against the injury of OGD/R-induced PC12 cells at 20 μM.


[Women and the painful experience of therapeutic abortion].
When the antenatal diagnosis reveals a serious anomaly of the fetus, the couple can envisage a therapeutic abortion. This qualitative study aims to bring a better understanding of emotional impact and perinatal grief after a therapeutic abortion. Seven women who have had a therapeutic abortion participated in a semidirective interview. The analysis of the collected data reveals the psychological trauma caused by a therapeutic abortion, the significant distress of the mothers accentuated by omnipresent guilt feelings, persistent symptoms of depression and anxiety. Different reactions within the couple are perceived and can lead to marital conflict. Results show a need for a psychological follow-up of the individual as well as the couple.


Bilateral total hip arthroplasty in a case with fibrous dysplasia: a case report.
Fibrous dysplasia (FD) is a benign neoplasm with a broad spectrum of presentations. The treatment of FD in the hip region is controversial among orthopedic surgeons. Several treatment options exist, including curettage and grafting, valgus osteotomy, medial displacement osteotomy, and so on. Performing total hip arthroplasty (THA) on these patients and their subsequent outcome is still in infancy. The patient is a 32-year-old white female with bilateral proximal femur FD who underwent bilateral THA with long stem implants. A year following surgery, she had no complications and had satisfactory radiological, pain, and functional outcomes. A bilateral THA with a long stem prosthesis showed promising results when performed following appropriate curettage of the proximal bone in an FD case. A cementless long stem could have enabled better diaphyseal fixation distal to the lesion site.


Determination of bismuth in open ocean waters by inductively coupled plasma sector-field mass spectrometry after chelating resin column preconcentration.
A novel low-blank method is described for the analysis of bismuth in seawater based on preconcentration using an ethylenediaminetriacetic acid chelating resin column followed by determination with inductively coupled plasma sector-field mass spectrometry (ICPSFMS). A sample is siphoned into and drains through the column with the flow rate being kept constant by using a flotation device. Bi in 250 mL of acidified seawater is extracted onto the column in this process and eluted with 2 mL of 3 M HNO(3) followed by 3 mL of ultra-high purity water. The concentration of Bi in the eluate is measured by ICPMS. The benefits of the method compared to others are its simplicity, a smaller amount of seawater, and lower procedural blanks and detection limits at pg kg(-1) levels. Data on dissolved Bi in open ocean reference samples of SAFe and GEOTRACES programs are presented for the first time.


An immunochemical method for the selective measurement of two triglyceride lipases in human postheparin plasma.
A new method for the selective measurement of postheparin plasma lipoprotein lipase and hepatic lipase is described and validated. The activity of lipoprotein lipase is determined at 0.1 M NaCl after removal of hepatic lipase by specific antiserum, and the hepatic lipase is assayed in a medium containing 1.0 M NaCl but no additional serum. The optimal conditions for the determination of the two postheparin plasma triglyceride hydrolases were shown to be similar to those described for the purified enzymes. The new assay methods are simple, accurate and highly specific for the two lipase activities. VLDL and LDL do not interfere with the measurement, making the methods suitable for studies of patients with various hyperlipidemias. More than 90% of the total triglyceride hydrolase activity in postheparin plasma is precipitated with antisera raised against purified human postheparin plasma hepatic lipase and bovine milk lipoprotein lipase. The time and dose dependence of the two postheparin plasma lipase responses differ. For optimal activity of both enzymes, plasma taken 15 minutes after intravenous administration of 100 I.U./kg of heparin, should be used. The activity of postheparin plasma lipoprotein lipase and hepatic lipase in 12 young, healthy males is reported.


Proteomic analysis of differentially expressed proteins in Penaeus vannamei hemocytes upon Taura syndrome virus infection.
To understand molecular responses of crustacean hemocytes to virus infection, we applied 2-DE proteomics approach to investigate altered proteins in hemocytes of Penaeus vannamei during Taura syndrome virus (TSV) infection. At 24 h postinfection, quantitative intensity analysis and nano-LC-ESI-MS/MS revealed 11 forms of 8 proteins that were significantly up-regulated, whereas 9 forms of 5 proteins were significantly down-regulated in the infected shrimps. These altered proteins play important roles in host defense (hemocyanin, catalase, carboxylesterase, transglutaminase, and glutathione transferase), signal transduction (14-3-3 zeta), carbohydrate metabolism (acetylglucosamine pyrophosphorylase), cellular structure and integrity (beta-tubulin, beta-actin, tropomyosin, and myosin), and ER-stress response (protein disulfide isomerase). Semiquantitative RT-PCR and Western blot analysis confirmed the upregulation of 14-3-3 at both mRNA and protein levels. Interestingly, several altered protein spots were identified as fragments of hemocyanin. Mass spectrometric analysis showed that the hemocyanin spots at acidic and basic regions represented the C- and N-terminal hemocyanin fragments, respectively. As three-quarters of C-terminal fragments were up-regulated, whereas two-thirds of N-terminal hemocyanin fragments were down-regulated, we therefore hypothesize that C- and N-terminal hemocyanin fragments may have differential roles in hemocytes. Further investigation of these data may lead to better understanding of the molecular responses of crustacean hemocytes to TSV infection.


Disclosing unwnated sexual experiences: results from a national sample of adolescent women.
The aims of this study are to identify factors that influence the disclosures made by female survivors of unwanted sexual experiences (USE) in childhood and adolescence. The predictors of both the timing of disclosure (short delay, long delay, non-disclosure) and the recipient of the disclosure (disclosing ever to an adult, disclosing to peers only, non-disclosure) were investigated. Participant characteristics, USE characteristics, and family contextual variables were explored. A sub-sample of 263 adolescent females who reported unwanted sexual experiences in the National Survey of Adolescents (NSA) provided data on the characteristics of their experience as well as the timing and recipients of disclosure. Two multinomial logistic regression analyses were conducted to determine significant predictors of each aspect of disclosure. Age of onset, a known perpetrator, a familial relationship with the perpetrator, and a history of drug abuse in the household are related to the timing of disclosure. Age of onset, penetration, fear for one's life during the USE, injury during the USE, family structure, and the age differential between the survivor and the perpetrator are linked to the recipient of the disclosure. Age is a critical variable in the disclosure process. Whereas aspects of the abuse experience were more important in predicting whom a victim would tell, the relationship to the perpetrator was more important in deciding to delay disclosure. As survivors grow into adolescence, the importance of peers provides a source of support that becomes increasingly important in decisions to disclose.


Low arterial pressure during cardiopulmonary bypass in piglets does not decrease fluid leakage.
Cardiopulmonary bypass (CPB) is associated with increased fluid filtration occasionally leading to post-operative organ dysfunction. One of the factors determining fluid filtration is the capillary hydrostatic pressure which depends on arterial pressure, venous pressure and pre- to post-capillary resistance ratio. The purpose of this study was to assess whether lowering of the mean arterial pressure and/or the central venous pressure could reduce fluid extravasation during normothermic and hypothermic CPB. Seven piglets were given nitroprusside to a mean arterial pressure of 35-40 mmHg during 60 min of normothermic and 90 min of hypothermic CPB (LP group). They were compared with a control group (C group, n = 7) without blood pressure interventions. Blood chemistry, net fluid balance, plasma volume, colloid osmotic pressure in plasma and interstitial fluid, intravascular protein masses, fluid extravasation rate and total tissue water content were measured or calculated. Mean arterial pressure was significantly lower in the LP group than in the C group during CPB. Plasma volume tended to increase in the LP group (P > 0.05), but remained essentially unchanged in the C group. Net fluid balance in the LP group was more positive than in the C group 30 min after CPB start [1.02 (0.15) vs. 0.56 (0.13) ml/kg/min (Mean (SEM) P < 0.05)]. Fluid extravasation rate tended to be higher in the LP group and total tissue water content of the gastrointestinal tract, left myocardium and skin was significantly elevated compared with the C group. During CPB, lowering of the mean arterial pressure using nitroprusside did not reduce fluid extravasation. On the contrary, the data may implicate an increase in edema formation during low pressure CPB.


CA125 over-release behavior following a 75-g oral glucose test as a predictive biomarker of multidrug resistance in patients with ovarian cancer.
Multidrug resistance is a major cause of death in patients with ovarian cancer. To improve patient survival, we developed a novel, noninvasive and convenient tool, the 75-gram oral glucose (75gOG)-stimulated CA125 test, to monitor cancer chemoresistance in real time. Our in vitro proof-of-principal experiments revealed that post-75gOG glucose and insulin peaks can synergistically increase cancer-derived CA125 levels, and the increase in CA125 secretion (ΔCA125) is correlated with the overactivation of the insulin receptor (IR)-PI3K-Akt axis and increases (ΔIC50 s) in cisplatin/taxol IC50 s. Correspondingly, among the 93 patients enrolled, post-75gOG CA125 over-release (i.e., enhanced ΔCA125) behavior was associated with overexpression of the IR-PI3K-Akt pathway and its downstream components, namely, IR, pAkt, pS6 and GLUT4, in cancer specimens. Furthermore, both pre- and postsurgical 75gOG CA125 tests demonstrated that CA125 over-release showed excellent prediction efficacy on the chemoresistance potential of ovarian cancer; notably, the former indicated the need for an optimal debulking surgery, and the latter suggested the use of IR-PI3K-Akt inhibitors. Both test results possess independent prognostic significance for the 2-year progression-free survival (PFS) and overall survival (OS) of patients. The odds ratios and corresponding 95% confidence intervals (95% CIs) were 2.680 (95% CI: 1.393-5.156) for patients with CA125 over-release behavior evidenced by a presurgical 75gOG CA125 test or 3.822 (95% CI: 1.942-7.522) for that evidenced by a postsurgical test in PFS; and 3.320 (95% CI: 1.508-7.309) for patients with CA125 over-release behavior evidenced by a presurgical test or 5.212 (95% CI: 2.241-12.121) for that evidenced by a postsurgical test in OS.


Synthesis and stability of isotopically labeled p-chloro-m-xylenol (PCMX).
The synthesis, reaction kinetics, and pH stability of isotopically labeled p-chloro-m-xylenol (PCMX) were evaluated. While base catalysis was more rapid than acid catalysis, the latter allowed the use of a cosolvent for deuterium and tritium labeling using as little as 250 microL labeled water. Both acid and base catalysis were markedly more rapid than that reported previously for the deuteration of PCMX and related phenols. Isotopic labeling occurred only at the 2 and 6 ring positions, ortho to the phenolic group of PCMX. No deuterium loss was observed after storage for 21 days at 37 degrees C over a pH range of 2-14. Isotopic loss was observed only below pH 2. The prepared 3H-labeled PCMX had a specific activity of 1.18 mCi/mmol, a radiochemical purity of 99.0%, and a chemical purity exceeding 99.0%, with a high stability during prolonged cold storage.


Donor site morbidity following DIEP flap for breast reconstruction in Asian patients: Is it different?
Despite the decrease in donor-site morbidity with the advent of deep inferior epigastric artery perforator (DIEP) flap breast reconstruction, abdominal complications still occur. There have been few studies on donor morbidity considering the ethnic differences in the Asian population, as represented by a lower BMI with less redundant tissue and a tendency for poor scarring. In the present study, the authors investigated the incidence of abdominal complications and their risk factors following DIEP flap breast reconstruction in an Asian population. The authors conducted a retrospective review of DIEP flap based breast reconstructions performed in the past 5 years. Data regarding patient demographics, surgical details, and abdominal complications were collected from our prospectively maintained database and analyzed. A total of 217 patients who underwent DIEP flap breast reconstruction were included. There were 51 abdominal complications (23.5%), including 18 delayed wound healing, 17 hypertrophic scarring, 12 seroma formation, and 8 abdominal bulges with no hernias. Secondary procedures were performed for the donor-site complications in 36 cases. Flap height was a significant risk factor for overall donor-site morbidity. Harvesting a bipedicle flap was significantly associated with abdominal fat necrosis and hypertrophic scarring. Harvesting a flap based on perforators from both rows was significantly associated with abdominal delayed wound healing and hypertrophic scarring. DIEP flap breast reconstruction performed in Asian patients showed acceptable donor-site morbidity without significant complications. This study suggests that donor-site morbidity from harvesting a DIEP flap is comparable to that described in Western literatures.


Outcomes following proton therapy for Ewing sarcoma of the cranium and skull base.
Despite the dosimetric advantages of proton therapy, little data exist on patients who receive proton therapy for Ewing sarcoma of the cranium and skull base. This study reports local disease control and toxicity in such patients. We reviewed 25 patients (≤21 years old) with nonmetastatic Ewing sarcoma of the cranium and skull base treated between 2008 and 2018. Treatment toxicity was graded per the Common Terminology Criteria for Adverse Events v4.0. The Kaplan-Meier product limit method provided estimates of disease control and survival. Median patient age was 5.9 years (range, 1-21.7). Tumor subsites included the skull base (48%), non-skull-base calvarial bones (28%), paranasal sinuses (20%), and nasal cavity (4%). All patients underwent multiagent alkylator- and anthracycline-based chemotherapy; 16% underwent gross total resection (GTR) before radiation. Clinical target volume (CTV) 1 received 45 GyRBE and CTV2 received 50.4 GyRBE following GTR or 54-55.8 GyRBE following biopsy or subtotal resection. Median follow-up was 3.7 years (range, 0.26-8.3); no patients were lost. The 4-year local control, disease-free survival, and overall survival rates were 96%, 86%, and 92%, respectively. Two patients experienced in-field recurrences. One patient experienced bilateral conductive hearing loss requiring aids, two patients developed intracranial vasculopathy, and 6 patients required hormone replacement therapy for neuroendocrine deficits. None developed a secondary malignancy. Proton therapy is associated with a favorable therapeutic ratio in children with large Ewing tumors of the cranium and skull base. Despite its high conformality, we observed excellent local control and no marginal recurrences. Treatment dosimetry predicts limited long-term neurocognitive and neuroendocrine side effects.


Subclavian artery angioplasty for the treatment of angina using a double balloon technique to protect a left internal mammary artery graft.
Percutaneous transluminal angioplasty (PTA) has proven to be a safe and effective method of treating subclavian stenosis with technical success rates ranging from 83 to 100%. This technique, however, can result in distal embolisation. In the presence of a previous internal mammary bypass graft this may prove catastrophic, especially when that graft provides the dominant supply to the heart. Clearly any technique of reducing the risk of graft embolisation is valuable in this small subgroup of patients. The deployment of a double balloon to protect the left internal mammary artery graft to prevent this potentially fatal event has not been described previously.


Catalepsy induced by combinations of ketamine and morphine: potentiation, antagonism, tolerance and cross-tolerance in the rat.
Previous studies demonstrated that both ketamine and morphine induced analgesia and catalepsy in the rat. Pre-treatment with ketamine produced cross-tolerance to morphine, whereas pretreatment with morphine did not induce cross-tolerance to ketamine but rather augmented the cataleptic response; this augmentation was attributed to residual morphine in the brain. The present studies explored the duration of the loss of righting reflex induced by sub-effective doses of ketamine and morphine, administered simultaneously. There was mutual potentiation between sub-effective doses of ketamine and morphine, but sub-effective doses of ketamine partly antagonized fully-effective doses of morphine. Latency to the loss of righting reflex, rigidity and behavior on recovery, reflected the relative predominance of ketamine or morphine in each combination. Naloxone inhibited the induced cataleptic effects. The degree and time course of development of tolerance to daily administration of sub-effective dose combinations of ketamine and morphine were similar. Rats, tolerant to ketamine-dominant combinations, were cross-tolerant to both drugs, while those tolerant to morphine-dominant combinations were cross-tolerant to morphine but showed either no cross-tolerance or an augmented response to ketamine. While the mutual potentiation, antagonism and tolerance suggest common mechanisms for the induced catalepsy, differences in latency, rigidity and behavior, asymmetry of cross-tolerance and a widely-different ID50 for naloxone would argue against an action at a single opioid site.


Distance perception warped by social relations: Social interaction information compresses distance.
Though distance perception feeds the fundamental input that constructs a visual structure of the world, the suggestion has been made that it is constrained by this constructed structure. Instead of focusing on the physically defined structure, this study investigates whether and how social relations, especially the quality of social interaction (how individuals interact) rather than its content (what type of social interaction), precisely influences distance perception. The quality of social interaction was framed as an actor's intent and incurred outcome regarding another individual, whether helpful or harmful. Through visual animations, intent was operationalized as an agent's (i.e., actor's) intentional or unintentional act having an influence on another agent (i.e., affectee). Two experiments were conducted. In Experiment 1, the act was helpful, resulting in small or great beneficial consequences to the affectee. In Experiment 2, the act was harmful and resulted in small or great losses to the affectee. We found that when the help or harm had a large effect on others (the great-benefits or great-losses conditions), distance was perceived as shorter than when help or harm was minor, and the actor's intent did not affect distance perception. This suggests that, regardless of the type of social interaction, distance perception is mainly influenced by the outcome of an act not by the actor's intent. It implies that the perceived quality of social interaction creates a social constraint on distance perception. These findings are consistent with the idea that the intent and outcome of an action are assessed differently, and they help us understand how social relation penetrates the perceptual system.


Ankle fracture-dislocation with the interposition of the tibialis posterior tendon in the ankle syndesmosis and tibiotalar joint - A case report and systematic literature review.
In rare cases of ankle fracture dislocation, PTT can be incarcerated in the ankle syndesmosis. We report a case of a patient who had a fracture-dislocation of the ankle with the interposition of PTT in the ankle syndesmosis and discuss a systematic review of injury mechanics, pathology, diagnosis, management, and outcomes of this injury. I reported a 43-year-old patient presented with an irreducible lateral displacement of the talus after ORIF of the malleolar ankle fractures and fixation of ankle syndesmosis. Subsequent open reduction and surgical management revealed an interposition of PTT in the syndesmosis 1- month post-operative. A systematic review was completed afterward with the following terms: "ankle fracture" OR "ankle dislocation" AND "tibialis posterior tendon interposition" OR "tibialis posterior tendon entrapment" OR "tibialis posterior tendon incarceration" on Medline, ScienceDirect, and Ovid for articles between 1970 and 2022. 5 months postoperative, the patient reported no pain and became capable of walking without a steppage gait. The systematic review showed that the entrapment of PTT could be concurrent with FHL, FDL, and tibial neurovascular. It usually occurs in patients with pronation/eversion injury, Weber C ankle fracture with a valgus deformity and a syndesmosis diastasis. The PTT entrapment usually occurs in patients with pronation/eversion injury, Weber C ankle fracture, a valgus deformity, a syndesmosis diastasis. The entrapment of PTT could be concurrent with FHL, FDL, and tibial neurovascular. The tibiofibular syndesmosis and retromalleolar groove should be explored intraoperatively with suspicion of irreducible ankle fracture-dislocations.


RNA-seq analysis reveals resistome genes and signalling pathway associated with vancomycin-intermediate Staphylococcus aureus.
Vancomycin-intermediate Staphylococcus aureus remains one of the most prevalent multidrug-resistant pathogens causing healthcare infections that are difficult to treat. This study uses a comprehensive computational analysis to systematically investigate various gene expression profiles of resistant and sensitive S. aureus strains on exposure to antibiotics. The transcriptional changes leading to the development of multiple antibiotic resistance were examined by an integrative analysis of nine differential expression experiments under selected conditions of vancomycin-intermediate and -sensitive strains for four different antibiotics using publicly available RNA-Seq datasets. For each antibiotic, three experimental conditions for expression analysis were selected to identify those genes that are particularly involved in the development of resistance. The results were further scrutinised to generate a resistome that can be analysed for their role in the development or adaptation to antibiotic resistance. The 99 genes in the resistome are then compiled to create a multiple drug resistome of 25 known and novel genes identified to play a part in antibiotic resistance. The inclusion of agr genes and associated virulence factors in the identified resistome supports the role of agr quorum sensing system in multiple drug resistance. In addition, enrichment analysis also identified the kyoto encyclopedia of genes and genomes (KEGG) pathways - quorum sensing and two-component system pathways - in the resistome gene set. Further studies on understanding the role of the identified molecular targets such as SAA6008_00181, SAA6008_01127, agrA, agrC and coa in adapting to the pressure of antibiotics at sub-inhibitory concentrations can help in learning the molecular mechanisms causing resistance to the pathogens as well as finding other potential therapeutics.


Application of a domino intramolecular enyne metathesis/cross metathesis reaction to the total synthesis of (+)-8-epi-xanthatin.
[reaction: see text] The first total synthesis of the novel sesquiterpene lactone (+)-8-epi-xanthatin (1) has been achieved starting from the commercially available ester 8. The synthesis features an asymmetric aldol reaction and palladium-catalyzed carbonylation/lactonization sequence leading to 4 and a domino ring-closing enyne metathesis/cross metathesis reaction to afford 1.


Using a multiomics approach to unravel a septic shock specific signature in skeletal muscle.
Sepsis is defined as a dysregulated host response to infection leading to organs failure. Among them, sepsis induces skeletal muscle (SM) alterations that contribute to acquired-weakness in critically ill patients. Proteomics and metabolomics could unravel biological mechanisms in sepsis-related organ dysfunction. Our objective was to characterize a distinctive signature of septic shock in human SM by using an integrative multi-omics approach. Muscle biopsies were obtained as part of a multicenter non-interventional prospective study. Study population included patients in septic shock (S group, with intra-abdominal source of sepsis) and two critically ill control populations: cardiogenic shock (C group) and brain dead (BD group). The proteins and metabolites were extracted and analyzed by High-Performance Liquid Chromatography-coupled to tandem Mass Spectrometry, respectively. Fifty patients were included, 19 for the S group (53% male, 64 ± 17 years, SAPS II 45 ± 14), 12 for the C group (75% male, 63 ± 4 years, SAPS II 43 ± 15), 19 for the BD group (63% male, 58 ± 10 years, SAPS II 58 ± 9). Biopsies were performed in median 3 days [interquartile range 1-4]) after intensive care unit admission. Respectively 31 patients and 40 patients were included in the proteomics and metabolomics analyses of 2264 proteins and 259 annotated metabolites. Enrichment analysis revealed that mitochondrial pathways were significantly decreased in the S group at protein level: oxidative phosphorylation (adjusted p = 0.008); branched chained amino acids degradation (adjusted p = 0.005); citrate cycle (adjusted p = 0.005); ketone body metabolism (adjusted p = 0.003) or fatty acid degradation (adjusted p = 0.008). Metabolic reprogramming was also suggested (i) by the differential abundance of the peroxisome proliferator-activated receptors signaling pathway (adjusted p = 0.007), and (ii) by the accumulation of fatty acids like octanedioic acid dimethyl or hydroxydecanoic. Increased polyamines and depletion of mitochondrial thioredoxin or mitochondrial peroxiredoxin indicated a high level of oxidative stress in the S group. Coordinated alterations in the proteomic and metabolomic profiles reveal a septic shock signature in SM, highlighting a global impairment of mitochondria-related metabolic pathways, the depletion of antioxidant capacities, and a metabolic shift towards lipid accumulation.ClinicalTrial registration: NCT02789995. Date of first registration 03/06/2016.


Apparent vs. effective mating in an experimental population of Raphanus sativus.
Effective mating in plant populations need not occur during periods of peak pollinator activity and flowering. We measured seasonal and diurnal patterns of pollinator activity, pollen and ovule availability, and seed production in an experimental population of Raphanus sativus to infer the times of reproductively effective mating. On a seasonal scale, we found that most "effective matings", those resulting in mature seeds, occurred very early in the season, well before the peak of flowering and pollinator activity. At a finer scale, diurnal schedules of flower opening, stigma saturation with pollen, and pollen removal indicated that most effective matings occurred before noon, even though pollinator activity increased later in the day. These patterns may be most common in populations that are not pollen limited, but other ecological factors (e.g. seed predation, resource depletion) could weaken the correspondence between pollination and effective mating.


Endoscopic resection versus radical gastrectomy for early gastric cancer in Asia: A meta-analysis.
To compare the efficacy and safety of endoscopic resection (ER) and radical gastrectomy (RG) for early gastric cancer (EGC) in Asia. We systematically searched relevant articles published before September 1, 2017. We evaluated the quality of the included non-randomized studies using the Newcastle-Ottawa Scale (NOS). Meta-analysis was carried out using RevMan 5.3 software. The odds ratio (OR) with 95% confidence intervals (CI) were used for the dichotomous data. Fifteen retrospective studies were included in this analysis (3737 patients in the ER group and 4246 patients in RG group). No significant differences in the three-year survival rate (OR, 0.87; 95%CI, 0.50-1.53) and five-year survival rate (OR, 0.81; 95%CI, 0.58-1.13) between the ER and RG groups were observed. Although patients undergoing ER had a higher risk of recurrence (OR, 6.07; 95%CI 4.17-8.84) and the occurrence of metachronous cancer (OR, 8.35; 95%CI, 5.48-12.75), recurrent or metachronous gastric cancers following ER were successfully detected and removed using the endoscopic technique. Higher recurrence in the ER group may be associated with its lower en bloc resection rate (OR, 0.05; 95%CI, 0.02-0.14) and complete resection rate (OR, 0.03; 95%CI, 0.01-0.08). Importantly, although the three-year survival and five-year survival were similar in the two groups, the complication rate in the ER group was significantly lower than that in the RG group. ER is a good choice for patients with small EGC lesions (≤2 cm) without lymph node metastasis, especially in elderly patients with various medical comorbidities and in patients who cannot tolerate abdominal surgery or who meet the criteria but decline surgery. In contrast, RG is recommended when the diameter of the tumor is large (>2 cm) and preoperative examination suggests the possible presence of lymph node metastasis.


Cardiac arrest due to aberrant left coronary artery originating from the right sinus of Valsalva in a young girl.
We report a 14-year-old girl who sustained a syncope followed by cardiac arrest. She was kept alive for three days by full cardiocirculatory support using left and right ventricular assist devices, but subsequently died in multiple organ failure. Autopsy revealed an anomalous origin of the left coronary artery (LCA) from the right sinus of Valsalva (RSV) and a major left anterior wall infarction. A cyclo-ergometric stress test performed two years before having been negative, we discuss its value in preventing sudden death due to coronary anomalies.