Child outcome following mid-trimester amniocentesis: development, behaviour, and physical status at age 4 years.
Four-year-old children whose mothers had mid-trimester amniocentesis (n = 88) were compared with children whose mothers chose not to have the procedure (n = 46). Intelligence, visual-motor-perceptual skills, language, behaviour, social competence, temperament, physical growth, hearing, and middle-ear function were measured using standardized procedures. Health histories were obtained by maternal report. The results suggest that the wide range of developmental and behavioural variables studied is not influenced by removal of amniotic fluid in the mid-trimester. However, mothers who had amniocentesis were more likely to report a history of ear infections in their child (P = 0.04). In support of this finding were the results of audiological assessment which demonstrated a trend toward a higher rate of bilateral middle-ear impedance abnormalities in children whose mothers had amniocentesis (P = 0.06). Further study of the upper respiratory system is recommended to explore potential long-term sequelae of mid-trimester amniocentesis.


Reprogramming of trunk neural crest to a cranial crest-like identity alters their transcriptome and developmental potential.
Neural crest cells along the body axis of avian embryos differ in their developmental potential, such that the cranial neural crest forms cartilage and bone whereas the trunk neural crest is unable to do so. Previous studies have identified a cranial crest-specific subcircuit that can imbue the trunk neural crest with the ability to form cartilage after grafting to the head. Here, we examine transcriptional and cell fate changes that accompany this reprogramming. First, we examined whether reprogrammed trunk neural crest maintain the ability to form cartilage in their endogenous environment in the absence of cues from the head. The results show that some reprogrammed cells contribute to normal trunk neural crest derivatives, whereas others migrate ectopically to the forming vertebrae and express cartilage markers, thus mimicking heterotypically transplanted cranial crest cells. We find that reprogrammed trunk neural crest upregulated more than 3000 genes in common with cranial neural crest, including numerous transcriptional regulators. In contrast, many trunk neural crest genes are downregulated. Together, our findings show that reprogramming trunk neural crest with cranial crest subcircuit genes alters their gene regulatory program and developmental potential to be more cranial crest-like.


Holmium Laser Enucleation of the Prostate Is Associated with Complications and Sequelae Even in the Hands of an Experienced Surgeon Following Completion of the Learning Curve.
Holmium laser enucleation of the prostate (HoLEP) is considered a challenging procedure even for surgeons who have completed the learning curve. To assess outcomes and complications following HoLEP performed by a highly experienced surgeon. This was a single-institution prospective study (NCT03583034) performed at a tertiary referral centre that included 243 consecutive patients with lower urinary tract symptoms (LUTS) due to benign prostatic enlargement (BPE) treated with HoLEP by a single experienced surgeon (>1600 cases). Patients were assessed using validated questionnaires and uroflowmetry at baseline and several follow-up dates. Intraoperative and postoperative complications were recorded. Kaplan-Meier analysis was used to estimate recovery rates for urinary continence and erectile function. Logistic regression models were constructed to assess predictors of postoperative complications. Of the 243 patients, 78 (32.1%) had an indwelling urethral catheter. The median prostate volume (PV) was 87 cm3 (interquartile range 60-115) and 146 patients (59.8%) had PV >80 cm3. At 3-mo follow-up, 219 patients (90.1%) had a peak flow rate >20 ml/s and 182 (74.9%) had no postvoid residual urine. The improvement in subjective symptoms was significant at 1-mo follow-up and was maintained until 12 mo after surgery. Urinary continence recovery was slow, with an estimated rate of 68% (95% confidence interval [CI] 62-74%) at 1 mo and 94% (95% CI 91-97%) at 12 mo after HoLEP. The recovery rate for erectile function was 53% (95% CI 46-61%) at 1 mo and 85% (95% CI 77-90%) at 12 mo. Postoperative complications occurred in 36 patients (14.8%) during their hospital stay, in 34 (14%) within 1 mo following discharge from hospital, and in ten (4.1%) at later follow-up dates. Clinically significant complications (Clavien-Dindo ≥2) were observed in 44 cases (18%) and were more common for patients with an indwelling catheter at baseline (odds ratio 5.05; p = 0.006). HoLEP is an effective procedure for treating LUTS due to BPE, although it is not devoid of complications and sequelae, even in the hands of a highly experienced surgeon. Holmium laser treatment of the prostate to reduce its size has positive results for urinary function when performed by an experienced surgeon, even in complex cases, although there can be complications.


Recidivism in stalking and obsessional harassment.
Despite the rapidly growth of mental health attention focused on the phenomenon of stalking, no empirical research to date has attempted to assess the frequency of repeat offending or attempted to identify predictors of recidivism. A total of 148 stalking and harassment offenders who were court-ordered to undergo a mental health evaluation were followed for a period of 2.5-13 years in order to assess the frequency of repeat offenses and the variables that differentiated high versus low risk offenders. Recidivism data were obtained from a variety of sources, including criminal justice records, mental health records, and reports from probation officers and victims. A number of potential "predictor" variables were selected on the basis of the existing recidivism literature in other criminal justice populations. Frequency analysis were used to identify variables that significantly differentiated offenders who did and did not reoffened while survival analysis was used to analyze the impact of these covariates on time to reoffense. A total of 49% of the offenders reoffended during the follow-up period, 80% of whom reoffended during the first year. The strongest predictors of recidivism included the presence of a personality disorder, and in particular, a "Cluster B" personality disorder (i.e., antisocial, borderline, and/or narcissistic). In addition, those offenders with both a personality disorder and a history of substance abuse were significantly more likely to reoffened compared to either of these risk factors alone. Surprisingly, the presence of a delusional disorder (e.g., erotomania) was associated with a lower risk of reoffender. The findings are discussed in terms of the legal system and treatment implications.


Chiral Fluorescent Recognition by Naphthalimide.
Chirality plays a very important role in medicine, biochemistry and other fields. Because the enantiomers of chiral drugs often show different pharmacology activity, metabolism, and toxicity, therefore, the recognition of chiral molecules is very important, and has become a hot spot and frontier of modern chemical research. In this paper, a new method for recognizing chiral molecular based on naphthalimide dye(NA)⊂cucurbit[5]uril(CB[7]) assembly is developed. NA as guest can be combined with the host CB[7] to form a 1:1 NA⊂CB[7] assembly. Furthermore, this assembly was used as a fluorescent probe to recognize D/L-phenylalanine and D/L-phenylalaninol by fluorescence titration. When D-phenylalanine or D-phenylalaninol was added to NA⊂CB[7] assembly, the fluorescent intensity of assembly was partially quenched, but when L-phenylalanine or L-phenylalaninol was added to NA⊂CB[7], the fluorescence intensity of the assembly almost unchanged. Herein, chiral recognition platform based on achiral NA⊂achiral CB[7] was constructed.


Interaction between Ca(2+) channel blockers and isoproterenol on L-type Ca(2+) current in canine ventricular cardiomyocytes.
The aim of this work was to study antagonistic interactions between the effects of various types of Ca(2+) channel blockers and isoproterenol on the amplitude of L-type Ca(2+) current in canine ventricular cells. Whole-cell version of the patch clamp technique was used to study the effect of isoproterenol on Ca(2+) current in the absence and presence of Ca(2+) channel-blocking agents, including nifedipine, nisoldipine, diltiazem, verapamil, CoCl(2) and MnCl(2) . Five micromolar Nifedipine, 1 μM nisoldipine, 10 μM diltiazem, 5 μM verapamil, 3 mM CoCl(2) and 5 mM MnCl(2) evoked uniformly a 90-95% blockade of Ca(2+) current in the absence of isoproterenol. Isoproterenol (100 nM) alone increased the amplitude of Ca(2+) current from 6.8 ± 1.3 to 23.7 ± 2.2 pA/pF in a reversible manner. Isoproterenol caused a marked enhancement of Ca(2+) current even in the presence of nifedipine, nisoldipine, diltiazem and verapamil, but not in the presence of CoCl(2) or MnCl(2) . The results indicate that the action of isoproterenol is different in the presence of organic and inorganic Ca(2+) channel blockers. CoCl(2) and MnCl(2) were able to fully prevent the effect of isoproterenol on Ca(2+) current, while the organic Ca(2+) channel blockers failed to do so. This has to be born in mind when the effects of organic Ca(2+) channel blockers are evaluated either experimentally or clinically under conditions of increased sympathetic tone.


Relay of peripheral oxytocin to central oxytocin neurons via vagal afferents for regulating feeding.
Oxytocin (Oxt), a neurohormone synthesized in the neurons of hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus induces milk-ejection and uterine contraction and regulates social behavior, stress responses, memory and food intake. Peripheral (intraperitoneal and subcutaneous) infusion of Oxt decreases food intake and body weight in obese animals via mechanisms involving vagal afferent nerves and in obese subjects when administered nasally. Peripherally injected and intracerebroventricularly injected Oxt inhibit food intake to similar extent and with similar time course. Thus, peripheral Oxt mimics the effects of central Oxt, however, underlying mechanisms are unclear. In the present study we explored whether intraperitoneal Oxt activates Oxt neurons in PVN via vagal afferents and whether this pathway is linked to inhibition of feeding. We here show that intraperitoneal Oxt injection induces c-Fos expression in PVN largely in Oxt neurons and inhibits food intake, and these effects are blunted by subdiaphragmatic vagotomy. The intraperitoneal Oxt-induced inhibition of food intake was blunted in Oxt KO mice, by intracerebroventricular injection of Oxt receptor antagonist, and by vagotomy. These results demonstrate that intraperitoneal Oxt injection activates PVN Oxt neurons via vagal afferent nerves, thereby inhibiting food intake. This vagal afferents-mediated Oxt's peripheral-to-central coupling may serve to promote satiety and possibly a series of neural functions of Oxt and to treat their disorders.


Pattern reversal visually evoked potentials in general anesthesia.
Various authors have tried to determine visual acuity both electrophysiologically (Sokol, 1976 and 1978; Marg et al., 1976; Maffei and Fiorentini, 1977) and with psychophysical methods (Teller et al., 1974; Banks and Salapatek, 1976; Atkinson et al., 1976) in awake children. Our experiments try to verify the possibility of assessing visual acuity in children under Ethrane anesthesia. We conclude that under Ethrane anesthesia VEPs produced by phase-alternating square-wave gratings do not allow a fine assessment of visual acuity. Gross indications of visual acuity can however be obtained.


Generation of a human induced pluripotent stem cell line (WMUi021-A) from a Gitelman syndrome patient carrying a SLC12A3 gene mutation (c.179C > T).
Gitelman Syndrome (GS) is an inherited autosome recessive disorder syndrome, which can be caused by the gene mutations of solute carrier family 12 member 3 gene (SLC12A3). In present study, the urine cells (UCs) of a 7-year-old male GS patient with the homozygote SLC12A3 gene mutation p.T60M (c.179C > T) were reprogrammed into induced pluripotent stem cells (iPSCs) named WMUi021-A through the commercial Sendai virus reprogramming kit. The pluripotent markers OCT4 and SOX2 can be expressed positively in WMUi021-A, which can be differentiated into three germ layers in vitro as well as maintain a stable karyotype (46, XY).


Automated SNOMED CT concept and attribute relationship detection through a web-based implementation of cTAKES.
Information in Electronic Health Records is largely stored as unstructured free text. Natural language processing (NLP), or Medical Language Processing (MLP) in medicine, aims at extracting structured information from free text, and is less expensive and time-consuming than manual extraction. However, most algorithms in MLP are institution-specific or address only one clinical need, and thus cannot be broadly applied. In addition, most MLP systems do not detect concepts in misspelled text and cannot detect attribute relationships between concepts. The objective of this study was to develop and evaluate an MLP application that includes generic algorithms for the detection of (misspelled) concepts and of attribute relationships between them. An implementation of the MLP system cTAKES, called DIRECT, was developed with generic SNOMED CT concept filter, concept relationship detection, and attribute relationship detection algorithms and a custom dictionary. Four implementations of cTAKES were evaluated by comparing 98 manually annotated oncology charts with the output of DIRECT. The F1-score was determined for named-entity recognition and attribute relationship detection for the concepts 'lung cancer', 'non-small cell lung cancer', and 'recurrence'. The performance of the four implementations was compared with a two-tailed permutation test. DIRECT detected lung cancer and non-small cell lung cancer concepts with F1-scores between 0.828 and 0.947 and between 0.862 and 0.933, respectively. The concept recurrence was detected with a significantly higher F1-score of 0.921, compared to the other implementations, and the relationship between recurrence and lung cancer with an F1-score of 0.857. The precision of the detection of lung cancer, non-small cell lung cancer, and recurrence concepts were 1.000, 0.966, and 0.879, compared to precisions of 0.943, 0.967, and 0.000 in the original implementation, respectively. DIRECT can detect oncology concepts and attribute relationships with high precision and can detect recurrence with significant increase in F1-score, compared to the original implementation of cTAKES, due to the usage of a custom dictionary and a generic concept relationship detection algorithm. These concepts and relationships can be used to encode clinical narratives, and can thus substantially reduce manual chart abstraction efforts, saving time for clinicians and researchers.


Clinical, virological, and operational aspects of a single-center Belgian experience with in-hospital infusions of casirivimab/imdevimab and sotrovimab for mild/moderate COVID-19.
To describe the clinical and virological characteristics of COVID-19 patients treated in a hospital with casirivimab/imdevimab and sotrovimab between June 2021 and April 2022 and to report the logistics for administering these monoclonal antibodies (mAbs). All COVID-19 adult patients treated with mAbs at CHU Charleroi (Belgium) were included. A multidisciplinary monoclonal antibodies team (MMT) was dedicated to identify eligible patients and coordinate the administration of mAbs in a temporary structure created within the hospital. A total of 69 COVID-19 patients were treated with casirivimab/imdevimab (11.6%) and sotrovimab (88.4%) within a median of 4 days of symptom onset, mainly during the Omicron B.1.1.529 period (71%); no severe adverse events occurred. Thirty-eight (55%) were outpatients, and among the 31 inpatients, 42% were nosocomial COVID-19. The median age was 65 years [IQR, 50-73], and 53.6% were male. The most common risk factors for progression to severe COVID-19 were immunosuppression (72.5%), arterial hypertension (60.9%) and age>65 years (47.8%). One fifth were SARS-CoV-2-unvaccinated patients. The median Belgian MASS score for patient prioritization was 6 [IQR, 4-8]. On Day 29, 10.5% of the outpatients were hospitalized, and 1.4% were admitted to an intensive care unit (ICU); there were no COVID-19-related deaths. General practitioners referred 19.4% of the outpatients. In our experience, mAbs were prescribed in very high-risk patients with no adverse events, few progressions to severe COVID-19, and no related deaths. Our MMT has improved coordination of COVID-19 treatment and contribute to enhance communication with primary care.


A nurse-assisted screening and referral program for depression among survivors of colorectal cancer: feasibility study.
To test the feasibility and acceptability of a telephone-based program to screen survivors of colorectal cancer (CRC) for distress, and to refer distressed patients to their treating health service. A prospective, multicentre study involving 59 patients with CRC recruited from six public and private health services in Melbourne, Victoria, from 15 June 2008 to 22 September 2009. Patients who had completed adjuvant chemotherapy for CRC were contacted (7-10 days after recruitment [outcall one] and again 4 weeks later [outcall two]) by the Cancer Council Victoria's helpline nurse, and screened for distress with the Distress and Impact Thermometer (DIT); participants were given tailored information and support and those with distress scores of > or = 5, and impact scores of > or = 4, were referred for follow-up. Telephone interviews were conducted 4 weeks after outcall two. Participating helpline and health service staff were surveyed on the feasibility and acceptability of the service. Anxiety and depression, measured by the Hospital Anxiety and Depression Scale (HADS). Of the 59 patients (87%) who agreed to participate, 63% were men; their mean age was 59 years (SD, 9.5 years). HADS depression decreased significantly from baseline (mean score, 4.93; SD, 4.22) to follow-up (mean score, 3.84; SD, 4.10; Z = -2.375; P = 0.02). However, there was no significant difference in HADS anxiety between baseline (mean score, 5.29; SD, 4.11) and follow-up (mean score, 4.78; SD, 3.65). Outcall one generated two referrals (4% of participants) and outcall two generated four referrals (8%); five of these six participants took up the referrals. Satisfaction with the program among participants was high; 82% found outcall one "quite or very helpful" and 79% found outcall two "quite or very helpful". Helpline and health service staff reported a straightforward process that did not adversely affect workloads. This model of care carries the potential to meet ongoing psychosocial needs of survivors of CRC.


Role of icosanoids in alveolar macrophage phagocytosis and aggregation.
Rat alveolar macrophages (AM) collected by bronchoalveolar lavage were incubated in the presence or absence of various icosanoids or inhibitors of the arachidonic acid cascade with either chrysotile asbestos (50 micrograms/ml) to determine cell aggregation, or human red blood cells (Rh+; preincubated with anti-D globulin) to measure phagocytosis. Phorbol myristate acetate (PMA) and ionophore A23187, two agents which stimulate arachidonic acid metabolism, reduced red blood cell phagocytosis by AM whereas arachidonic acid had no effect on this cellular event. Neither arachidonic acid nor its metabolites (prostaglandins E2, I2, F2 alpha, the thromboxane mimick U44069 and leukotrienes A4, B4, C4, D4) had a significant effect on phagocytosis. Inhibition of the synthesis of cyclooxygenase products with various concentrations of indomethacin, aspirin and OKY-1581 or of lipoxygenase products with eicosatetraynoic acid, BW755c, diethylcarbamazine and phenidone did not affect phagocytosis either. On the other hand, asbestos-induced aggregation was significantly reduced by nordihydroguaiaretic acid (NDGA), BW755C, benoxaprofen, and high concentrations of indomethacin but not by aspirin. These results suggested that metabolites of arachidonic acid (especially lipoxygenase products) play a modulatory role in non specific alveolar macrophage aggregation but not in specific, Fc receptor-mediated phagocytosis.


Early palliative intervention in septic patients reduces healthcare utilization.
While the role of palliative care in the emergency department is recognized, barriers against the effective integration of palliative interventions and emergency care remain. We examined the association between goals-of-care and palliative care consultations and healthcare utilization outcomes in older adult patients who presented to the emergency department (ED) with sepsis. We performed a retrospective review of 197 patients aged 65 years and older who presented to the ED with sepsis or septic shock. Healthcare utilization outcomes were compared between patients divided into 3 groups: no palliative care consultation, palliative care consultation within 4 days of admission (i.e., early consultation), and palliative care consultation after 4 days of admission (i.e., late consultation). 51% of patients did not receive any palliative consultation, 39% of patients underwent an early palliative care consultation (within 4 days), and 10% of patients underwent a late palliative care consultation (after 4 days). Patients who received late palliative care consultation had a significantly increased number of procedures, total length of stay, ICU length of stay, and cost (p < .01, p < .001, p < .05, p < .001; respectively). Regarding early palliative care consultation, there were no statistically significant associations between this intervention and our outcomes of interest; however, we noted a trend towards decreased total length of stay and decreased healthcare cost. In patients aged 65 years and older who presented to the ED with sepsis, early palliative consultations were associated with reduced healthcare utilization as compared to late palliative consultations.


Trends in the evolution of the elasmobranch melanocortin-2 receptor: Insights from structure/function studies on the activation of whale shark Mc2r.
To understand the mechanism for activation of the melanocortin-2 receptor (Mc2r) of the elasmobranch, Rhincodon typus (whale shark; ws), wsmc2r was co-expressed with wsmrap1 in CHO cells, and the transfected cells were stimulated with alanine-substituted analogs of ACTH(1-24) at the "message" motif (H6F7R8W9) and the "address" motif (K15K16R17R18P19). Complete alanine substitution of the H6F7R8W9 motif blocked activation, whereas single alanine substitution at this motif indicated the following hierarchy of position importance for activation: W9 > R8, and substitution at F7 and H6 had no effect on activation. The same analysis was done on a representative bony vertebrate Mc2r ortholog (Amia calva; bowfin; bf) and the order of position importance for activation was W9 > R8 = F7, (alanine substitution at H6 was negligible). Complete alanine substitution at the K15K16R17R18P19 motif resulted in distinct outcomes for wsMc2r and bfMc2r. For bfMc2r, this analog blocked activation-an outcome typical for bony vertebrate Mc2r orthologs. For wsMc2r, this analog resulted in a shift in sensitivity to stimulation of the analog as compared to ACTH(1-24) by two orders of magnitude, but the dose response curve did reach saturation. To evaluate whether the EC2 domain of wsMc2r plays a role in activation, a chimeric wsMc2r was made in which the EC2 domain was replaced with the EC2 domain from a melanocortin receptor that does not interact with Mrap1 (i.e., Xenopus tropicalis Mc1r). This substitution did not negatively impact the activation of the chimeric receptor. In addition, alanine substitution at a putative activation motif in the N-terminal of wsMrap1 did not affect the sensitivity of wsMc2r to stimulation by ACTH(1-24). Collectively, these observations suggest that wsMc2r may only have a HFRW binding site for melanocortin-related ligand which would explain how wsMc2r could be activated by either ACTH or MSH-sized ligands.


Rod-shaped nintedanib nanocrystals improved oral bioavailability through multiple intestinal absorption pathways.
Nintedanib (BIBF) is a biopharmaceutical classification system II (BCS II) drug that has a good therapeutic effect for the treatment of nonsmall cell lung cancer; however, it shows poor oral bioavailability due to low dissolution and intestinal absorption. This study aims to fabricate rod-shaped nanocrystals to enhance oral bioavailability by improving the dissolution and absorption of BIBF in the intestine. By prescription screening, BIBF nanocrystals (BIBF-NCs) with a particle size of 325.30 ± 1.03 nm and zeta potential of 32.70 ± 1.24 mV were fabricated by an antisolvent precipitation-ultrasound approach with a stabilizer of sodium carboxyl methyl cellulose (CMC-Na). BIBF-NCs exhibited a rod-shaped morphology by transmission electron microscopy (TEM). The results of powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) showed that the crystal form of BIBF in BIBF-NCs was altered. The BIBF-NCs remarkably improved the saturation solubility and dissolution of BIBF compared with BIBF powder. According to the results of in situ single-pass intestinal perfusion (SPIP), BIBF-NCs showed improved absorption and membrane permeability, with Ka and Papp values in the jejunum of 0.21 ± 0.01 min-1 and (4.34 ± 0.11) × 10-4 cm/min, respectively. Further, the Ka and Papp values of BIBF-NCs were all reduced significantly after the addition of inhibitors colchicine, chlorpromazine and indomethacin, which demonstrated that BIBF-NCs could be absorbed by endocytosis mediated by caveolae and clathrin and micropinocytosis in the intestine. The cell evaluation results showed that BIBF-NCs could be taken up by macrophages and transported from Caco-2 monolayers. The in vivo pharmacokinetic results showed that the bioavailability of the BIBF-NCs was 2.51-fold higher than that of the BIBF solution (BIBF-Sol) after oral administration with a longer Tmax (4.50 ± 1.00 h vs. 2.60 ± 1.92 h). In summary, rod-shaped BIBF-NCs could significantly improve oral bioavailability through multiple intestinal absorption pathways.


The "make or break" impact of family dynamics on psychological outcomes in focal epilepsy.
Living with epilepsy can shape the dynamics of the whole family unit. The first objective of this study was to establish the reliability and validity of our purpose-built online family mapping tool: "Living with Epilepsy." Our second objective was to identify distinct patterns of emotional closeness between family members (family typologies), and to explore (1) whether family typologies are shaped by epilepsy-related factors, and (2) which typologies confer optimal psychological outcomes to people with epilepsy. Ninety-one adults with chronic epilepsy and their caregivers (n = 56) participated and 70 similarly aged healthy controls and 36 caregiver controls (N = 253). Purpose-built software assessed a range of epilepsy-specific psychosocial issues, including family mapping. Questionnaires validated for epilepsy evaluated mood and quality of life (QOL). The reliability and validity of the family mapping tool was established. Family maps revealed three typologies varying in emotional closeness, each with distinct patterns of healthy vs maladaptive family behavior: Extremely Close (32%), Close (54%), and Fractured (14%). There was no difference in the frequency of typology between epilepsy and control families (p > .05). Within the epilepsy cohort, however, patients with seizure onset in childhood largely belonged to the extreme typologies: Extremely Close (47%) or Fractured (42%). In comparison, those with adolescent or adult onset commonly belonged to the moderate typology: Close (53%). People with epilepsy from Extremely Close families reported significantly higher QOL (p = .013) and lower mood symptoms (p = .008) relative to other typologies; no such association was found for controls or caregivers (p > .05). These findings suggest that adults whose epilepsy commenced in childhood are likely to have extreme family dynamics characterized by either being brought closer together or driven apart. Extremely close families appear highly adaptive for people with epilepsy, bringing benefits for mood and QOL not seen in their caregivers or controls. The results provide strong empirical support for the value of an emotionally supportive family when living with epilepsy and suggest that fostering healthy connections within epilepsy families can optimize long-term patient well-being.


The SF3B1R625H mutation promotes prolactinoma tumor progression through aberrant splicing of DLG1.
Recently, a hotspot mutation in prolactinoma was observed in splicing factor 3b subunit 1 (SF3B1R625H), but its functional effects and underlying molecular mechanisms remain largely unexplored. Using the CRISPR/Cas9 genome editing system and rat pituitary GH3 cells, we generated heterozygous Sf3b1R625H mutant cells. Sanger and whole-genome sequencing were conducted to verify the introduction of this mutation. Transcriptome analysis was performed in SF3B1-wild-type versus mutant human prolactinoma samples and GH3 cells. RT-PCR and minigene reporter assays were conducted to verify aberrant splicing. The functional consequences of SF3B1R625H were evaluated in vitro and in vivo. Critical makers of epithelial-mesenchymal transition and key components were detected using western blot, immunohistochemistry, and immunofluorescence. Suppressing proteins was achieved using siRNA. Transcriptomic analysis of prolactinomas and heterozygous mutant cells revealed that the SF3B1R625H allele led to different alterations in splicing properties, affecting different genes in different species. SF3B1R625H promoted aberrant splicing and DLG1 suppression in both rat cells and human tumors. In addition, SF3B1R625H and knocking down DLG1 promoted cell migration, invasion, and epithelial-mesenchymal transition through PI3K/Akt pathway. Our findings elucidate a mechanism through which mutant SF3B1 promotes tumor progression and may provide a potent molecular therapeutic target for prolactinomas with the SF3B1R625H mutation.


Beneficial effects of garlic (Allium sativum Linn) on rats fed with diets containing cholesterol and either of the oil seeds, coconuts or groundnuts.
Feeding of 2% cholesterol diet increased lipid parameters in serum and tissues of rats during a period of one month. In addition to the above, lipid peroxidation also increased and activities of certain enzymes were significantly altered in the tissues. Similar changes were also observed to a greater extent with diets containing 40% by weight of coconut kernel or groundnut with and without 2% cholesterol. The enzymes studied were HMGCoA reductase, AST, ALT and ALP in tissues and serum as the case may be. In general the atherogenic effects were observed more with groundnut containing diets than those with coconut. Even though the oil from the former is mostly unsaturated and that from the latter is mostly saturated, these analytical criteria do not relate to their atherogenic effects. When 5% garlic was incorporated with any of the high fat diets, the lipid parameters, their peroxidation and alterations in enzyme activities were significantly decreased. These results show that garlic contains some principles that counteract the atherogenicity of the above oil seeds.


The concentration of alpha-1-antitrypsin in cerebrospinal fluid and serum in a series of 40 intracranial tumors.
Forty patients with histologically proved intracranial tumors were submitted to preoperative lumbar and venous punctures. The concentration of alpha-1-antitrypsin in the serum and in cerebrospinal fluid was determined by radial immunodiffusion technique. In the series, both serum and cerebrospinal fluid alpha-1-antitrypsin concentrations are significantly higher than the mean normal values. No statistical differences are observed in serum alpha-1-antitrypsin levels between benign and malignant tumors, but cerebrospinal fluid alpha-1-antitrypsin is significantly increased in the group of malignant tumors if cases undergoing steroid treatment are excluded. The diagnostic value of alpha-1-antitrypsin determinations in groups of patients with intracranial tumors is suggested.


Cyclic uniaxial cell stretching in tissue culture using a LEGO®-based mechanical stretcher and a polydimethylsiloxane stretchable vessel.
Mechanical signals are essential for the regulation of many biological processes. Therefore, it has become paramount to account for these mechanical parameters when exploring biological processes. Here, we describe a protocol to apply cyclic uniaxial stretch on cells in culture using a LEGO®-based mechanical stretcher and a flexible custom-made polydimethylsiloxane culture vessel as well as validated downstream applications. While this system offers an out-of-the-box limited type of simulation, it provides a reliable and low-cost opportunity to perform cell stretching. For complete details on the use and execution of this protocol, please refer to Boulter et al. (2020).


Further characterization of Sendai virus DI-RNAs: a model for their generation.
Sendai virus DI-RNAs which contain complementary ends have been characterized as follows. First, the complementary ends of three DI-RNAs, although somewhat different in size (110-150 base pairs), contain sequences that are both identical to each other and to the 5' end of the nondefective (ND) genome. Second, almost all the sequences contained sequences that are both identical to each other and to the 5' end of the nondefective (ND) genome. Second, almost all the sequences contained in the DI-RNAs derive from sequences that are contiguous to the 5' end of the ND genome. The ND genome, on the other hand, does not contain any sequences that are complementary to its 5' end. A genetic map and a model for the generation of the Sendai DI-RNAs are presented.


Prevalence, Pattern, and Factors Associated With Self-reported Disability Among the Bhutanese Population: A Secondary Data Analysis of Population and Housing Census.
We analyzed the Population and Health Census of Bhutan (PHCB) 2017 to assess the prevalence and pattern of self-reported disability among people aged ≥15 years and the associated factors. The PHCB 2017 used the Washington Group Short Set on Functioning questionnaire to assess the disability ("lot of difficulty" or "cannot do at all") in seeing, hearing, mobility, cognition, self-care, and communication. Of the 536 443 persons included in the analysis, 384 101(71.6%) were aged <45 years, 283 453(52.8%) were men, and 206 103(38.4%) were from the rural area. The prevalence of any self-reported disability was 2.8%, among whom 34.2% reported multiple disabilities. The disability prevalence (any) was significantly higher among people aged ≥65 years, illiterate, economically inactive, permanent residents, residing in a rural area, and from central and eastern regions of the country compared with their respective counterparts. Further research on access to rehabilitation and linking with social protection schemes for the disabled is required in this country.


Aligned lovastatin-loaded electrospun nanofibers regulate collagen organization and reduce scar formation.
Excessive scar formation caused by cutaneous injury leads to pruritus, pain, contracture, dyskinesia, and unpleasant appearance. Functional wound dressings are designed to accelerate wound healing and reduce scar formation. In this study, we fabricated aligned or random polycaprolactone/silk fibroin electrospun nanofiber membranes with or without lovastatin loading, and then evaluated their scar-inhibitory effects on wounds under a specific tension direction. The nanofiber membranes exhibited good controlled-release performance, mechanical properties, hydrophilicity, and biocompatibility. Furthermore, nanofibers' perpendicular placement to the tension direction of the wound most effectively reduced scar formation (the scar area decreased by 66.9%) and promoted skin regeneration in vivo. The mechanism was associated with aligned nanofibers regulated collagen organization in the early stage of wound healing. Moreover, lovastatin-loaded nanofibers inhibited myofibroblast differentiation and migration. Both tension direction-perpendicular topographical cues and lovastatin synergistically inhibited mechanical transduction and fibrosis progression, further reducing scar formation. In summary, our study may provide an effective scar prevention strategy in which individualized dressings can be designed according to the local mechanical force direction of patients' wounds, and the addition of lovastatin can further inhibit scar formation. STATEMENT OF SIGNIFICANCE: In vivo, cells and collagen are always arranged parallel to the tension direction. However, the aligned topographic cues themselves promote myofibroblast differentiation and exacerbate scar formation. Electrospun nanofibers' perpendicular placement to the tension direction of the wound most effectively reduces scar formation and promotes skin regeneration in vivo. The mechanism is associated with tension direction-perpendicular nanofibers reregulate collagen organization in the early stage of wound healing. In addition, tension direction-perpendicular topographical cue and lovastatin could inhibit mechanical transduction and fibrosis progression synergistically, further reducing scar formation. This study proves that combining topographical cues of wound dressing and drugs would be a promising therapy for clinical scar management.


Platelet Lysate for Mesenchymal Stromal Cell Culture in the Canine and Equine Species: Analogous but Not the Same.
Platelet lysate (PL) is an attractive platelet-based therapeutic tool and has shown promise as xeno-free replacement for fetal bovine serum (FBS) in human and equine mesenchymal stromal cell (MSC) culture. Here, we established a scalable buffy-coat-based protocol for canine PL (cPL) production (n = 12). The cPL was tested in canine adipose MSC (n = 5) culture compared to FBS. For further comparison, equine adipose MSC (n = 5) were cultured with analogous equine PL (ePL) or FBS. During canine blood processing, platelet and transforming growth factor-β1 concentrations increased (p < 0.05 and p < 0.001), while white blood cell concentrations decreased (p < 0.05). However, while equine MSC showed good results when cultured with 10% ePL, canine MSC cultured with 2.5% or 10% cPL changed their morphology and showed decreased metabolic activity (p < 0.05). Apoptosis and necrosis in canine MSC were increased with 2.5% cPL (p < 0.05). Surprisingly, passage 5 canine MSC showed less genetic aberrations after culture with 10% cPL than with FBS. Our data reveal that using analogous canine and equine biologicals does not entail the same results. The buffy-coat-based cPL was not adequate for canine MSC culture, but may still be useful for therapeutic applications.


New biomarkers in non-Hodgkin lymphoma and acute leukemias.
Biomarkers play a critical role in the medical care of patients with cancer, including in early detection of the disease, diagnostic accuracy, risk stratification, treatment, and follow-up. Biomarkers in hematological malignancies can support the redefinition of the diagnosis and adjustments in the treatment plan. Biomarkers can be classified into 4 categories: (1) protein antigens, (2) cytogenetic abnormalities, (3) genetic polymorphisms, and (4) gene expression. Efforts in genomics, proteomics, and metabolomics to observe new biomarkers that contribute to the development of clinical medicine with greater precision in the strategies that improve prevention, diagnosis, and treatment of patients with malignant hematological disease. New biomarkers should accomplish several issues such as the biological plausibility, methodology used, analytical validation, intellectual property registry, and legal framework of application. This knowledge should be transferred to health professionals who can carry out the process of its implementation in clinical practice.


Modulation of xenobiotic metabolising enzymes by anticarcinogens -- focus on glutathione S-transferases and their role as targets of dietary chemoprevention in colorectal carcinogenesis.
There is evidence that consumption of certain dietary ingredients may favourably modulate biotransformation of carcinogens. Associated with this is the hypothesis that the risk for developing colorectal cancer could be reduced, since its incidence is related to diet. Two main groups of biotransformation enzymes metabolize carcinogens, namely Phase I enzymes, which convert hydrophobic compounds to more water-soluble moieties, and Phase II enzymes (e.g. glutathione S-transferases [GST]), which primarily catalyze conjugation reactions. The conjugation of electrophilic Phase I intermediates with glutathione, for instance, frequently results in detoxification. Several possible colon carcinogens may serve as substrates for GST isoenzymes that can have marked substrate specificity. The conjugated products could be less toxic/genotoxic if GSTs are induced, thereby reducing exposure. Thus, numerous studies have shown that the induction of GSTs by antioxidants enables experimental animals to tolerate exposure to carcinogens. One important mechanism of GST induction involves an antioxidant-responsive response element (ARE) and the transcription factor nuclear factor E2-related factor 2 (Nrf2), which is bound to the Kelch-like ECH associated protein 1 (Keap1) in the cytoplasm. Antioxidants may disrupt the Keap-Nrf2 complex, allowing Nrf2 to translocate to the nucleus and mediate expression of Phase II genes via interaction with the ARE. GSTs are also induced by butyrate, a product of gut flora-derived fermentation of plant foods, which may act via different mechanisms, e.g. by increasing histone acetylation. GSTs are expressed with high inter-individual variability in human colonocytes, which points to large differences in cellular susceptibility to xenobiotics. Enhancing expression of GSTs in human colon tissue could therefore contribute to reducing cancer risks. However, it has not been demonstrated in humans that this mechanism is associated with cancer prevention. In the future, it will be useful to determine GSTs during dietary intervention studies to enhance our understanding of this protective mechanism.


Genetic background and expressivity of histocompatibility genes.
A difference in the reactivity of F(1) hybrid female mice to skin grafts from male donors of each of their parental strains suggests that the genetic background can influence the efficacy of the Y antigen to elicit rejection of the graft.


Theoretical study of hinge bending in L-arabinose-binding protein. Internal energy and free energy changes.
The L-arabinose-binding protein of Escherichia coli is a periplasmic component of the L-arabinose transport system. Its three-dimensional structure has been determined by x-ray diffraction and shown to have two globular domains and a connecting hinge. These structural features enclose a cleft in which the L-arabinose-binding site is located. The flexibility of the protein hinge that allows hinge-bending motion is investigated here by theoretical analysis of the changes in conformational energy and molecular structure that accompany the opening and closing of the cleft. The hinge of the molecule is found to be quite permissive in that only moderate increases in the internal energy occur upon opening the cleft. Solvation changes of charged groups on the cleft-facing surfaces of the lobes are estimated to make important contributions to the overall energetics of the system. The results indicate that an open conformation for the unliganded protein is stabilized by the exposure and solvation of charged groups in the cleft, and that the cleft is induced to close upon ligand binding. This picture is consistent with experimental data on the structure and the binding kinetics of L-arabinose-binding protein, and provides a physical framework for interpreting such data.


Efficacy of renal preservation: comparative study of Celsior and University of Wisconsin solutions.
We sought to compare the efficacy of Celsior and University of Wisconsin (UW) solutions on the perfusion and cold storage of renal grafts for human transplantation. Retrospective analyses of 313 kidney transplants were performed between 2002 and 2005; group A (n = 160), UW solution and group B (n = 153), Celsior solution were used in the preservation of the organs. The mean donor age was lower in group B (group A = 42.67 years vs group B = 38.96 years; P < .05), living donors were more frequent in the UW group (group A = 10% vs group B = 0.9%; P < .001). Multiorgan procurement procedures were more common in the Celsior group (group A = 75% vs group B = 81.7%; P < .001). Recipients with no associated comorbidities were more frequent in the UW group (group A = 50% vs group B = 36%; P < .001). Recipient mean age, cold ischemia time, and HLA matches were comparable. Delayed graft function (group A = 22.7% vs group B = 20.6%), acute rejections (group A = 21.4% vs group B = 18.4%), and serum creatinine at 6 months (group A = 1.75 vs group B = 1.67 mg/dL), 1 year (group A = 1.47 vs group B = 1.74 mg/dL), and 2 years (group A = 1.43 vs group B = 1.58 mg/dL) showed no differences (P = NS). Graft (group A = 82.23% vs group B = 84.11%) and patient (group A = 93% vs group B = 93.69%) survivals at 3 years were similar (P = NS). There were no differences in the causes of graft loss. The efficacy of UW and Celsior solutions is equivalent in the cold storage and renal preservation for transplantation.


Short-term effects of a comprehensive, statewide smokefree law on perceived opportunities to smoke.
The goal of this study was to assess the effects of Minnesota's comprehensive, statewide smokefree law on young adults' perceived opportunities to smoke in restaurants and bars. Differential effects of the law were examined for those living with and without previous local smokefree ordinances. Telephone surveys were conducted 6-12 months prior, 0-6 months prior, and 0-6 months after Minnesota's statewide smokefree law went into effect. Participants included young adults from a population-based cohort in Minnesota (n = 1446) and from four other Upper Midwest states that serve as a comparison (n = 238). A greater proportion of Minnesota participants (regardless of previous law) reported it was very hard for an adult to find a place to smoke in both restaurants and bars/clubs after the statewide law, compared to the comparison group. Effects were greater among Minnesota participants who did not live with a local smokefree ordinance previously. Within 6 months of Minnesota's statewide smokefree law, Minnesota young adults, even those who lived with a prior local smoking ordinance, believed it was more difficult for adults to find a place to smoke in restaurants and bars/clubs. Changing perceived opportunities to smoke in the state may be an initial step in changing social norms and smoking behaviors. These results suggest that statewide smokefree laws may provide additional barriers to smoking, beyond those obtained through local ordinances.


Presynaptic nitric oxide/cGMP facilitates glutamate release via hyperpolarization-activated cyclic nucleotide-gated channels in the hippocampus.
In hippocampal neurons, synaptic transmission is affected by a variety of modulators, including nitric oxide (NO), which was proposed as a retrograde messenger as long as two decades ago. NO signals via two NO-sensitive guanylyl cyclases (NO-GCs) (NO-GC1 and NO-GC2) and the subsequent increase in cGMP. Lack of long-term potentiation in mice deficient in either one of the two NO-GCs demonstrates the involvement of both NO-GCs in synaptic transmission. However, the physiological consequences of NO/cGMP and the cellular mechanisms involved are unknown. Here, we analyzed glutamatergic synaptic transmission, most likely reflecting glutamate release, in the hippocampal CA1 region of NO-GC knockout mice by single-cell recording, and found glutamate release to be reduced under basal and stimulated conditions in the NO-GC1 knockout mice, but restorable to wild-type-like levels with a cGMP analog. Conversely, an inhibitor of NO/cGMP signaling, ODQ, reduced glutamate release in wild-type mice to knockout-like levels; thus, we conclude that presynaptic cGMP formed by NO-GC1 facilitates glutamate release. In this pathway, NO is supplied by endothelial NO synthase. In search of a cGMP target, we found that two mechanistically distinct blockers of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (ZD7288 and DK-AH269) abolished the cGMP-induced increase in glutamate release, suggesting that cGMP either directly or indirectly signals via HCN channels. In summary, we unravel a presynaptic role of NO/cGMP most likely in glutamate release and propose that HCN channels act as effectors for cGMP.


Adaptive composite dynamic surface neural control for nonlinear fractional-order systems subject to delayed input.
In the article, the adaptive composite dynamic surface neural controller design problem for nonlinear fractional-order systems (NFOSs) subject to delayed input is discussed. A fractional-order auxiliary system is first designed to solve the input-delay problem. By using the developed novel estimation models, the defined prediction errors and the states of error system can decide the weights of radial basis function neural networks (RBFNNs). During the dynamic surface controller design process, the developed fractional-order filters are designed to handle the complexity explosion problem when the classical backstepping control technique is utilized. It is shown that the designed adaptive composite neural controller ensures that all the system state variables are bounded and the tracking error of the considered system finally tends to a small neighborhood of zero. Finally, the results of the simulation explain the feasibility of the developed controller. In addition, the developed controller can also be applied to single input and single output(SISO) nonlinear systems subject to a unitary input function.


RNA polymerase rifampicin resistance mutations in Escherichia coli: sequence changes and dominance.
Five recombinant plasmids, pBK2646, pBK611, pRC3, pRC4 and pRC5, carrying rpoB rifampicin-resistant RNA-polymerase genes were obtained. The sequence analysis of these plasmids revealed certain structural changes in the rpoB gene which specify corresponding alterations in the beta-subunit of RNA polymerase. Some functional properties of the corresponding mutant strains and their RNA polymerases have been investigated.


Coevolution of reproducers and replicators at the origin of life and the conditions for the origin of genomes.
There are two fundamentally distinct but inextricably linked types of biological evolutionary units, reproducers and replicators. Reproducers are cells and organelles that reproduce via various forms of division and maintain the physical continuity of compartments and their content. Replicators are genetic elements (GE), including genomes of cellular organisms and various autonomous elements, that both cooperate with reproducers and rely on the latter for replication. All known cells and organisms comprise a union between replicators and reproducers. We explore a model in which cells emerged via symbiosis between primordial "metabolic" reproducers (protocells) which evolved, on short time scales, via a primitive form of selection and random drift, and mutualist replicators. Mathematical modeling identifies the conditions, under which GE-carrying protocells can outcompete GE-less ones, taking into account that, from the earliest stages of evolution, replicators split into mutualists and parasites. Analysis of the model shows that, for the GE-containing protocells to win the competition and to be fixed in evolution, it is essential that the birth-death process of the GE is coordinated with the rate of protocell division. At the early stages of evolution, random, high-variance cell division is advantageous compared with symmetrical division because the former provides for the emergence of protocells containing only mutualists, preventing takeover by parasites. These findings illuminate the likely order of key events on the evolutionary route from protocells to cells that involved the origin of genomes, symmetrical cell division, and antiparasite defense systems.


A Protoplast-Based Bioassay to Quantify Strigolactone Activity in Arabidopsis Using StrigoQuant.
Understanding the biological background of strigolactone (SL) structural diversity and the SL signaling pathway at molecular level requires quantitative and sensitive tools that precisely determine SL dynamics. Such biosensors may be also very helpful in screening for SL analogs and mimics with defined biological functions.Recently, the genetically encoded, ratiometric sensor StrigoQuant was developed and allowed the quantification of the activity of a wide concentration range of SLs. StrigoQuant can be used for studies on the biosynthesis, function and signal transduction of this hormone class.Here, we provide a comprehensive protocol for establishing the use of StrigoQuant in Arabidopsis protoplasts. We first describe the generation and transformation of the protoplasts with StrigoQuant and detail the application of the synthetic SL analogue GR24. We then show the recording of the luminescence signal and how the obtained data are processed and used to assess/determine SL perception.


An adenoviral vector expressing lipoprotein A, a major antigen of Mycoplasma mycoides subspecies mycoides, elicits robust immune responses in mice.
Contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides small colony type (MmmSC), is a devastating respiratory disease of cattle. In sub-Saharan Africa, where CBPP is enzootic, live attenuated vaccines are deployed but afford only short-lived protection. In cattle, recovery from experimental MmmSC infection has been associated with the presence of CD4(+) T lymphocytes that secrete interferon gamma in response to MmmSC, and in particular to the lipoprotein A (LppA) antigen. In an effort to develop a better vaccine against CBPP, a viral vector (Ad5-LppA) that expressed LppA was generated from human adenovirus type 5. The LppA-specific immune responses elicited by the Ad5-LppA vector were evaluated in mice, and compared to those elicited by recombinant LppA formulated with a potent adjuvant. Notably, a single administration of Ad5-LppA, but not recombinant protein, sufficed to elicit a robust LppA-specific humoral response. After a booster administration, both vector and recombinant protein elicited strong LppA-specific humoral and cell-mediated responses. Ex vivo stimulation of splenocytes induced extensive proliferation of CD4(+) T cells for mice immunized with vector or protein, and secretion of T helper 1-associated and proinflammatory cytokines for mice immunized with Ad5-LppA. Our study - by demonstrating the potential of a viral-vectored prototypic vaccine to elicit prompt and robust immune responses against a major antigen of MmmSC - represents a first step in developing a recombinant vaccine against CBPP.


3,5-Bis(4-methyl-phen-yl)-1-phenyl-4,5-dihydro-1H-pyrazole.
In the title compound, C(23)H(22)N(2), the dihedral angle between the methyl-benzene groups is 77.62 (6)°, and the dihedral angle between the envelope-shaped pyrazole ring [in which one C atom displaced by 0.109 (1) Å from the mean plane of the other four atoms] and the phenyl ring is 17.57 (7)°. The dihedral angles between the phenyl ring and the two methyl-benzene rings are 13.24 (6) and 81.02 (7)°. In the crystal, weak C-H⋯π inter-actions link the mol-ecules.


Impact of a Fast-track Esophagectomy Protocol on Esophageal Cancer Patient Outcomes and Hospital Charges.
To evaluate the effects of a fast-track esophagectomy protocol (FTEP) on esophageal cancer patients' safety, length of hospital stay (LOS), and hospital charges. FTEP involved transferring patients to the telemetry unit instead of the surgical intensive care unit (SICU) after esophagectomy. We retrospectively reviewed 708 consecutive patients who underwent esophagectomy for primary esophageal cancer during the 4 years before (group A; 322 patients) or 4 years after (group B; 386 patients) the institution of an FTEP. Postoperative morbidity and mortality, LOS, and hospital charges were reviewed. Compared with group A, group B had significantly shorter median LOS (12 days vs 8 days; P < 0.001); lower mean numbers of SICU days (4.5 days vs 1.2 days; P < 0.001) and telemetry days (12.7 days vs 9.7 days; P < 0.001); and lower rates of atrial arrhythmia (27% vs 19%; P = 0.013) and pulmonary complications (27% vs 20%; P = 0.016). Multivariable analysis revealed FTEP to be associated with shorter LOS (P < 0.001) even after adjustment for predictors like tumor histology and location. FTEP was also associated with a lower rate of pulmonary complications (odds ratio = 0.655; 95% confidence interval = 0.456, 0.942; P = 0.022). In addition, the median hospital charges associated with primary admission and readmission within 90 days for group B ($65,649) were lower than that for group A ($79,117; P < 0.001). These findings suggest that an FTEP reduces patients' LOS, perioperative morbidity, and hospital charges.


New technologies for developing phage-based tools to manipulate the human microbiome.
Gut bacteria play an essential role in the human body by regulating multiple functions, producing essential metabolites, protecting against pathogen invasion, and much more. Conversely, changes in their community structure are linked to several gastrointestinal (GI) and non-GI conditions. Fortunately, these bacteria are amenable to external perturbations, but we need specific tools for their safe manipulation as nonspecific changes can cause unpredicted long-term consequences. Here, we mainly discuss recent advances in cultivation-independent technologies and argue their relevance to different key steps, that is, identifying the modulation targets and developing phage-based tools to precisely modulate gut bacteria and restore a sustainable microbiome in humans. We finally suggest multiple modulating strategies for different dysbiosis-associated diseases.


Scar-modulating treatments for central nervous system injury.
Traumatic injury to the adult mammalian central nervous system (CNS) leads to complex cellular responses. Among them, the scar tissue formed is generally recognized as a major obstacle to CNS repair, both by the production of inhibitory molecules and by the physical impedance of axon regrowth. Therefore, scar-modulating treatments have become a leading therapeutic intervention for CNS injury. To date, a variety of biological and pharmaceutical treatments, targeting scar modulation, have been tested in animal models of CNS injury, and a few are likely to enter clinical trials. In this review, we summarize current knowledge of the scar-modulating treatments according to their specific aims: (1) inhibition of glial and fibrotic scar formation, and (2) blockade of the production of scar-associated inhibitory molecules. The removal of existing scar tissue is also discussed as a treatment of choice. It is believed that only a combinatorial strategy is likely to help eliminate the detrimental effects of scar tissue on CNS repair.


A longitudinal, narrative study of professional socialisation among health students.
Interprofessional collaboration (IPC) among health professionals is well-recognised to enhance care delivery and patient outcomes. Emerging evidence suggests that the early socialisation of students in health professional programmes to teamwork may have a positive impact on their future as collaborative practitioners. With a purpose of contributing to growing evidence on the processes of professional identity construction, and to explore how early expectations and perceptions of IPC develop during professional socialisation and pre-licensure education, our study examined the early professional socialisation experiences among five groups of health professional students. A qualitative, narrative approach was used to examine early professional socialisation among five programmes of health professional students (dentistry, medicine, nursing, pharmacy, physiotherapy) at an Atlantic Canadian University. In March and October 2016, students participated in interviews after first term (n = 44) and first year of study (n = 39). Interviews focused on participants' professional identify formation, as well as their perceptions and experiences of IPC. The authors analysed interview transcripts using narrative analysis. Findings identify that despite the espoused importance of IPC within health professional training, students have a limited understanding of their professional roles and are largely focused on developing a uniprofessional, vs. interprofessional identity. Clinical experiences, role models and exposure to teamwork are critical to contextualise collaborative practice and enhance the development of an interprofessional identity. Findings can be used to guide the development of curricula that promote interprofessional identity development and IPC during early professional socialisation.


Plasma hydroxyproline fractions in patients with dialysis osteodystrophy.
Plasma hydroxyproline fractions were measured in 17 normal subjects and in 54 patients on maintenance haemodialysis therapy (MHT) with various degrees of dialysis osteodystrophy. On the basis of both radiological and histological findings these patients were divided into three groups: radiologically normal, histologically normal and those with osteitis fibrosa. The mean total plasma hydroxyproline concentrations were significantly elevated in all groups of MHT patients. However, these increases were mainly due to peptide-bound and free hydroxyproline fractions. The highest values for these two fractions were found in patients with osteitis fibrosa. The free to peptide-bound hydroxyproline ratio was not significantly altered in the majority of patients on dialysis; the mean ratio was significantly lower in patients with osteitis fibrosa when compared with patients with no histological evidence of bone disease. This finding would suggest that there is no inhibition of hydroxyproline catabolism in patients on haemodialysis and the measurements of both free and peptide-bound hydroxyproline were equally sensitive in identifying patients with osteitis fibrosa.


Developmental abnormalities and epigenetic alterations in medaka (Oryzias latipes) embryos induced by triclosan exposure.
Triclosan (TCS), an antibacterial and antifungal agent present in some consumer products, has been detected in the environment at varying concentrations. TCS exposure has been found to cause developmental abnormalities and endocrine disruption in various species of fish. It is not clearly understood whether TCS exposure causes epigenetic alterations in developing embryos and their germ cells. In the present study, we examined the effects of TCS exposure (0, 50, 100 and, 200 μg/L) on embryonic development and primordial germ cells (PGCs), which are precursors of sperm and eggs, in medaka (Oyzias latipes). Developmental TCS exposure from 8 h post-fertilization through 15 days post-fertilization (dpf) resulted in several developmental abnormalities, including enlarged yolk sac, decreased head trunk angle (HTA), and severe edema in the pericardial region. The male ratio increased in the 100 μg/L TCS exposure group, which was negatively correlated with the expression of cyp19ala (a gene encoding aromatase) and arα (androgen receptor alpha). Developmental 50 μg/L TCS exposure resulted in global hypomethylation in the whole body but not in the isolated PGCs. Expression of the gene encoding DNA methyltransferases (dnmt1 and dnmt3aa) was decreased by 50 μg/L TCS exposure both in the whole body and PGCs. TCS altered the expression of genes encoding enzymes involved in DNA methylation and demethylation in PGCs, suggesting epigenetic effects on germ cells. The present results demonstrate that the embryos exposed to the tested concentrations of TCS develop deformities during the early life stages and that the TCS within this range possesses endocrine disrupting properties potential enough to alter sex ratios of developing embryos.


Pheochromocytoma-induced reverse tako-tsubo with rapid recovery of left ventricular function.
Pheochromocytoma is a rare, catecholamine-secreting tumor of neuroendocrine cells. It has been documented to present atypically as myocardial ischemia, arrhythmias, or congestive heart failure. We present the case of a patient who had transient cardiomyopathy with hypokinesia of the basal portions of the left ventricle and hyperkinesia of the apex triggered by a pheochromocytoma crisis similar to that of tako-tsubo cardiomyopathy, but with an inverse left ventricular contractile pattern ('inverted tako-tsubo').


Aqueous humor-stimulated protein biosynthesis in ocular tissue fibroblast culture.
Dilute concentrations of aqueous humor stimulate DNA synthesis and cell division in monolayer fibroblast culture of rabbit skin and human and rabbit Tenon's capsule. We used [35S]-methionine to study 20% aqueous humor's effect on protein biosynthesis. A non-specific stimulator, 10% fetal bovine serum, was also used for comparison. Incorporation of radioactivity into acid-precipitable material was measured in both the fibroblasts and the media containing extracellular labeled proteins. The extracellular and intracellular labeled proteins were resolved by gel electrophoresis. Both 20% aqueous humor and 10% fetal bovine serum stimulated increased incorporation of [35S]-methionine into intracellular proteins relative to control values (from fibroblasts maintained in 0.5% fetal bovine serum-supplemented medium). However, 20% aqueous humor caused only a slight increase in labeling of proteins exported into the medium, whereas 10% fetal bovine serum stimulated a several-fold increase in extracellular labeled proteins relative to control values. Gel electrophoresis of labeled proteins showed that the quantitative distribution of extracellular proteins varied depending on the growth stimulator present. We conclude that the protein biosynthesis modulation by aqueous humor differs from that by fetal bovine serum. Aqueous humor may selectively stimulate the synthesis of discrete proteins while a general stimulation occurs with fetal bovine serum.


Erratum to Application of magnetic resonance neurography in neonatal brachial plexus injury: A case report and literature review [Radiology Case Reports 17 (2022) 2859-2862].
[This corrects the article DOI: 10.1016/j.radcr.2022.04.017.].


Postkeratoplasty astigmatism control. Single continuous suture adjustment versus selective interrupted suture removal.
Two different suturing techniques performed during keratoplasty were retrospectively evaluated to compare postkeratoplasty astigmatism, number of suture manipulations, and time to optical stability. One group of patients (n = 31) received a combination of continuous 11.0 nylon suture and 12 or 16 interrupted 10.0 nylon sutures (CCIS), which were selectively removed post-operatively to reduce astigmatism. The second group of patients (n = 26) received a single continuous 10.0 nylon suture (SCS) that was adjusted postoperatively at the slit lamp to regulate corneal astigmatism. Compared with the CCIS technique, adjusting the single continuous suture resulted in less postoperative astigmatism (SCS, 1.5 +/- 1.1 diopters [D]; CCIS, 3.2 +/- 1.9 D), fewer suture manipulations per patient (SCS, 0.9 +/- 0.7; CCIS, 3.8 +/- 1.8), and earlier optical stability for visual rehabilitation (SCS, 2.6 +/- 1.5 months; CCIS, 9.6 +/- 4.7 months) (P less than 0.01). No continuous sutures were broken during adjustment. The adjustable single continuous suture may offer an improved method for early control of postkeratoplasty astigmatism.


Uridine-diphosphate-glucose 4-epimerase from Saccharomyces fragilis. Inactivation by heat and reconstitution of the inactive enzyme.
UDP-glucose 4-epimerase from Saccharomyces fragilis is rapidly inactivated by heating at 42 degrees C for 7 min and at 45 degrees C for 4 min. The effector site, specific for sugar phosphates, is destroyed still earlier. The enzyme is inactivated by the dissocation of NAD from it leaving the dimeric structure unaffected. It can be reactivated by mercaptoethanol and NAD, both of which are essential for reactivation, and NAD becomes associated with the dimeric protein moiety.


Use of a Modified Classic BT Shunt in a Patient With Multiple Conduit Obstructions With Positive Lupus Anticoagulant.
The use of a right ventricle-to-pulmonary artery conduit has re-emerged as a popular alternative to a systemic artery-to-pulmonary artery shunt in the Norwood procedure. Both proximal obstruction secondary to dynamic compression and distal obstruction at the anastomosis site with the pulmonary arteries are well described. In an effort to prevent complications, a technique where in the conduit is placed through the entire full thickness, or dunked, through the RV free wall has been described. We report a case of a patient with HLHS and positive lupus anticoagulant who developed recurrent conduit obstructions. The "Sano" was abandoned in favor of an autologous source of pulmonary blood flow-the modified Blalock-Taussig shunt using the "turn down" of the carotid artery.


Heterogeneity of the hemoglobin of the Ohrid trout (Salmo L. typicus).
We have analyzed the hemoglobins of five individual trout from the Ohrid Lake (Salmo L. typicus) by electrophoretic methods, by reversed-phase high-performance liquid chromatography, and by limited structural analyses. The two major classes of hemoglobin are type I (35% of total) and type IV (65%). Type IV is the major oxygen-transporting hemoglobin; it consists of three types of beta chain (in about equal quantities) and three types of alpha chain (one major and two minor types). Several structural differences have been observed between these three beta (IV) chains and between the three alpha (IV) chains, suggesting a complex genetic system governing the synthesis of these proteins. Moreover, a few amino acid substitutions occur at positions involved in contacts between chains, which suggests that differences in oxygen affinity may exist between these various type IV hemoglobins. Type I hemoglobin is less complex because it contains one type of beta chain and two alpha chains; the latter two differ in numerous positions, suggesting duplications of the alpha (I)-globin gene. The alpha and beta chains of type I hemoglobin differ considerably from the alpha and beta chains of type IV hemoglobin, indicating the existence of alpha (I)- and beta (I)-globin genes separate from the alpha (IV)- and beta (IV)-globin genes.


Pneumatic Vitreolysis With Intravitreal Air for Focal Vitreomacular Traction.
To determine whether pneumatic vitreolysis with intravitreal air is effective for focal vitreomacular traction (VMT). We conducted a retrospective consecutive case series of 20 eyes from 19 individuals with focal VMT who underwent pneumatic vitreolysis with intravitreal air (January 2017 to November 2018). We analyzed patients via spectral-domain optical coherence tomography before intravitreal air injection and at 1 month. The primary outcome measure was release of VMT. We observed release of VMT in 55% of individuals. An analysis limited to phakic eyes demonstrated release of VMT in 69%, and 65% developed improved best-corrected visual acuity. Individuals with persistent VMT and visual improvement had a significant reduction in angle of vitreoretinal insertion (P < .01), area under VMT (P < .05), and subfoveal cyst area (P < .05). Intravitreal air is an effective treatment for focal VMT. In individuals with persistent VMT, visual-acuity improvement was associated with a reduction in overall VMT.


Preparation of optically pure tert-leucine by penicillin G acylase-catalyzed resolution.
Penicillin G acylase, from Kluyvera citrophila, was used in kinetic resolution of DL-tert-leucine. N-phenylacetylated-DL-tert-leucine, chemically synthesized from DL-tert-leucine, was enantioselctively hydrolyzed by penicillin G acylase to obtain L-tert-leucine, D-tert-leucine was prepared by acid-catalyzed hydrolysis of the remaining substrate. The total yields of D-tert-leucine and L-tert-leucine are 80.6% and 83.1%, respectively. The enantiomeric excess of the two products, D-tert-leucine and L-tert-leucine, are 98.5% and 99%. This is a practical way for the preparation of D-tert-leucine and L-tert-leucine.


Development of diffuse fasciitis with eosinophilia during L-tryptophan treatment: demonstration of elevated type I collagen gene expression in affected tissues. A clinicopathologic study of four patients.
We describe the cases of four women who developed a scleroderma-like syndrome during L-tryptophan treatment for insomnia or tinnitus. The illness was characterized by swelling of the extremities, skin rash, myalgia, and elevation of the peripheral blood eosinophil count, followed by rapidly progressive cutaneous and subcutaneous induration. The histopathologic examination of affected skin showed thickening of the fascia, deep dermal fibrosis, and accumulation of mononuclear cells and abundant eosinophils. The expression of the type I procollagen gene was examined by in-situ hybridizations of affected skin with a human sequence-specific complementary DNA (cDNA). Increased hybridization signals were detected in the deep dermis and fascia, indicating enhanced expression of the collagen gene. The temporal association of L-tryptophan use and the development of a scleroderma-like illness in these four patients suggests a causal relation between L-tryptophan or its metabolites and the stimulation of fibroblast collagen gene expression that results in dermal and fascial fibrosis.


Early evaluation of a rechargeable pacemaker system.
A rechargeable demand pulse generator for permanent transvenous cardiac pacing was evaluated in 66 patients. During a cumulative follow-up period of 895 patient months there was no instance of failure of either the pulse generator or of the recharging circuit. Acceptance of the recharging concept was high, there being only one patient in whom it was necessary to replace the rechargeable generator because of inability to master the recharging technique. The early findings indicate that with proper patient selection the rechargeable pulse generator promises to be an important contribution to pacemaker therapy.


Antinociceptive effects of systemic paeoniflorin on bee venom-induced various 'phenotypes' of nociception and hypersensitivity.
Paeoniflorin (PF), one of the active chemical compounds identified from the root of Paeonia lactiflora Pall, has been well-established to exhibit various neuroprotective actions in the central nervous system (CNS) after long-term daily administration. In the present study, by using the bee venom (BV) model of nociception and hypersensitivity, antinociceptive effects of PF were evaluated by intraperitoneal administration in conscious rats. When compared with saline control, systemic pre- and post-treatment with PF resulted in an apparent antinociception against both persistent spontaneous nociception and primary heat hypersensitivity, while for the primary mechanical hypersensitivity only pre-treatment was effective. Moreover, pre- and early post-treatment with PF (5 min after BV injection) could successfully suppress the occurrence and maintenance of the mirror-image heat hypersensitivity, whereas late post-treatment (3 h after BV) did not exert any significant impact. In the Rota-Rod treadmill test, PF administration did not affect the motor coordinating performance of rats. Furthermore, systemic PF application produced no significant influence upon BV-induced paw edema and swelling. Finally, the PF-produced antinociception was likely to be mediated by endogenous opioid receptors because of its naloxone-reversibility. Taken together, these results provide a new line of evidence showing that PF, besides its well-established neuroprotective actions in the CNS, is also able to produce analgesia against various 'phenotypes' of nociception and hypersensitivity via opioid receptor mediation.


Biomechanical evaluation of the unilateral crossbite on the asymmetrical development of the craniofacial complex. A mechano-morphological approach.
The occlusion effect on the craniofacial development is a controversial topic that has attracted the interest of many researchers but that remains unclear, mainly due to the difficulties on measure its mechanical response experimentally. This mechano-morphological relationship of the craniofacial growth is often explained by the periosteal and capsular matrices of the functional matrix hypothesis (FMH); however, its outcomes have not been analytically demonstrated yet. This computational study aims, therefore, to analytically demonstrate the mechano-morphological relationship in the craniofacial development of children with unilateral crossbite (UXB) using the finite element (FE) method. The craniofacial complex asymmetry of ten children, five of whom exhibit UXB, was 3D-analysed and compared with the biomechanical response computed from a FE analysis of each patient's occlusion. Due to the complexity of the geometry and the multitude of contacts involved, the inherent limitations of the model were evaluated by comparing computed occlusal patterns with those recorded by an occlusal analysis on 3D printed copies. Comparison's outcomes proved the reliability of our models with just a deviation error below 6% between both approaches. Out of validation process, computational results showed that the significant elongation of mandibular branch in the contralateral side could be related to the mandibular shift and increase of thickness on the crossed side, and particularly of the posterior region. These morphological changes could be associated with periodontal overpressure (>4.7 kPa) and mandibular over deformation (0.002 ε) in that side, in agreement with the periosteal matrix's principles. Furthermore, the maxilla's transversal narrowing and the elevation of the maxillary and zygomatic regions on the crossed side were statistically demonstrated and seem to be related with their respective micro displacements at occlusion, as accounted by their specific capsule matrices. Our results were consistent with those reported clinically and demonstrated analytically the mechano-morphological relationship of children's craniofacial development based on the FMH's functional matrices. This study is a first step in the understanding of the occlusion's effect on the craniofacial development by computational methods. Our approach could help future engineers, researchers and clinicians to understand better the aetiology of some dental malocclusions and functional disorders improve the diagnosis or even predict the craniofacial development.


Clinicopathological analysis of the intestinal type and diffuse type of gastric carcinoma.
A clinicopathological study of gastric carcinoma was carried out according to Lauren's classification, on 207 patients, who underwent gastric resection at Department of Surgery II, Kyushu University, Faculty of Medicine from 1970 to 1972. Among them 93 cases (44.9%) were of intestinal-type carcinoma, 71 (34.3%) of diffuse carcinoma and 43 (20.8%) of other types. Intestinal-type carcinoma, often showing the protuberant type, was more common in the aged and in men. Most had a low grade of penetration, while in some, the penetration was moderate to high grade and was associated with lymph node metastasis, lymphatic and vascular involvement, or liver metastasis. Hematogenous recurrence was not infrequent. Diffuse carcinoma was more common in younger subjects and women, and was often of the depressed type. The serosa was involved in most cases. High grade penetration was associated with lymphatic permeation. Metastasis via the bloodstream was infrequent. Recurrence was often due to peritoneal dissemination. A better prognosis was indicated in cases of diffuse carcinoma with no serosal involvement, while prognosis in cases of invasion of the serosa was worse for diffuse carcinoma than for intestinal-type carcinoma.


CT-Guided Percutaneous Vertebroplasty for Vertebral Non-union Following Posterior Fixation: A Preliminary Retrospective Study.
Traumatic thoracolumbar vertebral fractures are frequently treated with posterior fixation (PF) and vertebral augmentation. Sometimes, it is deemed too risky to offer vertebral augmentation under fluoroscopic guidance alone. Adjuvant CT/fluoroscopy-guided percutaneous vertebroplasty (PVP) could be offered in certain scenarios. The aim was to evaluate feasibility, safety and effectiveness of PVP in patients presenting with vertebral non-union (VNU) following PF performed without concomitant vertebral augmentation. All patients treated in our institution with PVP between July 2015 and July 2020 were retrospectively reviewed. Patients treated with CT/fluoroscopy-guided PVP under local anesthesia for symptomatic VNU following PF were selected. Three criteria were established to assess cement distribution, considering vertebral filling of: (1) fracture cleft, (2) anterior two-thirds of the vertebral body, (3) from superior to inferior endplates. Numeric pain rating scale (NPRS) assessing grade of discomfort (0 = no pain; 10 = worst pain) and complications were evaluated before and 1 month after PVP. Ten patients were identified (mean age 53 ± 12y). Mean time between PF and PVP was 9.6 [2-35] months. Two patients required further cement injection with a second PVP. Eight patients had satisfactory vertebral filling according to the three criteria. Mean NPRS reduction was 2.7(-42%, p < 0.05). No significant complications occurred. Combined CT/fluoroscopy guidance seems a useful tool to perform PVP in VNU following PF, even in presence of orthopedic metalwork. Interventional radiologists may help in these scenarios, performing an adjuvant PVP under local anesthesia. In this small series, the procedure seems safe and effective and could be taken in consideration as alternative to revision surgery.


Transition to motherhood for Japanese primiparas from delivery to 6 months postpartum: A qualitative study.
This study investigates aspects of the socio-culturally influenced Japanese primiparas' transition to motherhood. A qualitative descriptive study approach with interviews of Japanese primiparas was used. Individual interviews with 21 Japanese primiparas were conducted, with a focus on their transition to motherhood and familiarization with the maternal role. The interviews were analysed, and categories and subcategories were established. This paper was developed using the COREQ guidelines for reporting qualitative studies. Seven major categories with 26 subcategories were identified in the transition to motherhood. The seven categories are listed as follows: "confusion with first childcare experience," "suffering related to childcare," "clinging to the image of an ideal mother," "internal conflict while comparing oneself to other mothers," "undertaking childcare by disengaging from one's stereotype," "realization of becoming a mother" and "changing relationship with surrounding people."


Impact of a public commitment charter, a non-prescription pad and an antibiotic information leaflet to improve antibiotic prescription among general practitioners: A randomised controlled study.
This study evaluated the effect of a multifaceted antibiotic stewardship intervention on the overall prescription of systemic antibiotics in primary care. Secondary objectives evaluated the effect on the prescription of broad-spectrum antibiotics and the seasonal variation of both total antibiotic and quinolone prescriptions, as a proxy for unnecessary prescribing. This pragmatic, randomised, controlled, before-after intervention study was conducted among general practitioners (GPs) who over prescribe antibiotics in Lorraine, France (Intervention group, n = 109; Control group, n = 236; Before period, 01/10/2017-30/09/2018; After period, 01/10/2018-30/09/2019). The intervention included a public commitment charter, a patient information leaflet and a non-prescription pad. Health Insurance data was obtained to calculate overall and broad-spectrum prescription rate (defined daily doses/1000 consultations) and the seasonal variation of prescriptions (%), by period. The intervention effect was measured with general linear mixed models including three independent variables (group, period and group x period interaction). Overall, compared to the Before period, GPs in both groups prescribed significantly fewer systemic antibiotics (p < 0.001) and broad-spectrum antibiotics (p < 0.001) after the intervention was implemented. However, the group x period interaction did not show any evidence that the intervention had an effect on these outcomes. Nevertheless, the intervention did result in a trend towards less seasonal variation in total systemic antibiotic prescription (p = 0.052). A tendency towards an effect of the intervention to reduce unnecessary antibiotic prescribing during winter months was observed. No effect was observed on the overall volume of systemic antibiotic prescription. This study invites discussion about the challenges faced when evaluating non-pharmacological interventions in primary care.


Plasma membrane repair involvement in parasitic and other pathogen infections.
Intracellular pathogens depend on specific mechanisms to be able to gain entry and survive into their host cells. For this, they subvert pathways involved in physiological cellular processes. Here we are going to focus on how two protozoan parasites, Trypanosoma cruzi and Leishmania sp, which may cause severe diseases in humans, use plasma membrane repair (PMR) mechanisms to gain entry in host intracellular environment. T. cruzi is the causative agent of Chagas disease, a disease originally endemic of central and South America, but that has become widespread around the globe. T. cruzi is able to invade any nucleated cell, but muscle cells are usually the main targets during chronic disease. During host cell contact, the parasite interacts with proteins at the host cell surface and may cause damage to their membrane, which has been shown to be responsible for inducing intracellular calcium increase and PMR-related events that culminate with parasite internalization. The same was recently observed for Leishmania sp, when infecting nonprofessional phagocytic cells, such as fibroblasts. Other pathogens, such as viruses or bacteria may also use PMR-related events for invasion and vacuole escape/maturation. In some cases, PMR may also be responsible to modulate pathogen intracellular development. These other PMR roles in pathogen infections will also be briefly discussed.


On assessing independence of competing risks when failure times are discrete.
The traditional approach to modelling for Competing Risks, via a multivariate distribution of latent failure times, is very natural for many applications but suffers from a well-documented problem of identifiability. However, the demonstrations of this problem in the literature apply to essentially continuous latent failure times where any atoms of probability in their distributions are not too intrusive. It is shown in this paper that for discrete failure times the classic results on the identifiability problem concerning the existence of equivalent independent risks are incomplete.


The connectional anatomy of the temporal lobe.
The idea of a temporal lobe separated from the rest of the hemisphere by reason of its unique structural and functional properties is a clinically useful artifact. While the temporal lobe can be safely defined as the portion of the cerebrum lodged in the middle cranial fossa, the pattern of its connections is a more revealing description of its functional subdivisions and specific contribution to higher cognitive functions. This chapter provides an historical overview of the anatomy of the temporal lobe and an updated framework of temporal lobe connections based on tractography studies of human and nonhuman primates and patients with brain disorders. Compared to monkeys, the human temporal lobe shows a relatively increased connectivity with perisylvian frontal and parietal regions and a set of unique intrinsic connections, which may have supported the evolution of working memory, semantic representation, and language in our species. Conversely, the decreased volume of the anterior (limbic) interhemispheric temporal connections in humans is related to a reduced reliance on olfaction and a partial transference of functions from the anterior commissure to the posterior corpus callosum. Overall the novel data from tractography suggest a revision of current dual stream models for visual and auditory processing.


Technoeconomic study on steam explosion application in biomass processing.
This work is based on the data collected during trials of a continuous steam explosion (SE) plant, with a treatment capacity of about 350 kg/h, including the biomass fractionation section. The energy and water consumption, equipment cost, and manpower needed to run this plant have been used as the base case for a techno-economic evaluation of productive plants. Three processing plant configurations have been considered: (I) SE pretreatment only; (II) SE followed by the hemicellulose extraction; (III) SE followed by the sequential hemicellulose and lignin extractions. The biomass treatment cost has been evaluated as a function of the plant scale. For each configuration, variable and fixed cost breakdown has been detailed in the case of a 50,000 t/y plant.


Reduction of ICAM-1 expression by carbon monoxide via soluble guanylate cyclase activation accounts for modulation of neutrophil migration.
Previously, it was demonstrated that the heme/heme oxygenase (HO)/carbon monoxide (CO) pathway inhibits neutrophil recruitment during the inflammatory response. Herein, we addressed whether the inhibitory effect of the HO pathway on neutrophil adhesion and migration involves the reduction of intracellular adhesion molecule type (ICAM)-1 and beta(2)-integrin expression. Mice pretreated with a specific inhibitor of inducible HO (HO-1), zinc protoporphyrin (ZnPP) IX, exhibit enhanced neutrophil adhesion and migration induced by intraperitoneal injection of Escherichia coli lipopolysaccharide (LPS). These findings are associated with an increase in ICAM-1 expression on mesentery venular endothelium. In accordance, HO-1 inhibition did not enhance LPS-induced neutrophil migration and adhesion in ICAM-1-deficient mice. Furthermore, the treatment with a CO donor (dimanganese decacarbonyl, DMDC) that inhibits adhesion and migration of the neutrophils, reduced LPS-induced ICAM-1 expression. Moreover, neither DMDC nor ZnPP IX treatments changed LPS-induced beta(2)-integrin expression on neutrophils. The effect of CO on ICAM-1 expression seems to be dependent on soluble guanylate cyclase (sGC) activation, since 1H-(1,2,4)oxadiazolo (4,3-a)quinoxalin-1-one (sGC inhibitor) prevented the observed CO effects. Finally, it was observed that the nitric oxide (NO) anti-inflammatory effects on ICAM-1 expression appear to be indirectly mediated by HO-1 activation, since the inhibition of HO-1 prevented the inhibitory effect of the NO donor (S-nitroso-N-acetylpenicillamine) on LPS-induced ICAM-1 expression. Taken together, these results suggest that CO inhibits ICAM-1 expression on endothelium by a mechanism dependent on sGC activation. Thus, our findings identify the HO-1/CO/guanosine 3'5'-cyclic monophosphate pathway as a potential target for the development of novel pharmacotherapy to control neutrophil migration in inflammatory diseases.


Management of Lisfranc Injuries: A Critical Analysis Review.
There is a spectrum of midtarsal injuries, ranging from mild midfoot sprains to complex Lisfranc fracture-dislocations. Use of appropriate imaging can reduce patient morbidity, by reducing the number of missed diagnoses and, conversely, avoiding overtreatment. Weight-bearing radiographs are of great value when investigating the so-called subtle Lisfranc injury. Regardless of the operative strategy, anatomical reduction and stable fixation is a prerequisite for a satisfactory outcome in the management of displaced injuries. Fixation device removal is less frequently reported after primary arthrodesis compared with open reduction and internal fixation based on 6 published meta-analyses. However, the indications for further surgery are often unclear, and the evidence of the included studies is of typically low quality. Further high-quality prospective randomized trials with robust cost-effectiveness analyses are required in this area. We have proposed an investigation and treatment algorithm based on the current literature and clinical experience of our trauma center.


Evaluation of Sub-Antarctic and Antarctic sea urchins' thermal reaction norm through righting behavior and comparison with in situ measurements.
Sea urchin's survival may depend on their capacity to recover proper orientation rapidly and effectively after inversion, enabling escape from predator and preventing desiccation. This righting behavior has been used as a repeatable and reliable indicator to assess echinoderms performance across environmental conditions, including thermal sensitivity and thermal stress. The current study aims at evaluating and comparing the thermal reaction norm for righting behavior (time for righting (TFR) and capacity to self-right) of three common sea urchins from high latitude, the Patagonian sea urchins Loxechinus albus and Pseudechinus magellanicus, and the Antarctic sea urchin Sterechinus neumayeri. In addition, to infer the ecological implications of our experiments, we compared laboratory-based and in situ TFR of these three species. We observed that populations of the Patagonian sea urchins L. albus and P. magellanicus presented similar trend of righting behavior, overly accelerating with increasing temperature (from 0 to 22°C). Little variations and high inter-individual variability were observed below 6°C in the Antarctic sea urchin TFR, and righting success strongly decreased between 7 and 11°C. For the three species, TFR was lower in in situ experiments compared to the laboratory. Overall, our results suggest that the populations of Patagonian sea urchin exhibit a wide thermal tolerance and, based on S. neumayeri's TFR, aligning with the narrow thermal tolerance of Antarctic benthos. Finally, the differences between laboratory and in situ experiments highlights the importance of considering the complexity of marine environments for future predictions.


Pedestrian crossing situations: quantification of comfort boundaries to guide intervention timing.
Technical systems that warn or brake for vehicle-pedestrian encounters reduce injuries more effectively the earlier an intervention is initiated. However, premature intervention can irritate drivers, leading to system deactivation and, consequently, no injury reduction whatsoever. It has been proposed that no intervention should be initiated as long as attentive drivers are within their comfort zones. This study aims at quantifying driver comfort boundaries for pedestrian crossing situations to offer guidance for the appropriate timing of interventions. Sixty two volunteers drove through an intersection on a test track at 30 and 50km/h. A pedestrian dummy was launched from behind an obstruction towards the driving path of the approaching car. Brake onset indicated discomfort. Time to collision (TTC), longitudinal and lateral distance were measured at brake onset. TTC was independent of driving speed ranging from 2.1 to 4.3s with a median of 3.2s. Longitudinal distance ranged from 19 to 48 meters with an apparent difference between driving speeds. Lateral distances differed slightly, but significantly between driving speeds. The median was 3.1m (3.2m for 30km/h and 2.9m for 50km/h) and values ranged from 1.9 to 4.1m. Lateral distance in seconds ranged from 1.9 to 4.3s with a median value of 3.1s (3.2s for 30km/h and 3.0s for 50km/h). TTC was independent of driving speed, trial order and volunteer age. It might be considered suitable to intervene in situations where, for example, 90% of drivers have exceeded their comfort boundary, i.e. when drivers have already initiated braking. This percentile value translates to intervention at a TTC of 2.5s (95% confidence 2.4-2.7s). The study was limited to Swedish nationals, fully aware drivers, and two driving speeds, but did not investigate behavioural changes due to system interaction. This study showed that TTC at brake onset was a suitable measure for the quantification of driver comfort boundaries in pedestrian crossing situations. All drivers applied their brakes prior to 2.1s TTC.


Sporotrichosis in the Highlands of Madagascar, 2013-20171.
Sporotrichosis is a saprozoonotic fungal infection found mostly in tropical and subtropical areas. Few case reports in Madagascar have been published. To document sporotrichosis epidemiology in Madagascar, we conducted a cross-sectional study. During March 2013-June 2017, we recruited from select hospitals in Madagascar patients with chronic cutaneous lesions suggestive of dermatomycosis. Sporotrichosis was diagnosed for 63 (42.5%) of 148 patients. All but 1 patient came from the central highlands, where the prevalence was 0.21 cases/100,000 inhabitants. Frequency was high (64.7%) among patients <18 years of age. Sporotrichosis was diagnosed for 73.8% of patients with arm lesions, 32.3% with leg lesions, and 15.4% with lesions at other sites. Molecular identification identified 53 Sporothrix schenckii isolates. Among the 32 patients who were followed up, response to itraconazole was complete or major for 15 and minor for 17. Overall, endemicity of sporotrichosis in Madagascar was high, concentrated in the highlands.