Toxicological Characterization of Six Plants of the Beninese Pharmacopoeia Used in the Treatment of Salmonellosis.
Recent studies reported interesting ethnopharmacological, antibacterial, and phytochemical data on some medicinal plants used in the traditional treatment of salmonellosis in Benin. Unfortunately, very little data exists on the toxicity of these species. This study aims to evaluate chemical characteristic of six Benin pharmacopoeial plants used in the traditional treatment of salmonellosis in Benin. The acute toxicity of aqueous and ethanolic extracts of Psidium guajava, Vernonia amygdalina, Cajanus cajan, Phyllanthus amarus, Uvaria chamae, and Lantana camara was evaluated according to OECD Guideline 423 at a single dose of 2000 mg/kg body weight on Wistar rats. Histological sections were performed on the liver and kidneys to confirm hematological and biochemical data. The content of aluminum, chromium, cadmium, copper, iron, lead, zinc, arsenic, selenium, and manganese was measured in 10 mg of each extract by the inductively coupled plasma optical emission spectroscopy (ICPOES) method. The results of our study generally show the absence of significant effect of the extracts on the hematological and biochemical parameters of the rats. However, with the exception of the aqueous and ethanolic extracts of Psidium guajava root and the ethanolic extract of Phyllanthus amarus (P>0.05), all the extracts have a significant effect on the aspartate aminotransferase (ASAT) level, with a variable threshold of significance (0.0001< P ≤ 0.05). No mortalities and no renal histological conditions were recorded in the treated rats. In general, the heavy metal contents of the extracts do not exceed the standards set by the WHO/FDA except for a few extracts. Arsenic was not detected in any extract, while aluminum and chromium were detected at levels above the WHO/FDA standards. On the basis of these data, it appears that the six plants studied do not show any toxicity. In view of the pharmacological and chemical data previously available, these plants are good candidates for the development of improved traditional medicines with antibacterial and particularly anti-Salmonella properties.


Tendons in health and disease.
SUMMARY. This article reviews the structure, functions and mechanical properties of normal tendons and surveys the range and causes of tendon diseases. Specialized regions of tendons are considered, including the myotendinous junction, enthesis and regions where tendons rub against bone. Particular emphasis is placed on recent literature and on aspects of tendons that are relevant to manual therapists. Copyright 1996 Harcourt Publishers Ltd.


Is Disrupted Nucleotide-Substrate Cooperativity a Common Trait for Cushing's Syndrome Driving Mutations of Protein Kinase A?
Somatic mutations in the PRKACA gene encoding the catalytic α subunit of protein kinase A (PKA-C) are responsible for cortisol-producing adrenocortical adenomas. These benign neoplasms contribute to the development of Cushing's syndrome. The majority of these mutations occur at the interface between the two lobes of PKA-C and interfere with the enzyme's ability to recognize substrates and regulatory (R) subunits, leading to aberrant phosphorylation patterns and activation. Rarely, patients with similar phenotypes carry an allosteric mutation, E31V, located at the C-terminal end of the αA-helix and adjacent to the αC-helix, but structurally distinct from the PKA-C/R subunit interface mutations. Using a combination of solution NMR, thermodynamics, kinetic assays, and molecular dynamics simulations, we show that the E31V allosteric mutation disrupts central communication nodes between the N- and C- lobes of the enzyme as well as nucleotide-substrate binding cooperativity, a hallmark for kinases' substrate fidelity and regulation. For both orthosteric (L205R and W196R) and allosteric (E31V) Cushing's syndrome mutants, the loss of binding cooperativity is proportional to the density of the intramolecular allosteric network. This structure-activity relationship suggests a possible common mechanism for Cushing's syndrome driving mutations in which decreased nucleotide/substrate binding cooperativity is linked to loss in substrate fidelity and dysfunctional regulation.


Morphology of platelet Golgi apparatus and their significance after acute cerebral infarction.
Blood samples were harvested from the antecubital vein of 20 fasting patients with acute cerebral infarction at 1, 7 and 15 days after onset to prepare blood platelet suspension. Fasting antecubital vein blood was collected from an additional 20 normal adults as controls. Under transmission tron microscope, platelet Golgi tubules and vesicles became significantly thickened, enlarged, and irregular after acute cerebral infarction. Alpha granules in platelets significantly reduced in number, especially 1 day after cerebral infarction. Under immunoelectron microscopy, a few alpha granules aggregated around Golgi tubules and vesicles after infarction. These results suggested that platelet Golgi apparatus displayed significant morphological changes, which were possibly associated with enhanced synthetic and secretory functions of activated platelets after acute cerebral infarction. This study used Golgi apparatus blocking agent Brefeldin A to block Golgi apparatus in an aim to study the effects of Golgi apparatus on CD40L expression on the surface of activated platelets. Flow cytometry revealed that CD40L expression on activated platelet surfaces decreased significantly when Golgi apparatus was blocked, which indicated that Golgi apparatus participated in the synthesis and transport of CD40L to the platelet surface.


Flow cytometric analysis of in vivo activation of murine spleen cells.
The in vivo effects of two polyclonal immune stimulators were studied in several strains of mice by analyzing the percentages of cells in various phases of the cell cycle by flow cytometry. Both lipopolysaccharide (LPS) and polyriboinosinic X cytidylic acid (rI X rC) were capable of inducing an increase in the percentage of cells undergoing DNA synthesis (S phase) in the spleens of several mouse strains. The response to both LPS and rI X rC was maximal between days 3 and 5 following injection. Optimal in vivo responses to LPS occurred at 3-30 micrograms, and to rI X rC at 100 micrograms; however, responses were observed over a broad dose range. No similar increase in S-phase cells was observed following injection of non-mitogenic T-independent antigens. Specific antibody was also measured after in vivo administration of rI X rC. There was a dissociation between the ability of an injection to induce specific antibody and to induce proliferation. These studies extend our knowledge of in vivo lymphocyte activation, and provide a basis for a detailed analysis of lymphocyte activation following a variety of immune modulators in vivo.


[Dynamic variation of landfill gas production under different landfill treatment].
Based on the landfill principles, large scale installations of anaerobic and semi-aerobic landfills were established, with the concentrations of CH4, O2 and CO2 detected regularly. The results showed that the average CH4 concentration in semi-aerobic and anaerobic landfill installations was 7%-13% and 35%-50%, respectively, indicating the better effect of semi-aerobic landfill in reducing CH4 production. The CH4 and O2 concentrations in the two landfill installations all presented obvious spatial layer effect, i.e., under-layer > middle layer > upper layer for CH4, while upper layer > middle level > under-layer for O2.


The Effects of Online Social Interactions on Life Satisfaction of Older Chinese Adults: New Insights Based on a Longitudinal Approach.
Population aging and digitalization have become universal phenomena. Over the past two decades, digital inclusion has started to play a crucial role in supporting successful aging. Based on a nationally representative sample of around 5200 older adults in China over the period of 2014-2018, we explore the effects of online social interactions (OSIs) on the life satisfaction of older adults. We find that OSIs can improve the levels of life satisfaction of older Chinese adults. Estimates from fixed effect and cross-lagged structural equation models further suggest that OSIs work by increasing physical activities, healthy time allocation, interpersonal trust, and informal social engagement and reducing loneliness. We also find that OSIs narrow the social inequality in life satisfaction across groups from rural-urban areas and groups with different social statuses. Moreover, a comparison among different online engagements shows that not all online activities positively affect older adults' life satisfaction. Different online activities have varying effects. Our results highlight that public digital interventions focusing on social functions can benefit the lives of older adults.


Transglutaminase immunoreactivity in the male genital tract of the rat.
The distribution of transglutaminase immunoreactivity in the male genital system of the rat has been studied at the light and electron microscopic levels using a highly specific polyclonal antibody. The antibody is obviously secreted in an apocrine fashion in the dorsal prostate as well as the coagulating gland. This moiety is responsible for semen clotting. In addition to the secretory moiety, epididymal sperm contain endogenous immunoreactive material in the cytoplasmic droplet. Whether this is added to the sperm within the epididymis--as is the immunoreactive material on the sperm head--or already present in developing sperm has to be elucidated by further immunoelectron microscopic studies.


The interplay of crossmodal attentional preparation and modality compatibility in cued task switching.
Two experiments examined the influence of preparation on modality compatibility effects in task switching. The term modality compatibility refers to the similarity between the stimulus modality and the modality of response-related sensory consequences. Previous research showed evidence for modality compatibility benefits in task switching when participants switched either between two modality compatible tasks (auditory-vocal and visual-manual) or between two modality incompatible tasks (auditory-manual and visual-vocal). In this study, we investigated the influence of active preparation on modality compatibility effects in task switching. To this end, in Experiment 1, we introduced unimodal modality cues, whereas in Experiment 2, bimodal abstract cues were used. In both experiments, the cue-stimulus interval (CSI) was manipulated while holding the response-stimulus interval (RSI) constant. In both experiments, we found not only decreased switch costs with long CSI but also the elimination of the residual switch costs. More importantly, this preparation effect did not modulate the modality compatibility effect in task switching. To account for this data pattern, we assume that cue-based preparation of switches by modality mappings was highly effective and produced no residual reaction time (RT) costs with long CSI.


Glucose administration downregulates lipoprotein lipase activity in vivo: a study using repeated intravenous fat tolerance test.
Lipoprotein lipase (LPL) is a key factor determining the clearance of triglycerides from the circulation. The enzyme activity is tissue-specifically regulated by insulin, but it is not clear yet how insulin regulates the total LPL activity in the circulation. To answer such question, we measured LPL activity using the intravenous fat tolerance test (IVFTT) that was carried out 1 h before as well as 2 h and 4 h after oral administration of glucose (75 g) in eleven healthy male volunteers. In control experiments, no glucose was given to the subjects. Glucose administration resulted in an expected increase in plasma glucose and insulin and in a suppression of non-esterified fatty acid concentration. The LPL activity assessed in IVFTT as a k(2) rate constant did not change in control experiments and decreased to 78 % and 73 % of baseline values 2 h and 4 h after glucose administration, respectively (p=0.01). Similarly, LPL activity measured in the plasma after intravenous injection of heparin at the end of the experiments was 16 % lower (p<0.05) after glucose administration. In conclusion, LPL activity is already downregulated in vivo 2 h after glucose administration. The results of our study indicate that repeated IVFTT is a promising approach for studying acute changes in LPL activity.


[Fresh homologous arterial transplant as aorto-iliac-femoral vascular replacement in prosthesis infection].
A patient with late graft infection in the groin following aorto-bifemoral-Dacron-bypass and recurrent infection of extra-anatomic bypasses is presented. Despite the evidence or graft infection (by preoperative imaging studies and intraoperative perigraft purulence) cultures did not identify the infective organism. Retrospectively a graft infection with Staphylococcus epidermidis is supposed as the most likely cause. A graft replacement with freshly harvested, not cryopreserved arterial homograft was performed. The perfusion of the extremities was excellent, the wounds healed perfectly. In special indications freshly harvested cadaveric arterial homografts are an acceptable substitute for infected aorto-femoral grafts.


Purple tea: chemical characterization and evaluation as inhibitor of pancreatic lipase and fat digestion in mice.
A variety of the classic green tea plant, Camellia sinensis, was developed and is exclusive to Kenya. Due to high content of anthocyanin polyphenols in its leaves, the beverage obtained from this variety is purple in color and is the origin of the name purple tea. This work had two main purposes. The first one was to identify and quantify the major anthocyanin polyphenols in a hot water aqueous extract of the purple tea leaves. The second one was to test the hypothesis if this extract is capable of inhibiting triglyceride absorption considering that anthocyanin polyphenolics have been frequently associated to antilipidemic effects. Parallel experiments were always done with a similar green tea extract for comparison purposes. The antioxidant, anti-inflammatory, and cytotoxic activities of both tea varieties are similar. The purple tea extract, however, was strongly inhibitory toward the pancreatic lipase (minimal IC50 = 67.4 μg mL-1), whereas the green tea preparation was a weak inhibitor. Triglyceride digestion in mice was inhibited by the purple tea extract starting at 100 mg kg-1 dose and with a well-defined dose dependence. Green tea had no effect on triglyceride digestion at doses up to 500 mg kg-1. The latter effect is probably caused by several components in the purple tea extract including non-anthocyanin and anthocyanin polyphenols, the first ones acting solely via the inhibition of the pancreatic lipase and the latter by inhibiting both the lipase and the transport of free fatty acids from the intestinal lumen into the circulating blood. The results suggest that the regular consumption of Kenyan purple tea can be useful in the control of obesity.


Developing a common health information exchange platform to implement a nationwide health information network in South Korea.
We aimed to develop a common health information exchange (HIE) platform that can provide integrated services for implementing the HIE infrastructure in addition to guidelines for participating in an HIE network in South Korea. By exploiting the Health Level 7 (HL7) Clinical Document Architecture (CDA) and Integrating the Healthcare Enterprise (IHE) Cross-enterprise Document Sharing-b (XDS.b) profile, we defined the architectural model, exchanging data items and their standardization, messaging standards, and privacy and security guidelines, for a secure, nationwide, interoperable HIE. We then developed a service-oriented common HIE platform to minimize the effort and difficulty of fulfilling the standard requirements for participating in the HIE network. The common platform supports open application program interfaces (APIs) for implementing a document registry, a document repository, a document consumer, and a master patient index. It could also be used for testing environments for the implementation of standard requirements. As the initial phase of implementing a nationwide HIE network in South Korea, we built a regional network for workers' compensation (WC) hospitals and their collaborating clinics to share referral and care record summaries to ensure the continuity of care for industrially injured workers, using the common HIE platform and verifying the feasibility of our technologies. We expect to expand the HIE network on a national scale with rapid support for implementing HL7 and IHE standards in South Korea.


Restoration of the striatal dopamine synthesis for Parkinson's disease: viral vector-mediated enzyme replacement strategy.
Parkinson's disease is the second most common neurodegenerative disease. It is charaterized by a progressive loss of dopamine (DA) producing neurons in the midbrain, which result in a decline of DA innervations present in the forebrain, in particular, the striatum. The disease leads to appearance of motor symptoms involving akinesia/bradykinesia, gait disturbances, postural imbalance and tremor. Oral administration of L-3,4-dihydroxyphenylalanine (L-DOPA), the precursor of DA, provides very good symptomatic relief, but this intermittent and pharmacological treatment is compromised by severe side effects, such as the appearance of abnormal involuntary movements. Viral vector-mediated direct gene transfer techniques are currently being explored in order to provide continuous and stable synthesis of DA in the brain. This review focuses on the basic idea of DA replacement, first describing the enzymatic machinery important for DA synthesis and secondly the various alternative strategies pursued in several laboratories. The DOPA delivery strategy, based on the co-transduction of tyrosine hydroxylase (TH), and GTP cyclohydrolase 1 (GCH1) genes, has been shown to be a powerful approach providing a robust behavioral recovery and reversal of side effects of the pulsatile administration of L-DOPA medication. The DA delivery strategy, on the other hand, aims at triple transduction of the TH, GCH1 and aromatic amino-acid decarboxylase (AADC) enzymes, and thereby provide a higher rate of conversion of DOPA to DA. Finally, transduction of AADC alone has been proposed as a means to improve the conversion of peripherally administered L-DOPA. As the basic scientific rationale behind these strategies are well understood and the results of the animal experiments are very encouraging, we are now entering into an exciting phase with increasing momentum toward the first clinical applications using this experimental therapy in patients suffering from PD.


Sensation Seeking and Adaptation in Parabonauts.
Evidence from extreme environments suggests that there are relationships between difficulties of adaptation and psychological factors such as personality. In the framework of microgravity research on humans, the aim of this exploratory study was to investigate inter-individual differences of parabonauts on the basis of quality of adaptation to the physical demands of parabolic flights. The personality characteristics of two groups of parabonauts with a different quality of adaptation (an Adaptive group, N = 7, and a Maladaptive group, N = 15) were assessed using the Sensation Seeking Scale, Brief COPE, and MSSQ-Short. Compared to the Maladaptive group, the individuals of the Adaptive group scored higher on Boredom Susceptibility (i.e., a subscale of the Sensation Seeking Scale), lower on scales of susceptibility to motion sickness (MSSQ-Short) and tended to score lower on Instrumental Support Seeking (i.e., a subscale of the Brief COPE). These results suggest that individuals of the Adaptive group are more intolerant to monotony, present an aversion to repetitive and routine activities, are less susceptible to motion sickness and less dependent on problem-focused strategies. These characteristics may have contributed to developing a certain degree of flexibility in these subjects when faced with the parabolic flight situation and thus, may have favored them. The identification of differences of personality characteristics between individuals who have expressed difficulties of adaptation from those who have adapted successfully could help to prevent the risk of maladaptation and improve the well-being of (future) commercial or occupational aerospace passengers. More generally, these results could be extended to extreme environments and professional and/or sports domains likely to involve risk taking and unusual situations.


Evaluation of thyroid nodules--combined use of (99m)Tc-methylisobutylnitrile scintigraphy and aspiration cytology to assess risk of malignancy and stratify patients for surgical or nonsurgical therapy--a retrospective cohort study.
Thyroid nodules are a common clinical problem, and differentiation between benign and malignant nodules is essential. The aim of this study was to evaluate an approach for cold thyroid nodules including (99m)Tc-methylisobutylnitrile (MIBI) scintigraphy to assess risk of malignancy and stratify patients for therapy. Retrospective cohort study; 391 patients with at least one cold thyroid nodule were consecutively admitted (between 1 January 2004 and 31 December 2006) and recommended for surgical or nonsurgical therapy. Thyroid ultrasonography, (99m)Tc-pertechnetate scintigraphy, laboratory tests, fine needle aspiration cytology (FNAC) and MIBI scintigraphy. 57·3% (224/391) had one cold nodule, 17·9% (70/391) had several cold nodules, and 24·8% (97/391) had both cold and hot nodules. MIBI scintigraphy was classified into 'positive' (16·1%, 63/391), 'weakly positive' (19·2%, 75/391) or 'negative' (64·7%, 253/391). FNAC was classified into benign (87·9%, 247/281), nondiagnostic (6·8%, 19/281) or suspicious/malignant (5·3%, 15/281). 127 patients received surgery, revealing malignancy in 13·3% (17/127), predominantly papillary (64·7%, 11/17) and follicular carcinoma (23·5%, 4/17). MIBI scintigraphy was 'positive' (64·7%, 11/17) or 'weakly positive' (23·5%, 4/17) in most patients with malignant findings. FNAC was unavailable in 23·5% (4/17) with malignancy, positive in 38·5% (5/13) and negative in 61·5% (8/13). Among patients undergoing surgery, sensitivity, specificity, negative and positive predictive values for MIBI scintigraphy were 88·2%, 35·5%, 95·1% and 17·4%, for FNAC 38·5%, 90·6%, 90·6% and 38·5%, respectively, and for the combination (MIBI scan + FNAC) 92·3%, 30·6%, 96·3% and 16·9%. Benign MIBI-positive nodules were predominantly follicular adenomas (68%, 33/48). Evaluation of cold thyroid nodules by MIBI scintigraphy aids therapeutic decisions: MIBI-negative findings support nonsurgical management in about two-thirds of patients, while MIBI-positive findings have an increased risk of malignancy, supporting surgical therapy. However, the positive predictive value was low, which requires further research.


Innovating workplace learning: Training methodology analysis based on content, instructional design, programmed learning, and recommendation framework.
The quality of sales processes is crucial in automotive and directly related to the firm's competitive advantage and financial success. Sales training is the most prevalent intervention to guarantee quality and productivity. Extant literature has attempted to measure training effectiveness adequately, and the Context, Input, Process, and Product evaluation (CIPP) model has been a popular approach. This study endeavored to advance current literature and suggest a novel effectiveness framework, Content, Instructional design, Programmed learning, and Recommendation (CIP-R). The framework was applied to examine three different methodologies-traditional, pure digital, and hybrid training-collecting 583 instances from the automotive sales training conducted from 2019 to 2020 in South Korea. The findings advocate the importance of human elements, the role of efficacy, and self-determination in generating learning transferability, leading to performance in the digital age.


Expression of Bcl-2 protects against photoreceptor degeneration in retinal degeneration slow (rds) mice.
The retinal degeneration slow or rds gene encodes rds/peripherin, an integral membrane glycoprotein in the outer segments of rod and cone photoreceptors. Mice homozygous for a null mutation in rds fail to develop outer segments and undergo subsequent degeneration of photoreceptors by the apoptotic pathway. Mutations in the human RDS gene are responsible for several forms of inherited blindness including autosomal-dominant retinitis pigmentosa and macular degeneration. Here, we examined the effects of ectopic Bcl-2 expression in transgenic photoreceptors on the rate of retinal degeneration in rds mutant mice. We observed an approximately twofold preservation of photoreceptors compared with nontransgenic rds mutant mice at 3 months. Immunoblot analysis showed similar levels of Bcl-2 in 2-, 3-, and 4-week-old transgenic mice. Expression of Bcl-2 in the rds mouse did not lead to outer segment formation and did not induce cell death. These results suggest that Bcl-2 expression may be an effective therapeutic strategy in humans with mutations in RDS or other genes that affect the integrity of photoreceptor outer segments.


Predictors of suicide attempters in substance-dependent patients: a six-year prospective follow-up.
This is a six-year prospective follow-up of a former cross sectional study of suicide attempters in a sample of treatment-seeking substance-dependent patients. The aims were to explore the frequency of patients with new suicide attempts (SA) during the six-year observation period, and to explore the predictive value of lifetime Axis I and II disorders, measured at index admission, on SA in the observation period, when age, gender and substance-use variables, measured both at admission and at follow-up, were controlled for. A consecutive sample of 156 alcohol-dependent and 131 poly-substance-dependent inpatients and outpatients in two Norwegian counties were assessed at index admission (T1) with the Composite International Diagnostic Interview (Axis I disorders), Mon's Clinical Multiaxial Inventory (Axis II disorders) and Hopkins Symptom Checklist-25 (mental distress). At follow-up six years later (T2), 56% (160/287 subjects, 29% women) were assessed using the HSCL-25 and measures of harmful substance use (Alcohol Use Disorders Identification Test and Drug Use Disorders Identification Test). The prevalence of patients with SA between T1 and T2 was 19% (30/160), with no difference between sexes or between patient type (alcohol-dependent versus poly-substance-dependent). Sober patients also attempted suicide. At the index admission, lifetime eating disorders, agoraphobia with and without panic disorder, and major depression were significantly and independently associated with SA. Prospectively, only lifetime dysthymia increased the risk of SA during the following six years, whereas lifetime generalized anxiety disorder reduced the risk of SA. Individually, neither the numbers of Axis I and Axis II disorders nor the sum of these disorders were independently related to SA in the observation period. Substance use measured at T1 did not predict SA in the follow-up period, nor did harmful use of substances at follow-up or in the preceding year. A high prevalence of SA was found six years later, both in patients still abusing substances and in sober patients. To prevent SA, treatment of both affective disorders and substance abuse is important.


Evaluation of Pseudomonas fulva PS9.1 and Bacillus velezensis NWUMFkBS10.5 as Candidate Plant Growth Promoters during Maize-Fusarium Interaction.
Based on in vitro assessments, molecular and chemical analysis, Pseudomonas fulva PS9.1 and Bacillus velezensis NWUMFkBS10.5 are candidate biocontrol agents for plant disease management including maize fusariosis, a disease caused by members of the Fusarium species. This in vivo study evaluated the bio-protective potential of the aforementioned rhizobacteria strains on maize against the proliferation of the pathogenic fungus Fusarium graminearum (Fg). The study results show that the bacterized plants were not susceptible to Fg aggression and the antagonists displayed the capability to proliferate in the presence of other likely competing microflora. The screen-house data also suggest that the presence of resident soil microbiota impacted the activity of antagonists (PS9.1 and NWUMFkBS10.5). This variation was recorded in the soil treatments (sterilized and unsterilized soil). In all the experimental periods, bacterized maize plants with or without Fg inoculation significantly (p = 0.05) grew better in unsterilized soil. Besides, during the experimental periods, all the consortia treatments with or without Fg infection regardless of the soil used demonstrated appreciable performance. The result of this study suggests that the microbial agents can actively colonize the surface of their maize plant host, improve plant growth, and suppress the growth of phytopathogens. Considering their overall performance in this screen-house evaluation, P. fulva PS9.1 and B. velezensis NWUMFkBS10.5 have potential for field applications. All safety issues regarding their use under field conditions and risks associated with their extended-release into the environmental will, however, be assessed prior to further bioformulation, field investigation, and scale-up.


An Unusual Case of Severe Trismus After Craniotomy.
Myositis ossificans Traumatica (MOT) is a non-neoplastic, heterotrophic ossifying disease process in muscle and soft tissue rarely involving the craniofacial area. Treatment depends on the extent of ossification and functional limitations. We present the first case of MOT of the temporalis muscle following neurosurgical intervention. This is the case of a 28-year-old male patient who underwent numerous neurosurgical interventions and reported progressive trismus following these interventions. Imaging demonstrated a right temporal region radio-opacity consistent with ossification of the temporalis muscle. The patient underwent coronoidectomy with excision of the ossified right temporalis muscle and reconstruction with an anterolateral thigh adipofascial vascular free flap. Postoperatively, he maintained intact function with increased incisal opening and no cosmetic defects. Limited mouth opening after the neurological procedure has a wide differential, and MOT must be considered. Surgical repair and reconstruction are multifaceted problems. Free flap reconstruction should be considered in multiple operated patients.


Developmental pattern of hepatic uridine diphosphoglucuronosyl transferase activity in growing male rats.
Hepatic uridine diphospho(UDP)glucuronosyl transferase activity was measured in growing male rats to gain the developmental activity pattern of this enzyme catalyzing conjugation of xenobiotics and endogenous substrates. The activity was at a very low level at the age of 14 days showing a 10-fold increase to the age of 72 days whereafter a slight decrease of activity was observed. Simultaneously there was about 30% increase in the hepatic postmitochondrial supernatant protein content. The highly enhanced UDPglucuronosyl transferase activity during the growth may be caused by increased synthesis of enzyme protein or by changes in the micro-environment of the enzyme.


Quantum efficiency and instrumental polarization of an optical monochromator.
Experiences from a determination of the over-all quantum efficiency and instrumental polarization of an optical monochromator and detection system (near ultraviolet, visible, and near infrared), including application of imperfect polarizers, are discussed and related to atomic and electronic collision studies.


Newest Therapies for Cholangiocarcinoma: An Updated Overview of Approved Treatments with Transplant Oncology Vision.
A minority of cholangiocarcinoma (CCA) can be cured by surgical intervention (i.e., liver resection (LR) and liver transplantation (LT)). When modern criteria for LT are met, this intervention along with neoadjuvant treatments may achieve unprecedented survival in selected patients. Liver resection is associated with a median overall survival (OS) of 40 months, this number drastically decreases for unresectable advanced cholangiocarcinoma (CCA), which is treated with systemic therapy. The first-line chemotherapy regimen of gemcitabine and cisplatin is associated with a median overall survival of only 11.7 months. Since the Food and Drug Administration (FDA)'s approval of the isocitrate dehydrogenase (IDH) 1 inhibitor ivosidenib in August 2021, there has been increasing interest in targeted therapy for CCA patients harboring mutations in fibroblast growth factor receptor (FGFR) 2, neurotrophic receptor tyrosine kinase (NTRK), B-raf kinase (BRAF), and HER2. At the same time, immunotherapy with immune checkpoint inhibitors isalso being used in relapsed CCA. This review looks into the most recently completed and ongoing studies of targeted therapy as monotherapy or in combination with chemo- and/or immunotherapy. Whether it is resection, liver transplant, radiotherapy, chemotherapy, immunotherapy, targeted therapy, or any combination of these treatment modalities, great strides are being made to improve outcomes for this challenging disease.


Oncostatin M (OSM) is increased in asthma with incompletely reversible airflow obstruction.
Oncostatin M, a unique member of the interleukin (IL)-6 cytokine family, is thought to be involved in airway remodeling. The expression of oncostatin M in the lower airways is unknown. The aim of this study was to measure the sputum expression of oncostatin M in patients with asthma with and without irreversible airflow obstruction. Induced sputum was collected from nonsmoking adults with stable asthma (n = 53), 31 with incomplete reversibility of airflow obstruction. Peripheral blood cells were isolated and stimulated with lipopolysaccharide in 10 participants with asthma and irreversible airflow obstruction. Oncostatin M protein levels were determined in supernatant, whereas RNA was extracted to determine Oncostatin M mRNA expression using real-time polymerase chain reaction (PCR). Oncostatin M mRNA expression and protein levels were significantly higher in the sputum of asthmatics with irreversible airflow obstruction. Sputum oncostatin M levels were highest in people with severe airflow obstruction and were localized to airway neutrophils and macrophages. Peripheral blood neutrophils released more oncostatin M when stimulated with lipopolysaccharide compared with unstimulated neutrophils. Sputum oncostatin M is increased in asthma with irreversible airflow obstruction and is present in airway neutrophils and macrophages. Oncostatin M may link airway inflammation to remodeling in asthma.


Iron metabolism: iron deficiency and iron overload.
Iron is an essential cofactor in a variety of cellular processes. Except for a few unusual bacterial species, iron is indispensable for living organisms. However, free iron is toxic because of its propensity to induce the formation of dangerous free radicals. Consequently, iron balance is tightly regulated. Disorders of iron homeostasis are among the most common afflictions of humans. This review discusses inherited iron deficiency and iron overload disorders and recent insights into their pathophysiology.


Mechanisms of hydride abstractions by quinones.
The kinetics of the hydride abstractions by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) from 13 C-H hydride donors (acyclic 1,4-dienes, cyclohexa-1,4-dienes, dihydropyridines), tributylstannane, triphenylstannane, and five borane complexes (amine-boranes, carbene-boranes) have been studied photometrically in dichloromethane solution at 20 °C. Analysis of the resulting second-order rate constants by the correlation log k2(20 °C) = sN(E + N) ( J. Am. Chem. Soc. 2001 , 123 , 9500 ) showed that the hydride abstractions from the C-H donors on one side and the Sn-H and B-H hydride donors on the other follow separate correlations, indicating different mechanisms for the two reaction series. The interpretation that the C-H donors transfer hydrogen to the carbonyl oxygen of DDQ while Sn-H and B-H hydride donors transfer hydride to a cyano-substituted carbon of DDQ is supported by quantum-chemical intrinsic reaction coordinate calculations and isotope labeling experiments of the reactions of D8-cyclohexa-1,4-diene, Bu3SnD, and pyridine·BD3 with 2,5-dichloro-p-benzoquinone. The second-order rate constants of the reactions of tributylstannane with different quinones correlate linearly with the electrophilicity parameters E of the quinones, which have previously been derived from the reactions of quinones with π-nucleophiles. The fact that the reactions of Bu3SnH with quinones and benzhydrylium ions are on the same log k2 vs E (electrophilicity) correlation shows that both reaction series proceed by the same mechanism and illustrates the general significance of the reactivity parameters E, N, and sN for predicting rates of polar organic reactions.


[Clinical studies of the effect of physical training therapy on oxygen absorption and pulmonary artery pressure in persons with chronic obstructive lung diseases].
Twenty patients with chronic obstructive bronchitis were submitted to a 6-week rehabilitation program including bicycle training, breathing exercise, inhalation, massage, short wave therapy and others. Before and after 6-week training we investigated ventilatory and blood gas parameters and pulmonary artery pressure at rest and during exercise. There was no change in the oxygen uptake on the same exercise stage. We found an insignificant decrease of the pulmonary artery pressure at rest and during exercise. The physical training has no negative influence on the behaviour of pulmonary pressure. We stated a good effect of physical conditioning on the systemic circulation. The working capacity of all patients improved at the end of the training period.


An ABC-ELISA for malaria serology in the field.
An avidin biotin peroxidase complex enzyme-linked immunosorbent assay (ABC-ELISA) was examined for the diagnosis of malaria in a controlled area in Sudan Gezira. The titers of the ABC-ELISA coincided with those of the IFAT. The method was more sensitive than the ordinary ELISA as the final enzyme reaction was amplified through the use of the ABC system. This allowed the resulting color spots on the dried plate wells to be read clearly with the naked eye. This test can be carried out without using major electrical equipment.


The Performance of Saccade Tasks Correlates with Cognitive Test Scores in Elderly Population: Evidence for the Usefulness of Oculomotor Tests in Cognitive Assessment.
Among the elderly, dementia is a common and disabling disorder with primary manifestations of cognitive impairments. Diagnosis and intervention in its early stages is the key to effective treatment. Nowadays, the test of cognitive function relies mainly on neuropsychological tests, such as the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). However, they have noticeable shortcomings, e.g., the biases of subjective judgments from physicians and the cost of the labor of these well-trained physicians. Thus, advanced and objective methods are urgently needed to evaluate cognitive functions. We developed a cognitive assessment system through measuring the saccadic eye movements in three tasks. The cognitive functions were evaluated by both our system and the neuropsychological tests in 310 subjects, and the evaluating results were directly compared. In general, most saccadic parameters correlate well with the MMSE and MoCA scores. Moreover, some subjects with high MMSE and MoCA scores have high error rates in performing these three saccadic tasks due to various errors. The primary error types vary among tasks, indicating that different tasks assess certain specific brain functions preferentially. Thus, to improve the accuracy of evaluation through saccadic tasks, we built a weighted model to combine the saccadic parameters of the three saccadic tasks, and our model showed a good diagnosis performance in detecting patients with cognitive impairment. The comprehensive analysis of saccadic parameters in multiple tasks could be a reliable, objective, and sensitive method to evaluate cognitive function and thus to help diagnose cognitive impairments.


Description of low back pain clinical trials in physical therapy: a cross sectional study.
To describe the main characteristics of low back pain randomized controlled trials on the Physiotherapy Evidence Database, and to rank the journals where these trials were published according to their Impact Factor. This is a cross sectional study based on a collection of randomized controlled trials. A random sample of 200 low back pain trials published between 2010 and 2015 were selected from Physiotherapy Evidence Database in February 2016. We collected the following main characteristics of trials: 2015 journal Impact Factor; if the paper was published as open access; CONSORT recommendations endorsement by the journal; methodological quality and statistical reporting measured by the 0-10 items Physiotherapy Evidence Database scale. Data was analyzed descriptively. Trials were published in journals with a mean Impact Factor of 2.5 (SD 2.5), from which 55.5% endorsed the CONSORT recommendations. The methodological quality was moderate with 5.8 points (SD 1.6). The top 3 journals according to Impact Factor were: (1) British Medical Journal; (2) Annals of Internal Medicine; and (3) BMC Medicine. Only 6 out of 97 journals publishing low back pain trials combined the following factors: journal Impact Factor higher than 2.0, mean trial methodological quality higher than 6.0 points, endorse CONSORT recommendations and offering papers as open access. Clinicians interested in low back pain trials must look for a wide variety of healthcare journals. A substantial number of low back pain randomized controlled trials did not follow adequate reporting and methodological recommendations.


The effects of medication adherence and health literacy on health-related quality of life in older people with hypertension.
This study investigated the effects of medication adherence and health literacy on health-related quality of life in vulnerable older people with hypertension. Health literacy is particularly critical for providing accurate information regarding correct medication intake to improve medication adherence. Additionally, health-related quality of life is directly related to impairment from chronic disease. A descriptive, cross-sectional study design was used. The participants were 160 low-income older people with hypertension registered in 16 public health centres in Busan, South Korea. They had received "visiting nursing services" for at least 6 months until the latest date and had belonged to the priority group of visiting nursing services. The Morisky Medication Adherence Scale, the Newest Vital Signs and EuroQol-5 Dimensions were used to assess medication adherence, health literacy and health-related quality of life, respectively. Medication adherence and health literacy were significantly associated with health-related quality of life in vulnerable older people with hypertension, although exercise and subjective health were more significant factors affecting health-related quality of life than medical adherence and health literacy. Level of education, monthly income and employment status were not associated with health-related quality of life. To effectively promote health-related quality of life in this population, medication adherence and health literacy of patients should be considered when developing health interventions, including subjective health and exercise. To effectively promote health-related quality of life in vulnerable older people, medication adherence and health literacy of patients should be assessed, and patient-centred intervention strategies that consider their individual differences should be developed.


Role of a clinical facilitator in introducing an integrated care pathway for the care of the dying.
Integrated care pathways (ICPs) have been developed as a tool for improving end-of-life care. The Liverpool Care Pathway for the Dying (LCP) is a multidisciplinary and evidence-based approach to caring for the dying person. At Wythenshawe hospital a clinical facilitator was appointed to facilitate the introduction of the LCP. This full-time post, which existed for 18 months, involved supporting and educating staff about the pathway. The LCP is now used through the general surgical and medical wards and acute and regional coronary care units. This article reflects on the different aspects of the role and the development of the project.


Diagnosis of acute myocardial infarction in the presence of left bundle branch block.
Patients with suspected acute myocardial infarction (AMI) in the setting of left bundle branch block (LBBB) present an important diagnostic and therapeutic challenge to the clinician. We prospectively evaluated the incidence of AMI and diagnostic performance of specific ECG and high-sensitivity cardiac troponin (hs-cTn) criteria in patients presenting with chest discomfort to 26 emergency departments in three international, prospective, diagnostic studies. The final diagnosis of AMI was centrally adjudicated by two independent cardiologists according to the universal definition of myocardial infarction. Among 8830 patients, LBBB was present in 247 (2.8%). AMI was the final diagnosis in 30% of patients with LBBB, with similar incidence in those with known LBBB versus those with presumably new LBBB (29% vs 35%, p=0.42). ECG criteria had low sensitivity (1%-12%) but high specificity (95%-100%) for AMI. The diagnostic accuracy as quantified by the receiver operating characteristics (ROC) curve of hs-cTnT and hs-cTnI concentrations at presentation (area under the ROC curve (AUC) 0.91, 95% CI 0.85 to 0.96 and AUC 0.89, 95% CI 0.83 to 0.95), as well as that of their 0/1-hour and 0/2-hour changes, was very high. A diagnostic algorithm combining ECG criteria with hs-cTnT/I concentrations and their absolute changes at 1 hour or 2 hours derived in cohort 1 (45 of 45(100%) patients with AMI correctly identified) showed high efficacy and accuracy when externally validated in cohorts 2 and 3 (28 of 29 patients, 97%). Most patients presenting with suspected AMI and LBBB will be found to have diagnoses other than AMI. Combining ECG criteria with hs-cTnT/I testing at 0/1 hour or 0/2 hours allows early and accurate diagnosis of AMI in LBBB. APACE: NCT00470587; ADAPT: ACTRN12611001069943; TRAPID-AMI: RD001107;Results.


Youth Self Report Thought Problems and Sleep Difficulties Are Linked to Suicidal Ideation Among Psychiatrically Hospitalized Adolescents.
Objectives: Thought problems, such as hallucinations and delusional or disorganized ideas, have been associated with increased sleep problems and risk for suicidal ideation (SI). Sleep problems have also been linked directly to suicidality in adolescence. The nature of the relationship between these symptoms among adolescents with acute suicidality is not well understood. This study aims to examine the interrelationships between thought problems, sleep difficulties, and SI in adolescents psychiatrically hospitalized for safety concerns, with the goal of informing suicide risk screening and intervention for this population. Methods: Participants included adolescents (n = 690) aged 11-18. A retrospective chart review was used to obtain scores on study measures, including the Suicidal Ideation Questionnaire Junior (SIQ-Jr), the thought problems and sleep disturbance scales on the Youth Self Report (YSR), and mental health diagnoses using the Children's Interview for Psychiatric Syndromes (ChIPS). Results: Findings indicate that SIQ-Jr scores are moderately correlated with both YSR thought problems (r = 0.51, p < 0.001) and YSR sleep disturbance (r = 0.47, p < 0.001). Further, linear regression analyses support the hypotheses that thought problems (β = 0.28) and sleep difficulties (β = 0.11) are uniquely associated with SI, beyond the significant effects of depression (β = 0.36) and female sex (β = -0.07); R2 = 0.43, F (8, 673) = 62.49, p < 0.001). Conclusions: These results suggest that sleep interventions and treatment of thought problems may be important for reducing SI, within and outside the context of depression. Furthermore, the adolescent version of the YSR may be a useful tool to evaluate these risk factors alongside other psychiatric concerns.


Hair hormones in male youth with internet gaming disorder.
Objectives: Internet gaming disorder (IGD) is associated with altered physiological reactivity to psychosocial stress. Findings from a previous study on alterations of basal hypothalamic-pituitary-adrenal (HPA) axis functioning, indexed by differences in hair hormone levels (i.e., cortisol) in IGD patients compared to matched controls, were limited by a small sample size. Methods: Following the protocol of the previous study, male patients with IGD (n = 31) and controls (n = 31) matched for age, educational status and smoking were recruited. Sociodemographic and clinical characteristics were assessed using structured interviews and self-reports. Hair samples were taken for the analysis of cortisol, cortisone, testosterone, progesterone, dehydroepiandrosterone (DHEA), and corticosterone. Results: Groups showed no significant differences on cortisol (d = -0.10, 95%CI (-0.60; 0.40)), cortisone (d = -0.10, 95%CI (-0.60; 0.40)), testosterone (d = -0.00, 95%CI (-0.51; 0.51)), progesterone (d = -0.46, 95%CI (-0.96; 0.05)), DHEA (d = -0.04, 95%CI (-0.54; 0.47)) or corticosterone (d = -0.19, 95%CI (-0.69; 0.32)). Associations between hair hormone concentrations, symptom severity and sociodemographic variables were weak and did not survive correction for multiple testing. Conclusions: Unlike other psychiatric disorders, effects of IGD and associated psychopathology on basal HPA axis functioning, indexed by hair hormone levels, are negligible. Future studies need to rule out potential effects of sex, age and long-term pathology on these findings.


Simple and novel technique for fabrication of prosthetic vaginal dilators.
Vaginal agenesis is one of the major congenital anomalies affecting women. Postoperative prosthetic vaginal dilators are indicated in patients treated surgically for vaginal agenesis. Although different dental materials such as acrylics and silicone-coated materials are used, addition silicones alone have never been used for the fabrication of prosthetic vaginal dilators. Addition silicone materials have advantages, such as high elastic recovery, high tear and tensile strengths, which aid in the definitive use of vaginal dilators. Vaginal dilators fabricated using addition silicone materials act as an efficient prosthesis in terms of function and ease of use in surgically treated vaginal agenesis patients.


Evaluation and treatment of posterior neck pain in family practice.
Neck pain is almost universal and is a common patient complaint. Although the differential diagnosis is extensive, most symptoms are from biomechanical sources, such as axial neck pain, whiplash-associated disorder (WAD), and radiculopathy. Most symptoms abate quickly with little intervention. There is relatively little high-quality treatment evidence available, and no consensus on management of axial neck pain or radiculopathy. A number of general pain management guidelines are applicable to neck pain, and specific guidelines are available on the management of WAD. The goal of diagnosis is to identify the anatomic pain generator(s). Patient history and examination are important in distinguishing potential causes and identifying red flags. Diagnostic imaging should be ordered only when necessary because of the high incidence of asymptomatic radiographic abnormalities. First-line drug treatments include acetaminophen, cyclo-oxygenase 2-specific inhibitors, or nonsteroidal anti-inflammatory drugs. Short-term use of muscle relaxants may be considered. Opioids should be used if other treatments are ineffective and continued if improved function outweighs impairment. Adjuvant antidepressants and anticonvulsants should be considered in chronic or neuropathic pain and coincident depression. Epidural steroids should be considered only in radiculopathy. Physical modalities supported by evidence should be used. If symptoms have not resolved in 4 to 6 weeks, re-evaluation and additional workup should be considered.


Value-assessment of computer-assisted navigation strategies during percutaneous needle placement.
Navigational strategies create a scenario whereby percutaneous needle-based interventions of the liver can be guided using both pre-interventional 3D imaging datasets and dynamic interventional ultrasound (US). To score how such technologies impact the needle placement process, we performed kinematic analysis on different user groups. Using a custom biopsy phantom, three consecutive exercises were performed by both novices and experts (n = 26). The exercise came in three options: (1) US-guidance, (2) US-guidance with pre-interventional image-registration (US + Reg) and (3) US-guidance with pre-interventional image-registration and needle-navigation (US + Reg + Nav). The traveled paths of the needle were digitized in 3D. Using custom software algorithms, kinematic metrics were extracted and related to dexterity, decision making indices to obtain overall performance scores (PS). Kinematic analysis helped quantifying the visual assessment of the needle trajectories. Compared to US-guidance, novices yielded most improvements using Reg (PSavg(US) = 0.43 vs. PSavg(US+Reg) = 0.57 vs. PSavg(US+Reg+Nav) = 0.51). Interestingly, the expert group yielded a reversed trend (PSavg(US) = 0.71 vs PSavg(US+Reg) = 0.58 vs PSavg(US+Reg+Nav) = 0.59). Digitizing the movement trajectory allowed us to objectively assess the impact of needle-navigation strategies on percutaneous procedures. In particular, our findings suggest that these advanced technologies have a positive impact on the kinematics derived performance of novices.


Renal biopsy findings in children receiving long-term treatment with cyclosporine a given as a single daily dose.
Long-term treatment of childhood nephrotic syndrome (NS) and rheumatic diseases with cyclosporine A (CsA) given as a single daily dose may yield better results and allow safer use of the drug than the conventional twice-daily dosing. However, the safety of such long-term treatment from the histological standpoint remains to be established. Posttreatment renal biopsy was conducted in a total of eight children (5 with minimal change NS, 2 with focal segmental glomerulosclerosis and 1 with X-linked immune dysregulation, polyendocrinopathy and enteropathy) receiving CsA as a single daily dose, after a mean treatment duration of 20 months (9-36 months). The initial daily dose of CsA (Neoral) was 2.0 mg/kg, given as a single daily dose before breakfast. The dose was subsequently adjusted to achieve a peak (between 1 and 2 hrs post-dosing, C1-C2) blood level of around 800 ng/ml. The mean daily CsA dose, mean C1-C2 blood level, and mean trough blood level in the subjects were 1.9 +/- 0.6 mg/kg, 803.8 +/- 117.2 ng/ml and 36.1 +/- 12.7 ng/ml, respectively. The result revealed no evidence of CsA-related nephrotoxicity, including arteriopathy, striped interstitial fibrosis or tubular atrophy, in any of the study participants. Also, no significant changes were observed in the mean estimated glomerular filtration rate as compared to the pretreatment values (127.6 +/- 14.9 ml/min/1.73 m(2) vs 115.6 +/- 22.8 ml/min/1.73 m(2), and except for mild hypertrichosis, no significant adverse effects of CsA were observed. These findings lend further support to the safety of long-term low-dose CsA treatment (median treatment duration in this study, 20 months), with the drug administered as a single daily dose while maintaining a peak (C1-C2) blood level of around 800 ng/ml.


Insights of Doping and the Photoluminescence Properties of Mn-Doped Perovskite Nanocrystals.
Doping Mn2+ in semiconductor nanocrystals is widely known for its long-lifetime Mn d-d orange emission. While this had been extensively studied for chalcogenide nanostructures, recently this was also extended to perovskite nanocrystals. Being that CsPbCl3 has a wide bandgap, the exciton energy transfer was found to be more efficient, but the dopant-induced photoluminescence was also obtained for layered perovskites and quantum-confined CsPbBr3 nanocrystals. In recent years significant advances have been achieved in understanding the physical insights of doping following various approaches and optimizing the conditions for obtaining intense dopant emission. In addition, several new properties associated with these doped nanocrystals were also reported, and by modulating the compositions, the host bandgap and the dopant emission positions were also tuned. Keeping all of these developments in mind, this Perspective focuses on the insights of doping and the photoluminescence properties of Mn2+-doped perovskite nanocrystals. In addition, it also proposes possible future prospects of both synthesis and optical properties of these nanomaterials.


BeWell: quality assurance health promotion pilot.
The purpose of this paper is to determine the experience participating in a health promotion program for refugee and asylum seekers and torture survivors in a safety net clinical setting. Refugee and asylum seeker torture survivors participated in a seven-week health promotion program at a safety-net clinic. Participants interviewed before, during and after the program was designed to improve and maintain health promotion program quality. Six major themes emerged: social networks; tools/techniques/skills; wellness planning; spiritualism; health maintenance; and social/group interaction. Preliminary results suggest that this multi-pronged approach is feasible and acceptable to foreign-born torture survivors. Torture impacts many facets of one's life. A program which addresses health from a multidisciplinary perspective has promise to facilitate healing. The impact of torture and human rights violations significantly affects many facets of peoples' lives including emotional, social, physical and spiritual dimensions. Therefore a program which utilizes a multidisciplinary integrated bio-psychosocial and spiritual approach has the potential to simultaneously address many domains facilitating healing. BeWell, a bio-psychosocio-spiritual health promotion strategy aimed at improving health service quality and increasing patient satisfaction to support positive health outcomes by implementing in-classroom/person modules for patients, to the authors' knowledge is unique in its efforts to encompass multiple domains simultaneously and fully integrate an approach to wellbeing.


Protective Effects of Total Flavones of Elaeagnus rhamnoides (L.) A. Nelson against Vascular Endothelial Injury in Blood Stasis Model Rats.
The aim was to evaluate the protective effects of total flavones of Elaeagnus rhamnoides (L.) A. Nelson (TFE) against vascular endothelial injury in blood stasis model rats and explore the potential mechanisms preliminarily. The model of blood stasis rat model with vascular endothelial injury was induced by subcutaneous injection of adrenaline combined with ice-water bath. Whole blood viscosity (WBV), histological examination, and prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) were measured. Meanwhile, the levels of Thromboxane B2 (TXB2), 6-keto-PGF1α , von Willebrand factor (vWF), and thrombomodulin (TM) were detected. In addition, Quantitative Real-Time PCR (qPCR) was performed to identify PI3K, Erk2, Bcl-2, and caspase-3 gene expression. The results showed that TFE can relieve WBV, increase PT and APTT, and decrease FIB content obviously. Moreover, TFE might significantly downregulate the levels of TXB2, vWF, and TM in plasma and upregulate the level of 6-keto-PGF1α in plasma. Expressions of PI3K and Bcl-2 were increased and the expression of caspase-3 was decreased by TFE pretreatment in the rat model. Consequently, the study suggested that TFE may have the potential against vascular endothelial injury in blood stasis model rats induced by a high dose of adrenaline with ice-water bath.


Uveal effusion syndrome.
The terms uveal effusion, choroidal effusion, ciliochoroidal effusion, ciliochoroidal detachment, and choroidal detachment have been used interchangeably in the literature. These labels all describe an abnormal collection of fluid that expands the suprachoroidal space, producing internal elevation of the choroidal. There are various inflammatory and hydrostatic conditions that can cause uveal effusion, but in some cases no obvious cause exists. In this setting, patients are thought to have a distinct, primary abnormality of the choroid or sclera, called uveal effusion syndrome (UES). UES may be idiopathic, or associated with hypermetropia, and should be considered a diagnosis of exclusion. Histological studies show amorphous glycosaminoglycan-like material filling the interfibrillary spaces of excised scleral tissue, with disruption of collagen fibers. In some patients there may be reduced macromolecular diffusion that interferes with the normal transscleral egress of albumin out of the eye, perhaps causing choroidal fluid retention due to altered osmotic forces. An alternative, and perhaps complementary hypothesis, is that swollen sclera compresses the transscleral vessels with resulting fluid retention. Patients with UES are most typically middle-aged men who have a relapsing remitting clinical course. There is often co-existing, shifting subretinal fluid that may involve the macula. Chronic disease may lead to secondary retinal pigment epithelial (leopard spot) changes and permanently reduced visual acuity. Treatment with systemic steroids does not appear to be effective. Surgical decompression of the vortex veins as they pass through the sclera has been described, but the most common treatment is full-thickness sclerectomies to provide an exit for choroidal fluid. The largest case series suggests that this produces an anatomic improvement in approximately 83% of treated eyes after a single procedure and in about 96% after one or two procedures. Final visual acuity improves by two or more lines in 56% of the eyes, is stable in 35%, and worsens in 9%. Although extremely rare, UES is a serious condition that is difficult to treat and can lead to severe and permanent visual loss in both eyes.


Efficacy of HL036 versus Cyclosporine A in the Treatment of Naturally Occurring Canine Keratoconjunctivitis Sicca.
To (i) evaluate the efficacy and safety of HL036, a tumor-necrosis factor (TNF)-α-blocking protein, in the treatment of naturally occurring canine keratoconjunctivitis sicca (KCS) and (ii) compare these features with those of 1% cyclosporine A (CsA). Dogs (n = 29) diagnosed with KCS were randomly assigned to receive one drop topical aqueous HL036 (0.2, 1, or 5 mg/mL) or 1% CsA in the affected eye(s) at 12-h intervals for 42 days. Schirmer's tear test (STT), fluorescein corneal staining (FCS), and clinical-sign scores were evaluated prior to application (day-0) and on days 14, 28, and 42 post-treatment. Of the 29 dogs enrolled, 19 (65.5%) received HL036 (HL036 group) and 10 (34.5%) received 1% CsA (CsA group). A linear mixed-effects model analysis was performed to determine score differences between groups and over time. After treatment, clinical-sign scores and STT values had significantly improved compared with baseline levels in dogs of both treatment groups. Decreases in total clinical-sign scores for the HL036-group were greater than those of 1% CsA group. No severe adverse reactions were noted in either group. Our findings suggest that topical aqueous HL036 is well-tolerated and more effective than 1% CsA for treating naturally occurring canine KCS.


[Problem of the referral-for-referral system of obstetrical emergencies and the community involvement in the Bamako district].
This study aims to evaluate the difficulties of the referral-for-referral system in the V municipality sanitary district of Bamako. A descriptive cross-sectional study was carried out from 5th September to 5th November 2011 in the sanitary district of the V municipality in Bamako. Included in the study were patients referred or evacuated for obstetrical care in the health center during the period of study. Not included were the patients referred or evacuated from other sanitary districts and patients referred or evacuated or self-referred for no obstetrical reasons. Data was recorded on the Excel 8.0 software and analyzed on the software packages Epi info 3.5.3 and STATA. During the period of study we recorded 1824 deliveries among which 180 fit the inclusion criteria. During our study 92.2% of references were adequate; 78.3% were justified and 72.2% were opportune. Only the sanitary district of the V Municipality had paid its quotation due at the time of the study. Our study showed that inadequate logistics and the lack of involvement of communities hamper the proper functioning of the referral system.


Control of oxidative stress and metabolic homeostasis by the suppression of postprandial hyperglycemia.
Repeated mental stress may lead to chronic alterations in cortisol and catecholamine concentrations and to insulin resistance. Furthermore, chronically elevated cortisol concentrations may favour the development of abdominal obesity and of the metabolic syndrome. Oxidative stress impairs glucose uptake in muscle and fat and correlates with BMI. Obese subjects with type 2 diabetes, especially soon after the onset of diabetes, usually exhibit postprandial hyperglycemia with delayed hyperinsulinemia. It is recognized that insulin resistance causes postprandial hyperglycemia; however, it is also possible that impairment of early insulin secretion in response to an oral glucose load is the reason why postprandial hyperglycemia occurs. Since even modest increases in postprandial glucose values can be a risk factor for cardiovascular disease. Therefore, the effects of palatinose based functional food which reduces postprandial hyperglycemia and hyperinsulinemia were investigated in rats. This novel food definitely reduced visceral fat accumulation and improved insulin sensitivity. Therefore, it is suggested that functional food which suppresses postprandial glucose level is beneficial for both stress and metabolic controls.


Effect of High-Energy Milling on Bioactive Compounds and Antioxidant Capacity in Nixtamalized Creole Corn Flours.
This study aimed at evaluating the effect of high-energy milling (HEM) and traditional nixtamalization (TN) on bioactive compounds and antioxidant capacity in nixtamalized creole corn flours obtained from a maize genotype cultivated under rainy temporal conditions in the Mexican semidesert. Four creole grains, including San José de Gracia white and blue (WG and BG), Negritas (NG), and Ahualulco white corn grains (SG), were used. For HEM nixtamalization, corn grains were hammer-milled; then, two different conditions were evaluated: treatment H1, with raw flours with 14% moisture content and 1.1% Ca(OH)2, and treatment H2, with raw corn flours with a 23% moisture content and 1.4% Ca(OH)2. The TN process was utilized as a control. TN recorded significant losses in luminosity value L* (p < 0.05), while HEM nixtamalized blue corn flours remained close to -b* values, that is, near to those of raw flour. Anthocyanin content showed higher content values in HEM treatments compared with TN (759.55 and 252.53 mg cyanidin 3-O-β-D-glucoside (C3G)/kg, respectively) (p < 0.05). Total soluble phenolic content was higher in HEM nixtamalization compared with the traditional process, except for WH2 and SH2 (H2 treatment for WG and SG). Two redundant radical scavenging assays were used: antioxidant capacity (DPPH assay) exhibited less value in nixtamalized flours than in raw flour (p < 0.05). Antioxidant activity by (ABTS) assay was higher in HEM than in TN. Nixtamalized flours produced by HEM demonstrated more improvement in nutraceutical properties than those produced employing TN.


Virtual Combinatorial Chemistry and Pharmacological Screening: A Short Guide to Drug Design.
Traditionally, drug development involved the individual synthesis and biological evaluation of hundreds to thousands of compounds with the intention of highlighting their biological activity, selectivity, and bioavailability, as well as their low toxicity. On average, this process of new drug development involved, in addition to high economic costs, a period of several years before hopefully finding a drug with suitable characteristics to drive its commercialization. Therefore, the chemical synthesis of new compounds became the limiting step in the process of searching for or optimizing leads for new drug development. This need for large chemical libraries led to the birth of high-throughput synthesis methods and combinatorial chemistry. Virtual combinatorial chemistry is based on the same principle as real chemistry-many different compounds can be generated from a few building blocks at once. The difference lies in its speed, as millions of compounds can be produced in a few seconds. On the other hand, many virtual screening methods, such as QSAR (Quantitative Sturcture-Activity Relationship), pharmacophore models, and molecular docking, have been developed to study these libraries. These models allow for the selection of molecules to be synthesized and tested with a high probability of success. The virtual combinatorial chemistry-virtual screening tandem has become a fundamental tool in the process of searching for and developing a drug, as it allows the process to be accelerated with extraordinary economic savings.


Neural differentiation of human embryonic stem cells at the ultrastructural level.
Neurodegerative disorders affect millions of people worldwide. Neural cells derived from human embryonic stem cells (hESC) have the potential for cell therapies and/or compound screening for treating affected individuals. While both protein and gene expression indicative of a neural phenotype has been exhibited in these differentiated cells, ultrastuctural studies thus far have been lacking. The objective of this study was to correlate hESC to neural differentiation culture conditions with ultrastructural changes observed in the treated cells. We demonstrate here that in basic culture conditions without growth factors or serum we obtain neural morphology. The addition of brain-derived neurotrophic factor (BDNF) and serum to cultures resulted in more robust neural differentiation. In addition to providing cues such as cell survival or lineage specification, additional factors also altered the intracellular structures and cell morphologies. Even though the addition of BDNF and serum did not increase synaptic formation, altered cellular structures such as abundant polyribosomes and more developed endoplasmic reticulum indicate a potential increase in protein production.


Description and phylogenetic relationships of a new trans-Andean species of Elachistocleis Parker 1927 (Amphibia, Anura, Microhylidae).
Elachistocleis is a Neotropical genus of microhylid frogs with 18 species, most of which occur east of the Andes in South America. Here, we present a new phylogeny of Gastrophryninae and describe and name a new species of Elachistocleis from southern Ecuador-the first to be found west of the Andes and also the first from Ecuador. Our phylogeny is based on DNA sequences of the mitochondrial genes 12S rRNA, 16S rRNA, COI, and the nuclear genes BDNF, cmyc2, H3A, 28S, SIA1, and Tyr. Elachistocleis araios sp. n., is the sister species of all other Elachistocleis. The finding of this taxon highlights the probability of the existence of more Elachistocleis species west of the Andes.


Severe Myasthenic Manifestation of Leptospirosis Associated with New Sequence Type of Leptospira interrogans.
We report the rapid development of a myasthenic crisis as the first-time manifestation of myasthenia gravis. The symptoms developed in the course of acute leptospirosis associated with a new sequence type of Leptospira interrogans. Antibiotic treatment led to rapid amelioration of myasthenia.


[Penile horn].
Two cases of penile horn are reported. This infrequent condition appears usually after a surgical circumcision. One of the cases presented with generalized metastasis. The nosology, prognosis and treatment of this entity is discussed.


Effect of noise on tasks in operating theatres: a survey of the perceptions of healthcare staff.
Noise in the operating theatre has an adverse impact on healthcare professionals, both physically and psychologically. It can be distracting, make communication difficult, and contribute to a perceived increase in stress. Staff in theatre must deliver high quality care, and overlook noise as a potentially damaging influence. The aim of this survey was to obtain further information about the perspective of healthcare professionals on how noise can affect their practice and whether it affects their work in theatre. We distributed six closed-ended questions in the form of a Survey Monkey® questionnaire to about 50 hospitals across the UK and target groups such as medical students, the Leeds Advanced Trauma Life Support faculty group, the Court of Examiners of the Royal College of Surgeons of England, and surgical trainees sitting the Member of the Royal College of Surgeons examination. We received 519 responses of which 415 respondents (83%) thought that noise contributed to human errors. A total of 282 participants (57%) thought that the theatre was the noisiest area within the theatre suite. Both communication among staff (n=400, 80%) and concentration (n=384, 77%) were thought to be adversely affected by noise. However, 385 (78%) did not feel that music adversely affected their performance. The results provide insights into the interplay of noise and its effect on people. Although the role of music remains contentious, our results suggest that it might have a calming influence.


Unraveling the Synergy of Anion Modulation on Co Electrocatalysts by Pulsed Laser for Water Splitting: Intermediate Capturing by In Situ/Operando Raman Studies.
Herein, the authors produce Co-based (Co3 (PO4 )2 , Co3 O4 , and Co9 S8 ) electrocatalysts via pulsed laser ablation in liquid (PLAL) to explore the synergy of anion modulation on phase-selective active sites in the electrocatalytic hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Co3 (PO4 )2 displays an ultralow overpotential of 230 mV at 10 mA cm-2 with 48.5 mV dec-1 Tafel slope that outperforms the state-of-the-art Ir/C in OER due to its high intrinsic activity. Meanwhile, Co9 S8 exhibits the highest HER performance known to the authors among the synthesized Co-based catalysts, showing the lowest overpotential of 361 mV at 10 mA cm-2 with 95.8 mV dec-1 Tafel slope in the alkaline medium and producing H2 gas with ≈500 mmol g-1 h-1 yield rate under -0.45 V versus RHE. The identified surface reactive intermediates over in situ electrochemical-Raman spectroscopy reveal that cobalt(hydr)oxides with higher oxidation states of Co-cation forming under oxidizing potentials on the electrode-electrolyte surface of Co3 (PO4 )2 facilitate the OER, while Co(OH)2 facilitate the HER. Notably, the fabricated two-electrode electrolyzers using Co3 (PO4 )2 , Co3 O4 , and Co9 S8 electrocatalysts deliver the cell potentials ≈2.01, 2.11, and 1.89 V, respectively, at 10 mA cm-2 . This work not only shows PLAL-synthesized electrocatalysts as promising candidates for water splitting, but also provides an underlying principle for advanced energy-conversion catalysts and beyond.


Immunohistological detection of mu, delta and kappa opioid-like receptors in the gill, gonad, and hemocytes of the scallop Chlamys farreri.
Endogenous opioid peptides and opioid receptors form a neuromodulatory system, which plays an important part in the control of physiological pathways. In addition, some opioid peptides can function as endogenous messengers of the immune system and participate in the regulation of the immune response. The present studies indicated that mu, delta, and kappa opioid-like receptors were present in the gill and gonad of the scallop Chlamys farreri. Furthermore, the significance of opioid peptides involvement with the immune system is ascertained from the presence of mu, delta, and kappa opioid-like receptors on hemocytes of the scallop. Our report constitutes the first characterization of mu, delta, and kappa opioid-like receptors in the gill and gonad of the scallop Chlamys farreri.


Epigenetic methodologies for behavioral scientists.
Hormones are essential regulators of many behaviors. Steroids bind either to nuclear or membrane receptors while peptides primarily act via membrane receptors. After a ligand binds, the conformational change in the receptor initiates changes in cell signaling cascades (membrane receptors) or direct alternations in DNA transcription (steroid receptors). Changes in gene transcription that result are responsible for protein production and ultimately behavioral modifications. A significant part of how hormones affect DNA transcription is via epigenetic modifications of DNA and/or the chromatin in which it is entwined. These alterations lead to transcriptional changes that ultimately define the phenotype and function of a given cell. Importantly we now know that environmental stimuli influence epigenetic marks, which in the context of neuroendocrinology can lead to behavioral changes. Importantly tracking epigenetic states and profiling the epigenome within cells require the use of epigenetic methodologies and subsequent data analysis. Here we describe the techniques of particular importance in the mapping of DNA methylation, histone modifications and occupancy of chromatin bound effector proteins that regulate gene expression. For researchers wanting to move into these levels of analysis we discuss the application of modern sequencing technologies applied in assays such as chromatin immunoprecipitation and the bioinformatics analysis involved in the rich datasets generated.


Biochemical characterization of the helicase Sen1 provides new insights into the mechanisms of non-coding transcription termination.
Pervasive transcription is widespread and needs to be controlled in order to avoid interference with gene expression. In Saccharomyces cerevisiae, the highly conserved helicase Sen1 plays a key role in restricting pervasive transcription by eliciting early termination of non-coding transcription. However, many aspects of the mechanism of termination remain unclear. In this study we characterize the biochemical activities of Sen1 and their role in termination. First, we demonstrate that the helicase domain (HD) is sufficient to dissociate the elongation complex (EC) in vitro. Both full-length Sen1 and its HD can translocate along single-stranded RNA and DNA in the 5΄ to 3΄ direction. Surprisingly, however, we show that Sen1 is a relatively poorly processive enzyme, implying that it must be recruited in close proximity to the RNA polymerase II (RNAPII) for efficient termination. We present evidence that Sen1 can promote forward translocation of stalled polymerases by acting on the nascent transcript. In addition, we find that dissociation of the EC by Sen1 is favoured by the reannealing of the DNA upstream of RNAPII. Taken together, our results provide new clues to understand the mechanism of Sen1-dependent transcription termination and a rationale for the kinetic competition between elongation and termination.


Stimulation of interferon regulatory factor-1 by prolactin.
Prolactin (PRL), a pituitary peptide hormone, is known to regulate diverse cellular functions including proliferation, differentiation, angiogenesis and protection against apoptosis and inflammation. To understand the mechanism of PRL signaling in T cells, we have cloned both PRL and its receptor (PRL-R), one potent mediator of PRL signaling, Stat5b, and a panel of PRL-inducible immediate early genes from T cells. We are employing these genes as tools with which to understand how PRL regulates the expression of one target gene, the transcription factor interferon regulatory factor-1 (IRF-1), which is a multifunctional immune regulator gene. In investigating regulatory events along the PRL-R/JAK/Stat/IRF-1 signaling pathway, we show that Stat factors can activate as well as inhibit IRF-1 promoter activity and that cross-talk between Stat and NFkappaB signaling pathways also regulates IRF-1 promoter activity. These findings have much broader implications not only for T lymphocytes but also for other PRL responsive target cells and tissues.


Myeloperoxidase content is a marker of systemic inflammation in a chronic condition: the example given by the periodontal disease in rats.
The study aimed to evaluate the suitability of myeloperoxidase (MPO) content as a local indicator of chronic inflammation, using the periodontal disease model. Anesthetized adult male Holtzman rats had their second left maxilar molar tied by a thread for 11 days and were then killed. Blood samples and photographic images from histopathological inflamed and noninflamed (contralateral) neighboring gingivomucosal specimens were collected for cell counts and MPO level analysis. Diseased animals were also treated with pharmacological tools such as the anti-inflammatory drug celecoxib or the opioid morphine. Increased blood neutrophils and local cell numbers characterized diseased animals. However, local MPO content was increased in inflamed and noninflamed tissues from diseased animals. Celecoxib and morphine reduced blood neutrophils and bilateral MPO content, but only celecoxib reduced local cell numbers in diseased animals. It is concluded that MPO content is a good indicator of a systemic rather than a local inflammation in a chronic inflammatory condition.


The differences of anaesthetic care in paediatrics compared to adults.
In the study of holistic perspectives in perioperative care the following article focuses on the care required for paediatric patients through the perioperative period. This incorporates an understanding of the anatomical, physiological and pharmacological differences from adult practice, acknowledging the most important principles of patient safety. The planning, implementation, equipment adaptations and psychological challenges associated with this group will be discussed in relation to improving the overall perioperative experience.


Genomic Profiling on an Unselected Solid Tumor Population Reveals a Highly Mutated Wnt/β-Catenin Pathway Associated with Oncogenic EGFR Mutations.
Oncogenic epidermal growth factor receptors (EGFRs) can recruit key effectors in diverse cellular processes to propagate oncogenic signals. Targeted and combinational therapeutic strategies have been successfully applied for treating EGFR-driven cancers. However, a main challenge in EGFR therapies is drug resistance due to mutations, oncogenic shift, alternative signaling, and other potential mechanisms. To further understand the genetic alterations associated with oncogenic EGFRs and to provide further insight into optimal and personalized therapeutic strategies, we applied a proprietary comprehensive next-generation sequencing (NGS)-based assay of 435 genes to systematically study the genomic profiles of 1565 unselected solid cancer patient samples. We found that activating EGFR mutations were predominantly detected in lung cancer, particularly in non-small cell lung cancer (NSCLC). The mutational landscape of EGFR-driven tumors covered most key signaling pathways and biological processes. Strikingly, the Wnt/β-catenin pathway was highly mutated (48 variants detected in 46% of the EGFR-driven tumors), and its variant number topped that in the TP53/apoptosis and PI3K-AKT-mTOR pathways. Furthermore, an analysis of mutation distribution revealed a differential association pattern of gene mutations between EGFR exon 19del and EGFR L858R. Our results confirm the aggressive nature of the oncogenic EGFR-driven tumors and reassure that a combinational strategy should have advantages over an EGFR-targeted monotherapy and holds great promise for overcoming drug resistance.


Parafalcine chondrosarcoma: report of a case and review of the literature.
Intracranial chondrosarcomas are cartilaginous tumours that are extremely rare with an estimated incidence of less than 0.16% of all intracranial neoplasms. They arise from the skull base synchondrosis or exceptionally from cartilaginous rests within the dura mater. This kind of tumours presents clinical features mimicking meningiomas, with symptoms secondary to mass effect (increased intracranial pressure, local brain dysfunction, cranial nerve palsies) and seizures. Intracranial chondrosarcomas are more frequently seen between 3 months and 76 years of age, with a peak around the third decade, with an equal sex distribution. The authors report a case of a 32-year-old woman with a chondrosarcoma of the falx cerebri.


A web-based interactive physiologically based pharmacokinetic (iPBPK) model for meloxicam in broiler chickens and laying hens.
Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) commonly used in food-producing animals, including chickens in an extralabel manner. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model for meloxicam in broiler chickens and laying hens to facilitate withdrawal interval (WDI) estimations. The model structure for broiler chickens contained six compartments including plasma, muscle, liver, kidney, fat and rest of body, while an additional compartment of ovary was included for laying hens. The model adequately simulated available pharmacokinetic data of meloxicam in plasma of broiler chickens as well as tissue and egg data of laying hens. The model was converted to a web-based interface and used to predict WDIs following extralabel administrations. The results showed that the estimated WDIs were 50, 44, 11, 3, 3, 22 and 4 days for liver, kidney, muscle, fat, ovary, yolk and white, respectively in laying hens after 14 repeated oral administrations of meloxicam (1 mg/kg) at 24-h intervals. This model provides a useful and flexible tool for risk assessment and management of residues for meat and eggs from chickens treated with meloxicam and will serve as a basis for extrapolation to other NSAID drugs and other poultry species to aid animal-derived food safety assessment.


A prospective study of sodium-lithium countertransport and hypertension in Utah.
A 7-year prospective study of a cohort of 1,458 normotensive adults from Utah pedigrees, screened from 1980 to 1985, was done to determine whether baseline levels of sodium-lithium countertransport were associated with an increased risk of future hypertension. Subsequent new hypertension (n = 39) was ascertained in 1989 from detailed follow-up medical questionnaires (67% response). Previous segregation analyses on a subset of these pedigree members who responded (n = 342) using family relationships in addition to countertransport levels have shown statistically inferred major gene segregation of sodium-lithium countertransport levels. In the normotensive adults inferred by segregation analysis to carry the recessive major gene for high sodium-lithium countertransport, new-onset hypertension occurred in 18.8% (3 of 16) compared with 3.7% (12 of 326) in the low sodium-lithium countertransport genotype group (relative risk, 4.6 [1.6, 13.9]; p = 0.03). However, an elevated baseline sodium-lithium countertransport level without genotype information from segregation analysis did not increase the risk of future hypertension in the complete cohort of adult pedigree members (relative risk, 1.02 [0.85, 1.22]). Adjustment for other risk factors reduced the relative risk to 0.90 (0.72, 1.11). We conclude that the presence of a major gene for sodium-lithium countertransport or another closely linked gene, rather than the actual level of sodium-lithium countertransport, may increase the risk of hypertension onset. High sodium-lithium countertransport levels do not increase the risk of future hypertension for individuals in whom only polygenic and environmental effects determine sodium-lithium countertransport level.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum Metabolomic Profiles in Neonatal Mice following Oral Brominated Flame Retardant Exposures to Hexabromocyclododecane (HBCD) Alpha, Gamma, and Commercial Mixture.
Hexabromocyclododecane (HBCD) is a high production volume brominated flame retardant added to building insulation foams, electronics, and textiles. HBCD is a commercial mixture (CM-HBCD) composed of three main stereoisomers: α-HBCD (10%), β-HBCD (10%), and γ-HBCD (80%). A shift from the dominant stereoisomer γ-HBCD to α-HBCD is detected in humans and wildlife. Considering CM-HBCD has been implicated in neurodevelopment and endocrine disruption, with expected metabolism perturbations, we performed metabolomics on mice serum obtained during a window-of-developmental neurotoxicity to draw correlations between early-life exposures and developmental outcomes and to predict health risks. Six female C57BL/6 mice at postnatal day (PND) 10 were administered a single gavage dose of α-, γ-, or CM-HBCD at 3, 10, and 30 mg/kg. Nuclear magnetic resonance metabolomics was used to analyze 60 μL serum aliquots of blood collected 4 days post-oral exposure. Infantile mice exposed to α-, γ-, or CM-HBCD demonstrated differences in endogenous metabolites by treatment and dose groups, including metabolites involved in glycolysis, gluconeogenesis, lipid metabolism, citric acid cycle, and neurodevelopment. Ketone bodies, 3-hydroxybutyrate, and acetoacetate, were nonstatistically elevated, when compared with mean control levels, in all treatment and dose groups, while glucose, pyruvate, and alanine varied. Acetoacetate was significantly increased in the 10 mg/kg α-HBCD and was nonsignificantly decreased with CM-HBCD. A third ketone body, acetone, was significantly lower in the 30 mg/kg α-HBCD group with significant increases in pyruvate at the same treatment and dose group. Metabolites significant in differentiating treatment and dose groups were also identified, including decreases in amino acids glutamate (excitatory neurotransmitter in learning and memory) and phenylalanine (neurotransmitter precursor) after α-HBCD and γ-HBCD exposure, respectively. We demonstrated that 4 days following a single neonatal oral exposure to α-, γ-, and CM-HBCD resulted in different serum metabolomic profiles, indicating stereoisomer- and mixture-specific effects and possible mechanisms of action.


Immune responses to Schistosoma haematobium infection.
Urogenital schistosomiasis is one of the greatest single infectious sources of human morbidity and mortality known. Through a complex cycle of infection, migration and eventual maturation and mating, S. haematobium (the aetiological agent of urogenital schistosomiasis) deposits highly immunogenic eggs within the bladder and other pelvic organs, activating a wide range of immune programs that determine both infection outcome as well as downstream immunopathology. In this review, we discuss the experimental and observational bases for our current understanding of these immune programs, focusing specifically on how the balance of type 1 and type 2 responses governs subsequent immunopathology and clinical outcome.


[Diagnosis and treatment of calcium pyrophosphate crystal-induced arthropathy].
Calcium pyrophosphate dihydrate deposition (CPPDD) disease is the term used to describe a group of common and potentially severe metabolic arthropathies. In these, CPPD crystals form and are deposited in the cartilage matrix (chondrocalcinosis) and induce inflammatory and/or destructive mechanisms. Most cases are idiopathic, but hyperparathyroidism, hemochromatosis, hypomagnesemia and hypophosphatemia can promote or cause chondrocalcinosis. Early disease (with onset before the age of 60 years) thus requires that the patient be examined for these metabolic conditions, particularly hemochromatosis. The prevalence of CPPDD disease in the general population increases with age, being 10-15% in the age group 65-75 years and more than 40% in the over-80s. Although frequently asymptomatic, chondrocalcinosis can involve severe acute attacks of inflammatory arthritis (pseudogout) and also various types of chronic arthropathy including pseudorheumatoid arthritis, pseudo-osteoarthritis, and pseudoneuropathic joint disease. CPPD crystals can also be deposited in the bursae, ligaments, and tendons and generate inflammation and/or ruptures. The diagnosis is based on synovial fluid analysis (positively birefringent CPPD crystals visualized by compensated polarized light microscopy) and X-rays (punctate and linear radiodense areas in fibrocartilage and hyaline cartilage). Treatment is primarily symptomatic, since there is no known drug that can prevent progression of the joint destruction). Nonsteroid anti-inflammatory drugs (NSAIDs) and intra-articular or systemic glucocorticoids (amounts must be only small if use is prolonged) are the most useful treatments. Colchicine can be effective in recurring pseudogout, and magnesium can be used prophylactically. In a small uncontrolled series methotrexate was effective and aroused interest; it can be used when other treatments fail.


Assessment of bruise age on dark-skinned individuals using tristimulus colorimetry.
Studies on the ageing of bruises have been reported on Caucasians or individuals of fair ethnicity. This study focuses on bruise changes in dark-skinned individuals using tristimulus colorimetry for forensic analysis in such individuals. Eighteen subjects of South Indian or Sri-Lankan ethnicity were recruited. Subjects were bruised using a vacuum pump and then daily colour measurements were taken of the bruise using a tristimulus colorimeter. The L*a*b* readings were recorded of a control area and of the bruise until it disappeared. Two Caucasians were used for comparison. This study showed that, using colorimetry, bruises on dark-skinned individuals can be measured and analysed even if the bruises are unclear visually. As the bruise is beneath the skin, the colour difference ΔL*, Δa* and Δb* were calculated. All values showed a trend, indicating that the L*a*b* measuring technique is a reliable method to analyse bruises on dark-skinned individuals. Comparisons of Asian subjects and Caucasian subjects were performed. The largest difference was seen in the b* value. Statistical analysis showed that ΔL* colour difference was the most consistent (95% CI -4.05 to -2.49) showing a significant difference between days 1-4 and 5-8. Objective assessment of bruises on dark-skinned individuals using the L*a*b* method of measuring gave reproducible results. Furthermore, the study showed that the yellowing of a bruise cannot be seen or measured with a tristimulus colorimeter on dark-skinned individuals due to the pigmentation of the skin. With further studies and more subjects, the age of bruises could potentially be assessed for use in forensic analysis.


A longitudinal investigation of dietary diversity during the COVID-19 pandemic in Mandinka households in Kanifing, Brikama, and the West Kiang region in The Gambia.
The Covid pandemic has exposed fissures of inequality through heightened food insecurity and nutritional deficiency for vulnerable social cohorts with limited coping mechanisms. Given the multi-dimensional pathways through which its effects have been felt, several researchers have highlighted the need to analyse the pandemic in specific contexts. Using random and fixed effect regression models, this study analyzed longitudinal survey data collected from 103 Mandinka households in rural and urban Gambia. The study employed convenience and snowball sampling and involved the monthly collection of detailed income, food consumption, expenditure, sourcing, migration, health, and coping mechanism data through mobile phone interviews which yielded 676 observations. Food insecurity was manifest in terms of quality, not quantity, and spread unevenly across food types and households. Dietary outcomes and sourcing strategies were associated with location, improved sanitation, household size, changes in monthly income, Covid policy stringency, and Covid cases but these associations varied by food group. Staples were the most frequently consumed food group, and dark green vegetables were the least. Rural communities were more likely to eat more healthy millets but much less likely to consume dairy products or roots and tubers. Access to own production was also important for Vitamin A-rich foods but higher incomes and markets were key for protein and heme-iron-rich foods. Tighter Covid policy stringency was negatively associated with dietary diversity and, along with fear of market hoarding, was positively associated with reliance on a range of consumption and production coping mechanisms. Resilience was higher in larger households and those with improved water and sanitation. The number of Covid cases was associated with higher consumption of protein-rich foods and greater reliance on own produced iron-rich foods. Very few households received Government aid and those that did already had access to other income sources. Our findings suggest that the nature of food insecurity may have evolved over time during the pandemic. They also reiterate not only the importance of access to markets and employment but also that the capacity to absorb affordability shocks and maintain food choices through switching between sources for specific nutritious food groups varied by household and location.